A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Adolescent-Onset Epilepsy: Clinical Features and Predictive Factors for First-Year Seizure Freedom.

BACKGROUND: Teenagers with epilepsy require special attention to ensure a successful treatment journey. Our objective was to delineate the clinical characteristics of adolescent-onset epilepsy (AOE) and investigate the predictive factors influencing first-year seizure freedom. METHODS: We retrospectively analyzed the medical records of patients whose first seizure occurred between the ages of 10 and 19 years and who received antiseizure medication (ASM) treatment for at least 12 months. RESULTS: A total of 67 patients were included, with an average age of 13.5 ± 2.3 years at the onset of their first seizure. The average follow-up period was 45.2 ± 16.9 months, and comorbid conditions were present in 23 patients (34.3%). The majority of the patient population (83.6%) was affected by generalized epilepsy. The most common epilepsy syndrome was epilepsy with generalized tonic-clonic seizures alone at 70.1% (juvenile myoclonic epilepsy 11.9%, juvenile absence epilepsy 1.5%). Regarding ASM treatment, 31 patients (46.3%) received monotherapy, and 28 (41.8%) received dual therapy. Five patients (7.5%) encountered issues related to medication adherence. First-year seizure freedom was observed in 42 patients (62.7%). In multivariate analysis, a negative family history of epilepsy (odds ratio 12.1, 95% confidence interval 1.27-115.44, p = 0.030) was identified as a strong predictive factor of first-year seizure freedom, along with ASM monotherapy (odds ratio 3.99, 95% confidence interval 1.05-15.21, p = 0.043). CONCLUSION: These findings suggest that AOE typically exhibits effective control of seizures. A negative family history of epilepsy and ASM monotherapy emerges as robust predictor of achieving favorable outcomes within the early stage of treatment.

Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research.

In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.

Repair of medial meniscus posterior root tear is effective for root healing and cartilage regeneration in opening wedge high tibial osteotomy.

PURPOSE: This study aimed to determine whether the repair of a medial meniscus posterior root tear (MMPRT) is effective for MMPRT healing, cartilage regeneration, and clinical outcomes in opening wedge high tibial osteotomy (OWHTO). METHODS: This retrospective study included 80 patients who underwent OWHTO and subsequent second-look arthroscopy. The patients were divided into OWHTO-with-MMPRT-repair (n = 40) and OWHTO alone (n = 40) groups, and the healing rates (complete/partial/failure) were compared. Each group was further divided into over- and under-corrected subgroups to compare healing rates. The International Cartilage Repair Society (ICRS) grade, cartilage defect size, Koshino stage, ICRS cartilage repair assessment score of the medial femoral condyle (MFC), and International Knee Documentation Committee (IKDC) scores between the OWHTO-with-MMPRT-repair and OWHTO alone groups were compared according to whether microfracture was performed on the MFC. RESULTS: The overall healing rate of the MMPRT was higher in the OWHTO-with-MMPRT-repair group than that in the OWHTO alone group (P < 0.001). In addition, in the subgroup analysis, no difference in the MMPRT healing rate between the over-correction and under-correction groups when MMPRT repair was performed (n.s). In contrast, without MMPRT repair, the healing rate was lower in the under-correction group than that in the over-correction group (P = 0.03). Cartilage regeneration of the OWHTO-with-MMPRT-repair group was superior to that of the OWHTO alone group (P < 0.05). The IKDC subjective scores of the OWHTO-with-MMPRT-repair and OWHTO alone groups were 34.5 and 33.1 before surgery (n.s) and 50 and 47.2 at one year after surgery, respectively (n.s). These differences between the two groups for cartilage regeneration and IKDC subjective scores showed the same pattern regardless of microfractures. CONCLUSIONS: MMPRT repair during OWHTO might improve MMPRT healing, even with under-correction, and cartilage regeneration of MFC, regardless of microfracture. However, OWHTO with MMPRT repair might not improve short-term clinical outcomes compared to OWHTO alone. Further randomized clinical trials are necessary. LEVEL OF EVIDENCE: III, Retrospective cohort study.

NXC736 Attenuates Radiation-Induced Lung Fibrosis via Regulating NLRP3/IL-1ß Signaling Pathway.

Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown. NLRP3 activation is an important trigger for the development of RILF. Thus, we aimed to evaluate the therapeutic effect of NXC736 on lung fibrosis inhibition using a RILF animal model and to elucidate its molecular signaling pathway. The left lungs of mice were irradiated with a single dose of 75 Gy. We observed that NXC736 treatment inhibited collagen deposition and inflammatory cell infiltration in irradiated mouse lung tissues. The damaged lung volume, evaluated by magnetic resonance imaging, was lower in NXC736-treated mice than in irradiated mice. NXC736-treated mice exhibited significant changes in lung function parameters. NXC736 inhibited inflammasome activation by interfering with the NLRP3-ASC-cleaved caspase-1 interaction, thereby reducing the expression of IL-1ß and blocking the fibrotic pathway. In addition, NXC736 treatment reduced the expression of epithelial-mesenchymal transition markers such as α-SMA, vimentin, and twist by blocking the Smad 2,3,4 signaling pathway. These data suggested that NXC736 is a potent therapeutic agent against RILF.

Efferocytosis and enhanced FPR2 expression following apoptotic cell instillation attenuate radiation-induced lung inflammation and fibrosis.

Lung inflammation and fibrosis are common side effects of radiotherapy that can lead to serious reduction in the quality of life of patients. However, no effective treatment is available, and the mechanisms underlying its pathophysiology are poorly understood. Irradiation increases formyl peptide receptor 2 (FPR2) expression in lung tissue, and FPR2 agonists are known to promote the uptake of apoptosis cells, referred to as efferocytosis that is a hallmark of the resolution of inflammation. Herein, in a mouse model of radiation-induced lung injury (RILI), efferocytosis was induced by injecting apoptotic cells into the lung through the trachea, and its correlation with FPR expression and the effect of efferocytosis and FPR expression on RILI were assessed. Interestingly, when apoptotic cells were injected into the lung, the radiation-induced increase in FPR2 expression was further amplified. In the mouse model of RILI, apoptotic cell instillation reduced the volume of the damaged lung and prevented the decrease in lung function. Additionally, the expression of inflammatory cytokines, fibrosis-related markers, and oxidative stress-related markers was reduced by apoptotic cell instillation. Co-administration of apoptotic Jurkat cells and WRW4, the FPR2 antagonist, reversed these effects. These findings suggest that efferocytosis induced by apoptotic cell instillation and enhanced FPR2 expression attenuate RILI, thereby alleviating lung inflammation and fibrosis.

Injectable Hydrogels of Stimuli-Responsive Elastin and Calmodulin-Based Triblock Copolypeptides for Controlled Drug Release.

A variety of block copolypeptides with stimuli responsiveness have been of growing interest for dynamic self-assembly. Here, multistimuli-responsive triblock copolypeptides composed of thermosensitive elastin-based polypeptides (EBP) and ligand-responsive calmodulin (CalM) were genetically engineered, over-expressed, and nonchromatographically purified by inverse transition cycling. Diluted EBP-CalM-EBP (ECE) triblock copolypeptides under physiological conditions self-assembled into vesicles at the nanoscale by temperature-triggered aggregation of the EBP block with lower critical solution temperature behaviors. Furthermore, concentrated ECE triblock copolypeptides under identical conditions exhibited thermally induced gelation, resulting in physically crosslinked hydrogels. They showed controlled rheological and mechanical properties depending on the conformational change of the CalM middle block induced by binding either Ca2+ or Ca2+ and trifluoperazines (TFPs) as ligands. In addition, both Ca2+-free and Ca2+-bound ECE triblock copolypeptide hydrogels exhibited biocompatibility, while those bound to both Ca2+ and TFPs showed severe cytotoxicity because of controlled TFP release of the CalM blocks. The ECE triblock hydrogels with stimuli responsiveness would be useful as injectable drug delivery depots for biomedical applications.

Next Generation Sequencing is a Reliable Tool for Detecting BRCA1/2 Mutations, Including Large Genomic Rearrangements.

BACKGROUND: Next-generation sequencing (NGS) has been implemented as a rapid and cost-effective BRCA1/2 test strategy. The Oncomine™ BRCA Research Assay is an NGS-based tool for simultaneous detection of small-scale mutations and large genomic rearrangements (LGRs). We evaluated this NGS assay using different versions of Ion Reporter™ (IR) software. METHODS: A total of 258 patients with breast, ovarian, primary peritoneal, and fallopian tube cancer, or a family history thereof, were enrolled in the study. The NGS assay was implemented for all samples, and the results were compared with those of Sanger sequencing and MLPA. RESULTS: All small-scale variations in Sanger sequencing were successfully detected by NGS assay. For the detection of LGRs, this assay showed 100% sensitivity from IR v5.10, and the latest version of the software (v5.16) showed the highest sensitivity and specificity. CONCLUSIONS: NGS with an appropriately updated workflow proved reliable for comprehensive BRCA1/2 gene testing, including LGR screening, which could facilitate efficient and accurate decision-making regarding treatment.

