Few reports have investigated the efficacy of using inhaled corticosteroid (ICS)-containing inhalers to treat patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO).
To ...investigate the effect of ICS treatment on patients with ACO using 5 sets of diagnostic criteria.
Patients with stable COPD enrolled in the Korean COPD subgroup study cohort were assessed for asthma overlap. Patients who were prospectively followed up for 1 year were included in an exacerbation analysis.
Among 1067 patients with COPD, 138 (12.9%), 32 (3.0%), 171 (16%), 221 (20.7%), and 264 (24.7%) were classified as having ACO by the Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, the American Thoracic Society roundtable criteria, the modified Spanish criteria, the updated Spanish criteria, and specialists' diagnoses, respectively. According to the specialists' diagnoses, the ACO exacerbation rate was higher than that for COPD alone (incidence rate ratio IRR = 1.65; P < .01), even after adjustment for covariates. Patients with ACO who used ICSs experienced less exacerbation, according to the specialists' diagnoses and the GINA/GOLD criteria (IRR = 0.55, P = .026; IRR = 0.69, P = .046, respectively). The only factor associated with a decrease in ACO exacerbation after ICS use was a blood eosinophil count of ≥300 cells/μL (IRR = 0.52, P = .03) irrespective of the diagnosis of ACO by any set of criteria.
This study suggests that ICS treatment can decrease the risk of exacerbation in patients with ACO, and that a blood eosinophil count of ≥300 cells/μL can predict the response to ICS treatment.
The use of recombinant human bone morphogenetic proteins-2(rhBMP-2) for spinal fusion has been reported to be effective. However, most studies have focused on posterolateral and anterior lumbar ...interbody fusion, and few have investigated posterior lumbar interbody fusion (PLIF).
This study aimed to determine the effectiveness and safety of the delivery of Escherichia coli–derived rhBMP-2 (E.BMP-2) with hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) poloxamer hydrogel composite carriers for PLIF.
A retrospective study.
Patients who underwent 1–3 levels of PLIF for lumbar degenerative disc disorders between 2015 and 2020 with a follow-up of ≥1 year were enrolled. In total, 254 patients (357 levels) were included in the analysis. Evaluation was performed at each segment level. In the E.BMP-2 group, 160 patients (221 levels) received autologous local bone with E.BMP-2 (maximum 0.5 mg/level), and in the control group, 94 patients (136 levels) received only local bone graft.
The primary outcome of this study was to compare the X-ray and CT fusion rates between the two groups. Secondary outcomes included analysis of the patients’ clinical outcomes and postoperative complications on CT scans.
Clinical evaluations were performed using a visual analog scale for back pain, the Oswestry Disability Index for disability, and physical and mental component summaries of the Short Form 36-Item Form Health Survey to assess functional effects and quality of life. The fusion was evaluated using radiography and CT. On radiography, solid fusion was defined when the difference between extension and flexion was less than 5°. On CT, solid fusion was defined when the upper and lower vertebral bodies were connected by the trabecular bone (bone bridge formation). In addition, complications such as osteolysis, cage subsidence, and screw loosening were investigated using CT.
All clinical results for low back pain, disability, and quality of life in both groups were excellent and showed statistically significant improvements compared with baseline (p<.0001). According to the X-ray evaluations, fusion was achieved in 92.31% (204/221) of the patients in the E.BMP-2 group and 82.35% (112/136) of the patients in the control group (p=.0041). According to the CT evaluations, the fusion rates were 93.21% (206/221) and 88.24% (120/136) in the E.BMP-2 and control groups (p=.1048), respectively. Except for screw loosening, which had a significantly higher incidence in the control group (p=.0014), the rates of most postoperative complications were not significantly different between the groups.
This study demonstrated that the adjunctive use of a low dose of E.BMP-2 with HA and β-TCP hydrogel can effectively promote bone fusion, making it a promising option for patients with limited autograft availability or compromised bone quality in PLIF.
