IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications.

BACKGROUND: Atezolizumab intravenous (IV) is approved for the treatment of various solid tumours. To improve treatment convenience and health care efficiencies, a coformulation of atezolizumab and recombinant human hyaluronidase PH20 was developed for subcutaneous (SC) use. Part 2 of IMscin001 (NCT03735121) was a randomised phase III, open-label, multicentre, noninferiority study comparing the drug exposure of atezolizumab SC with atezolizumab IV. PATIENTS AND METHODS: Eligible patients with locally advanced/metastatic non-small-cell lung cancer were randomised 2 : 1 to receive atezolizumab SC (1875 mg; n = 247) or IV (1200 mg; n = 124) every 3 weeks. The co-primary endpoints were cycle 1 observed trough serum concentration (Ctrough) and model-predicted area under the curve from days 0 to 21 (AUC0-21 d). The secondary endpoints were steady-state exposure, efficacy, safety, and immunogenicity. Exposure following atezolizumab SC was then compared with historical atezolizumab IV values across approved indications. RESULTS: The study met both of its co-primary endpoints: cycle 1 observed Ctrough {SC: 89 µg/ml [coefficient of variation (CV): 43%] versus IV: 85 µg/ml (CV: 33%); geometric mean ratio (GMR), 1.05 [90% confidence interval (CI) 0.88-1.24]} and model-predicted AUC0-21 d [SC: 2907 µg d/ml (CV: 32%) versus IV: 3328 µg d/ml (CV: 20%); GMR, 0.87 (90% CI 0.83-0.92)]. Progression-free survival [hazard ratio 1.08 (95% CI 0.82-1.41)], objective response rate (SC: 12% versus IV: 10%), and incidence of anti-atezolizumab antibodies (SC: 19.5% versus IV: 13.9%) were similar between arms. No new safety concerns were identified. Ctrough and AUC0-21 d for atezolizumab SC were consistent with the other approved atezolizumab IV indications. CONCLUSIONS: Compared with IV, atezolizumab SC demonstrated noninferior drug exposure at cycle 1. Efficacy, safety, and immunogenicity were similar between arms and consistent with the known profile for atezolizumab IV. Similar drug exposure and clinical outcomes following SC and IV administration support the use of atezolizumab SC as an alternative to atezolizumab IV.

Regional and annual patterns in respiratory virus co-infection etiologies and antibiotic prescriptions for pediatric mycoplasma pneumoniae pneumonia.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae) pneumonia is the second-most common cause of community-acquired pneumonia (CAP). This study aimed at investigating into the prevalence of macrolide-resistant M. pneumoniae (MRMP) with respiratory virus co-infection and the antibiotic prescriptions in children with CAP in four provinces in Korea, and to assess the variations in the findings across regions and throughout the year. PATIENTS AND METHODS: This prospective study was conducted in 29 hospitals in Korea between July 2018 and June 2020. Among the enrolled 1,063 children with CAP, all 451 patients with M. pneumoniae underwent PCR assays of M. pneumoniae and respiratory viruses, and the presence of point mutations of residues 2063 and 2064 was evaluated. RESULTS: Gwangju-Honam (88.6%) showed the highest prevalence of MRMP pneumonia, while Daejeon-Chungcheong (71.3%) showed the lowest, although the differences in prevalence were not significant (p=0.074). Co-infection of M. pneumoniae pneumonia and respiratory virus was observed in 206 patients (45.4%), and rhinovirus co-infection (101 children; 22.2%) was the most frequent. The prevalence of MRMP pneumonia with respiratory virus co-infection and the antibiotic prescriptions differed significantly among the four provinces (p < 0.05). The monthly rate of MRMP pneumonia cases among all cases of M. pneumoniae pneumonia and tetracycline or quinolone prescriptions did not differ significantly among the four regions (trend p > 0.05) during the study period. CONCLUSIONS: The prevalence of M. pneumoniae pneumonia with virus co-infection and antibiotic prescriptions could differ according to region, although the MRMP pneumonia rate showed no difference within Korea.

Past the Precipice? Projected Coral Habitability Under Global Heating.

