The Immune Suppressor IGSF1 as a Potential Target for Cancer Immunotherapy.

The development of first-generation immune-checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 ushered in a new era in anticancer therapy. Although immune-checkpoint blockade therapies have shown clinical success, a substantial number of patients yet fail to benefit. Many studies are under way to discover next-generation immunotherapeutic targets. Immunoglobulin superfamily member 1 (IGSF1) is a membrane glycoprotein proposed to regulate thyroid function. Despite containing 12 immunoglobin domains, a possible role for IGSF1, in immune response, remains unknown. Here, our studies revealed that IGSF1 is predominantly expressed in tumors but not normal tissues, and increased expression is observed in PD-L1low non-small cell lung cancer (NSCLC) cells as compared with PD-L1high cells. Subsequently, we developed and characterized an IGSF1-specific human monoclonal antibody, WM-A1, that effectively promoted antitumor immunity and overcame the limitations of first-generation immune-checkpoint inhibitors, likely via a distinct mechanism of action. We further demonstrated high WM-A1 efficacy in humanized peripheral blood mononuclear cells (PBMC), and syngeneic mouse models, finding additive efficacy in combination with an anti-PD-1 (a well-characterized checkpoint inhibitor). These findings support IGSF1 as an immune target that might complement existing cancer immunotherapeutics.

Early life exposure to perfluorooctanesulfonate (PFOS) impacts vital biological processes in Xenopus laevis: Integrated morphometric and transcriptomic analyses.

Perfluorooctanesulfonate (PFOS) is a ubiquitous environmental pollutant associated with increasing health concerns and environmental hazards. Toxicological analyses of PFOS exposure are hampered by large interspecies variations and limited studies on the mechanistic details of PFOS-induced toxicity. We investigated the effects of PFOS exposure on Xenopus laevis embryos based on the reported developmental effects in zebrafish. X. laevis was selected to further our understanding of interspecies variation in response to PFOS, and we built upon previous studies by including transcriptomics and an assessment of ciliogenic effects. Midblastula-stage X. laevis embryos were exposed to PFOS using the frog embryo teratogenesis assay Xenopus (FETAX). Results showed teratogenic effects of PFOS in a time- and dose-dependent manner. The morphological abnormalities of skeleton deformities, a small head, and a miscoiled gut were associated with changes in gene expression evidenced by whole-mount in situ hybridization and transcriptomics. The transcriptomic profile of PFOS-exposed embryos indicated the perturbation in the expression of genes associated with cell death, and downregulation in adenosine triphosphate (ATP) biosynthesis. Moreover, we observed the effects of PFOS exposure on cilia development as a reduction in the number of multiciliated cells and changes in the directionality and velocity of the cilia-driven flow. Collectively, these data broaden the molecular understanding of PFOS-induced developmental effects, whereby ciliary dysfunction and disrupted ATP synthesis are implicated as the probable modes of action of embryotoxicity. Furthermore, our findings present a new challenge to understand the links between PFOS-induced developmental toxicity and vital biological processes.

Ruvbl1 is Essential for Ciliary Beating during Xenopus laevis Embryogenesis.

The Ruvb-like AAA ATPase1 (Ruvbl1; also known as Pontin) is an evolutionary conserved protein belonging to the adenosine triphosphates associated with diverse cellular activities (AAA+) superfamily of ATPases. Ruvbl1 is a component of various protein supercomplexes and is involved in a variety of cellular activities, including chromatin remodeling, DNA damage repair, and mitotic spindle assembly however, the developmental significance of this protein is unknown and needs detailed investigation. We investigated the developmental significance of Ruvbl1 in multiciliated cells of the Xenopus laevis epidermis since ruvbl1 is expressed in the multiciliated cells and pronephros during X. laevis embryogenesis. The knockdown of ruvbl1 significantly impaired cilia-driven fluid flow and basal body polarity in the X. laevis epidermis compared to control embryos, but did not affect cilia morphology. Our results suggest that Ruvbl1 plays a significant role in embryonic development by regulating ciliary beating; however, further investigation is needed to determine the mechanisms involved.

Effect of the Chemical Properties of Silane Coupling Agents on Interfacial Bonding Strength with Thermoplastics in the Resizing of Recycled Carbon Fibers.

