Anesthesia for a Patient with Undiagnosed Myotonic Dystrophy.

ABSTRACT: Myotonic dystrophy (DM) is an autosomal dominant genetic disorder characterized by progressively worsening loss of muscle mass and weakness. Anesthesiologists face challenges in managing these patients due to risks such as prolonged intubation and delayed recovery associated with anesthesia in such conditions. We report a case of a 40-year-old male patient undergoing open total gastrectomy under general anesthesia. After the surgery, we administered sugammadex to reverse neuromuscular blockade and confirmed the patient's spontaneous breathing. We then proceeded to extubate the patient. However, the patient experienced complications such as apnea, desaturation, and mental changes. The patient was re-intubated and transferred to the intensive care unit for ventilator support. He was diagnosed with DM by genetic test later. Poor preoperative assessment or undiagnosed DM in surgical patients can lead to severe complications. Thus, it is important to carefully check preoperative laboratory results, patient history, and physical findings.

The relationship of sinus opacification, olfaction and dupilumab efficacy in patients with CRSwNP.

BACKGROUND: Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is unclear. Dupilumab improves sense of smell and radiographic severity of sinus disease in patients with CRSwNP. We investigated the relationship of sinus opacification severity and loci to olfactory impairment and dupilumab efficacy in patients with CRSwNP from the SINUS-24/SINUS-52 (NCT02912468/NCT02898454) studies. METHODS: Sinus opacification was evaluated using the Lund-Mackay computed tomography (LMK-CT) score and sense of smell using patient-reported loss of smell (LoS) score, University of Pennsylvania Smell Identification Test (UPSIT) score and the 22-item Sino-Nasal Outcome Test (SNOT-22) smell/taste item. RESULTS: At baseline, 95% of patients (688/724) had impaired sense of smell and opacification was extensive across all sinuses. Greater olfactory impairment was associated with greater opacification, especially in the ethmoid, sphenoid and frontal sinuses. At Week 24, reductions in LMK-CT total score and ethmoid and sphenoid sinus scores with dupilumab were weakly correlated with improvements in sense of smell assessed by LoS, UPSIT and SNOT-22 smell/taste item. More dupilumab than placebo patients achieved clinically meaningful improvement in LMK-CT total score at Week 24 and Week 52. CONCLUSION: Radiographic disease severity on imaging was associated with smell outcomes in this cohort. Opacification of the ethmoid, sphenoid and frontal sinuses was associated with severe smell loss. These data suggest that dupilumab effects on smell may be partly mediated through reduced sinus inflammation.

Eosinophil-derived TGFß1 controls the new bone formation in chronic rhinosinusitis with nasal polyps

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by chronic eosinophilic inflammation and new bone formation (NBF). These processes may be associated with each other in the pathogenesis and influence the severity and prognosis of the disease. However, it is still unclear how eosinophilic inflammation is involved in the NBF. METHODOLOGY: Sinus bone cells were isolated from ethmoid bone tissues of patients with CRSwNP and controls. Transforming growth factor beta 1 (TGFß1) and alkaline phosphatase (ALP) expression in sinus bone cells was determined using quantitative RT-PCR, immunoblotting, and immunohistochemistry. The co-localization of TGFß1 with eosinophils was assessed by immunofluorescence staining. Sinus bone cells were co-cultured with eosinophils (Eol-1 cell line), which were differentiated with butyrate, to measure the osteoblast differentiation activity of sinus bone cells. RESULTS: TGFß1 expression was increased in sinus bone tissues and correlated with CT scores in CRSwNP. TGFß1 was also increased in the submucosa of CRSwNP and co-localized predominantly with eosinophils compared with neutrophils Differentiated Eol-1 cells-derived TGFß1 increased ALP expression in sinus bone cells. Treatment with a TGFß inhibitor attenuated TGFß1-induced ALP expression and staining in sinus bone cells of CRSwNP, leading to loss of bone formation. CONCLUSIONS: Eosinophil-derived TGFß1 was enriched in the submucosa of CRSwNP, which induced ALP expression in sinus bone cells and NBF. Therefore, eosinophil-derived TGFß1 may mediate aberrant bone remodeling in CRSwNP.

Accelerated Synthetic MRI with Deep Learning-Based Reconstruction for Pediatric Neuroimaging.

