Effects of Intra-operative Cardiopulmonary Variability On Post-operative Pulmonary Complications in Major Non-cardiac Surgery: A Retrospective Cohort Study.

Intraoperative cardiopulmonary variables are well-known predictors of postoperative pulmonary complications (PPC), traditionally quantified by median values over the duration of surgery. However, it is unknown whether cardiopulmonary instability, or wider intra-operative variability of the same metrics, is distinctly associated with PPC risk and severity. We leveraged a retrospective cohort of adults (n = 1202) undergoing major non-cardiothoracic surgery. We used multivariable logistic regression to evaluate the association of two outcomes (1)moderate-or-severe PPC and (2)any PPC with two sets of exposure variables- (a)variability of cardiopulmonary metrics (inter-quartile range, IQR) and (b)median intraoperative cardiopulmonary metrics. We compared predictive ability (receiver operating curve analysis, ROC) and parsimony (information criteria) of three models evaluating different aspects of the intra-operative cardiopulmonary metrics: Median-based: Median cardiopulmonary metrics alone, Variability-based: IQR of cardiopulmonary metrics alone, and Combined: Medians and IQR. Models controlled for peri-operative/surgical factors, demographics, and comorbidities. PPC occurred in 400(33%) of patients, and 91(8%) experienced moderate-or-severe PPC. Variability in multiple intra-operative cardiopulmonary metrics was independently associated with risk of moderate-or-severe, but not any, PPC. For moderate-or-severe PPC, the best-fit predictive model was the Variability-based model by both information criteria and ROC analysis (area under the curve, AUCVariability-based = 0.74 vs AUCMedian-based = 0.65, p = 0.0015; AUCVariability-based = 0.74 vs AUCCombined = 0.68, p = 0.012). For any PPC, the Median-based model yielded the best fit by information criteria. Predictive accuracy was marginally but not significantly higher for the Combined model (AUCCombined = 0.661) than for the Median-based (AUCMedian-based = 0.657, p = 0.60) or Variability-based (AUCVariability-based = 0.649, p = 0.29) models. Variability of cardiopulmonary metrics, distinct from median intra-operative values, is an important predictor of moderate-or-severe PPC.

Transdermal scopolamine for the treatment of recurrent parotid sialocele: a case report.

Recurrent parotid sialocele is rare and challenging to treat. Treatment options are limited for cases of parotid sialocele that recur despite ductal ligation. This case study presents a patient who underwent wide excision of the right buccal mucosa due to squamous cell carcinoma. During the wide excision, a segment of the parotid duct was excised, and ductal ligation was performed to prevent the occurrence of a sialocele, followed by reconstruction using a folded anterolateral thigh free flap. Twenty-two days after surgery, parotid sialocele occurred despite the initial ductal ligation and subsequent ductal ligation was performed; however, the sialocele recurred. As an alternative therapeutic option, a transdermal scopolamine patch was applied for 3 weeks, with one patch used every 3 days. The results were encouraging, with complete resolution of the sialocele. A transdermal scopolamine offers a noninvasive, convenient method of treating parotid sialocele with minimal side effects. The successful outcome of this case suggests that a transdermal scopolamine can be an effective therapeutic option for recurrent parotid sialocele in conjunction with surgical treatment.

Malignant Extrapleural Solitary Fibrous Tumor.

Solitary fibrous tumors (SFTs) are rare spindle cell neoplasms of mesenchymal origin that are most commonly found in the pleura, although they have also been documented in extrapleural locations. SFTs affect males and females in equal distribution, and they typically occur between the fourth and seventh decades of life. Since SFTs are usually benign and asymptomatic, the majority of them are discovered incidentally on computed tomography (CT) or magnetic resonance imaging (MRI) imaging, unless they grow to a size that causes mass effect symptoms on other organs. Nonetheless, imaging is not sufficient to diagnose an SFT, and therefore, biopsy is recommended for further analysis. Advances in immunohistochemistry and molecular diagnostics have identified CD34 and NAB2-STAT6, respectively, as the most consistent markers for SFTs. The risk of SFT metastasis can be determined through the use of a four-variable risk-stratification model developed by Demicco et al., which is based upon the risk factors of patient age, tumor size, mitotic count per 10 high-power fields, and the degree of tumor necrosis. The management of SFTs involves a wide surgical resection of the tumor while preserving surrounding organs and structures. Post-operative surveillance involves imaging the primary tumor site for up to five years due to the risk of local recurrence. At this time, neither radiation therapy nor chemotherapy after resection have yet to show benefit, and therefore, they are not currently recommended. This case report discusses the management of a 68-year-old woman who was diagnosed with a malignant extrapleural SFT in her right medial upper thigh.

