Structural identification and comprehension of human ALDH1L1-Gossypol complex.

The folate metabolism enzyme ALDH1L1 catalyzed 10-formyltetrahydrofolate to tetrahydrofolate and CO2. Non-small cell lung cancer cells (NSCLC) strongly express ALDH1L1. Gossypol binds to an allosteric site and disrupts the folate metabolism by preventing NADP+ binding. The Cryo-EM structures of tetrameric C-terminal aldehyde dehydrogenase human ALDH1L1 complex with gossypol were examined. Gossypol-bound ALDH1L1 interfered with NADP+ by shifting the allosteric site of the structural conformation, producing a closed-form NADP+ binding site. In addition, the inhibition activity of ALDH1L1 was targeted with gossypol in NSCLC. The gossypol treatment had anti-cancer effects on NSCLC by blocking NADPH and ATP production. These findings emphasize the structure characterizing ALDH1L1 with gossypol.

Structural basis for T cell immunoglobulin and mucin protein 3 and Toxascaris leonina galectin complex.

T-cell immunoglobulin and mucin protein 3 (Tim-3), also known as Hepatitis A virus cellular receptor 2, has been discovered to have a negative regulatory effect on murine T-cell responses. Galectin-9 exhibits various biological effects, including cell aggregation, eosinophil chemoattraction, activation, and apoptosis, observed in murine thymocytes, T-cells, and human melanoma cells. Such approach demonstrated that Galectin-9 acts as a binding partner on Tim-3 and mediates the T-cell inhibitory effects. Tl-gal is a homologous protein to galectin-9, isolated from the adult stage of the canine gastrointestinal nematode parasite Toxascaris leonina. However, molecular mechanism between Tim-3 and galectin-9 is still remain unknown. Here, we describe the cryo-electron microscopy and X-ray structures and interactions of the Tim-3 and Tl-gal complex as well as their biochemical and biophysical characterization. In the structure, Ser46 residue of Tl-gal NCRD was bound to Asp25 residue of hTim-3. Compared to our previous study, the binding site of the complex is the same as the sugar binding site (the Ser46 residue) of Tl-gal. In addition, analysis of the complex structure revealed that the four Tl-gal molecules were in an open form packing and one mTim-3 peptide was bound to one Tl-gal molecule. These observations suggest that how Tl-gal binds hTim3 is essential to understanding the molecular mechanism for the Tim-3-galectin 9 interaction that regulates immune responses. This could potentially serve as a therapeutic target for inflammatory diseases.

Comparative Analysis of CT Findings and Clinical Outcomes in Adult Patients With Disseminated and Localized Pulmonary Nocardiosis.

BACKGROUND: Pulmonary nocardiosis is a rare opportunistic infection with occasional systemic dissemination. This study aimed to investigate the computed tomography (CT) findings and prognosis of pulmonary nocardiosis associated with dissemination. METHODS: We conducted a retrospective analysis of patients diagnosed with pulmonary nocardiosis between March 2001 and September 2023. We reviewed the chest CT findings and categorized them based on the dominant CT findings as consolidation, nodules and/or masses, consolidation with multiple nodules, and nodular bronchiectasis. We compared chest CT findings between localized and disseminated pulmonary nocardiosis and identified significant prognostic factors associated with 12-month mortality using multivariate Cox regression analysis. RESULTS: Pulmonary nocardiosis was diagnosed in 75 patients, of whom 14 (18.7%) had dissemination, including involvement of the brain in 9 (64.3%) cases, soft tissue in 3 (21.4%) cases and positive blood cultures in 3 (21.4%) cases. Disseminated pulmonary nocardiosis showed a higher frequency of cavitation (64.3% vs. 32.8%, P = 0.029) and pleural effusion (64.3% vs. 29.5%, P = 0.014) compared to localized infection. The 12-month mortality rate was 25.3%. The presence of dissemination was not a significant prognostic factor (hazard ratio [HR], 0.80; confidence interval [CI], 0.23-2.75; P = 0.724). Malignancy (HR, 9.73; CI, 2.32-40.72; P = 0.002), use of steroid medication (HR, 3.72; CI, 1.33-10.38; P = 0.012), and a CT pattern of consolidation with multiple nodules (HR, 4.99; CI, 1.41-17.70; P = 0.013) were associated with higher mortality rates. CONCLUSION: Pulmonary nocardiosis with dissemination showed more frequent cavitation and pleural effusion compared to cases without dissemination, but dissemination alone did not affect the mortality rate of pulmonary nocardiosis.