BACKGROUND AND PURPOSE: Synthetic MR imaging is a time-efficient technique. However, its rather long scan time can be challenging for children. This study aimed to evaluate the clinical feasibility of accelerated synthetic MR imaging with deep learning-based reconstruction in pediatric neuroimaging and to investigate the impact of deep learning-based reconstruction on image quality and quantitative values in synthetic MR imaging. MATERIALS AND METHODS: This study included 47 children 2.3-14.7 years of age who underwent both standard and accelerated synthetic MR imaging at 3T. The accelerated synthetic MR imaging was reconstructed using a deep learning pipeline. The image quality, lesion detectability, tissue values, and brain volumetry were compared among accelerated deep learning and accelerated and standard synthetic data sets. RESULTS: The use of deep learning-based reconstruction in the accelerated synthetic scans significantly improved image quality for all contrast weightings (P < .001), resulting in image quality comparable with or superior to that of standard scans. There was no significant difference in lesion detectability between the accelerated deep learning and standard scans (P > .05). The tissue values and brain tissue volumes obtained with accelerated deep learning and the other 2 scans showed excellent agreement and a strong linear relationship (all, R 2 > 0.9). The difference in quantitative values of accelerated scans versus accelerated deep learning scans was very small (tissue values, <0.5%; volumetry, -1.46%-0.83%). CONCLUSIONS: The use of deep learning-based reconstruction in synthetic MR imaging can reduce scan time by 42% while maintaining image quality and lesion detectability and providing consistent quantitative values. The accelerated deep learning synthetic MR imaging can replace standard synthetic MR imaging in both contrast-weighted and quantitative imaging.

COVID-19 susceptibility and clinical outcomes in autoimmune inflammatory rheumatic diseases (AIRDs): a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to assess the susceptibility to and clinical outcomes of COVID-19 in autoimmune inflammatory rheumatic disease (AIRD) and following AIRD drug use. MATERIALS AND METHODS: We included observational and case-controlled studies assessing susceptibility and clinical outcomes of COVID-19 in patients with AIRD as well as the clinical outcomes of COVID-19 with or without use of steroids and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). RESULTS: Meta-analysis including three studies showed that patients with AIRD are not more susceptible to COVID-19 compared to patients without AIRD or the general population (OR: 1.11, 95% CI: 0.58 to 2.14). Incidence of severe outcomes of COVID-19 (OR: 1.34, 95% CI: 0.76 to 2.35) and COVID-19 related death (OR: 1.21, 95% CI: 0.68 to 2.16) also did not show significant difference. The clinical outcomes of COVID-19 among AIRD patients with and without csDMARD or steroid showed that both use of steroid (OR: 1.69, 95% CI: 0.96 to 2.98) or csDMARD (OR: 1.35, 95% CI: 0.63 to 3.08) had no effect on clinical outcomes of COVID-19. CONCLUSIONS: AIRD does not increase susceptibility to COVID-19, not affecting the clinical outcome of COVID-19. Similarly, the use of steroids or csDMARDs for AIRD does not worsen the clinical outcome.

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.

Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2).

BACKGROUND: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. METHODS: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885. RESULTS: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period. CONCLUSIONS: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.

Momentum dependent [Formula: see text] band splitting in LaFeAsO.

The nematic phase in iron based superconductors (IBSs) has attracted attention with a notion that it may provide important clue to the superconductivity. A series of angle-resolved photoemission spectroscopy (ARPES) studies were performed to understand the origin of the nematic phase. However, there is lack of ARPES study on LaFeAsO nematic phase. Here, we report the results of ARPES studies of the nematic phase in LaFeAsO. Degeneracy breaking between the [Formula: see text] and [Formula: see text] hole bands near the [Formula: see text] and M point is observed in the nematic phase. Different temperature dependent band splitting behaviors are observed at the [Formula: see text] and M points. The energy of the band splitting near the M point decreases as the temperature decreases while it has little temperature dependence near the [Formula: see text] point. The nematic nature of the band shift near the M point is confirmed through a detwin experiment using a piezo device. Since a momentum dependent splitting behavior has been observed in other iron based superconductors, our observation confirms that the behavior is a universal one among iron based superconductors.