Severe Acute Respiratory Syndrome Coronavirus-2 Antibody Responses in Hospitalized Patients with Coronavirus Disease 2019 in Daegu, Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started to spread in Daegu beginning at the end of February 2020. IgG and IgM antibodies against SARS-CoV-2 were measured in hospitalized patients with COVID-19 with moderate to severe symptoms to improve the understanding of antibody responses. METHODS: We enrolled 312 patients with COVID-19 admitted to seven hospitals located in Daegu. Using serum (or plasma) samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infections, both IgG and IgM antibodies were measured using commercial enzyme-linked immunosorbent assay (R-FIND CO¬VID-19 ELISA, SG medical, Seoul, Korea). RESULTS: The median value from the initial diagnosis, confirmed by SARS-CoV-2 PCR, to the sampling date was 24 days (day 1 to 88). The total positive rate of IgG was 93.9% and the positive IgM rate was 39.4%, without considering the elapsed period after diagnosis. Positive IgG and IgM rates were highest at 100.0% and 59.0%, respectively, at 3 weeks (15 - 21 days). IgG showed a high positive rate of 79.3% even within 7 days after the initial diag-nosis of the disease and maintained a positive rate of 97.8% until after 8 weeks. CONCLUSIONS: Among hospitalized patients with COVID-19, IgG was detected from the beginning of the diagnosis and persisted for an extended time period.

Surge Capacity and Mass Casualty Incidents Preparedness of Emergency Departments in a Metropolitan City: a Regional Survey Study.

BACKGROUND: Emergency departments (EDs) generally receive many casualties in disaster or mass casualty incidents (MCI). Some studies have conceptually suggested the surge capacity that ED should have; however, only few studies have investigated measurable numbers in one community. This study investigated the surge capacity of the specific number of accommodatable patients and overall preparedness at EDs in a metropolitan city. METHODS: This cross-sectional study officially surveyed surge capacity and disaster preparedness for all regional and local emergency medical centers (EMC) in Seoul with the Seoul Metropolitan Government's public health division. This study developed survey items on space, staff, stuff, and systems, which are essential elements of surge capacity. The number of patients acceptable for each ED was investigated by triage level in ordinary and crisis situations. Multivariate linear regression analysis was performed on hospital resource variables related to surge capacity. RESULTS: In the second half of 2018, a survey was conducted targeting 31 EMC directors in Seoul. It was found that all regional and local EMCs in Seoul can accommodate 848 emergency patients and 537 non-emergency patients in crisis conditions. In ordinary situations, one EMC could accommodate an average of 1.3 patients with Korean Triage and Acuity Scale (KTAS) level 1, 3.1 patients with KTAS level 2, and 5.7 patients with KTAS level 3. In situations of crisis, this number increased to 3.4, 7.8, and 16.2, respectively. There are significant differences in surge capacity between ordinary and crisis conditions. The difference in surge capacity between regional and local EMC was not significant. In both ordinary and crisis conditions, only the total number of hospital beds were significantly associated with surge capacity. CONCLUSION: If the hospital's emergency transport system is ideally accomplished, patients arising from average MCI can be accommodated in Seoul. However, in a huge disaster, it may be challenging to handle the current surge capacity. More detailed follow-up studies are needed to prepare a surge capacity protocol in the community.

Apoptotic and antihepatofibrotic effect of honokiol via activation of GSK3ß and suppression of Wnt/ß-catenin pathway in hepatic stellate cells.

