To determine the immediate and long-term therapeutic efficacies of Gufoni and head-shaking maneuvers in apogeotropic type of benign paroxysmal positional vertigo involving the horizontal semicircular ...canal (HC-BPPV), a randomized, prospective, sham-controlled study was conducted.
In 10 nationwide dizziness clinics in Korea, 157 consecutive patients (95 women, age range: 18-89 years, mean age ± SD = 59.9 ± 13.6) with apogeotropic HC-BPPV were randomized to Gufoni (n = 52), head-shaking (n = 54), or sham maneuver (n = 51). For Gufoni maneuver, patients underwent ipsilesional side-lying and upward head-turn for migration of the debris toward the vestibule. Immediate responses were determined within 1 hour after a maximum of 2 trials of each maneuver and in the following day. The patients also had weekly follow-ups for 1 month after the initial maneuver.
After a maximum of 2 maneuvers on the initial visit day, Gufoni (38/52, 73.1%) and head-shaking (33/53, 62.3%) maneuvers showed better responses than the sham maneuver (17/49, 34.7%). The cumulative therapeutic effects were also better with Gufoni (p < 0.001) and head-shaking (p = 0.026) maneuvers compared with the sham maneuver. However, therapeutic efficacies did not differ between the Gufoni and head-shaking groups in terms of both immediate (p = 0.129) and long-term (p = 0.239) outcomes.
Using a prospective randomized trial, we demonstrated that the Gufoni and head-shaking maneuvers are effective in treating apogeotropic HC-BPPV.
This study provides Class II evidence that Gufoni and head-shaking maneuvers are effective in treating apogeotropic horizontal BPPV up to 1 month after initial treatment.
NCT00810641.
Summary
Background
Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects ...of human umbilical cord blood‐derived MSCs (huMSCs) remain largely unexamined for asthma.
Objective
This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)‐induced murine asthma model.
Methods
Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen‐specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells.
Results
Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA‐specific IgE and IgG1 levels along with Th2 cytokine production (IL‐4, IL‐5, and IL‐13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs.
Conclusions
Our results suggest that huMSC treatment reduces OVA‐induced allergic inflammation, which could be mediated by regulatory T cells.
The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the ...prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment.
We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital.
In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS.
NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.
Summary
Background
Asthma in the elderly (aged ≥ 65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late‐onset asthma. Recent studies ...suggest staphylococcal enterotoxin IgE (SE‐IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late‐onset elderly asthma.
Objective
We aimed to examine the associations of SE‐IgE sensitization with late‐onset asthma in the elderly, using a database of elderly asthma cohort study.
Methods
A total of 249 elderly patients with asthma and 98 controls were analysed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE‐IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12‐month follow‐up period.
Results
At baseline, serum SE‐IgE concentrations were significantly higher in patients with asthma than in controls median 0.16 (interquartile range 0.04–0.53) vs. 0.10 (0.01–0.19), P < 0.001. Elderly asthma patients with high SE‐IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE‐IgE levels. In multivariate logistic regression analyses, the associations between serum SE‐IgE concentrations and severe asthma were significant, independently of covariables SE‐IgE‐high (≥ 0.35 kU/L) vs. negative (< 0.10 kU/L) group: odds ratio 7.47, 95% confidence interval 1.86–30.03, P = 0.005. Multiple correspondence analyses also showed that high serum SE‐IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together.
Conclusions and Clinical Relevance
This is the first report on the significant associations of SE‐IgE sensitization with late‐onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma and suggest clues to the pathogenesis of severe late‐onset eosinophilic asthma in the elderly.
Summary
Background
Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult‐onset asthma ...in community‐based populations.
Objective
We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community‐based adult populations.
Methods
The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age = 60.2 years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin‐specific IgE using ImmunoCAP.
Results
Staphylococcal enterotoxin sensitization (≥ 0.35 kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (≥ 61 years), and inhalant allergen sensitization. Current asthma was mostly adult onset (≥ 18 years old) and showed independent associations with high enterotoxin‐specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin‐specific IgE level was identified as the major determinant factor for total IgE level.
Conclusions and Clinical Relevance
Staphylococcal enterotoxin sensitization was independently associated with adult‐onset asthma in adult community populations. Strong correlations between the enterotoxin‐specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis.
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.
Patients were randomized 1:1 to DHP107 (200mg/m2 orally twice daily days 1, 8, 15 every 4weeks) or i.v. paclitaxel (175mg/m2 day 1 every 3weeks). 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 6weeks. 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.
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%).
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.
NCT01839773.