Clinical features of chronic fungal rhinosinusitis in Korean geriatric and non-geriatric patients.

PURPOSE: Worldwide, the incidence of chronic fungal rhinosinusitis (CFRS) has increased. Although ageing leads to weakening of the immune system, which increases susceptibility to CFRS, the CFRS characteristics in geriatric patients are unclear. Therefore, we comparatively analysed the clinical characteristics of CFRS in geriatric and non-geriatric patients. METHODS: This retrospective analysis compared the demographics, rhinologic symptoms, multiple allergen simultaneous tests, olfactory function tests, paranasal sinus computed tomography findings, and outcomes of 131 patients with CFRS who underwent functional endoscopic sinus surgery and 131 enrolled patients were divided in geriatric (> 65 years) and non-geriatric (≤ 65 years) groups. RESULTS: Among the geriatric and non-geriatric participants (n = 65, 49.6% and n = 66, 50.4%, respectively), hypertension and diabetes mellitus were more common in the geriatric group. Demographics, including symptoms, showed no significant intergroup differences. Normosmia and hyposmia were significantly less prevalent, whereas phantosmia and parosmia were more prevalent in the geriatric group than in the non-geriatric group (p = 0.03 and p = 0.01, respectively). Sphenoidal sinus involvement was significantly higher in geriatric patients than in non-geriatric patients (p = 0.02). CONCLUSION: Based on greater sphenoidal sinus involvement, a deeper anatomical area is more vulnerable to fungal infection in the geriatric group than in the non-geriatric group. Increasing clinicians' awareness of CFRS in geriatric patients with olfactory dysfunction, including phantosmia and parosmia, is important for early intervention.

Comparison of a Tobacco-Specific Carcinogen in Tobacco Cigarette, Electronic Cigarette, and Dual Users.

BACKGROUND: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is known as a lung carcinogen. The objective of this study was to investigate associations of urine NNAL concentrations and smoking status. METHODS: This was a cross-sectionally designed study based on data from the 2016-2018 Korean National Health and Nutrition Examination Survey. A total of 2,845 participants were classified into past-smoker, electronic cigarette (e-cigar) only, dual-user, and cigarette only smoker groups. All sampling and weight variables were stratified and analysis was conducted accounting for the complex sampling design. Analysis of covariance was used to compare the geometric mean of urine NNAL concentrations and log-transformed urine NNAL level among smoking status with weighted survey design. Post hoc paired comparisons with Bonferroni adjustment was performed according to smoking status. RESULTS: The estimated geometric mean concentrations of urine NNAL were 1.974 ± 0.091, 14.349 ± 5.218, 89.002 ± 11.444, and 117.597 ± 5.459 pg/mL in past-smoker, e-cigar only, dual-user, and cigarette only smoker groups, respectively. After fully adjusting, log-transformed urine NNAL level was significantly different among groups (P < 0.001). Compared with the past-smoker group, e-cigar only, dual-user, and cigarette only smoker groups showed significantly higher log-transformed urine NNAL concentrations in post hoc test (all P < 0.05). CONCLUSION: E-cigar only, dual-user, and cigarette only smoker groups showed significantly higher geometric mean concentrations of urine NNAL than the past-smoker group. Conventional cigarette, dual users, and e-cigar users can potentially show harmful health effects from NNAL.

Mesenchymal stem cell-derived exosomes for treatment of sepsis.