Coral reefs are rapidly declining due to local environmental degradation and global climate change. In particular, corals are vulnerable to ocean heating. Anomalously hot sea surface temperatures (SSTs) create conditions for severe bleaching or direct thermal death. We use SST observations and CMIP6 model SST to project thermal conditions at reef locations at a resolution of 1 km, a 16-fold improvement over prior studies, under four climate emissions scenarios. We use a novel statistical downscaling method which is significantly more skillful than the standard method, especially at near-coastal pixels where many reefs are found. For each location we present projections of thermal departure (TD, the date after which a location with steadily increasing heat exceeds a given thermal metric) for severe bleaching recurs every 5 years (TD5Y) and every 10 years (TD10Y), accounting for a range of post-bleaching reef recovery/degradation. As of 2021, we find that over 91% and 79% of 1 km2 reefs have exceeded TD10Y and TD5Y, respectively, suggesting that widespread long-term coral degradation is no longer avoidable. We project 99% of 1 km2 reefs to exceed TD5Y by 2034, 2036, and 2040 under SSP5-8.5, SSP3-7.0, and SSP2-4.5 respectively. We project that 2%-5% of reef locations remain below TD5Y at 1.5°C of mean global heating, but 0% remain at 2.0°C. These results demonstrate the importance of further improving ecological projection capacity for climate-vulnerable marine and terrestrial species and ecosystems, including identifying refugia and guiding conservation efforts. Ultimately, saving coral reefs will require rapidly reducing and eliminating greenhouse gas emissions.

High Estimated 24-Hour Urinary Sodium Excretion Is Related to Symptomatic Knee Osteoarthritis: A Nationwide Cross-Sectional Population-Based Study.

OBJECTIVES: High salt intake results in various harmful effects on human health including hypertension, cardiovascular disease, and reduced bone density. Despite this, there are very few studies in the literature that have investigated the association between sodium intake and osteoarthritis (OA). Therefore, we aimed to explore these associations in a Korean population. METHODS: This study used cross-sectional data from adult subjects aged 50-75 years from two consecutive periods of the Korean National Health and Nutrition Examination Survey V-VII (2010-2011 and 2014-2016). The estimated 24-hour urinary sodium excretion (24HUNa) was used as a surrogate marker of salt intake. In the 2010-2011 dataset, knee OA (KOA) was defined as the presence of the radiographic features of OA and knee pain. The association between KOA and salt intake was analysed using univariable and multivariable logistic regression methods. For the sensitivity analysis, the same procedures were conducted on subjects with self-reported OA (SR-OA) with knee pain in the 2010-2011 dataset and any site SR-OA in the 2014-2016 dataset. RESULTS: Subjects with KOA had significantly lower energy intake, but higher 24HUNa than those without KOA. The restricted cubic spline plots demonstrated a J-shaped distribution between 24HUNa and prevalent KOA. When 24HUNa was stratified into five groups (<2, 2-3, 3-4, 4-5 and ≥5 g/day), subjects with high sodium intake (≥5 g/day) had a higher risk of KOA (odds ratio [OR] = 1.64, 95% confidence interval [CI] 1.03-2.62) compared to the reference group (3-4 g/day) after adjusting for covariates. The sensitivity analysis based on SR-OA with knee pain showed that high sodium intake was also significantly associated with increased prevalence of OA (OR = 1.84, 95% CI 1.10-3.10) compared with the reference group. Regarding SR-OA at any site in the 2014-2016 dataset, estimated 24HUNa showed a significantly positive association with the presence of SR-OA after adjusting for potential confounders. CONCLUSIONS: This nationwide Korean representative study showed a significant association between symptomatic KOA and high sodium intake (≥5 g/day). Avoidance of a diet high in salt might be beneficial as a non-pharmacologic therapy for OA.

Effect of negative-pressure wound therapy on wound complications in obese women after caesarean birth: a systematic review and meta-analysis.