Though honokiol, derived from the Magnolia tree, was known to suppress renal fibrosis, pulmonary fibrosis, non-alcoholic steatoheptitis, inflammation and cancers, the underlying antifibrotic mechanisms of honokiol are not fully understood in hepatic stellate cells until now. Thus, in the present study, inhibitory mechanism of honokiol on liver fibrosis was elucidated mainly in hepatic stellate cells (HSCs) by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle analysis and western-blotting. Honokiol exerted cytotoxicity in LX-2, HSC-T6 and Hep-G2 cells. Honokiol increased sub G1 population and activated caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) in HSCs. Moreover, honokiol attenuated the expression of alpha smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-ß1), phospho-Smad3, phospho-AKT, cyclin D1, c-Myc, Wnt3a, ß-catenin, and activated phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) in HSCs. Conversely, GSK3ß inhibitor SB216763 reversed the effect of honokiol on PARP, α-SMA, phospho-GSK3ß, ß-catenin and sub G1 population in LX-2 cells. Overall, honokiol exerts apoptotic and antifibrotic effects via activation of GSK3ß and inhibition of Wnt3a/ß-catenin signalling pathway.

Serum cytokine profiles in infants with infantile hemangiomas on oral propranolol treatment: VEGF and bFGF, potential biomarkers predicting clinical outcomes.

BACKGROUND: Oral propranolol has become first-line treatment for infantile hemangiomas (IHs). This study focused on identifying cytokines related to the biology of IH and early regression indicators of IH after propranolol treatment. METHODS: For inclusion, the patients had to be aged less than 1 year and have an IH with a largest diameter ≥2 cm. Patients were scheduled to receive 1 year of propranolol treatment. Serum cytokines involved in angiogenesis, vasculogenesis, and/or chronic inflammation were analyzed at 0, 1, and/or 12 months after treatment using Multiplex Luminex assays. RESULTS: Among the 49 evaluable patients, 33 completed the 1-year treatment: 16 showed excellent response and 12 had good response to propranolol. Significant decreases in serum MMP-2, bFGF, VEGF-α, and MCP-1 levels were observed after 1 year of treatment compared to pretreatment values. The maximal diameters of the lesions significantly correlated with pretreatment serum VEGF-α, bFGF, and MMP-9. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. CONCLUSION: MMP-2, VEGF-α, bFGF, and MCP-1 may involve in the biology of IH and their downregulation may be associated with involution processes of IH. Pretreatment bFGF and VEGF could be novel biomarkers for predicting response to propranolol. IMPACT: We found that decreases in the concentrations of MMP-2, bFGF, VEGF, and MCP-1 were associated with regression of the hemangioma, which indicates that one of the mechanisms of propranolol in the treatment of proliferative hemangiomas may involve downregulation of those cytokines. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. Importantly, serum bFGF higher than 37.07 pg/mL may predict an excellent response to propranolol. Therefore, along with the patient's age and the size and visual characteristics of the lesion, bFGF levels could help determine the viability of propranolol use in the treatment of IHs. Our study represented extensive serum profiling in IH, reporting the indicators and molecules clearly related to IH regression with propranolol treatment. The authors believe that monitoring serum cytokines, including MMP-2, bFGF, VEGF, and MCP-1, in IH patients could be important, in addition to clinical follow-up, for determining when to start and end propranolol treatment.

Anisotropic Bimetallic Core-Satellite-Poly(aniline) Nanohybrids for Detection of Autoantibodies.

Bimetallic core-satellite nanoparticles are widely exploited in surface-enhanced Raman scattering (SERS)-based applications due to their enhanced optical properties compared to single-component metallic nanoparticles (MNPs). In addition, anisotropic hybrid nanostructures containing both MNPs and polymeric compartments constitute a new class of functional nanomaterials for photonic applications because they show different functionalities and physicochemical characteristics at two distinct compartments. Herein, synthesis of two kinds of anisotropic bimetallic core-satellite-poly(aniline) nanohybrids (ABCPNs) using small or polymeric ligand-coated gold nanospheres or gold nanorods as seeds is reported. The ABCPNs exhibit enhanced optical properties due to a local electromagnetic field generated in the narrow interparticle gap between core and satellite nanoparticles. Furthermore, a SERS-based quantitative analysis of autoantibodies against cyclic citrullinated peptide using the ABCPNs as SERS nanoprobes for a diagnosis of early rheumatoid arthritis is demonstrated, suggesting that these multifunctional nanostructures will be potential for advanced SERS-based biosensors.

The title: serum neutrophil Gelatinase-associated Lipocalin at 3 hours after return of spontaneous circulation in patients with cardiac arrest and therapeutic hypothermia: early predictor of acute kidney injury.