Developmentally Supportive Care Among Neonatal Intensive Care Unit Nurses in South Korea: Knowledge, Perceived Importance, Perception, and Perceived Competence.

BACKGROUND: The concept of developmentally supportive care in preterm infants is of considerable significance in the neonatal intensive care unit (NICU) setting with regard to preventing complications from preterm birth and promoting optimal growth and development. To provide high-quality developmentally supportive care, NICU nurses must possess high levels of knowledge, importance, perception, and competence. PURPOSE: The purpose of this study was to investigate South Korean NICU nursing staff's level of knowledge concerning developmentally supportive care, as well as the perceived importance, perception, and perceived competence regarding this concept. METHODS: This study employed a cross-sectional descriptive design. Between June 1 and 19, 2020, 160 nurses completed a self-report questionnaire pertaining to developmentally supportive care, which covered the aspects of knowledge, perceived importance, perception (including attitudes, perceived behavioral control, subjective norms, and intentions), and perceived competence. RESULTS: The levels of knowledge, attitude, and intention as a subfactor of perception, and perceived competence pertaining to developmentally supportive care were not high. There was no significant difference in the knowledge and perceived competence of skilled nurses compared with novice nurses. However, skilled nurses recognized that they could provide better developmentally supportive care than novice nurses. Perceived competence was positively correlated with perceived importance and perception. IMPLICATIONS FOR PRACTICE AND RESEARCH: Systematic educational programs that can enhance developmentally supportive care competence should be provided to NICU staff nurses. These must clarify the importance of developmentally supportive care and improve NICU nurses' knowledge, attitudes, self-efficacy, and intentions.

Migratory grief and mental health in first-generation Korean American immigrants.

OBJECTIVE: The purpose of this study was to examine first-generation Korean immigrants' migratory grief in relation to cultural, social, and mental health variables. We examined (a) how behavioral and value acculturation and enculturation as well as mainstream and ethnic connectedness predicted migratory grief and (b) how mainstream and ethnic connectedness moderated the relationships of migratory grief and mental health outcomes (i.e., depression, life satisfaction, positive and negative affect). METHOD: Data were collected from 188 self-identified first-generation Korean immigrant adults (N = 188, Mage = 43.63, SD = 12.18) and were analyzed using hierarchical multiple regression. RESULTS: Age and behavioral enculturation positively predicted migratory grief, while European American values and mainstream connectedness negatively predicted migratory grief. Migratory grief and mainstream and ethnic connectedness had significant main effects on mental health, but social connectedness did not moderate the relationships between migratory grief and mental health. CONCLUSION: Acculturation, enculturation, and social connectedness were significant predictors of first-generation Korean immigrants' migratory grief. Additionally, migratory grief and social connectedness significantly predicted mental health. We discussed implications for research and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Development and validation of the fingertip unit for assessing Facial Vitiligo Area Scoring Index.

BACKGROUND: Facial involvement of vitiligo is an important factor in a patient's life and has often been evaluated separately from body surface area in clinical trials. However, no reliable tools to measure facial vitiligo specifically are available thus far. OBJECTIVE: To develop and validate a practical instrument for assessing facial vitiligo. METHODS: The ratios of a hand to a fingertip unit (FTU) of 98 healthy volunteers (age range, 2-69 years) were calculated to define the FTU. Facial Vitiligo Area Scoring Index was measured as the sum of all FTUs of each vitiligo lesion on the face (range, 0-112 FTU). In the validation study, 6 raters evaluated 11 patients with facial vitiligo twice at an interval of 2 weeks. RESULTS: One hand was measured at 32.1 ± 1.3 FTU, which was highly consistent among subjects across different age groups, sexes, and races. Facial Vitiligo Area Scoring Index showed remarkably high accuracy (concordance correlation coefficient, 0.946; smallest detectable change, 2.2 FTU) as well as high intrarater reliability (intraclass correlation coefficient, 0.903; inter-rater reliability, 0.903). LIMITATIONS: Lack of dynamic validation of responsiveness. CONCLUSION: Facial Vitiligo Area Scoring Index using the FTU is an intuitive, precise, and reliable instrument for assessing the extent of facial involvement in vitiligo patients.