Furoxan derivatives demonstrated in vivo efficacy by reducing Mycobacterium tuberculosis to undetectable levels in a mouse model of infection.

OBJECTIVES: The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. RESULTS: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 µM and 9.84 µM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 µM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 µM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. CONCLUSION: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.

Overexpression and Mutation of p53 Exons 4-8 in Canine Intestinal Adenocarcinoma.

p53 is mutated and overexpressed during malignant transformation, including in human colorectal cancer. This study investigated the overexpression of p53 protein and mutations in the p53 gene in canine intestinal neoplasia (CIN). Immunohistochemical analysis of p53 was carried out in formalin-fixed and paraffin wax-embedded (FFPE) sections of intestinal tissues from 35 dogs with CIN by the standard peroxidase-anti-peroxidase method. Expression of p53 protein in malignant (adenocarcinoma, n = 20) and benign (adenoma and polyp, n = 8) CINs was compared with tissue from negative controls (samples with no proliferation, n = 7). DNA was extracted from FFPE tissue from one control and 13 cases with overexpression of p53, and exons 4-8 were sequenced. p53 expression was higher in malignant than in benign tissues (P = 0.001). Sequencing was successfully performed in nine cases and mutations were confirmed in three of these cases. One non-sense mutation, one missense mutation and one germline mutation were confirmed for the three cases. This study suggests that p53 overexpression can be a prognostic factor for CIN; however, p53 overexpression in CIN may occur through a mechanism distinct from mutations within the p53 exon 4-8 region.

Hearing loss is associated with cortical thinning in cognitively normal older adults.

BACKGROUND AND PURPOSE: Hearing loss (HL) is one of the most influential risk factors of dementia in older adults. However, its potential association with neurodegeneration is not well established. The association between HL and cortical thickness in cognitively normal older adults was evaluated. METHODS: In all, 982 cognitively normal older adults (age ≥65 years) were identified from the Health Promotion Center at the Samsung Medical Center from September 2008 to December 2014. The participants underwent pure-tone audiometry and brain magnetic resonance imaging. HL was evaluated according to a four-frequency (0.5, 1, 2, 4 kHz) pure-tone average. Participants were divided into three groups according to pure-tone average (normal hearing ≤15 dB, minimal HL 16-25 dB, mild-to-severe HL >25 dB). Cortical thickness in the HL groups was compared with that of the normal hearing group. RESULTS: In women, right ear HL was associated with cortical thinning: the minimal HL group showed cortical thinning in the left frontal and bilateral occipital areas and the mild-to-severe HL group showed cortical thinning in the bilateral frontal, right temporal and bilateral occipital areas compared to the normal hearing group. In men, there was no significant association between HL on either side and cortical thickness. CONCLUSION: In older women, right ear HL is associated with neurodegeneration even in a cognitively normal state. Therefore, managing HL especially in older women may be an effective strategy for dementia prevention.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions Associated With Low-Osmolar Iodinated Contrast Media: A Longitudinal Study Based on a Real-Time Monitoring System.

OBJECTIVES: We investigated the incidence of immediate hypersensitivity reaction (HSR) caused by different types of low-osmolar contrast media (LOCM) and cumulative exposure to LOCM. METHODS: This cohort study included all consecutive patients who underwent LOCM-enhanced computed tomography from 2012 through 2014. We assessed 5 LOCM (iobitridol, iohexol, iomeprol, iopamidol, and iopromide). All patients were monitored for adverse events, and new symptoms and signs were recorded in real time using the Contrast Safety Monitoring and Management System (CoSM2oS). RESULTS: The overall incidence of immediate HSR to LOCM was 0.97% (2004 events resulting from 205 726 exposures). Incidence differed significantly depending on whether the patient had a previous history of HSR to LOCM (0.80% in patients with no history and 16.99% in patients with a positive history of HSR to LOCM, P=.001). The incidence of HSR to individual LOCM ranged from 0.72% (iohexol) to 1.34% (iomeprol), although there were no significant differences across the 5 LOCM. A longitudinal analysis demonstrated that the incidence of HSR increased gradually with more frequent previous exposure to LOCM (HR=2.006 [95%CI, 1.517-2.653], P<.001). However, this cumulative increase in risk was observed in patients who had experienced HSR to LOCM, but not in those who had not. CONCLUSION: The incidence of HSR did not differ significantly across the 5 LOCM assessed in the study. Repeated exposure to LOCM did not increase the risk of HSR among patients who had never experienced HSR to LOCM.