BACKGROUND: Obesity is associated with increased surgical-site infection (SSI) following caesarean section (CS). OBJECTIVE: To summarise the evidence on the effectiveness of negative-pressure wound therapy (NPWT) for preventing SSI and other wound complications in obese women after CS. SEARCH STRATEGY: MEDLINE, Embase, CINAHL, Cochrane CENTRAL databases and ClinicalTrials.gov were systematically searched in March 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs) of NPWT compared with standard dressings after CS birth. DATA COLLECTION AND ANALYSIS: Pooled effect sizes were calculated using either fixed or random effects models based on heterogeneity. The Cochrane risk of bias and Grading of Recommendations Assessment, Development and Evaluation tools were used to assess the quality of studies and overall quality of evidence. MAIN RESULTS: Ten RCTs with 5583 patients were included; studies were published between 2012 and 2021. Nine RCTs with 5529 patients were pooled for the outcome SSI. Meta-analysis results suggest a significant difference favouring the NPWT group (relative risk [RR] 0.79, 95% CI 0.65-0.95, P < 0.01), indicating an absolute risk reduction of 1.8% among those receiving NPWT compared with usual care. The risk of blistering in the NPWT group was significantly higher (RR 4.13, 95% CI 1.53-11.18, P = 0.005). All studies had high risk of bias relative to blinding of personnel/participants. Only 40% of studies reported blinding of outcome assessments and 50% had incomplete outcome data. CONCLUSIONS: The decision to use NPWT should be considered both in terms of its potential benefits and its limitations. TWEETABLE ABSTRACT: NPWT was associated with fewer SSI in women following CS birth but was not effective in reducing other wound complications.

Optomechanical crystals for spatial sensing of submicron sized particles.

Optomechanical crystal cavities (OMC) have rich perspectives for detecting and indirectly analysing biological particles, such as proteins, bacteria and viruses. In this work we demonstrate the working principle of OMCs operating under ambient conditions as a sensor of submicrometer particles by optically monitoring the frequency shift of thermally activated mechanical modes. The resonator has been specifically designed so that the cavity region supports a particular family of low modal-volume mechanical modes, commonly known as -pinch modes-. These involve the oscillation of only a couple of adjacent cavity cells that are relatively insensitive to perturbations in other parts of the resonator. The eigenfrequency of these modes decreases as the deformation is localized closer to the centre of the resonator. Thus, by identifying specific modes that undergo a frequency shift that amply exceeds the mechanical linewidth, it is possible to infer if there are particles deposited on the resonator, how many are there and their approximate position within the cavity region. OMCs have rich perspectives for detecting and indirectly analysing biological particles, such as proteins, viruses and bacteria.

[Clinicopathological features and differential diagnosis of eosionphilic chromophobe renal cell carcinoma].