Upcycling recycled carbon fibers recovered from waste carbon composites can reduce the price of carbon fibers while improving disposal-related environmental problems. This study assessed and characterized recycled carbon fibers subjected to sizing treatment using N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (APS) chemically coordinated with polyamide 6 (PA6) and polypropylene (PP) resins. Sizing treatment with 1 wt.% APS for 10 s yielded O=C-O on the surface of the carbon fiber, and the -SiOH in the APS underwent a dehydration-condensation reaction that converted O=C-O (lactone groups) into bonds of C-O (hydroxyl groups) and C=O (carbonyl groups). The effects of C-O and C=O on the interfacial bonding force increased to a maximum, resulting in an oxygen-to-carbon ratio (O/C) of 0.26. The polar/surface energy ratio showed the highest value of 32.29% at 10 s, and the interfacial bonding force showed the maximum value of 32 MPa at 10 s, which is about 15% better than that of commercial carbon fiber (PA6-based condition). In 10 s resizing treatments with 0.5 wt.% 3-methacryloxypropyltrimethoxysilane (MPS), C-O, C=O, and O=C-O underwent a dehydration-condensation reaction with -SiOH, which broke the bonds between carbon and oxygen and introduced a methacrylate group (H2C=C(CH3)CO2H), resulting in a significant increase in C-O and C=O, with an O/C of 0.51. The polar/surface free energy ratio was about 38% at 10 s, with the interfacial bonding force increasing to 27% compared to commercial carbon fiber (PP-based conditions). MPS exhibited a superior interfacial shear strength improvement, two times higher than that of APS, with excellent coordination with PP resin and commercial carbon fiber, although the interfacial bonding strength of the PP resin was significantly lower.

Comparison of the end-of-life decisions of patients with hospital-acquired pneumonia after the enforcement of the life-sustaining treatment decision act in Korea.

BACKGROUND: Although the Life-Sustaining Treatment (LST) Decision Act was enforced in 2018 in Korea, data on whether it is well established in actual clinical settings are limited. Hospital-acquired pneumonia (HAP) is a common nosocomial infection with high mortality. However, there are limited data on the end-of-life (EOL) decision of patients with HAP. Therefore, we aimed to examine clinical characteristics and outcomes according to the EOL decision for patients with HAP. METHODS: This multicenter study enrolled patients with HAP at 16 referral hospitals retrospectively from January to December 2019. EOL decisions included do-not-resuscitate (DNR), withholding of LST, and withdrawal of LST. Descriptive and Kaplan-Meier curve analyses for survival were performed. RESULTS: Of 1,131 patients with HAP, 283 deceased patients with EOL decisions (105 cases of DNR, 108 cases of withholding of LST, and 70 cases of withdrawal of LST) were analyzed. The median age was 74 (IQR 63-81) years. The prevalence of solid malignant tumors was high (32.4% vs. 46.3% vs. 54.3%, P = 0.011), and the ICU admission rate was lower (42.9% vs. 35.2% vs. 24.3%, P = 0.042) in the withdrawal group. The prevalence of multidrug-resistant pathogens, impaired consciousness, and cough was significantly lower in the withdrawal group. Kaplan-Meier curve analysis revealed that 30-day and 60-day survival rates were higher in the withdrawal group than in the DNR and withholding groups (log-rank P = 0.021 and 0.018). The survival of the withdrawal group was markedly decreased after 40 days; thus, the withdrawal decision was made around this time. Among patients aged below 80 years, the rates of EOL decisions were not different (P = 0.430); however, mong patients aged over 80 years, the rate of withdrawal was significantly lower than that of DNR and withholding (P = 0.001). CONCLUSIONS: After the LST Decision Act was enforced in Korea, a DNR order was still common in EOL decisions. Baseline characteristics and outcomes were similar between the DNR and withholding groups; however, differences were observed in the withdrawal group. Withdrawal decisions seemed to be made at the late stage of dying. Therefore, advance care planning for patients with HAP is needed.

Awareness and Needs of Smoking Cessation Services for Female Emotional Laborers, Parcel Delivery Workers, Transportation Workers, and Construction Workers in South Korea.