Incidental Thyroid Nodule on Chest Computed Tomography: Application of Computed Tomography Texture Analysis in Prediction of Ultrasound Classification.

OBJECTIVE: The aim of the study was to evaluate the value of computed tomography (CT) texture analysis (CTTA) in predicting ultrasound (US) classification of incidentally detected thyroid nodule (ITN) on chest CT. METHODS: A total of 117 ITNs (≥1 cm in the longest diameter) on chest CT scan of 107 patients was divided into 4 categories according to the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) classification on recent thyroid US within 3 months. Computed tomography texture features were extracted with or without filtration using commercial software. The texture features were compared between the benign (K-TIRADS 2; n = 21) and the suspicious (K-TIRADS 3, 4, 5; n = 96) nodules. Multivariate regression and area under the receiver operating characteristic curve analysis were performed to determine significant prediction factors of the suspicious nodules. RESULTS: The mean value of positive pixels was significantly higher in the suspicious nodules except the unfiltered image (P < 0.05). Entropy of the suspicious nodules was significantly higher with unfiltered and fine filters (P < 0.05), and kurtosis of the suspicious nodules was significantly higher with medium and coarse filters (P < 0.05). A logistic regression model incorporating mean value of positive pixels and kurtosis with a medium filter using volumetric analysis demonstrated the best performance to predict the suspicious nodules with an area under the receiver operating characteristic curve of 0.842 (P < 0.001, sensitivity 82.3%, and specificity 81.0%). CONCLUSIONS: Computed tomography texture analysis for ITN larger than 1 cm showed significant correlation with systematic thyroid US classification and presented excellent performance to predict the suspicious nodules.

Structural basis of the p53 DNA binding domain and PUMA complex.

PUMA (p53-upregulated modulator of apoptosis) is localized in mitochondria and a direct target in p53-mediated apoptosis. p53 elicits mitochondrial apoptosis via transcription-dependent and independent mechanisms. p53 is known to induce apoptosis via the transcriptional induction of PUMA, which encodes proapoptotic BH3-only members of the Bcl-2 protein family. However, the transcription-independent mechanisms of human PUMA remain poorly defined. For example, it is not known whether PUMA interacts directly with the DNA binding domain (DBD: residues 92-293) of p53 in vitro. Here, the structure of the complex between the DBD of p53 and PUMA peptide was elucidated by X-ray crystallography. Isothermal titration calorimetry showed that PUMA peptide binds strongly with p53 DBD, and the crystal structure of p53-PUMA peptide complex revealed it contains four molecules of p53 DBD and one PUMA peptide per asymmetric unit in space group P1. PUMA peptide bound to the N-terminal residues of p53 DBD. A cell proliferation assay demonstrated PUMA peptide inhibited the growth of a lung cancer cell line. These results contribute to understanding of the mechanism responsible for p53-mediated apoptosis.

Artificial cell factory design for shikimate production in Escherichia coli.

Shikimate is a key intermediate in high demand for synthesizing valuable antiviral drugs, such as the anti-influenza drug and oseltamivir (Tamiflu®). Microbial-based shikimate production strategies have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. Although shikimate biosynthesis has been reported in several engineered bacterial species, the shikimate production yield is still unsatisfactory. This study designed an Escherichia coli cell factory and optimized the fed-batch culture process to achieve a high titer of shikimate production. Using the previously constructed dehydroshikimate (DHS)-overproducing E. coli strain, two genes (aroK and aroL) responsible for converting shikimate to the next step were disrupted to facilitate shikimate accumulation. The genes with negative effects on shikimate biosynthesis, including tyrR, ptsG, and pykA, were disrupted. In contrast, several shikimate biosynthetic pathway genes, including aroB, aroD, aroF, aroG, and aroE, were overexpressed to maximize the glucose uptake and intermediate flux. The shiA involved in shikimate transport was disrupted, and the tktA involved in the accumulation of both PEP and E4P was overexpressed. The rationally designed shikimate-overproducing E. coli strain grown in an optimized medium produced approximately 101 g/l of shikimate in 7-l fed-batch fermentation, which is the highest level of shikimate production reported thus far. Overall, rational cell factory design and culture process optimization for microbial-based shikimate production will play a key role in complementing traditional plant-derived shikimate production processes.

