Background To date, no study has evaluated the diversity of TH cell cytokine patterns of patients with chronic rhinosinusitis (CRS) among centers in different continents using identical methods. ...Objective We sought to assess TH cytokine profiles in patients with CRS from Europe, Asia, and Australia. Methods Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP; n = 435) and control subjects (n = 138) were recruited from centers in Adelaide, Benelux, Berlin, Beijing, Chengdu, and Tochigi. Nasal mucosal concentrations of TH 2, TH 17, and TH 1 cytokines; eosinophilic cationic protein (ECP); myeloperoxidase (MPO); IL-8; and tissue total and Staphylococcus aureus enterotoxin (SE)–specific IgE were measured by using identical tools. Results Combinations of TH 1/TH 2/TH 17 cytokine profiles in patients with CRSwNP varied considerably between regions. CRSwNP tissues from patients from Benelux, Berlin, Adelaide, and Tochigi were TH 2 biased, whereas those from Beijing mainly demonstrated TH 2/TH 1/TH 17 mixed patterns, and patients from Chengdu showed an even lower TH 2 expression. Concentrations of IL-8 and tissue total IgE in patients with CRSwNP were significantly higher than those in control subjects in all regions. More than 50% of patients with CRSwNP in Benelux, Berlin, Adelaide, and Tochigi showed a predominantly eosinophilic endotype compared with less than 30% of patients in Beijing and Chengdu. SE-specific IgE was found in significantly greater numbers in patients with CRSwNP from Benelux, Adelaide, and Tochigi and significantly lower numbers in patients from Beijing and Chengdu. Moreover, the TH 1/TH 2/TH 17 cytokine profiles in patients with CRSsNP showed diversity among the 6 regions. Conclusion TH cytokine levels, eosinophilic/neutrophilic patterns, and SE-specific IgE expressions show extreme diversity among patients with CRS from Europe, Asia, and Oceania.
Background Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately ...reflect the pathophysiologic diversity within patients with CRS. Objective We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. Methods In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin–specific IgE, and albumin. We used partition-based clustering. Results Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5–negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a TH 17 profile and had mixed CRSsNP/CRSwNP. The IL-5–positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin–specific IgE. Conclusion Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.
Abstract Background Managing anticoagulation in pregnant women with mechanical heart valves remains challenging. Our aim was to evaluate the effectiveness and safety of 4 regimens in these women. ...Methods Relevant studies published before June 2015 were collected in several databases and analyzed with RevMan version 5.3 and SPSS version 19.0. Four regimens were defined as follows: a regimen of a vitamin K antagonist (VKA) throughout pregnancy; a heparin (H)/VKA regimen using VKAs except for unfractionated heparin (UFH) or low molecular weight heparin (LMWH) during 6-12 weeks of pregnancy; a LMWH regimen of adjusted LMWH doses throughout pregnancy; and a UFH regimen of adjusted UFH doses throughout pregnancy. The low warfarin dose in the VKA regimen was defined as 5 mg/d or less. Results Fifty-one studies comprising 2113 pregnancies in 1538 women were included. The rate of fetal wastage was significantly higher in the high warfarin dose subgroup than in the low dose one. Compared with the H/VKA regimen, the rate of maternal major thromboembolic event in the low-dose VKA regimen group was significantly lower, although the fetal outcomes were similar. Compared with the H/VKA regimen, the rate of fetal wastage in the LMWH regimen group was significantly lower, and the maternal outcomes were similar. The UFH regimen presented the worst maternal and fetal outcomes. Conclusions In the absence of large prospective trials, this meta-analysis showed that the VKA regimen should be best for pregnant women with a low warfarin dose, and the H/VKA regimen might be reasonable for those with a high warfarin dose. The LMWH regimen could be used for those who refuse VKA.
According to the manufacturers' information, both of the detergents were composed of more than 20 ingredients, with the anionic surfactant SDBS as the major active surfactant. Once the anionic ...surfactant or detergent was removed by washing, both TER and FITC results recovered gradually to baseline level within 72 hours (see Fig E6 in this article's Online Repository at www.jacionline.org). Because TJ proteins must be correctly assembled into TJ structures to efficiently contribute to the barrier function of cells, we investigated the distribution of the TJ molecule occludin after treatment with surfactants or detergents.
Higher or lower blood pressure may relate to cognitive impairment, whereas the relationship between blood pressure and cognitive impairment among the elderly is not well-studied. The study objective ...was to determine whether blood pressure is associated with cognitive impairment in the elderly, and, if so, to accurately describe the association.
Cross-sectional data from the sixth wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted in 2011.
Community-based setting in longevity areas in China.
A total of 7144 Chinese elderly aged 65 years and older were included in the sample.
Systolic blood pressures (SBP) and diastolic blood pressures (DBP) were measured, pulse pressure (PP) was calculated as (SBP) - (DBP) and mean arterial pressures (MAP) was calculated as 1/3(SBP) + 2/3(DBP). Cognitive function was assessed via a validated Mini-Mental State Examination (MMSE).
Based on the results of generalized additive models (GAMs), U-shaped associations were identified between cognitive impairment and SBP, DBP, PP, and MAP. The cutpoints at which risk for cognitive impairment (MMSE <24) was minimized were determined by quadratic models as 141 mm Hg, 85 mm Hg, 62 mm Hg, and 103 mm Hg, respectively. In the logistic models, U-shaped associations remained for SBP, DBP, and MAP but not PP. Below the identified cutpoints, each 1-mm Hg decrease in blood pressure corresponded to 0.7%, 1.1%, and 1.1% greater risk in the risk of cognitive impairment, respectively. Above the cutpoints, each 1-mm Hg increase in blood pressure corresponded to 1.2%, 1.8%, and 2.1% greater risk of cognitive impairment for SBP, DBP, and MAP, respectively.