Objective: To investigate the clinicopathological characteristics of eosionphilic Chromophobe renal cell carcinoma (eChRCC), and differences in morphology, immunophenotype and clinical prognosis betweeneChRCC, renal oncocytoma(RO) and classic Chromophobe renal cell carcinoma (cChRCC). Methods: The clinicopathologic data of 17 patients diagnosed as eChRCC from the Affiliated Hospital of Qingdao University (13 cases) and 971 Hospital of PLA Navy (4 cases) from October 2006 to February 2019 were collected. Immunohistochemical analysis was carried out to compare the immunophenotypes between 17 cases with ChRCC, 27 cases with RO and 30 cases with cChRCC. Resuls: Among the 17 patients, seven were males and ten were females, and the age ranged from 40 to 75 years (median 54 years). Clinically, 15 cases of 17 were found accidentally by physical examination. The tumor size ranged from 1.8 cm to 10.0 cm (average 5.7 cm) and the cut surface of 15 cases were solid, one case was solicl and cystic, and one was cystic. Most showed gray to red, and partially soft, gray to yellow appearances. Microscopically, most tumors presented solid growth pattern with vary number of alveolar structures (12 cases). Some were predominately characterized by cystic structure (3 cases), alveolar structure(1 case) and microcapsule structure (1 case). There were boundaries with varying degrees of clarity between tumor cells in 16 cases. The cytoplasm of tumor cells was eosinophilic and the nuclei were small round or irregular with focal perinuclear haloes in 14 cases. Large polygonal cells with light-stained cytoplasm appeared focally in 9 cases, and edematous areas with scarce tumor cells were found in 4 cases. Among 7 cases, 4 cases focally invaded peripheral renal parenchyma, 2 cases invaded adipose tissues outside the renal capsule, and 1 case presented invasion of renal sinus. Immunohistochemically, all cases were moderate to strong positive for EMA and claudin-7. CK7, CD117 and Ksp-cad were highly expressed with the expression rates of 12/17, 15/17, 14/17, respectively. Cyclin D1, AMACR, CD10, S100A1, and RCC were rarely expressed with the expression rates of 4/17, 3/17, 4/17, 1/17 and 1/17, respectively. On the contrary, all cases were negative for vimentin, CAⅨ, HMB45 and Melan A. The Ki-67 proliferation index of the 17 cases was 1%‒5%. Follow-up data were available for all 17 patients from 7 to 154 months. Among them, 15 patients were alive without tumor recurrence or metastasis, one patient died of pulmonary metastasis after 31 months of surgery and one patient died of hepatic metastasis after 38 months of surgery. Conclusion: eChRCC has overlapping morphology and immunophenotype with RO. eChRCC is characterized by solid nest or alveolar structure, distinct border between tumor cells, perinuclear halos and lacking of interstitial looseness and edema. Scattered large polygonal cells with light-stained cytoplasm in tumor tissue play a significant role in the diagnosis of eChRCC. The positive expression of CK7, CD117, claudin-7 and Ksp-cad, and negative expression of cyclin D1, S100A1 are helpful to the diagnosis and differential diagnosis of eChRCC. The prognosis of eChRCC after complete surgical resection is excellent and few cases may have long-term metastasis. There is no significant difference in prognosis between eChRCC and cChRCC, but eChRCC shows better outcome than RO.

Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study.

In this population-based cohort study on comparative osteoporotic fracture risks between different biologic disease-modifying drugs among patients with rheumatoid arthritis (RA), we did not find a significant difference in the risk of osteoporotic fractures between RA patients receiving TNF inhibitors versus abatacept or tocilizumab. INTRODUCTION: We aimed to investigate the comparative risk of osteoporotic fractures between rheumatoid arthritis (RA) patients who initiated TNF inhibitors (TNFis) versus abatacept or tocilizumab. METHODS: Using the Korea National Health Insurance Service datasets from 2002 to 2016, RA patients who initiated TNFis, abatacept, or tocilizumab were identified. The primary outcome was a composite end point of non-vertebral fractures and hospitalized vertebral fractures; secondary outcomes were two components of the primary outcome and fractures occurring at the humerus/forearm. Propensity score (PS) matching with a variable ratio up to 10 TNFi initiators per 1 comparator drug initiator was used to adjust for > 50 baseline confounders. We estimated hazard ratios (HRs) and 95% confidence interval (CI) of fractures comparing TNFi initiators to abatacept and to tocilizumab by Cox proportional hazard models stratified by a matching ratio. RESULTS: After PS-matching, 2307 TNFi initiators PS-matched on 588 abatacept initiators, and 2462 TNFi initiators on 640 tocilizumab initiators were included. A total of 77 fractures occurred during a mean follow-up of 454 days among TNFi and abatacept initiators and 83 fractures during 461 days among TNFi and tocilizumab initiators. The PS-matched HR (95% CI) was 0.91 (0.48-1.71) comparing TNFi versus abatacept initiators, and 1.00 (0.55-1.83) comparing TNFi versus tocilizumab initiators. Analysis on vertebral and non-vertebral fractures showed similar results. CONCLUSIONS: In this nationally representative cohort, we did not find a significant difference in the risk of fractures between TNFi initiators versus abatacept or tocilizumab among RA patients.

Development of an After-School Day Treatment Program for Children with Severe Emotional/Behavioral Disturbances.