Retrosternal hematoma in sternal fracture for prediction of concomitant injury on chest CT.

BACKGROUND: Isolated sternal fracture, a benign injury, has been increasing in the pan-scan era, although one-third of patients with sternal fracture still has trouble with concomitant injury. The differentiation of these two entities is important to optimize patient management. PURPOSE: To evaluate correlation between retrosternal hematoma and concomitant injury in patients with sternal fracture and to identify predicting factors for concomitant injury in sternal fracture. MATERIAL AND METHODS: A total of 139 patients (84 men; mean age = 54.9 ± 15.3 years) with traumatic sternal fracture were enrolled in this study. We reviewed medical charts and multiplanar computed tomography (CT) images to evaluate cause, location, and degree of sternal fracture, retrosternal hematoma, and concomitant injury. Univariate and multivariate analysis were used to identify variables that were associated with concomitant injury. RESULTS: Concomitant injury on chest CT was observed in 85 patients with sternal fracture. Of the patients, 98 (70.5%) were accompanied by retrosternal hematoma. Multivariate analysis revealed that retrosternal hematoma (odds ratio [OR] = 5.350; P < 0.001), manubrium fracture (OR = 6.848; P = 0.015), and motor vehicle accident (OR = 0.342; P = 0.015) were significantly associated with sternal fracture with concomitant injury. CONCLUSION: Manubrium fracture and retrosternal hematoma portend a high risk of concomitant injury and indicate the need for further clinical and radiologic work-up.

Dexmedetomidine combined with suprascapular nerve block and axillary nerve block has a synergistic effect on relieving postoperative pain after arthroscopic rotator cuff repair.

PURPOSE: Suprascapular nerve block (SSNB) is the most commonly used block for the relief of postoperative pain from arthroscopic rotator cuff repair and can be used in combination with axillary nerve block (ANB). Dexmedetomidine (DEX) is a type of alpha agonist that can elongate the duration of regional block. The aim of this study was to compare the effects of the use of dexmedetomidine combined with SSNB and ANB with those of the use of SSNB and ANB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair. METHODS: Forty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single-center, double-blinded randomized controlled trial study. Twenty patients were randomly allocated to group 1 and received ultrasound-guided SSNB and ANB using a mixture of 0.5 ml (50 µg) of DEX and 9.5 ml of 0.75% ropivacaine preemptively. The other 20 patients were allocated to group 2 and underwent ultrasound-guided SSNB and ANB alone using a mixture of 0.5 ml of normal saline and 9.5 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were postoperatively checked within 48 h. The plasma interleukin (IL)-6, IL-8, IL-1ß, cortisol, and serotonin levels were also postoperatively measured within 48 h. RESULTS: Group 1 showed a significantly lower mean VAS (visual analog scale of pain) score 1, 3, 6, 12, 18 and 24 h after operation, and a significantly higher mean SAT (patient satisfaction) score 1, 3, 6, 12, 18, 24 and 36 h after the operation than group 2. Group 1 showed a significantly lower mean plasma IL-8 level 1 and 48 h after the operation, and a significantly lower mean IL-1ß level 48 h after the operation than group 2. Group 1 showed a significantly lower mean plasma serotonin level 12 h after the operation than group 2. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (36 h > 23 h, p = 0.007). Six patients each in groups 1 and 2 showed rebound pain. The others did not show rebound pain. CONCLUSIONS: Ultrasound-guided SSNA and ANB with DEX during arthroscopic rotator cuff repair resulted in a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h after the operation than SSNB and ANB alone. Additionally, SSNB and ANB with DEX tended to result in a later mean timing of rebound pain accompanied by significant changes in IL-8, IL-1ß, and serotonin levels within 48 h after the operation. The present study could provide the basis for selecting objective parameters of postoperative pain in deciding the optimal use of medication for relieving pain. LEVEL OF EVIDENCE: Level I. TRIAL REGISTRATION: 2015-20, ClinicalTrials.gov Identifier: NCT04398589. IRB NUMBER: 2015-20, Hallym University Chuncheon Sacred Heart Hospital.

Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer.

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer's disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.

Protein phosphatase magnesium-dependent 1A induces inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a highly inflammatory autoimmune disease. Although proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-6, play a key role in the pathogenesis of RA, the causes of chronic inflammation are not fully understood. Here, we report that protein phosphatase magnesium-dependent 1A (PPM1A) levels were increased in RA synovial fluid compared with osteoarthritis (OA) synovial fluid and positively correlated with TNF levels. In addition, PPM1A expression was increased in synovial tissue from RA patients and joint tissue from a mouse model of arthritis. Finally, extracellular PPM1A induced inflammation by stimulating macrophages to produce TNF through toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein 88 (MyD88) signaling pathway. Our findings suggest that extracellular PPM1A may contribute to the pathogenesis of RA by functioning as a damage-associated molecular pattern (DAMP) to induce inflammation.

Diagnostic outcome and safety of CT-guided core needle biopsy for mediastinal masses: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the diagnostic outcomes and complication rates and to identify potential covariates that could influence these results for computed tomography (CT)-guided core needle biopsy (CNB) of mediastinal masses. METHODS: A computerized search of the PubMed and EMBASE databases was performed to identify original articles on the use of CT-guided CNB for mediastinal mass. The pooled proportions of the diagnostic yield and accuracy were assessed using random effects modeling. We assessed the pooled proportion of complication rates using random effects or fixed effects modeling. Multivariate meta-regression analyses were performed to evaluate the potential sources of heterogeneity. RESULTS: Eighteen eligible studies (1310 patients with 1345 CT-guided CNBs) were included. The pooled proportions of the diagnostic yield and accuracy of CT-guided CNB for mediastinal masses were 92% (18 studies, 1345 procedures) and 94% (15 studies, 803 procedures), respectively. In the subgroup analysis, the pooled proportions of the total complication rate and major complication rate were 13% and 2%, respectively. In the meta-regression analyses, the number of tissue samplings (odds ratio [OR], 3.3; p = 0.03), real-time fluoroscopy-guided (OR, 2.1; p = 0.02), and percentage of lymphoma (OR, 2.2; p < 0.001) for diagnostic yield, number of tissue samplings (OR = 2.0, p = 0.02) for diagnostic accuracy, and biopsy needle diameter (OR, 2.5; p = 0.002) for total complication rate were all sources of heterogeneity. CONCLUSIONS: CT-guided CNB for mediastinal mass demonstrates high diagnostic outcomes and low complication rates. The use of 20-gauge biopsy needles and obtaining ≥ 3 samples may be recommended to improve diagnostic outcomes and decrease complication rates. KEY POINTS: • The pooled estimates of diagnostic yield and accuracy of computed tomography (CT)-guided core needle biopsy (CNB) for mediastinal masses are 92% and 94%, respectively. • The pooled estimates of the total complication rate and major complication rate were 13% and 2%, respectively. • The use of a 20-gauge needle and ≥ 3 tissue samplings are recommended for CT-guided mediastinal CNB to achieve high diagnostic outcomes and lower complication rates.

Dexmedetomidine combined with interscalene brachial plexus block has a synergistic effect on relieving postoperative pain after arthroscopic rotator cuff repair.

PURPOSE: Interscalene brachial plexus block (ISB) is one of the most commonly used regional blocks in relieving postoperative pain after arthroscopic rotator cuff repair. Dexmedetomidine (DEX) is an alpha 2 agonist that can enhance the effect of regional blocks. The aim of this study was to compare the effects of DEX combined with ISB with ISB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair. METHODS: Fifty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single center, double-blinded randomized controlled trial study. Twenty-five patients were randomly allocated to group 1 and received ultrasound-guided ISB using a mixture of 1 ml (100 µg) of DEX and 8 ml of 0.75% ropivacaine preemptively. The other 25 patients were allocated to group 2 and underwent ultrasound-guided ISB alone using a mixture of 1 ml of normal saline and 8 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were checked within 48 h postoperatively. The plasma interleukin (IL)-6, -8, -1ß, cortisol, and substance P levels were also measured within 48 h, postoperatively. RESULTS: Group 1 showed a significantly lower mean VAS score and a significantly higher mean SAT score than group 2 at 1, 3, 6, 12, and 18 h postoperatively. Compared with group 2, group 1 showed a significantly lower mean plasma IL-6 level at 1, 6, 12, and 48 h postoperatively and a significantly lower mean IL-8 level at 1, 6, 12, 24, and 48 h postoperatively. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (12.7 h > 9.4 h, p = 0.006). CONCLUSIONS: Ultrasound-guided ISB with DEX in arthroscopic rotator cuff repair led to a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h postoperatively than ISB alone. In addition, ISB with DEX showed lower mean plasma IL-6 and IL-8 levels than ISB alone within 48 h postoperatively, with delayed rebound pain. LEVEL OF EVIDENCE: I. TRIAL REGISTRATION: 2013-112, ClinicalTrials.gov Identifier: NCT02766556.