Although South Korea has implemented various smoking cessation services, women who are emotional laborers, as well as parcel delivery, transportation, and construction workers, have poor access to these services. This study evaluated the smoking-related characteristics of workers in these four occupations as well as the awareness of and need for smoking cessation services. In total 808 workers in these four occupations aged 19 years and above were recruited nationwide and had their data analyzed. The participants' age, marital status, number of work hours per week, job-related stress, age when they started smoking, average number of cigarettes a day, types of tobacco products, close relationships to others who smoke, number of attempts to quit smoking, plans to quit smoking, awareness of cessation services, prior utilization of cessation services, and need for cessation services were surveyed. Compared with parcel delivery workers, female emotional laborers and transportation and construction workers had more attempts to quit smoking, plans to quit smoking, and prior utilization of smoking cessation services, moreover, construction workers had a significantly lower awareness of smoking cessation services. Parcel delivery workers need smoking cessation programs, mobile applications to help them quit smoking, and improvements in their work environments. Cessation services and education should be promoted at workplaces and among managers.

Impact of nutrition and physical activity on outcomes of hospital-acquired pneumonia.

Frailty is an important risk factor for adverse health-related outcomes. It is classified into several phenotypes according to nutritional state and physical activity. In this context, we investigated whether frailty phenotypes were related to clinical outcome of hospital-acquired pneumonia (HAP). During the study period, a total of 526 patients were screened for HAP and 480 of whom were analyzed. The patients were divided into four groups according to physical inactivity and malnutrition: nutritional frailty (Geriatric Nutritional Risk Index [GNRI] < 82 and Clinical Frailty Scale [CFS] ≥ 4), malnutrition (GNRI < 82 and CFS < 4), physical frailty (GNRI ≥ 82 and CFS ≥ 4), and normal (GNRI ≥ 82 and CFS < 4). Among the phenotypes, physical frailty without malnutrition was the most common (39.4%), followed by nutritional frailty (30.2%), normal (20.6%), and malnutrition (9.8%). There was a significant difference in hospital survival and home discharge among the four phenotypes (p = 0.009), and the nutritional frailty group had the poorest in-hospital survival and home discharge (64.8% and 34.6%, respectively). In conclusion, there were differences in clinical outcomes according to the four phenotypes of HAP. Assessment of frailty phenotypes during hospitalization may improve outcomes through adequate nutrition and rehabilitation treatment of patients with HAP.

Clinical outcomes of hyperprogression based on volumetry in non-small cell lung cancer after immune checkpoint inhibitor treatment.

BACKGROUND: Hyperprogressive disease (HPD) is a novel pattern of the treatment course after immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics, outcomes, and associated factors of HPD using a semiautomatic volume measurement. METHODS: This retrospective study enrolled patients with recurrent and/or metastatic NSCLC treated with ICIs between January 2015 and August 2019 at eight tertiary centers in Korea. HPD was defined according to the tumor growth kinetics and time to treatment failure. Tumor volume was measured using a semiautomatic software. RESULTS: A total of 219 NSCLC patients with 35 HPD by volumetric measurement (HPDv) (15.9%) were enrolled. The median duration of overall survival (OS) and OS after ICI treatment (ICI-OS) were 34.5 and 18.4 months, respectively. HPDv patients had significantly worse progression-free survival (PFS) than progressive disease patients without HPDv (1.16 vs. 1.82 months, p-value <0.001). ICI-OS did not significantly differ between patients with HPDv and those without HPDv (2.66 vs. 5.4 months, p = 0.105). PD-L1 expression lower than 50%, more than three metastatic sites, neutrophil-to-lymphocyte ratio equal to or higher than 3.3, and hemoglobin level lower than 10 were found to be associated with HPDv. CONCLUSIONS: There is no standardized definition of HPD. However, defining HPD in NSCLC patients treated with ICI using a semiautomatic volume measurement software is feasible.

Microbiologic pattern and clinical outcome of non-ICU-acquired pneumonia: Korean HAP registry analysis.