Introduction: The pathogenesis of sepsis is an imbalance between pro-inflammatory and anti-inflammatory responses. At the onset of sepsis, the lungs are severely affected, and the injury progresses to acute respiratory distress syndrome (ARDS), with a mortality rate of up to 40%. Currently, there is no effective treatment for sepsis. Cellular therapies using mesenchymal stem cells (MSCs) have been initiated in clinical trials for both ARDS and sepsis based on a wealth of pre-clinical data. However, there remains concern that MSCs may pose a tumor risk when administered to patients. Recent pre-clinical studies have demonstrated the beneficial effects of MSC-derived extracellular vesicles (EVs) for the treatment of acute lung injury (ALI) and sepsis. Methods: After recovery of initial surgical preparation, pneumonia/sepsis was induced in 14 adult female sheep by the instillation of Pseudomonas aeruginosa (~1.0×1011 CFU) into the lungs by bronchoscope under anesthesia and analgesia. After the injury, sheep were mechanically ventilated and continuously monitored for 24 h in a conscious state in an ICU setting. After the injury, sheep were randomly allocated into two groups: Control, septic sheep treated with vehicle, n=7; and Treatment, septic sheep treated with MSC-EVs, n=7. MSC-EVs infusions (4ml) were given intravenously one hour after the injury. Results: The infusion of MSCs-EVs was well tolerated without adverse events. PaO2/FiO2 ratio in the treatment group tended to be higher than the control from 6 to 21 h after the lung injury, with no significant differences between the groups. No significant differences were found between the two groups in other pulmonary functions. Although vasopressor requirement in the treatment group tended to be lower than in the control, the net fluid balance was similarly increased in both groups as the severity of sepsis progressed. The variables reflecting microvascular hyperpermeability were comparable in both groups. Conclusion: We have previously demonstrated the beneficial effects of bone marrow-derived MSCs (10×106 cells/kg) in the same model of sepsis. However, despite some improvement in pulmonary gas exchange, the present study demonstrated that EVs isolated from the same amount of bone marrow-derived MSCs failed to attenuate the severity of multiorgan dysfunctions.

Lymphaticovenular anastomosis for Morbihan disease: a case report.

Morbihan disease (MD) is a very rare condition characterized by rosaceous or erythematous lymphedema on the upper twothirds of the face. A definitive management strategy for MD is lacking, and treatment is challenging. Herein, we present a case of persistent bilateral eyelid edema treated by lymphaticovenular anastomosis (LVA) and lymph node-vein bypass surgery. The patient experienced persistent bilateral eyelid edema. Indocyanine green lymphography was performed, and the diagnosis of bilateral facial lymphedema was confirmed. On the right side, a preauricular lymphatic vessel was anastomosed to a vein. On the left side, lymphostomy on the preauricular lymph node was done, with anastomosis to the transected proximal end of the concomitant vein of the transverse facial artery. Furthermore, a preauricular lymphatic vessel was anastomosed to a vein. Eyelid edema decreased and progressively improved on both sides. The outcome of this case suggests that LVA and lymph node-vein bypass surgery are appropriate for treating persistent eyelid edema related to MD.

Robotic Ventral Transabdominal Preperitoneal Repair of Uncomplicated Spigelian Hernia.

Spigelian hernias are rare herniations through the Spigelian fascia, with an incidence rate of 0.12-2.0% of all hernias. Diagnosis may be difficult due to a potential lack of symptoms until complications arise. Therefore, imaging with either ultrasound or CT with oral contrast is recommended to confirm the diagnosis if a Spigelian hernia is suspected. Once the diagnosis has been established, it is essential that operative repair be performed as soon as possible because 24% of Spigelian hernias become incarcerated, and 27% of Spigelian hernias lead to strangulation. Management options include open surgery, laparoscopic surgery, and robotic surgery. This case report discusses the management of a 47-year-old man with an uncomplicated Spigelian hernia that was repaired with the robotic ventral transabdominal preperitoneal repair technique.

Endoscopic Removal of Supraperiosteal Heterotopic Ossification of the Forehead.

Heterotopic ossification (HO) refers to the mature lamellar bone structure that develops locally in soft-tissue sites. Heterotopic ossification is known to occur mainly in the traumatic area or the muscle and joint capsule after surgery such as total hip arthroplasty or total knee arthroplasty. The pathophysiological cause of HO is not precisely known, but it seems to be related to some genetic predisposition. Craniomaxillofacial HO is rare and, in several reported cases, is primarily related to previous surgeries involving the masticatory muscles. The authors report on a patient who underwent endoscopic removal of a bone mass in the forehead. He completely denied any history of forehead trauma or surgery. There were no scars, trauma, or surgical marks found on the patient's forehead. Preoperative magnetic resonance imaging showed that the mass was granuloma, but histological examination after surgical removal confirmed it as HO.

Temporary blindness caused by corneal edema after a local anesthetic injection in the eyebrow region: a case report.

