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.
Background and purpose
High blood pressure (BP) at presentation is associated with poor outcomes in acute ischaemic stroke, but serial BP measurements may better delineate the clinical implications ...of BP. The aim was to investigate the association between various BP parameters and functional outcomes in acute ischaemic stroke patients treated with endovascular thrombectomy (EVT).
Methods
This study reports a retrospective analysis of a prospective registry of a comprehensive stroke centre. Patients treated with EVT due to large vessel occlusion in the anterior circulation were enrolled. BP was measured hourly during the first 24 h after admission. Associations of various BP parameters, including BP variability, with functional outcomes at 3 months, including good outcomes (modified Rankin Scale score of 0–2), were analysed.
Results
Of the 378 enrolled patients (mean age 70 ± 11 years, male 54.2%), 313 (82.8%) achieved successful reperfusion after EVT, and 149 (39.4%) had good outcomes at 3 months. Higher mean systolic BP each 10 mmHg increase, odds ratio 0.82 (0.69–0.97) and higher systolic successive variation (SV) each 10% increase, odds ratio 0.37 (0.18–0.76) were associated with a reduced likelihood of achieving good outcomes. In addition, reperfusion status after EVT moderated the influence of higher systolic SV on good outcomes (Pint = 0.05).
Conclusion
The results showed that a higher mean systolic BP and systolic SV during the first 24 h of EVT reduced the likelihood of good outcomes at 3 months. The effects of these parameters on outcomes are more substantial amongst patients with successful reperfusion after EVT, suggesting that different BP control strategies should be employed according to reperfusion status.
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Summary
Population-based cohort study of 6,548,784 Korean subjects demonstrates that the risk of fracture was higher in patients with diabetes than in nondiabetic subjects. Furthermore, patients with ...type 1 diabetes were associated with a higher risk of fracture than patients with type 2 diabetes for all measurement sites.
Introduction
Diabetes mellitus is associated with increased fracture risk. Although the pathophysiologic effect on bone metabolism differs according to the type of diabetes, a higher risk of fracture in patients with diabetes than in nondiabetic patients has been consistently demonstrated. Considering the ever-increasing number of patients with diabetes, we aimed to provide updated information on whether this phenomenon remains valid in real-world settings by using large-scale population datasets.
Methods
We conducted a retrospective longitudinal study using data from the Korean National Health Insurance Service dataset of preventive health check-ups between January 2009 and December 2016. The hazard ratios were calculated for any fracture, vertebral fracture, and hip fracture and were analyzed according to the presence and type of diabetes. Among 10,585,818 subjects, 6,548,784 were eligible for the analysis (2418 patients with type 1 diabetes mellitus T1DM and 506,208 patients with type 2 diabetes mellitus T2DM).
Results
The mean follow-up duration (in years) was 7.0 ± 1.3 for subjects without diabetes, 6.4 ± 2.0 for those with T1DM, and 6.7 ± 1.7 for T2DM. Patients with T1DM had a higher incidence rate for all types of fractures per 1000 person-years. The fully adjusted hazard ratios (HRs) for any fracture, vertebral fracture, and hip fracture were higher in T1DM than in T2DM (1.37 95% confidence interval (CI): 1.23–1.52 for any fracture, 1.33 95% CI: 1.09–1.63 for vertebral fracture, and 1.99 95% CI: 1.56–2.53 for hip fracture).
Conclusions
In this large-scale population analysis, diabetes was associated with a higher risk of all types of fractures. Patients with T1DM had a higher risk of fracture than those with T2DM for all measurement sites, and hip fractures had the highest risk. Therefore, fracture prevention training for patients with diabetes is advisable.
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
To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment.
We prospectively ...collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group.
Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00–2.83; p 0.05).
Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.
Summary
Follow-up raloxifene therapy after denosumab discontinuation resulted in a decrease in bone mass to the pre-denosumab levels and a rebound increase of bone turnover markers. The decrease in ...lumbar bone mineral density was particularly evident when the body mass index was low, there were previous vertebral fractures, or lumbar bone mineral density before denosumab administration was low.
Introduction
Selective estrogen receptor modulators may be an alternative to bisphosphonates for treating rebound resorption after discontinuing denosumab. This study aimed to investigate the effects of follow-up raloxifene therapy after denosumab discontinuation in postmenopausal women.
Methods
This retrospective observational study included 61 patients who received 12-month follow-up raloxifene therapy after denosumab discontinuation. The primary endpoint was the bone mineral density change. The secondary endpoints were the changes in bone turnover markers and the incidence of new vertebral fractures.
Results
Raloxifene administration for 12 months after denosumab discontinuation resulted in a significantly lower bone mineral density at all sites compared to the level at 6 months after the last denosumab treatment (lumbar spine, − 5.48%; femoral neck, − 2.95%; total hip, − 3.52%; all,
p
< 0.001). The decrease in lumbar bone mineral density was particularly evident when the body mass index was low, there were previous vertebral fractures, or lumbar bone mineral density before denosumab administration was low. Marked increases in the bone turnover markers from baseline were noted after switching to raloxifene. However, no new vertebral fractures occurred during raloxifene treatment.
Conclusions
Follow-up raloxifene therapy after denosumab discontinuation resulted in a decrease in bone mass to the pre-denosumab levels and a rebound increase of bone turnover markers. Therefore, raloxifene administered sequentially after denosumab discontinuation was not effective in preventing rebound phenomenon.
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.
Despite the emerging importance of fibroblast growth factor 21 (FGF21) as a metabolic hormone regulating energy balance, its direct effects on renal function remain unexplored. FGF21 was injected ip ...daily for 12 weeks into db/db mice. Compared with control vehicle injection, FGF21 treatment significantly improved lipid profiles and insulin resistance and resulted in significantly higher serum adiponectin levels. In contrast, serum insulin and 8-isoprostane levels were significantly decreased. Interestingly, FGF21 and its receptor components in the kidneys were found to be significantly up-regulated in db/db mice, which suggests an FGF21-resistant state. FGF21 treatment significantly down-regulated FGF21 receptor components and activated ERK phosphorylation. FGF21 administration also markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic molecule synthesis. Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. In cultured renal cells, FGF21 was mainly expressed in mesangial cells, and knockdown of FGF21 expression by stealth small interfering RNA further aggravated high-glucose-induced profibrotic cytokine synthesis in mesangial cells. Our results suggest that FGF21 improves insulin resistance and protects against renal injury through both improvement of systemic metabolic alterations and antifibrotic effects in type 2 diabetic nephropathy. Targeting FGF21 could therefore provide a potential candidate approach for a therapeutic strategy in type 2 diabetic nephropathy.
No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia.
A prospective observational ...cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics.
Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group.
Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.
Background and purpose
The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion‐weighted magnetic ...resonance imaging (DWI‐MRI) and whether ischaemic core size affects this rate remain to be investigated.
Methods
This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI‐MRI that was categorized into three groups: small Diffusion‐Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) (8–10), moderate (5–7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0–2). The interaction between onset‐to‐groin puncture time (OTP) and DWI‐ASPECTS categories regarding functional outcomes was investigated.
Results
Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI‐ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction = 0.06). Every 60‐min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity = 0.15).
Conclusions
Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI‐ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.
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