BACKGROUND/AIMS: Most studies on hospital-acquired pneumonia (HAP) have been conducted in intensive care unit (ICU) settings. This study aimed to investigate the microbiological and clinical characteristics of non-ICU-acquired pneumonia (NIAP) and to identify the factors affecting clinical outcomes in Korea. METHODS: This multicenter retrospective cohort study was conducted in patients admitted to 13 tertiary hospitals between July 1, 2019 and December 31, 2019. Patients diagnosed with NIAP were included in this study. To assess the prognostic factors of NIAP, the study population was classified into treatment success and failure groups. RESULTS: Of 526 patients with HAP, 379 were diagnosed with NIAP. Overall, the identified causative pathogen rate was 34.6% in the study population. Among the isolated organisms (n = 113), gram-negative bacilli were common pathogens (n = 91), such as Pseudomonas aeruginosa (n = 25), Acinetobacter baumannii (n = 23), and Klebsiella pneumoniae (n = 21). The multidrug resistance rates of A. baumannii, P. aeruginosa, and K. pneumoniae were 91.3%, 76.0%, and 57.1%, respectively. Treatment failure was significantly associated with K. pneumoniae (odds ratio [OR], 3.50; 95% confidence interval [CI], 1.35 to 9.05; p = 0.010), respiratory viruses (OR, 3.81; 95% CI, 1.34 to 10.82; p = 0.012), hematological malignancies (OR, 3.54; 95% CI, 1.57 to 8.00; p = 0.002), and adjunctive corticosteroid treatment (OR, 2.40; 95% CI, 1.27 to 4.52; p = 0.007). CONCLUSION: The causative pathogens of NIAP in Korea are predominantly gram-negative bacilli with a high rate of multidrug resistance. These were not different from the common pathogens of ICU-acquired pneumonia.

Successful treatment of induced oligometastasis and repeated oligoprogression of advanced lung adenocarcinoma with immunotherapy and radiotherapy.

Highly active and durable systemic therapies such as targeted therapy and immunotherapy can convert widespread metastatic disease into oligometastatic status, for which metastasis-directed local intervention can control and potentially prolong survival. Radiation therapy is an effective therapeutic option for oligometastatic and oligoprogressive disease. Here, we present a case of induced oligometastasis and repeated oligoprogressive lung cancer in which more than 6 years of survival was achieved with a combination of immunotherapy and radiotherapy.

Zic5 stabilizes Gli3 via a non-transcriptional mechanism during retinal development.

The Zic family of zinc finger transcription factors plays a critical role in multiple developmental processes. Using loss-of-function studies, we find that Zic5 is important for the differentiation of retinal pigmented epithelium (RPE) and the rod photoreceptor layer through suppressing Hedgehog (Hh) signaling. Further, Zic5 interacts with the critical Hh signaling molecule, Gli3, through the zinc finger domains of both proteins. This Zic5-Gli3 interaction disrupts Gli3/Gli3 homodimerization, resulting in Gli3 protein stabilization via a reduction in Gli3 ubiquitination. During embryonic Hh signaling, the activator form of Gli is normally converted to a repressor form through proteosome-mediated processing of Gli3, and the ratio of Gli3 repressor to full-length (activator) form of Gli3 determines the Gli3 repressor output required for normal eye development. Our results suggest Zic5 is a critical player in regulating Gli3 stability for the proper differentiation of RPE and rod photoreceptor layer during Xenopus eye development.

CEP97 phosphorylation by Dyrk1a is critical for centriole separation during multiciliogenesis.

Proper cilia formation in multiciliated cells (MCCs) is necessary for appropriate embryonic development and homeostasis. Multicilia share many structural characteristics with monocilia and primary cilia, but there are still significant gaps in our understanding of the regulation of multiciliogenesis. Using the Xenopus embryo, we show that CEP97, which is known as a negative regulator of primary cilia formation, interacts with dual specificity tyrosine phosphorylation regulated kinase 1A (Dyrk1a) to modulate multiciliogenesis. We show that Dyrk1a phosphorylates CEP97, which in turn promotes the recruitment of Polo-like kinase 1 (Plk1), which is a critical regulator of MCC maturation that functions to enhance centriole disengagement in cooperation with the enzyme Separase. Knockdown of either CEP97 or Dyrk1a disrupts cilia formation and centriole disengagement in MCCs, but this defect is rescued by overexpression of Separase. Thus, our study reveals that Dyrk1a and CEP97 coordinate with Plk1 to promote Separase function to properly form multicilia in vertebrate MCCs.