Membrane fusion is mediated by the SNARE complex which is formed through a zippering process. Here, we developed a chemical controller for the progress of membrane fusion. A hemifusion state was ...arrested by a polyphenol myricetin which binds to the SNARE complex. The arrest of membrane fusion was rescued by an enzyme laccase that removes myricetin from the SNARE complex. The rescued hemifusion state was metastable and long-lived with a decay constant of 39 min. This membrane fusion controller was applied to delineate how Ca(2+) stimulates fusion-pore formation in a millisecond time scale. We found, using a single-vesicle fusion assay, that such myricetin-primed vesicles with synaptotagmin 1 respond synchronously to physiological concentrations of Ca(2+). When 10 μM Ca(2+) was added to the hemifused vesicles, the majority of vesicles rapidly advanced to fusion pores with a time constant of 16.2 ms. Thus, the results demonstrate that a minimal exocytotic membrane fusion machinery composed of SNAREs and synaptotagmin 1 is capable of driving membrane fusion in a millisecond time scale when a proper vesicle priming is established. The chemical controller of SNARE-driven membrane fusion should serve as a versatile tool for investigating the differential roles of various synaptic proteins in discrete fusion steps.
To evaluate prevalence, incidence, morbidity, and mortality rates of cervical ossification of posterior longitudinal ligament (OPLL) using data from a 12-year national cohort of 1,025,340 Korean ...people.
A nested case-control cohort study was performed from 2002 to 2013 using the insurance claims database provided by the National Health Insurance Service. We examined prevalence and incidence of cervical OPLL. Age- and sex-matched control subjects were randomly extracted, with 10 times the number of OPLL cases. Differences in sex, comorbidity, and relative survival rate compared with control subjects were assessed.
Cumulative prevalence was 20,960 per 1,025,340 people for 12 years. Annual incidence was approximately 199–371 per 1 million people. Overall crude mortality rate was 7.64%. Relative survival rate of OPLL cases was not significantly different from control cases. Diabetes, hypertension, cardiovascular disease, and cerebrovascular disease, except renal disease, correlated significantly with OPLL compared with control cases (P < 0.001). Additionally, between dead and surviving patients among OPLL cases, all comorbidities correlated more significantly with death (P < 0.001). Furthermore, between surgery and nonsurgery cases of OPLL, diabetes, hypertension, and renal disease (P < 0.05) were significantly associated with surgery.
Annual incidence of OPLL was 199–371 per 1,025,340 people for 10 years. Diabetes, hypertension, cardiovascular disease, and cerebrovascular disease, except renal disease, correlated significantly with OPLL compared with control cases. Especially, diabetes, hypertension, and renal disease were associated with patients with OPLL who underwent surgery.
•Prevalence, incidence, comorbidity, and mortality of cervical spine OPLL was analyzed in a nested case-control cohort study.•Cumulative prevalence was 20,960 per 1,025,340 people for 12 years.•Annual incidence of OPLL was 199–371 per 1,025,340 people for 10 years.•Diabetes, hypertension, cardiovascular disease, and cerebrovascular disease were associated significantly with OPLL.•Diabetes, hypertension, and renal disease were associated with patients with OPLL who underwent surgery.
Background
In cases of EGFR‐tyrosine kinase inhibitor (TKI) failure, re‐biopsy may be useful to understand resistance mechanisms and guide further treatment decisions. However, performing re‐biopsy ...is challenging because of several hurdles. We assessed the feasibility of re‐biopsy in advanced non‐small cell lung cancer (NSCLC) patients in real‐world clinical practice.
Methods
We retrospectively reviewed the clinical and pathologic data of advanced NSCLC patients who experienced disease progression after previous treatment with EGFR‐TKIs at a single tertiary hospital in Korea between January 2014 and December 2016. Re‐biopsy specimens included small biopsy, surgical tissue, or liquid‐based cytology. EGFR mutation was tested using peptide nucleic acid‐mediated clamping PCR.