BACKGROUND: Serum neutrophil gelatinase-associated lipocalin (NGAL) could be used as a predictive marker of acute kidney injury (AKI) in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) who are managed with targeted temperature management (TTM). However, the NGAL measurement timepoints vary from immediately after ROSC to several days later. The primary objective of this study was to determine an association between AKI and NGAL, both immediately (ROSC-NGAL) and 3 h after ROSC (3 h-NGAL), in OHCA patients with TTM. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge. METHODS: This prospective observational study was conducted between January 2016 and December 2018 and enrolled adult OHCA patients (≥18 years) with TTM after ROSC. The serum NGAL level was measured both immediately and 3 h after ROSC. Univariate and multivariate analyses were performed to identify the associations between AKI, poor neurologic outcome, and NGAL. RESULTS: Among 861 OHCA patients, 89 patients were enrolled. AKI occurred in 48 (55.1%) patients. On multivariate logistic regression analysis, 3 h-NGAL was significantly associated with AKI (odds ratio [OR] 1.022; 95% confidence interval [CI] 1.009-1.035; p = 0.001). The area under the receiver operating characteristic curve of 3 h-NGAL for AKI was 0.910 (95% CI 0.830-0.960), and a cut-off value of 178 ng/mL was identified. Both ROSC-NGAL and 3 h-NGAL were not significantly associated with poor neurologic outcome on multivariate logistic regression analysis (ROSC-NGAL; OR 1.017; 95% CI 0.998-1.036; p = 0.084, 3 h-NGAL; OR 0.997; 95% CI 0.992-1.001; p = 0.113). CONCLUSIONS: The serum NGAL concentration measured 3 h after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Future research is needed to identify the optimal measurement timepoint to establish NGAL as a predictor of neurologic outcome and to validate the findings of this research.

Epidemiology of Congenital Bleeding Disorders: a Nationwide Population-based Korean Study.

BACKGROUND: Except for data in the Korea Hemophilia Foundation Registry, little is known of the epidemiology of congenital bleeding disorders in Korea. METHODS: Data were obtained from the Korean Health Insurance Review and Assessment Service (HIRA) database. RESULTS: From 2010 to 2015, there were 2,029 patients with congenital bleeding disorders in the Korean HIRA database: 38% (n = 775) of these patients had hemophilia A (HA), 25% (n = 517) had von Willebrand disease (vWD), 7% (n = 132) had hemophilia B (HB), and 25% (n = 513) had less common factor deficiencies. The estimated age-standardized incidence rate (ASR) of HA and HB was 1.78-3.15/100,000 and 0.31-0.51/100,000, respectively. That of vWD was 1.38-1.95/100,000. The estimated ASR of HA showed increase over time though the number of new patients did not increase. Most patients with congenital bleeding disorders were younger than 19 years old (47.8%), and most were registered in Gyeonggi (22.1%) and Seoul (19.2%). CONCLUSION: This is the first nationwide population-based study of congenital bleeding disorders in Korea. This study provides data that will enable more accurate estimations of patients with vWD. This information will help advance the comprehensive care of congenital bleeding disorders. We need to continue to obtain more detailed information on patients to improve the management of these diseases.

Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997-2016: a Nationwide Retrospective Cohort Study.

BACKGROUND: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. METHODS: We collected the data of a newly diagnosed pediatric HHA cohort (2007-2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997-2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. RESULTS: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. CONCLUSION: In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.

Langerhans Cell Histiocytosis of the Gastrointestinal Tract: Evidence for Risk Organ Status.

OBJECTIVE: To investigate the "risk status" of Langerhans cell histiocytosis (LCH) of the gastrointestinal tract. STUDY DESIGN: Outcomes from 43 published cases of patients with LCH and gastrointestinal tract involvement were matched to 43 patients with LCH without gastrointestinal tract involvement cared for at our institution. Comparisons were made of the 5-year overall survival rates determined from Kaplan-Meier survival curves for the entire cohort of patients, as well as subgroups defined by lack of risk organ involvement and later era of treatment (to control for temporal changes in LCH treatment regimens). In addition, an association between LCH-gastrointestinal tract and risk organ involvement was investigated. RESULTS: The 5-year overall survival for children with LCH-gastrointestinal tract (45.3%) was significantly worse than for those without gastrointestinal tract involvement (94.6%; P = .001). This difference remained significant after we excluded risk organ involvement (53.6%% vs 100%; P = .001), and analyzing subjects diagnosed after 2000 (75% vs 100%; P = .012). A 4-fold increase in risk organ involvement with LCH-gastrointestinal tract was observed (OR 4.359; 95% CI 1.75-10.82, P = .001). CONCLUSIONS: This limited retrospective study suggests that patients with LCH-gastrointestinal tract involvement may have decreased survival, independent of risk organ involvement, and provides evidence to support a prospective study to evaluate risk organ status of LCH-gastrointestinal tract. LCH-gastrointestinal tract may be associated with a 4-fold risk for risk organ involvement. Attention to gastrointestinal symptoms and LCH-gastrointestinal tract in young children diagnosed with LCH is warranted.