This article introduces Aizone, an after-school day treatment program for children with emotional/behavioral disturbances, and examines its effectiveness. Aizone targets children whose problems require intensive care, but are not severe enough to warrant hospitalization, and prioritizes those from low-income families. Based on the bio-psycho-social model, this program provides a variety of therapeutic interventions for both children and their parents, including individual and group therapy integrated under the concept of milieu therapy, as well as community linkage services. This study uses a prospective comparative method to examine the effectiveness of Aizone by comparing and validating the treatment outcomes of seven Aizone programs across Seoul. The Korean Child Behavior Checklist was administered by caregivers before and after intervention and the data was used in a repeated measures analysis. The effectiveness of the program in terms of reduction in emotional, behavioral symptoms, as well as the implications of the results are discussed.

Spatial analysis and visualization of global data on multi-resolution hexagonal grids.

In this article, computation for the purpose of spatial visualization is presented in the context of understanding the variability in global environmental processes. Here, we generate synthetic but realistic global data sets and input them into computational algorithms that have a visualization capability; we call this a simulation-visualization system. Visualization is key here, because the algorithms which we are evaluating must respect the spatial structure of the input. We modify, augment, and integrate four existing component technologies: statistical conditional simulation, Discrete Global Grids (DGGs), Array Set Addressing, and a visualization platform for displaying our results on a globe. The internal representation of the data to be visualized is built around the need for efficient storage and computation as well as the need to move up and downresolutions in a mutually consistent way. In effect, we have constructed a Geographic Information System that is based on a DGG and has desirable data storage, computation, and visualization capabilities. We provide an example of how our simulation-visualization system may be used, by evaluating a computational algorithm called Spatial Statistical Data Fusion that was developed for use on big, remote-sensing data sets.

Use of acidified versus non-acidified liquid human milk fortifier in very low birth weight infants: A retrospective comparison of clinical outcomes.

BACKGROUND: Use of human milk is recommended for low birth weight (VLBW) infants, but must be safety fortified with sterile liquid fortifiers to be nutritionally sufficient. Due to clinical concern for a high incidence of metabolic acidosis among VLBW infants fed human milk fortified with acidified liquid human milk fortifier (ALHMF), we aimed to retrospectively compare the outcomes of infants fed ALHMF to those fortified with non-acidified liquid HMF (NLHMF). METHODS: Medical records of VLBW neonates admitted to our institution's neonatal intensive care unit from July 1st, 2013 to June 30th, 2014 were reviewed. 129 patients were included in the study, 61 of which received ALHMF and 68 received NLHMF. Metabolic, nutritional and clinical outcomes, including growth, were compared between the two cohorts. RESULTS: Of the infants who received ALHMF, 70.5% developed metabolic acidosis compared to only 11.8% in the NLHMF group (p < 0.001). In addition, infants who received NLHMF had a 10% greater growth velocity during the period of fortification (p = 0.01). During the full course of hospitalization, no difference in growth velocity was seen between the groups and greater length gains were found in the ALHMF group. CONCLUSIONS: The use of human milk fortified with ALHMF was associated with an increased incidence of metabolic acidosis and poorer growth during the period of fortification when compared to NLHMF-fortified feedings. These growth effects were not apparent when the duration of hospitalization was considered, suggesting a need for further study to better characterize the advantages and disadvantages of each fortifier.

Dietary threonine prevented stress-related mucosal diseases in rats.

Stress-related mucosal disease (SRMD), or stress ulceration, is a group of conditions ranging from stress-related superficial gastric mucosal damage to deep gastric ulcers that are primarily correlated with mucosal ischemia, and pharmacologic interventions that optimize tissue perfusion or preserve defensive mucus aim to decrease the occurrence of conditions, such as gastric acidity, or enhance gastric defenses. However, the identification of multifactorial pathogenesis may be effective in preventing SMRD, and the use of stress prophylaxis is generally preferred. Since threonine is a component in the polymerization and synthesis of gastric mucin and possibly enhanced defense actions and lignin may provide structural support for defense and antioxidative function, we hypothesized that dietary intake of threonine and/or lignin can enhance defense against SRMD. The water immersion-restraint stress (WIRS) was used in rats and additional groups were pretreated with threonine alone or the combination of threonine and lignin. Based on gross and microscopic evaluations, threonine alone or the combination of threonine and lignin, a natural antioxidant, significantly reduced the development of SRMD (P < 0.05). According to molecular explorations, the levels of inflammatory mediators, such as interleukin (IL)-8, IL-6, IL-1ß, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ), all of which are mediators that play a significant role in controlling WIRS, significantly decreased in the groups pretreated with either threonine alone or the combination of threonine and lignin (P < 0.01). WIRS significantly increased apoptosis in the stomach. However, the apoptotic index significantly decreased with threonine pretreatment. According to periodic acid Schiff staining results, the expression of gastric mucin was significantly preserved in groups pretreated with threonine but remarkedly decreased in the WIRS group. The gastric heme oxygenase-1 levels significantly increased in the group treated with threonine. In conclusion, the dietary intake of threonine or the combination of threonine and lignin is effective in preventing SRMD.