Results
Of the 230 NSCLC patients that experienced progression after EGFR‐TKI therapy, 105 (45.7%) underwent re‐biopsy. Re‐biopsy was successfully performed in 94 (89.5%) patients, and 11 patients were diagnosed with no malignancy. The complication rate was 8.6%, including seven cases of pneumothorax. EGFR mutation testing was performed on 75 patients using re‐biopsy specimens. Of the 57 patients who had sensitizing mutations at diagnosis, T790M mutations were found in 19 (33.3%), while 38 (66.7%) had no T790M mutation. Multivariate analysis showed that the re‐biopsy group was younger (P = 0.002) and exhibited a previous response to EGFR‐TKIs (P < 0.001).
Conclusion
Re‐biopsy in advanced NSCLC is feasible in real world clinical practice, particularly in younger patients and those who achieved a previous response to EGFR‐TKIs.
Acid treatment is the most widely used surface modification method for enhancing the electroless metal deposition (EMD) on carbon reinforcement materials (CRMs) for metal matrix nanocomposites. ...However, specific microstructural and physicochemical origins of the enhanced EMD on carbon surfaces by acid treatments have been rarely studied. Here, we investigated the effects of the nitric acid treatment on graphite, a prototypical combination of acid treatment and CRM, on the fidelity of Cu EMD and their structural and chemical origins. Complementary materials characterizations and density functional theory calculations revealed the acid-induced formation of broken C–C/CC graphitic bonds and resulting surface micropores on graphite; this enabled a uniform dispersion of catalytic Sn/Pd nanoparticles during pre-EMD sensitization/activation processes via spontaneous binding of Sn and Pd ions and, consequently, a much more uniform Cu layer EMD compared to the untreated graphite. We proposed a general mechanism illustrating how the acid-induced microstructural and chemical modifications of carbon surface affected the spatial uniformity of catalytic metal reduction during EMD and, finally, the quality of deposited metal layer. The results clearly reveal the origins of the enhanced EMD on carbon materials by acid treatments, providing guidelines for optimizing EMD on general CRMs for high-performance metal matrix nanocomposites.
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•Nitric acid treatment induces the formation of numerous, well-distributed fine pores on the graphite surface.•Sn and Pd ions are preferentially adsorbed on broken C–C/CC bonds and CO groups formed by acid treatment.•Nitric acid treatment leads to uniform formation of Sn/Pd nanoparticles during the sensitization and activation processes.•Well-dispersed small catalytic Sn/Pd nanoparticles enable a uniform deposition of a Cu layer on the graphite surface.
Observations of galaxies and primordial radiation suggest that the Universe is made mostly of non-luminous dark matter
. Several new types of fundamental particle have been proposed as candidates for ...dark matter
, such as weakly interacting massive particles (WIMPs)
. These particles would be expected to interact with nuclei in suitable detector materials on Earth, for example, causing them to recoil. However, no definitive signal from such dark-matter interactions has been detected despite concerted efforts by many collaborations
. One exception is the much-debated claim by the DAMA collaboration of a statistically significant (more than nine standard deviations) annual modulation in the rate of nuclear interaction events. Annual modulation is expected because of the variation in Earth's velocity relative to the Galaxy's dark-matter halo that arises from Earth's orbital motion around the Sun. DAMA observed a modulation in the rate of interaction events in their detector
with a period and phase consistent with that expected for WIMPs
. Several groups have been working to develop experiments with the aim of reproducing DAMA's results using the same target medium (sodium iodide)
. To determine whether there is evidence for an excess of events above the expected background in sodium iodide and to look for evidence of an annual modulation, the COSINE-100 experiment uses sodium iodide as the target medium to carry out a model-independent test of DAMA's claim. Here we report results from the initial operation of the COSINE-100 experiment related to the first task
. We observe no excess of signal-like events above the expected background in the first 59.5 days of data from COSINE-100. Assuming the so-called standard dark-matter halo model, this result rules out spin-independent corrected WIMP-nucleon interactions as the cause of the annual modulation observed by the DAMA collaboration.
. The exclusion limit on the WIMP-sodium interaction cross-section is 1.14 × 10
cm
for 10-GeV c
WIMPs at a 90% confidence level. The COSINE-100 experiment will continue to collect data for two more years, enabling a model-independent test of the annual modulation observed by the DAMA collaboration.