Plastic surgery around the eyes is usually performed under local anesthesia, using a mixture of lidocaine and epinephrine. Blindness is a rare but devastating complication after the injection of local anesthesia in this region. Most cases reported to date have been caused by occlusion of the ophthalmic artery or central retinal artery. In this case report, however, we present a highly unusual case of blindness caused by corneal edema after a local anesthetic injection. A patient visited the emergency room with a laceration on the eyebrow, and local anesthesia was injected before suturing. Immediately after the injection, severe corneal edema developed, making it impossible to observe the structures in the anterior chamber in detail or check the light reflex and visual acuity of the naked eye. An antibiotic (moxifloxacin hydrochloride) and high-concentration steroid eyedrops were promptly applied. High-concentration steroids were also administered orally. On day 13 post-injury, the visual acuity of the naked eye improved to 1.0, and no recurrence of corneal lesions was observed. Although the cause of corneal edema after the local injection could not be conclusively identified, we hope that this report will help raise clinicians' awareness of this complication and appropriate treatment methods.

Outcomes of lipectomy in patients with advanced unilateral upper extremity lymphedema with regard to the difference in time required for indocyanine green to reach the axilla: A retrospective cohort study in a single center.

This study aimed to compare and analyze the prognosis after lipectomy with respect to the difference in time required for indocyanine green (ICG) to reach the axilla in patients with advanced unilateral upper extremity lymphedema. The study population was divided into 2 groups, according to the time required by ICG to reach the axilla after injection, that is, <1 hour (<1 hour; n = 9) and over 1 hour (>1 hour; n = 8). The patient's arm volume was examined before surgery and up to 12 months after surgery. The volume difference between the 2 groups was compared using the excess volume ratio. Statistically significant differences were not observed before surgery (P = .847) and 1 month (P = .336), 3 months (P = .630), and 6 months after surgery (P = .124) between the excess volume ratio values of the < 1 hour and > 1 hour groups. A statistically significant difference was confirmed 12 months after surgery (P = .034). The difference in the time when ICG reached the axilla in patients with lymphedema was associated with prognosis after lipectomy. The difference in time could possibly be used as a variable to classify the progress of lymphedema in the future.

Role of extracellular vesicles in lung diseases.

ABSTRACT: Extracellular vesicles (EVs) are anuclear particles composed of lipid bilayers that contain nucleic acids, proteins, lipids, and organelles. EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components, including lipids, proteins, messenger RNAs, DNA, microRNAs, organelles, etc, to nearby or distant target cells to activate and regulate the function and phenotype of target cells. Under physiological conditions, EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease, asthma, acute lung injury/acute respiratory distress syndrome, idiopathic pulmonary fibrosis (IPF), and pulmonary artery hypertension. In addition, in multiple preclinical studies, EVs derived from mesenchymal stem cells (EVs) have shown promising therapeutic effects on reducing and repairing lung injuries. Furthermore, in recent years, researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects. This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.

Characterization of Immunopathology and Small Airway Remodeling in Constrictive Bronchiolitis.

Rationale: Constrictive bronchiolitis (ConB) is a relatively rare and understudied form of lung disease whose underlying immunopathology remains incompletely defined. Objectives: Our objectives were to quantify specific pathological features that differentiate ConB from other diseases that affect the small airways and to investigate the underlying immune and inflammatory phenotype present in ConB. Methods: We performed a comparative histomorphometric analysis of small airways in lung biopsy samples collected from 50 soldiers with postdeployment ConB, 8 patients with sporadic ConB, 55 patients with chronic obstructive pulmonary disease, and 25 nondiseased control subjects. We measured immune and inflammatory gene expression in lung tissue using the NanoString nCounter Immunology Panel from six control subjects, six soldiers with ConB, and six patients with sporadic ConB. Measurements and Main Results: Compared with control subjects, we found shared pathological changes in small airways from soldiers with postdeployment ConB and patients with sporadic ConB, including increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and lymphocyte infiltration. Using principal-component analysis, we showed that ConB pathology was clearly separable both from control lungs and from small airway disease associated with chronic obstructive pulmonary disease. NanoString gene expression analysis from lung tissue revealed T-cell activation in both groups of patients with ConB with upregulation of proinflammatory pathways, including cytokine-cytokine receptor interactions, NF-κB (nuclear factor-κB) signaling, TLR (Toll-like receptor) signaling, T-cell receptor signaling, and antigen processing and presentation. Conclusions: These findings indicate shared immunopathology among different forms of ConB and suggest that an ongoing T-helper cell type 1-type adaptive immune response underlies airway wall remodeling in ConB.

Postoperative pulmonary complications with adjuvant regional anesthesia versus general anesthesia alone: a sub-analysis of the Perioperative Research Network study.