CO2/N2 Gas Separation Using Pebax/ZIF-7-PSf Composite Membranes.

In this study, we mixed the zeolitic imidazolate framework-7 (ZIF-7) with poly(ether-b-amide)® 2533 (Pebax-2533) and used it as a selective layer for a composite membrane. We prepared the composite membrane's substrate using polysulfone (PSf), adjusted its pore size using polyethylene glycol (PEG), and applied polydimethylsiloxane (PDMS) to the gutter layer and the coating layer. Then, we investigated the membrane's properties of gases by penetrating a single gas (N2, CO2) into the membrane. We identified the peaks and geometry of ZIF-7 to determine if it had been successfully synthesized. We confirmed that ZIF-7 had a BET surface area of 303 m2/g, a significantly high Langmuir surface area of 511 m2/g, and a high CO2/N2 adsorption selectivity of approximately 50. Considering the gas permeation, with ZIF-7 mixed into Pebax-2533, N2 permeation decreased from 2.68 GPU in a pure membrane to 0.43 GPU in the membrane with ZIF-7 25 wt%. CO2 permeation increased from 18.43 GPU in the pure membrane to 26.22 GPU in the ZIF-7 35 wt%. The CO2/N2 ideal selectivity increased from 6.88 in the pure membrane to 50.43 in the ZIF-7 25 wt%. Among the membranes, Pebax-2533/ZIF-7 25 wt% showed the highest permeation properties and the characteristics of CO2-friendly ZIF-7.

Genotype and Phenotype Analysis in X-Linked Hypophosphatemia.

Background: X-linked hypophosphatemia (XLH) is the most frequent form of hypophosphatemic rickets and is caused by mutations in the PHEX gene. We analyzed genotype-phenotype correlations in XLH patients with proven PHEX mutations. Methods: PHEX mutations were detected in 55 out of 81 patients who clinically presented with hypophosphatemic rickets. The patients were grouped into nontruncating (n = 9) and truncating (n = 46) mutation groups; their initial presentation as well as long-term clinical findings were evaluated according to these groups. Results: Initial findings, including presenting symptoms, onset age, height standard deviation scores (SDS), and laboratory tests, including serum phosphate level and tubular resorption of phosphate, were not significantly different between the two groups (onset age: nontruncating mutation group, 2.0 years, truncating mutation group, 2.2 years; height SDS: nontruncating mutation group, -1.9, truncating mutation group, -1.7; serum phosphate: nontruncating mutation group, 2.5 mg/dL, truncating mutation group, 2.6 mg/dL). However, at their last follow-up, the serum phosphate level was significantly lower in patients with truncating mutations (nontruncating mutation group: 3.2 mg/dl, truncating mutation group: 2.3 mg/dl; P = 0.006). Additionally, 62.5% of patients with truncating mutations developed nephrocalcinosis at their last follow-up, while none of the patients with nontruncating mutations developed nephrocalcinosis (P = 0.015). Orthopedic surgery due to bony deformations was performed significantly more often in patients with truncating mutations (52.3 vs. 10.0%, P = 0.019). Conclusion: Although considerable inconsistency exists regarding the correlation of truncating mutations and their disease phenotype in several other studies, we cautiously suggest that there would be genotype-phenotype correlation in some aspects of disease manifestation after long-term follow-up. This information can be used when consulting patients with confirmed XLH regarding their disease prognosis.

Successful Smoking Cessation among Women Smokers Based on Utilizing National Smoking Cessation Service Type in Korea.

BACKGROUND: This study aimed to evaluate the successful smoking cessation across different national smoking cessation services. METHODS: This study included data that had been previously entered into the integrated information system for smoking cessation services and comprised 144,688 participants after excluding missing data. These clinics provide face-to-face counseling, phone calls, text messages, and e-mail services for six months and nine sessions. RESULTS: The women-only program had the lowest success rate (11.3%). Compared with the women-only program, the six-month success rate of smoking cessation clinic at public health centers (OR = 3.72, CI = [3.52, 3.92]), visiting-type smoking cessation clinics (OR = 2.97, CI = [2.79, 3.16]), the residential 4 -night 5-day program (OR = 7.79, CI = [6.49, 9.35]), and a program for inpatients (OR = 2.36, CI = [1.89, 2.94]) showed a significant increase. CONCLUSIONS: Emotional labor workers who participated in the women-only program had low smoking cessation success rates, while those who participated in the residential 4-night 5-day program had high success rates.