Osseous versus Nonosseous Spinal Epidural Arteriovenous Fistulas: Experiences of 13 Patients.

BACKGROUND AND PURPOSE: Spinal epidural arteriovenous fistulas are rare vascular malformations. We present 13 patients with spinal epidural arteriovenous fistulas, noting the various presenting symptom patterns, imaging findings related to bone involvement, and outcomes. MATERIALS AND METHODS: Among 111 patients with spinal vascular malformations in the institutional data base from 1993 to 2017, thirteen patients (11.7%) had spinal epidural arteriovenous fistulas. We evaluated presenting symptoms and imaging findings, including bone involvement and mode of treatment. To assess the treatment outcome, we compared initial and follow-up clinical status using the modified Aminoff and Logue Scale of Disability and the modified Rankin Scale. RESULTS: The presenting symptoms were lower back pain (n = 2), radiculopathy (n = 5), and myelopathy (n = 7). There is overlap of symptoms in 1 patient (No. 11). Distribution of spinal epidural arteriovenous fistulas was cervical (n = 3), thoracic (n = 2), lumbar (n = 6), and sacral (n = 2). Intradural venous reflux was identified in 7 patients with congestive venous myelopathy. The fistulas were successfully treated in all patients who underwent treatment (endovascular embolization, n = 10; operation, n = 1) except 2 patients who refused treatment due to tolerable symptoms. Transarterial glue (n = 7) was used in nonosseous types; and transvenous coils (n = 3), in osseous type. After 19 months of median follow-up, the patients showed symptom improvement after treatment. CONCLUSIONS: Although presenting symptoms were diverse, myelopathy caused by intradural venous reflux was the main target of treatment. Endovascular treatment was considered via an arterial approach in nonosseous types and via a venous approach in osseous types.

A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

Expression of Oestrogen Receptor, Progesterone Receptor and Akt in Canine Circumanal Gland Tumours.

We investigated the expression of oestrogen receptor alpha (OR-α), progesterone receptor (PR) and Akt in canine circumanal gland tumours. Immunohistochemistry was conducted on seven normal circumanal glands, 30 circumanal gland adenomas and 40 circumanal gland carcinomas. The expression of OR-α and PR was significantly lower in circumanal gland carcinomas than in circumanal gland adenomas. In contrast, the expression of Akt was markedly higher in circumanal gland carcinomas than in circumanal gland adenomas. These results indicate that the progression of canine circumanal gland tumours is influenced by changes in the expression levels of OR-α, PR and Akt. Identifying the molecular mechanisms of canine circumanal gland tumours requires further study.

Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients.

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.

Severe Asthma Phenotypes Classified by Site of Airway Involvement and Remodeling via Chest CT Scan.

OBJECTIVES: This study aimed to establish a system that can classify severe asthma on the basis of airway remodeling patterns visualizedusing computed tomography (CT) images and to evaluate the clinical characteristics of individual image-based subtypes. METHODS: Chest CT images from severe asthma patients were retrospectively evaluated to classify phenotypes by site of airway involvement and remodeling. The association between radiologic subtypes and clinical characteristics was assessed. RESULTS: Of 91 patients with severe asthma, 74 (81.3%) exhibited abnormal radiologic findings, including bronchial wall thickening (BT), mucus plugging (MP), and bronchiectasis (BE). The severity of BT and the extent of MP were independently associated with peripheral blood eosinophil count (P=.012, r2=0.112) and sputum eosinophil count (P=.022, r2=0.090), respectively. The large-to-medium airway remodeling type, which showed diffuse BT combined with MP and BE, accounted for 44% of patients and revealed higher peripheral blood eosinophil counts than other types. In the small airway remodeling type, which accounted for 6.6% of patients, we observed a higher rate of fixed airflow obstruction, along with a predominance of males and smokers and more frequent use of controller medication than other phenotypes. In 26% of patients with severe asthma, no prominent airway remodeling was observed (near-normal type); the near-normal type required oral corticosteroids less frequently than the large-to-medium airway and small airway remodeling types. CONCLUSIONS: Depending on the site of airway involvement and remodeling pattern, 3 different structural types can be distinguished in chest CT findings from patients with severe asthma. Remodeling in large-to-medium sized airways revealed an association with systemic eosinophilic inflammation in patients with severe asthma.

Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus i.v. paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy.

Background: Paclitaxel is currently only available as an intravenous (i.v.) formulation. DHP107 is a novel oral formulation of lipid ingredients and paclitaxel. DHP107 demonstrated comparable efficacy, safety, and pharmacokinetics to i.v. paclitaxel as a second-line therapy in patients with advanced gastric cancer (AGC). DREAM is a multicenter, open-label, prospective, randomized phase III study of patients with histologically/cytologically confirmed, unresectable/recurrent AGC after first-line therapy failure. Methods and materials: Patients were randomized 1 : 1 to DHP107 (200 mg/m2 orally twice daily days 1, 8, 15 every 4 weeks) or i.v. paclitaxel (175 mg/m2 day 1 every 3 weeks). Patients were stratified by Eastern Cooperative Oncology Group performance status, disease status, and prior treatment; response was assessed (Response Evaluation Criteria in Solid Tumors) every 6 weeks. Primary end point: non-inferiority of progression-free survival (PFS); secondary end points: overall response rate (ORR), overall survival (OS), and safety. For the efficacy analysis, sequential tests for non-inferiority were carried out, first with a non-inferiority margin of 1.48, then with a margin of 1.25. Results: Baseline characteristics were balanced in the 236 randomized patients (n = 118 per arm). Median PFS (per-protocol) was 3.0 (95% CI 1.7-4.0) months for DHP107 and 2.6 (95% CI 1.8-2.8) months for paclitaxel (hazard ratio [HR] = 0.85; 95% CI 0.64-1.13). A sensitivity analysis on PFS using independent central review showed similar results (HR = 0.93; 95% CI 0.70-1.24). Median OS (full analysis set) was 9.7 (95% CI 7.1 - 11.5) months for DHP107 versus 8.9 (95% CI 7.1-12.2) months for paclitaxel (HR = 1.04; 95% CI 0.76-1.41). ORR was 17.8% for DHP107 (CR 4.2%; PR 13.6%) versus 25.4% for paclitaxel (CR 3.4%; PR 22.0%). Nausea, vomiting, diarrhea, and mucositis were more common with DHP107; peripheral neuropathy was more common with paclitaxel. There were only few Grade≥3 adverse events, most commonly neutropenia (42% versus 53%); febrile neutropenia was reported infrequently (5.9% versus 2.5%). No hypersensitivity reactions occurred with DHP107 (paclitaxel 2.5%). Conclusions: DHP107 as a second-line treatment of AGC was non-inferior to paclitaxel for PFS; other efficacy and safety parameters were comparable. DHP107 is the first oral paclitaxel with proven efficacy/safety for the treatment of AGC. ClinicalTrials.gov: NCT01839773.

Estimates of genetic parameters for fatty acid compositions in the longissimus dorsi muscle of Hanwoo cattle.

We estimated the heritabilities (h 2) and genetic and phenotypic correlations among individual and groups of fatty acids, as well as their correlations with six important carcass and meat-quality traits in Korean Hanwoo cattle. Meat samples were collected from the longissimus dorsi muscles of 1000 Hanwoo steers that were 30-month-old (progeny of 85 proven Hanwoo bulls) to determine intramuscular fatty acid profiles. Phenotypic data on carcass weight (CWT), eye muscle area (EMA), back fat thickness (BFT), marbling score (MS), Warner-Bratzler shear force (WBSF) and intramuscular fat content (IMF) were also investigated using this half-sib population. Variance and covari.ance components were estimated using restricted maximum likelihood procedures under univariate and pairwise bivariate animal models. Oleic acid (C18:1n-9) was the most abundant fatty acid, accounting for 50.69% of all investigated fatty acids, followed by palmitic (C16:0; 27.33%) and stearic acid (C18:0; 10.96%). The contents of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) were 41.64%, 56.24% and 2.10%, respectively, and the MUFA/SFA ratio, PUFA/SFA ratio, desaturation index (DI) and elongation index (EI) were 1.36, 0.05, 0.59 and 0.66, respectively. The h 2 estimates for individual fatty acids ranged from very low to high (0.03±0.14 to 0.63±0.14). The h 2 estimates for SFAs, MUFAs, PUFAs, DI and EI were 0.53±0.14, 0.49±0.14, 0.23±0.10, 0.51±0.13 and 0.53±0.13, respectively. The genetic and phenotypic correlations among individual fatty acids and fatty acid classes varied widely (-0.99 to 0.99). Notably, C18:1n-9 had favourable (negative) genetic correlations with two detrimental fatty acids, C14:0 (-0.76) and C16:0 (-0.92). Genetic correlations of individual and group fatty acids with CWT, EMA, BFT, MS, WBSF and IMF ranged from low to moderate (both positive and negative) with the exception of low-concentration PUFAs. Low or near-zero phenotypic correlations reflected potential non-genetic contributions. This study provides insights on genetic variability and correlations among intramuscular fatty acids as well as correlations between fatty acids and carcass and meat-quality traits, which could be used in Hanwoo breeding programmes to improve fatty acid compositions in meat.