Oligonol prevented the relapse of dextran sulfate sodium-ulcerative colitis through enhancing NRF2-mediated antioxidative defense mechanism.

Repeated bouts of ulcerative colitis featured troublesome course of inflammatory bowel disease leading to fatal colitis-associated cancer, which is strongly associated with oxidative stress and sustained inflammation. Since oligonol, low molecular weighted polyphenol extracted from fruit lychee, showed antioxidative and anti-inflammatory actions, we hypothesized that oligonolcan prevent relapse of colitis. We compared oligonol with current gold standard therapeutics, sulfasalazine in preventive efficacy of relapse. First, dextran sulfate sodium (DSS)-induced colitis were made following pretreatment with oligonol, 10, 50, and 100 mg/kg for 7 days to measure therapeutic effect of oligonol and relapse model via repeated DSS administration was made following with either 50 mg/kg oligonol or 30 mg/kg sulfasalazine to explore relapse preventing action of oligonol in C57BL/6 mice. Detailed changes in colon were measured to explain molecular mechanisms. Pretreatment of 10, 50, 100 mg/kg oligonol (p.o.), significantly reduced DSS-induced colitis; total pathologic scores, colon length, and clinical symptom scores (P < 0.05). Oligonol pretreatment significantly decreased the levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) as well as nuclear factor-κB (NF-κB), c-Fos, and c-Jun in affected colon tissues, but the expression of heme oxygenase-1 (HO-1) and NADH: quinone oxidoreductase-1(NQO-1) as well as total antioxidant concentration (P < 0.005) was significantly increased with oligonol. A relapse model established with repeated DSS administration led to high mortality. However, oligonol significantly ameliorated exacerbations of colitis, while sulfasalazine did not (P < 0.01). Significantly decreased expressions of cyclooxygenase-2 (COX-2), TNF-α, and macrophages inhibition were relapse preventing actions of oligonal, but significant action of oligonol relevant to relapse prevention was either significantly increased expressions of NQO-1 or significantly preserved mucin (P < 0.05). Concerted anti-inflammatory, antioxidative, and host defense enhancing actions of oligonol can be applied during maintenance therapy of IBD to prevent relapse of IBD.

Sarcopenia is associated with the risk of significant liver fibrosis in metabolically unhealthy subjects with chronic hepatitis B.

BACKGROUND: Sarcopenia is significantly associated with the degree of liver fibrosis. This study investigated the influence of sarcopenia on liver fibrosis in individuals with chronic hepatitis B. METHODS: Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analysed. The sarcopenia index (total appendicular skeletal muscle mass [kg]/body mass index [kg/m2 ]) was calculated using dual-energy X-ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cut-offs: 0.89 for men and 0.58 for women). The fibrotic burden was assessed using the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index. Significant fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile and a fibrosis-4 index ≥2.67. RESULTS: Among the 506 respondents with chronic hepatitis B (258 men and 248 women), the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index identified sarcopenia and significant fibrosis in 126 (24.9%) and 217 (42.9%), respectively. Sarcopenia was significantly associated with significant fibrosis, regardless of the fibrosis prediction model used (all P < 0.05). When the study population was stratified according to metabolic factors, sarcopenia was specifically associated with an increased risk of significant fibrosis among subgroups with obesity, insulin resistance, metabolic syndrome and liver steatosis (odds ratio 2.37-3.57; all P < 0.05). An independent association between sarcopenia and significant fibrosis was identified after adjusting for other confounders (odds ratio 2.67-3.62 by the nonalcoholic fatty liver disease fibrosis score and 2.04-2.62 by the fibrosis-4 index; all P < 0.05). CONCLUSIONS: Sarcopenia is associated with significant fibrosis in subjects with chronic hepatitis B, specifically those with obesity, insulin resistance, metabolic syndrome and liver steatosis.