The Utilization of National Tobacco Cessation Services among Female Smokers and the Need for a Gender-Responsive Approach.

Despite the steadily increasing prevalence of female smoking, gender-responsive tobacco cessation services have not been widely provided worldwide. The purpose of this study is to identify factors associated with the use of tobacco cessation services among female tobacco product users in Korea from a national perspective. We performed a logistic regression analysis using data from 663 female smokers; 11.0% of female smokers had used government-supported smoking cessation services. A logistic regression model showed a statistically significant association between the utilization of smoking cessation services and a history of pregnancy and childbirth, depression, current use of heated tobacco products and multiple tobacco products, parental smoking status and receiving advice to quit. With regard to the motivation ruler, those in their 50s reported a higher importance than those in their 20s. Weight gain concerns when quitting smoking were the lowest among the participants aged 19-29. The need to develop gender-specific smoking cessation programs is the highest among the participants aged 39-49 and the lowest among those aged 19-29. This study suggests several factors related to the utilization of national health services among female smokers. Further studies considering gender-specific needs for the development of gender-responsive tobacco cessation support are needed.

Prognostic Factors of Second-line Immune Checkpoint Inhibitors in Patients With Advanced-stage Non-Small Cell Lung Cancer: A Multicenter, Retrospective Study.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting the programmed cell death receptor-1 and its ligand have achieved impressive success in treating patients with advanced-stage non-small cell lung cancer (NSCLC) after failed first-line cytotoxic chemotherapy. However, knowledge on clinical biomarkers that could help select patients who will respond well to second-line ICI therapy is limited. PATIENTS AND METHODS: Medical records of patients with NSCLC treated with first-line platinum-based chemotherapy and subsequent second-line ICI were collected from 6 medical centers between January 2018 and June 2020. Clinical information, pathologic variables, and radiologic findings of the data collected were reviewed. The patients were followed up until the date of the last visit, the death of any cause, or the end of data recording (December 31, 2020). RESULTS: A total of 181 patients with NSCLC were treated with second-line ICI following first-line platinum-based doublet chemotherapy. The median progression-free survival was 2.0 months (interquartile range, 1.0 to 5.5 mo), and the median overall survival was 12.0 months (interquartile range, 6.0 to 20.0 mo). Low body mass index (BMI) was independently associated with progression-free survival (odds ratio [OR], 0.826; 95% confidence interval [CI], 0.723-0.945; P=0.005). Similarly, a low BMI (OR, 0.839; 95% CI, 0.740-0.952; P=0.005) and a high number of metastatic organs (OR, 1.682; 95% CI, 1.156-2.448; P=0.007) were independently associated with the overall survival after second-line ICI therapy. CONCLUSION: BMI and the number of metastatic sites were significantly associated with second-line ICI therapy outcomes in patients with NSCLC receiving first-line platinum-based chemotherapy.

Erlotinib Activates Different Cell Death Pathways in EGFR-mutant Lung Cancer Cells Grown in 3D Versus 2D Culture Systems.

BACKGROUND/AIM: Non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation have been shown to have a good response to erlotinib, a receptor tyrosine kinase inhibitor of EGFR. In this study, we found that the cell death pathways activated by erlotinib in 2D and 3D culture systems are different. MATERIALS AND METHODS: The cell death pathways induced by erlotinib were evaluated by flow cytometry and immunoblotting in both 2D and 3D culture systems of EGFR mutant lung cancer cells. RESULTS: Treatment with erlotinib induced caspase 8 activation and up-regulation of TNF-related apoptosis-inducing ligand (TRAIL) expression only in 3D cultures. Knockdown of TRAIL attenuated both erlotinib-induced activation of caspase-8 and apoptosis in 3D cultures. Erlotinib also increased LC3, an autophagy marker, expression and c-Jun N terminal kinase (JNK) activation. Both 3-MA as an autophagy inhibitor and SP600125 as a JNK inhibitor, significantly inhibited erlotinib-induced cell death. CONCLUSION: Erlotinib induces apoptotic cell death in 3D cultures through an autophagy-TRAIL-JNK pathway.