Clinical and Radiologic Characteristics of Human Metapneumovirus Infections in Adults, South Korea.

Clinical features of human metapneumovirus (HMPV) infection have not been well documented for adults. We investigated clinical and radiologic features of HMPV infection in 849 adults in a tertiary hospital in South Korea. We classified patients into groups on the basis of underlying diseases: immunocompetent patients, solid tumor patients, solid organ transplantation recipients, hematopoietic stem cell transplant recipients, hematologic malignancy patients, and patients receiving long-term steroid treatment. Of 849 HMPV-infected patients, 756 had community-acquired infections, 579 had pneumonia, and 203 had infections with other pathogens. Mortality rates were highest in hematopoietic stem cell transplantation recipients (22% at 30 days). Older age, current smoking, and underlying disease were associated with HMPV pneumonia. Body mass index and an immunocompromised state were associated with 30-day mortality rates in HMPV-infected patients. Bronchial wall thickening, ground-glass opacity, and ill-defined centrilobular nodules were common computed tomography findings for HMPV pneumonia. Macronodules and consolidation were observed in <50% of patients.

Effects of emphysema on physiological and prognostic characteristics of lung function in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Combined pulmonary fibrosis and emphysema (CPFE) is characterized by preserved lung volume and slower lung function decline. However, it is unclear at what extent emphysema begins to impact respiratory physiology and prognostic characteristics in idiopathic pulmonary fibrosis (IPF). We estimated the extent of emphysema that could be used to define CPFE in IPF. METHODS: The extent of emphysema was observed on high-resolution computed tomography scans and measured by a texture-based automated quantification system in 209 IPF patients. We analysed the impact of differences in the extent of emphysema on the annual decline rate and prognostic significance of lung function parameters. RESULTS: The extent of emphysema was ≥5% in 53 patients (25%), ≥10% in 23 patients (11%) and ≥15% in 12 patients (6%). Patients with emphysema to an extent of ≥5% were more frequently men and ever-smokers; they had more preserved lung volume and lower forced vital capacity (FVC) decline rates than those with no or trivial emphysema. The FVC decline rate was a significant predictor of mortality in patients with no or trivial emphysema (hazard ratio (HR): 0.933, P < 0.001) and in patients with an extent of emphysema ≥5% (HR: 0.906, P < 0.001). However, diffusing capacity of the lung for carbon monoxide (DLCO ) was the most significant prognostic factor in those patients with an extent of emphysema ≥10% (HR: 0.972, P = 0.040) and ≥15% (HR: 0.942, P = 0.023). A 10% cut-off value for the extent of emphysema created the most significant difference in the annual FVC decline rate in IPF patients. CONCLUSION: In IPF, emphysema to an extent of ≥10% affects both the annual decline rate and the prognostic significance of FVC. This extent could be used to define CPFE.

Comparison of 311-nm Titanium:Sapphire laser and 308-nm excimer laser treatment for vitiligo: A randomized controlled non-inferiority trial.