BACKGROUND: Adjuvant regional anesthesia is often selected for patients or procedures with high risk of pulmonary complications after general anesthesia. The benefit of adjuvant regional anesthesia to reduce postoperative pulmonary complications remains uncertain. In a prospective observational multicenter study, patients scheduled for non-cardiothoracic surgery with at least one postoperative pulmonary complication surprisingly received adjuvant regional anesthesia more frequently than those with no complications. We hypothesized that, after adjusting for surgical and patient complexity variables, the incidence of postoperative pulmonary complications would not be associated with adjuvant regional anesthesia. METHODS: We performed a secondary analysis of a prospective observational multicenter study including 1202 American Society of Anesthesiologists physical status 3 patients undergoing non-cardiothoracic surgery. Patients were classified as receiving either adjuvant regional anesthesia or general anesthesia alone. Predefined pulmonary complications within the first seven postoperative days were prospectively identified. Groups were compared using bivariable and multivariable hierarchical logistic regression analyses for the outcome of at least one postoperative pulmonary complication. RESULTS: Adjuvant regional anesthesia was performed in 266 (22.1%) patients and not performed in 936 (77.9%). The incidence of postoperative pulmonary complications was greater in patients receiving adjuvant regional anesthesia (42.1%) than in patients without it (30.9%) (site adjusted p = 0.007), but this association was not confirmed after adjusting for covariates (adjusted OR 1.37; 95% CI, 0.83-2.25; p = 0.165). CONCLUSION: After adjusting for surgical and patient complexity, adjuvant regional anesthesia versus general anesthesia alone was not associated with a greater incidence of postoperative pulmonary complications in this multicenter cohort of non-cardiothoracic surgery patients.

Exposure to Secondhand Smoke and a Tobacco-Specific Carcinogen in Non-Smokers.

BACKGROUND: The International Agency for Research on Cancer classifies 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) as a known carcinogen. This study aimed to investigate the association between exposure to secondhand smoke (SHS) and NNAL concentrations in non-smokers. METHODS: This was a cross-sectional study based on data from the 2016 to 2018 Korea National Health and Nutrition Examination Survey. Urine NNAL concentrations were categorized into tertiles of 3,615 study participants who were non-smokers. All sampling and weight variables were stratified, and analyses to account for the complex sampling design were conducted. RESULTS: The overall, male, and female percentages of SHS exposure among non-smokers were 22.4%, 29.2%, and 20.4%, respectively. The geometric means of urine NNAL concentrations were 1.896±0.098 pg/mL and 1.094±0.028 pg/mL in the SHS exposure and non-exposure groups, respectively. After adjusting for confounding variables, in the total group, the geometric mean of urine NNAL concentrations was significantly higher in the SHS exposure group than in the SHS non-exposure group (adjusted P-value <0.001). Compared with the non-exposure group, the adjusted odds ratios (95% confidence intervals) for the highest NNAL tertile group of overall SHS exposure in the total, men, and women groups were 2.44 (1.95-3.05), 1.65 (1.08-2.53), and 2.73 (2.11-3.52), respectively, after full adjustment. CONCLUSION: The urine NNAL concentration in the SHS exposure group was significantly higher than that in the non-exposure group. Exposure to SHS was associated with a higher risk of elevated urine NNAL concentrations in non-smokers.

Reconstruction of temporal hollowing deformities using silicone implants made using a toy-clay model: a report of three cases.

Severe temporal hollowing deformities can occur in patients who undergo craniectomy after intracranial hemorrhage. Reconstruction surgery for cosmetic purposes using silicone implants in patients with temporal hollowing deformities after craniectomy is advantageous because the procedure is simple and rapid, with a short recovery time, resulting in lower overall treatment costs. Of paramount importance, this option yields highly satisfactory results for patients. The authors present three cases of simple and fast surgery using silicone implants where highly satisfactory outcomes were obtained.

Recent trends in opioid prescriptions in Korea from 2002 to 2015 based on the Korean NHIS-NSC cohort.

OBJECTIVES: Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015. METHODS: The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC). RESULTS: The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids. CONCLUSIONS: Consumption of opioids greatly increased in Korea over the 14-year study period.