Hydrographic data collected from research cruises, bottom‐anchored moorings, drifting Ice‐Tethered Profilers, and satellite altimetry in the Beaufort Gyre region of the Arctic Ocean document an ...increase of more than 6,400 km3 of liquid freshwater content from 2003 to 2018: a 40% growth relative to the climatology of the 1970s. This fresh water accumulation is shown to result from persistent anticyclonic atmospheric wind forcing (1997–2018) accompanied by sea ice melt, a wind‐forced redirection of Mackenzie River discharge from predominantly eastward to westward flow, and a contribution of low salinity waters of Pacific Ocean origin via Bering Strait. Despite significant uncertainties in the different observations, this study has demonstrated the synergistic value of having multiple diverse datasets to obtain a more comprehensive understanding of Beaufort Gyre freshwater content variability. For example, Beaufort Gyre Observational System (BGOS) surveys clearly show the interannual increase in freshwater content, but without satellite or Ice‐Tethered Profiler measurements, it is not possible to resolve the seasonal cycle of freshwater content, which in fact is larger than the year‐to‐year variability, or the more subtle interannual variations.
Plain Language
The Beaufort Gyre centered in the Canada Basin of the Arctic Ocean is the major reservoir of fresh water in the Arctic. The primary focus of this study is on quantifying variability and trends in liquid (water) and solid (sea ice) freshwater content in this region. The Beaufort Gyre Exploration Program was initiated in 2003 to synthesize results of historical data analysis, design and conduct long‐term observations, and to provide information for numerical modeling under the umbrella of the FAMOS (Forum for Arctic Observing and Modeling Synthesis) project. The data collected from research cruises, moorings, Ice‐Tethered Profiler observations, and satellite altimetry document an increase of more than 6,400 km3 of liquid freshwater content from 2003 to 2018, a 40% growth relative to the climatology of the 1970s. This fresh water volume is comparable to the fresh water volume released to the sub‐arctic seas during the Great Salinity Anomaly episode of the 1970s. Thus, since the 2000s, the stage has been set for another possible release of fresh water to lower latitudes with accompanying climate impacts, including changes to sea ice conditions, ocean circulation, and ecosystems of the Sub‐Arctic similar to the influence of the Great Salinity Anomaly observed in the 1970s.
Key Points
Beaufort Gyre freshwater content time series (2003–2018) from different data sets are updated, compared, and analyzed
Qualitative and quantitative estimates of factors and mechanisms driving freshwater content changes are provided
In 2003–2018, the major sources of accumulated fresh water were sea ice melt, Mackenzie River runoff, and Bering Strait transport
AMoRE is an international project to search for the neutrinoless double beta decay of
100
Mo
using a detection technology consisting of magnetic microcalorimeters (MMCs) and molybdenum-based ...scintillating crystals. Data collection has begun for the current AMORE-I phase of the project, an upgrade from the previous pilot phase. AMoRE-I employs thirteen
48
depl
.
Ca
100
MoO
4
crystals and five
Li
2
100
MoO
4
crystals for a total crystal mass of 6.2 kg. Each detector module contains a scintillating crystal with two MMC channels for heat and light detection. We report the present status of the experiment and the performance of the detector modules.
(
) promoter methylation status in primary and recurrent glioblastoma may change during treatment. The purpose of this study was to correlate
promoter methylation status changes with DWI and DSC PWI ...features in patients with recurrent glioblastoma after standard treatment.
Between January 2008 and November 2016, forty patients with histologically confirmed recurrent glioblastoma were enrolled. Patients were divided into 3 groups according to the
promoter methylation status for the initial and recurrent tumors: 2 groups whose
promoter methylation status remained, group methylated (
= 13) or group unmethylated (
= 18), and 1 group whose
promoter methylation status changed from methylated to unmethylated (
= 9). Normalized ADC and normalized relative CBV values were obtained from both the enhancing and nonenhancing regions, from which histogram parameters were calculated. The ANOVA and the Kruskal-Wallis test followed by post hoc tests were performed to compare histogram parameters among the 3 groups. The
test and Mann-Whitney
test were used to compare parameters between group methylated and group methylated to unmethylated. Receiver operating characteristic curve analysis was used to measure the predictive performance of the normalized relative CBV values between the 2 groups.
Group methylated to unmethylated showed significantly higher means and 90th and 95th percentiles of the cumulative normalized relative CBV values of the nonenhancing region of the initial tumor than group methylated and group unmethylated (all
< .05). The mean normalized relative CBV value of the nonenhancing region of the initial tumor was the best predictor of methylation status change (
< .001), with a sensitivity of 77.78% and specificity of 92.31% at a cutoff value of 2.594.
promoter methylation status might change in recurrent glioblastoma after standard treatment. The normalized relative CBV values of the nonenhancing region at the first preoperative MR imaging were higher in the
promoter methylation change group from methylation to unmethylation in recurrent glioblastoma.
We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg ...of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.
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