Genetic parameters of carcass and meat quality traits in different muscles (longissimus dorsi and semimembranosus) of Hanwoo (Korean cattle).

We estimated heritability () and genetic and phenotypic correlations for carcass and meat quality traits of longissimus dorsi (LD) and semimembranosus (SM) muscles in 30-mo-old Hanwoo steers. Variance and covariance components were estimated using REML procedures under univariate and bivariate models. The mean carcass weight (CWT), eye muscle area (EMA), back fat thickness (BFT), and marbling score (MS) were 428.20 ± 46.30 kg, 87.38 ± 8.54 cm2, 13.00 ± 5.14 mm, and 5.21 ± 1.56, respectively. The mean CIE reflectance of meat lightness (L*), redness (a*), and yellowness (b*) were 40.01 ± 2.73, 22.37 ± 2.18, and 10.35 ± 1.46, respectively, in LD muscles and 36.33 ± 2.44, 22.91 ± 2.43, and 10.25 ± 1.65, respectively, in SM muscles. The mean Warner-Bratzler shear force (WBSF), intramuscular fat content (IMF), water-holding capacity (WHC), and protein and ash content in LD and SM muscles were 3.84 ± 0.96 and 6.52 ± 1.21 kg, 15.91 ± 4.39 and 5.10 ± 1.94%, 62.07 ± 3.38 and 71.61 ± 2.06%, 20.01 ± 1.39 and 21.34 ± 0.89%, and 0.80 ± 0.10 and 0.93 ± 0.07, respectively. The estimates of CWT, EMA, BFT, and MS were 0.51 ± 0.13, 0.45 ± 0.13, 0.29 ± 0.09, and 0.22 ± 0.08, respectively. The estimates were moderate for meat quality traits and were 0.37 ± 0.12, 0.40 ± 0.12, 0.33 ± 0.10, 0.33 ± 0.10, 0.30 ± 0.11, and 0.24 ± 0.09 for L*, WBSF, IMF, WHC, and protein and ash content, respectively, in LD muscle; estimates from SM muscle were comparatively low (0.08 ± 0.06 to 0.25 ± 0.09). Estimates of for a* and b* were also low (0.08 ± 0.06 to 0.13 ± 0.07). Carcass weight had a moderate, positive genetic correlation with EMA (0.60 ± 0.13) and a weak correlation with MS and BFT. The genetic correlations among the 3 colorimeter variants were strong and positive within and between muscles. Intramuscular fat content had moderate to strong and negative genetic correlations with WBSF (-0.49 ± 0.18), WHC (-0.99 ± 0.01), and protein (-0.93 ± 0.04) and ash content (-0.98 ± 0.06) in LD muscle, whereas the associations were less pronounced in SM muscle. In general, CWT and EMA had low genetic and phenotypic correlations with meat quality traits, which suggests that the traits are independent and have distinct genetic contributions in each muscle. Conversely, with few exceptions, meat quality traits had genetic and phenotypic correlations with MS and BFT. In conclusion, the estimated genetic parameters for carcass and meat quality traits could be used for genetic evaluation and breeding programs in Korean Hanwoo cattle populations.