A Novel Regulatory Role of Activated Leukocyte Cell-Adhesion Molecule in the Pathogenesis of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by fibroproliferative matrix molecule accumulation, collagen deposition, and apoptosis. Activated leukocyte cell-adhesion molecule (ALCAM; CD166) is a cell-adhesion molecule that has been implicated in adhesive and migratory attribution, including leukocyte homing and trafficking and cancer metastasis. We investigated the role of ALCAM on pulmonary fibrosis development in murine models. Thus, a bleomycin-induced pulmonary fibrosis model was established with wild-type and ALCAM-/- mice. Pulmonary fibrosis was also induced in transforming growth factor-ß1 (TGF-ß1)-transgenic mice that conditionally overexpress TGF-ß1 upon doxycycline administration. In both models, observed reduced ALCAM levels in lung tissue and BAL fluid in pulmonary fibrosis-induced wild-type mice compared with control mice. We also observed reduced ALCAM expression in the lung tissue of patients with pulmonary fibrosis compared with normal lung tissue. ALCAM-/- mice showed an exacerbated lung fibrosis response compared with wild-type mice, and this was accompanied by increased cell death. Further investigation for identification of the signaling pathway revealed that PI3K and ERK signaling pathways are involved in bleomycin-induced fibrosis. Collectively, these results highlight that ALCAM plays a protective role in the pathogenesis of pulmonary fibrosis that inhibits epithelial cell apoptosis through the PI3K-Akt signaling pathway. Our findings demonstrate the potential of ALCAM as a therapeutic target for IPF and may aid the development of new strategies for the management and treatment of patients with IPF.

Chitinase 3-like 1 is involved in the induction of IL-8 expression by double-stranded RNA in airway epithelial cells.

Viral respiratory infection causes inflammatory lung disease. Chitinase 3-like 1 (CHI3L1) contributes to airway inflammation, but its role in human airway epithelial cells following viral infection is unclear. Thus, we investigated whether CHI3L1 regulates inflammatory responses caused by viral infections in airway epithelial cells. Human bronchial epithelial cells, BEAS-2B, were stimulated with a synthetic analog of viral double-stranded RNA, polyinosinic:polycytidylic acid (poly(I:C)). To confirm the specific role of CHI3L1, CHI3L1 was knocked down in BEAS-2B cells using shRNA lentivirus. The expression of CHI3L1 and proinflammatory cytokines such as IL-8 and phosphorylation of mitogen-activated protein kinase (MAPK) pathways were analyzed. In addition to poly(I:C), BEAS-2B cells were infected with the human respiratory syncytial virus (RSV) A2 strain, and CHI3L1 and IL-8 expression was analyzed. Stimulating the cells with poly(I:C) increased CHI3L1 and IL-8 expression, whereas IL-8 expression was abrogated in CHI3L1 knockdown BEAS-2B cells. Poly(I:C) stimulation of BEAS-2B cells resulted in phosphorylation of MAPK pathways, and inhibition of MAPK pathways significantly abolished IL-8 secretion. Phosphorylation of MAPK pathways was diminished in CHI3L1 knockdown BEAS-2B cells. Infection with RSV increased CHI3L1 and IL-8 expression. IL-8 expression induced by RSV infection was abrogated in CHI3L1 knockdown cells. In conclusion, CHI3L1 may be involved in IL-8 secretion by regulating MAPK pathways during respiratory viral infections in airway epithelial cells.

Cost-Effectiveness Analysis of Home-Based Hospice-Palliative Care for Terminal Cancer Patients.

Purpose: We compared cost-effectiveness parameters between inpatient and home-based hospice-palliative care services for terminal cancer patients in Korea. Methods: A decision-analytic Markov model was used to compare the cost-effectiveness of hospice-palliative care in an inpatient unit (inpatient-start group) and at home (home-start group). The model adopted a healthcare system perspective, with a 9-week horizon and a 1-week cycle length. The transition probabilities were calculated based on the reports from the Korean National Cancer Center in 2017 and Health Insurance Review & Assessment Service in 2020. Quality of life (QOL) was converted to the quality-adjusted life week (QALW). Modeling and cost-effectiveness analysis were performed with TreeAge software. The weekly medical cost was estimated to be 2,481,479 Korean won (KRW) for inpatient hospice-palliative care and 225,688 KRW for home-based hospice-palliative care. One-way sensitivity analysis was used to assess the impact of different scenarios and assumptions on the model results. Results: Compared with the inpatient-start group, the incremental cost of the home-start group was 697,657 KRW, and the incremental effectiveness based on QOL was 0.88 QALW. The incremental cost-effectiveness ratio (ICER) of the home-start group was 796,476 KRW/QALW. Based on one-way sensitivity analyses, the ICER was predicted to increase to 1,626,988 KRW/QALW if the weekly cost of home-based hospice doubled, but it was estimated to decrease to -2,898,361 KRW/QALW if death rates at home doubled. Conclusion: Home-based hospice-palliative care may be more cost-effective than inpatient hospice-palliative care. Home-based hospice appears to be affordable even if the associated medical expenditures double.