Intraoperative Magnetic Resonance Imaging for Low-Grade and High-Grade Gliomas: What Is the Evidence? A Meta-Analysis.

BACKGROUND: The benefit of intraoperative magnetic resonance imaging (iMRI) in gliomas remains unclear. We performed a meta-analysis of outcomes with iMRI-guided surgery in high-grade gliomas (HGGs) and low-grade gliomas (LGGs). METHODS: Databases were searched until November 29, 2018 for randomized controlled trials (RCTs) and observational studies (OBS) comparing iMRI use with conventional neurosurgery. Pooled risk ratios (RRs) or hazard ratios were evaluated with the random-effects model. Outcomes included extent of resection (EOR), gross total resection (GTR), progression-free survival (PFS), overall survival (OS), and length of surgery (LOS), stratified by study design and glioma grade. RESULTS: Fifteen articles (3 RCTs and 12 OBS) were included. In RCTs, GTR was higher in iMRI compared with conventional neurosurgery (RR, 1.42; 95% confidence interval [CI], 1.17-1.73; I2, 7%) overall, for LGGs (1.91; 95% CI, 1.19-3.06), but not HGGs (1.24; 95% CI, 0.89-1.73), with no difference in EOR, PFS, OS, and LOS. For OBS, GTR was higher (RR, 1.65; 95% CI, 1.43-1.90; I2, 4%) overall, and for LGGs (1.63; 95% CI, 1.17-2.28; I2, 0%) and HGGs (1.62; 95% CI, 1.36-1.92; I2, 19%). EOR was greater with iMRI (6%; 95% CI, 4%-8%; I2, 44%) overall, in LGGs (5%; 95% CI, 2%-8%; I2, 37%) and HGGs (7%; 95% CI, 4%-10%; I2, 13%). There was no difference in PFS, OS, and LOS with iMRI. CONCLUSIONS: IMRI use improved GTR in gliomas, including LGGs. However, no PFS and OS benefit was shown in the meta-analysis.

Longitudinal Changes in Clinical Features, Management, and Outcomes of Idiopathic Pulmonary Fibrosis. A Nationwide Cohort Study.

Rationale: In recent decades, diagnosis and treatment recommendations for idiopathic pulmonary fibrosis (IPF) have changed. In Korea, the average life expectancy has increased, unmet healthcare needs have been reduced, and the number of computed tomographic examinations performed has nearly doubled. The Korean Interstitial Lung Disease Study Group conducted a nationwide cohort study for idiopathic interstitial pneumonia, including IPF, and established a registry for IPF.Objectives: Using study data collected by the study group, this study aimed to evaluate longitudinal changes in clinical features, diagnosis, treatment, and mortality and analyze the extent to which changes in medication usage affected IPF-associated mortality.Methods: The study population included newly diagnosed patients with IPF from a cohort study (January 2002 to September 2008, n = 1,839, 2008 group) and prospective registry (January 2012 to August 2018, n = 1,345, 2018 group). Survival curves were estimated using the Kaplan-Meier method, and Cox regression models were used to identify mortality-associated risk factors in each group.Results: The 2018 group was younger, had fewer symptoms, had less honeycombing, underwent more serologic autoimmune marker and pulmonary function tests, had higher oxygen partial pressure and lower carbon dioxide partial pressure values, was less frequently diagnosed by surgical biopsy, and had better survival than the 2008 group. Steroid use and conservative care declined, whereas N-acetylcysteine use increased in this group. Antifibrotic agents were used in only the 2018 group. In the 2008 group, N-acetylcysteine was associated with lower mortality, whereas conservative care was associated with higher mortality. In the 2018 group, the use of antifibrotic agents was associated with lower mortality, and steroid use was associated with higher mortality. The survival rates in the 2008 and 2018 non-antifibrotic agent subgroups were similar.Conclusions: This study analyzed national IPF cohort data spanning 17 years. In clinical practice, the IPF diagnosis was made earlier, steroid and immunosuppressive agent use was reduced, and antifibrotic agents were administered. The survival of patients with IPF has improved over the decades, and antifibrotic use was consistently associated with improved survival.Clinical trial registered with clinicaltrials.gov (NCT04160715).