A low lymphocyte count puts immune‐compromised patients at risk of mortality. hIL‐7‐hyFc is a homodimeric interleukin‐7 (IL‐7), a potent T‐cell amplifier, fused to the hybridizing IgD/IgG4 ...immunoglobulin domain. We performed a randomized, double‐blind, placebo‐controlled, dose‐escalation, phase I study to assess the pharmacokinetic, pharmacodynamic, safety, tolerability, and immunogenicity profiles of hIL‐7‐hyFc administered s.c. and i.m. to healthy volunteers. Thirty subjects randomly received hIL‐7‐hyFc or its matching placebo in an 8:2 ratio at 20, 60 μg/kg s.c., or 60 μg/kg i.m. The hIL‐7‐hyFc was slowly absorbed and its terminal half‐life was 63.26 hours after i.m. administration. The hIL‐7‐hyFc increased absolute lymphocyte count, mostly in T‐cells, which peaked 3 weeks after administration and then lasted for several additional weeks. The hIL‐7‐hyFc was well‐tolerated after a single s.c. and i.m. administration. Injection site reaction was the most common treatment‐emergent adverse event, which resolved spontaneously without treatment. The hIL‐7‐hyFc can be developed into a beneficial treatment option for patients with compromised T‐cell immunity. This trial was registered at www.clinicaltrials.gov as #NCT02860715.
Previous studies have used various definitions to classify chronic obstructive pulmonary disease (COPD) patients into chronic bronchitis (CB) and non-CB patients. This study was performed to identify ...differences among three definitions of CB based on the classical method, St. George's Respiratory Questionnaire (SGRQ), and the CAT (COPD Assessment Test) score.
We extracted data from the multicenter Korea COPD Subgroup Study (KOCOSS) cohort, for which patients recruited from among 47 medical centers in South Korea beginning in April 2012. Patients were classified according to three different definitions of CB: 1) classical definition; 2) SGRQ (using questions regarding cough and sputum); and 3) CAT score (comprising cough CAT1 and sputum CAT2 subscale scores).
A total of 2694 patients were enrolled in this study. The proportions of CB were 10.8%, 35.8%, and 24.0% according to the classical, SGRQ, and CAT definitions, respectively. The three definitions yielded consistently significant differences between CB and non-CB patients in modified Medical Research Council dyspnea scale CAT score, SGRQ score, number of moderate-to-severe exacerbations per year and forced expiratory volume in 1 second. By three definitions, CB consistently predicted future risk of exacerbation. The kappa coefficient of agreement between the classical definition and SGRQ definition was 0.29, that of the classical definition and CAT definition was 0.32, and that of the SGRQ definition and CAT definition was 0.44.
Patients with CB according to the new definitions based on SGRQ or CAT score showed similar clinical characteristics to those defined according to the classical definition. The new CB definitions may be used as alternatives to the classical definition.
Pelvic reconstruction after sacral resection is challenging in terms of anatomical complexity, excessive loadbearing, and wide defects. Nevertheless, the technological development of 3D-printed ...implants enables us to overcome these difficulties. Here, we present a case of sacral osteosarcoma surgically treated with hemisacrectomy and sacral reconstruction using a 3D-printed implant. The implant was printed as a customized titanium prosthesis from a 3D real-sized reconstruction of a patient's CT images. It consisted mostly of a porous mesh and incorporated a dense strut. After 3-months of neoadjuvant chemotherapy, the patient underwent hemisacretomy with preservation of contralateral sacral nerves. The implant was anatomically installed on the defect and fixed with a screw-rod system up to the level of L3. Postoperative pain was significantly low and the patient recovered sufficiently to walk as early as 2 weeks postoperatively. The patient showed left-side foot drop only, without loss of sphincter function. In 1-year follow-up CT, excellent bony fusion was noticed. To our knowledge, this is the first report of a case of hemisacral reconstruction using a custom-made 3D-printed implant. We believe that this technique can be applied to spinal reconstructions after a partial or complete spondylectomy in a wide variety of spinal diseases.
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