OBJECTIVES: The 308-nm excimer laser (EL) has been widely used for localized vitiligo. The recently developed Titanium:Sapphire laser, emits a wavelength of 311 nm, would be expected to be as effective as excimer laser in treatment of vitiligo but few controlled trials have been reported. We sought to compare the efficacy and safety of the TSL and EL as vitiligo treatments. METHODS: A randomized controlled non-inferiority trial based on split-body was conducted. Patients with stable vitiligo between June 2016 and May 2017 were enrolled. Paired symmetrical vitiligo lesions were randomized to either the EL or TSL treatment group, and treated with a 308-nm EL or a 311-nm TSL twice weekly for 12 weeks. The extent of repigmentation was assessed every 4 weeks, and the non-inferiority margin was set to 10%. We also recorded any adverse events. RESULTS: Seventy-four paired lesions in 21 patients were assigned to both the EL group or TSL group. The mean difference between two groups (EL minus TSL) was -2.862%, and the 95% confidence interval (-6.531% to 0.807%) was lower than the non-inferiority margin. No serious adverse events were noted in either group. CONCLUSIONS: The Titanium:Sapphire laser showed similar therapeutic effect to excimer laser in localized vitiligo with good safety profiles in this non-inferiority randomized controlled trial. The Titanium: Sapphire laser can serve as an alternative treatment option for localized vitiligo. Lasers Surg. Med. 51:239-244, 2019. © 2019 Wiley Periodicals, Inc.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio as predictors of 12-week treatment response and drug persistence of anti-tumor necrosis factor-α agents in patients with rheumatoid arthritis: a retrospective chart review analysis.

Data are scarce regarding the association of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with treatment response and persistence of anti-TNF-α agents in patients with rheumatoid arthritis (RA). Thus, we investigated whether baseline NLR and PLR could predict 12-week treatment response and long-term persistence of anti-TNF-α agents in RA patients. This is a retrospective chart review analysis of 82 women with RA who started anti-TNF-α agents as the first-line biologic therapy and 328 healthy age-matched women. RA patients were divided into high and low baseline NLR or PLR subgroups using the median split. European League against Rheumatism (EULAR) treatment response was evaluated at 12 weeks. RA patients had significantly higher NLR and PLR than controls. High baseline NLR and PLR groups showed higher 12-week EULAR non-response rate than low NLR (30% vs 7.1%, p = 0.01) and PLR groups (27.5% vs 9.5%, p = 0.047), respectively. After adjusting for confounding factors, high baseline NLR (OR 5.57, p = 0.014) and PLR (OR 4.24, p = 0.04) were significantly associated with a higher risk of EULAR non-response at 12 weeks. During the study period, 47 (57.3%) RA patients (lack of efficacy: n = 31; adverse events: n = 16) discontinued anti-TNF-α agents. High baseline NLR was associated with an increased risk of anti-TNF-α agent withdrawal due to lack of efficacy (HR 2.12, p = 0.045). Our data suggest that baseline NLR and PLR are useful markers for predicting the treatment outcome of anti-TNF-α agents in RA patients.

Increased serum uric acid levels are associated with digital ulcers in patients with systemic sclerosis.

Endothelial injury/dysfunction is thought to be one of the earliest events in the development of vascular diseases in systemic sclerosis (SSc). Although hyperuricemia is also known to induce endothelial dysfunction and vascular inflammation, the effect of uric acid on the microvascular involvement in SSc has not been well established. We investigated whether increased serum uric acid (SUA) levels are associated with digital ulcers (DUs) in SSc. In this cross-sectional study, we consecutively recruited 71 women with SSc and 349 age- and sex-matched healthy subjects, and SUA levels were measured in all study subjects. SSc patients had significantly higher mean SUA levels than healthy subjects (4.5 ± 1 mg/dL vs 4.2 ± 0.9 mg/dL, p = 0.017), although a significantly lower body mass index (BMI) was observed in SSc patients than in controls. Among 71 SSc patients, 22 (31%) had DUs ever (active DUs, 8; healed DUs, 14). SSc patients presenting with DUs ever showed significantly higher SUA levels than those without this feature (median, 5.2 mg/dL vs 4.1 mg/dL, p = 0.009). In multivariable logistic regression models adjusted for confounders such as BMI and estimated glomerular filtration rate, increased SUA levels were associated with a significantly higher risk for the presence of DUs ever (OR 2.3, 95% CI 1.16-4.57, p = 0.018). Our data revealed that elevated SUA levels are independently associated with the presence of DUs in SSc patients, thereby suggesting the potential role of hyperuricemia in the pathogenesis of SSc vasculopathy.