Neutrophil-lymphocyte ratio predicts response to chemotherapy in triple-negative breast cancer.

Background: The neutrophil-lymphocyte ratio (nlr) has been reported to correlate with patient outcome in several cancers, including breast cancer. We evaluated whether the nlr can be a predictive factor for pathologic complete response (pcr) after neoadjuvant chemotherapy (nac) in patients with triple-negative breast cancer (tnbc). Methods: We analyzed the correlation between response to nac and various factors, including the nlr, in 87 patients with tnbc who underwent nac. In addition, we analyzed the association between the nlr and recurrence-free survival (rfs) in patients with tnbc. Results: Of the 87 patients, 25 (28.7%) achieved a pcr. A high Ki-67 index and a low nlr were significantly associated with pcr. The pcr rate was higher in patients having a high Ki-67 index (≥15%) than in those having a low Ki-67 index (35.7% vs. 0%, p = 0.002) and higher in patients having a low nlr (≤1.7) than in those having a high nlr (42.1% vs. 18.4%, p = 0.018). In multiple logistic analysis, a low nlr remained the only predictive factor for pcr (odds ratio: 4.274; p = 0.008). In the survival analysis, the rfs was significantly higher in the low nlr group than in the high nlr group (5-year rfs rate: 83.7% vs. 66.9%; log-rank p = 0.016). Conclusions: Our findings that the nlr is a predictor of pcr to nac and also a prognosticator of recurrence suggest an association between response to chemotherapy and inflammation in patients with tnbc. The pretreatment nlr can be a useful predictive and prognostic marker in patients with tnbc scheduled for nac.

Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice.

BACKGROUND/OBJECTIVES: We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice. METHODS: Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg-1 daily) was injected intraperitoneally for 20 weeks. RESULTS: Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes. CONCLUSIONS: Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

Host nuclear factor erythroid 2-related factor-2 defense system determines the outcome of dextran sulfate sodium-induced colitis in mice.

Administration of dextran sulfate sodium (DSS) in drinking water led to significant bout of colitis simulating ulcerative colitis of human. However, colitis usually developed 5 - 7 days after DSS administration. Therefore, we hypothesized host defense system might protect colitis up to 5 days of DSS administration. 2.5% DSS-induced colitis were administered to C57BL/6 mice and sequential measurements of pathology, cyclooxygenase-2 (COX-2), nuclear factor-κB (NF-κB), heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase-1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS), nuclear factor erythroid 2-related factor-2 (Nrf2), and keap1 were done at 2, 6, 12, 24, 48, 96, 120, and 168 hour of DSS administration, respectively. DSS-induced colitis was repeated in either COX-2-/- or Nrf2-/- mice. On serial pathological analysis, significant colitis was noted after 120 h of DSS administration, during which both activations of COX-2/NF-κB and HO-1/Nrf2 were noted. Nrf2 activations after keap1 inactivation led to significant increases in HO-1 after 168 hours of DSS administration, when NF-κB nuclear translocation was noted. Significantly attenuated colitis was noted in DSS-challenged COX-2-/- mice, in which the levels of HO-1 were significantly decreased compared to DSS-challenged WT littermates (p < 0.01), while the levels of NQO1 were significantly increased. On DSS administration to Nrf2-/- mice, colitis was significantly aggravated (p < 0.01), in which the expressions of COX-2 as well as expressions of HO-1 and γ-GCS were significantly increased (p < 0.01). Reciprocal activations of inflammatory and antioxidative defense signaling after DSS administration might be prerequisite to make intestinal homeostasis and host defense Nrf2 system can determine colitis.