Performance Evaluation of Allplex Respiratory Panels 1, 2, and 3 for the Detection of Respiratory Viral Infection.

BACKGROUND: The Allplex Respiratory Panels 1, 2, and 3 (Allplex; Seegene, Republic of Korea) is a one-step real-time reverse transcription-PCR method based on the multiple detection temperature (MuDT) technology for the detection of respiratory viral infections. In this study, we evaluated the performance of the Allplex assay by comparing it with that of the Anyplex II RV16 detection kit (Anyplex; Seegene), a multiplex real-time PCR assay based on the tagging oligonucleotide cleavage and extension technology. METHODS: A total of 400 clinical respiratory specimens that were previously tested by the Anyplex assay (300 samples that revealed positive results, and 100 samples that revealed negative results) were analyzed using the Allplex assay. RESULTS: After comparing both assays for detecting each virus, the range of positive percent agreement, negative percent agreement, and kappa values were found to be 91.7% to 100%, 94.1% to 100%, and 0.659 to 1.000, respectively. The uniplex PCR and sequencing for the samples with discrepant results revealed that a majority of the results were concordant with the results from the Allplex assay. In addition, the Allplex assay was superior in detecting multiple viruses. CONCLUSIONS: The Allplex assay produces results comparable to those of the Anyplex assay. Thus, the Allplex assay can be proposed as a rapid and accurate method for detecting respiratory viruses, especially for the detection of multiple viral infections.

Seven Co-Occurring Mutations in a Patient with Acute Myeloid Leukemia Identified by Next-Generation Sequencing.

BACKGROUND: Most cases of acute myeloid leukemia (AML) have multiple driver mutations. METHODS: We report a rare AML case with seven mutations and an aggressive clinical course. RESULTS: A 69-year-old woman presented with nausea and vomiting. A bone marrow smear showed increased mye-loblasts, promonocytes, and monocytes. Immunophenotyping identified myeloid and monocytic markers. Fusion transcripts were not detected. Massive parallel sequencing showed seven variants in DNMT3A, FLT3, KRAS, NPM1, PTPN11, and TET2. Five days after beginning chemotherapy, the patient expired. CONCLUSIONS: These findings may provide insight into the link between multiple mutations and poor prognosis.

Major environmental characteristics of swine husbandry that affect exposure to dust and airborne endotoxins.

Inhalation of organic dust or endotoxin in the dust is considered a major risk factor for occupational respiratory illnesses. Eighteen environmental characteristics associated with animal husbandry were surveyed at 36 swine farms in seven provinces throughout South Korea. Association of these factors with levels of indoor inhalable or respirable dust or endotoxin in each type of dust was analyzed using backward stepwise multiple linear regression models. Mean levels of inhalable and respirable dust were 0.5 ± 0.35 and 0.13 ± 0.12 mg/m3 air, respectively, and mean endotoxin levels were 676 ± 463 and 48.4 ± 68.2 EU/m3, respectively, in each dust. Factors negatively associated with inhalable dust levels included pig age, indoor farm temperature, number of pigs in the building, hr/week of indoor farm work, and partly slatted floor. Factors positively associated with inhalable dust levels included floor cleaning by manual scraping and slurry deposit duration. Factors negatively associated with the level of endotoxin in inhalable dust included pig age, temperature, number of pigs, hr/week of indoor farm work, and partly slatted floor. Factors negatively associated with respirable dust level included area of the confinement building, whereas factors positively associated with respirable dust level included the number of pigs and stocking density. Endotoxin levels in respirable dust were negatively associated with h/week of indoor farm work and partly slatted floor. Overall, data suggest that husbandry variables may be adjusted to control dust and airborne endotoxin levels in swine farms.