A U-shaped association between blood pressure and cognitive function in an elderly Chinese population was found. Recognition of these instances is important in identifying the high-risk population for cognitive impairment and to individualize blood pressure management for cognitive impairment prevention.
Objectives Surgical lung biopsy plays an important role in providing pathologic results, thus complementing the diagnostic rationale for suspected interstitial lung diseases. We performed a ...systematic review and meta-analysis regarding the diagnostic yield and postoperative mortality rate of surgical lung biopsy in patients with suspected interstitial lung diseases because of the wide variation in previously reported effectiveness and safety concerns. Methods We systematically searched for published studies between 2000 and 2014 evaluating surgical lung biopsy in the diagnosis of interstitial lung diseases. Subgroup analysis was performed to identify the possible source of study heterogeneity. Results Twenty-three studies contributed 2148 patients for the analysis. The median diagnostic yield was 95% (range, 42%-100%), with idiopathic pulmonary fibrosis as the most frequent diagnosis (618, 33.5%). Surgical lung biopsy was mainly guided by high-resolution computed tomography manifestations. Biopsy site, biopsy number, and the surgical lung biopsy method may not be associated with the diagnostic accuracy. The pooled postoperative mortality rate for included studies was 3.6% (95% confidence interval, 2.1-5.5), with significant heterogeneity observed. Subgroup analysis revealed that exclusion criteria based on immunocompromised status, mechanical ventilation, and severe respiratory dysfunction (diffusing capacity of lung for carbon monoxide <35% or forced vital capacity <55% predicted), but not surgical lung biopsy technique or underlying interstitial lung disease subtype, may be possible sources of heterogeneity. Conclusions We demonstrated a satisfactory diagnostic performance with a favorable safety profile of surgical lung biopsy in the diagnosis of suspected interstitial lung diseases. Surgical lung biopsy is especially recommended in patients with clinical information indicative but atypical of idiopathic pulmonary fibrosis, whereas the benefit of surgical lung biopsy should be carefully balanced against the risk for patients with immunocompromised status, mechanical ventilation dependence, or severe respiratory dysfunction.
Periostin expression has been shown to be regulated by several mediators, including TGF-β1, TGF-β2, and TGF-β4; bone morphogenic proteins 2 and 4; vascular endothelial growth factor; and IL-3, ...IL-4, IL-6, and IL-13.5 Our study showed that concomitant with the significantly increased periostin expression in nasal tissue of IL-5high patients with CRSwNP, expression of IL-4 and IL-13, but not IFN-γ, IL-17, and TGF-β1 (Fig 1, E), was also significantly increased in IL-5high patients with CRSwNP compared with that seen in IL-5low patients with CRSwNP and control subjects, with a significant correlation between periostin and IL-4 expression (r = 0.342, P = .038). Periostin has been reported to interact with extracellular matrix (ECM) proteins, such as type 1 collagen, fibronectin, tenascin C, and heparin.10 Accordingly, our results showed that the expression patterns of fibronectin and tenascin C were similar to that of periostin (Fig 1, F), with tenascin C expression correlated with periostin expression (r = 0.397, P = .015) in patients with CRSwNP and fibronectin and tenascin C expression colocalized with eosinophil counts and periostin expression in the subepithelial region of NP tissue (Fig 2, A). ...eosinophils adhered to fibronectin and tenascin C (Fig 2, D).
The aberrant expression in some of the circadian clock-related proteins is associated with the pathogenesis of immune disorders.5 On the basis of results of Fig E1, we reasoned that one or some of ...the circadian clock-related proteins interfered with the expression of Foxp3 in CD4+ T cells. ...after treating with ACC, we isolated CD4+ T cells from the mouse intestine; the cells were analyzed by chromatin immunoprecipitation assay. Occurrence of food allergy after the career of day-/night-shift rotation Time (y) Patients with food allergy Percent Participants, n 668 668 40 Sex: male/female, n 334/334 334/334 20/20 Age (y), mean ± SD 38.5 ± 16 37.8 ± 15 38.8 ± 18 Total food allergy patients 86 (12.9) 26 (3.9)low * 0 Allergen distribution    Fish 18 (20.9) 5 (19.2) 0 Shell fish 12 (13.9) 3 (11.5) 0 Milk 11 (12.8) 3 (11.5) 0 Tree nuts 10 (11.6) 3 (11.5) 0 Soy 10 (11.6) 1 (3.8) 0 Fruit 8 (9.3) 6 (23.1) 0 Sesame seed 6 (6.9) 0 0 Wheat 6 (6.9) 0 0 Egg 6 (6.9) 5 (19.2) 0 Peanut 5 (5.8) 5 (19.2) 0 With other allergies    Asthma 1 (0.15) 1 (0.15)  Allergic rhinitis 2 (0.3) 0  Allergic dermatitis 1 (0.15) 2 (0.3)  Serum vitamin D (ng/mL) 30.8 ± 1.9 30.5 ± 1.3  Serum cortisol (ng/mL) 19.8 ± 2.4 20.2 ± 2.3  Height (m) 1.59 ± 0.06 1.58 ± 0.06  Weight (kg) 61.5 ± 3.5 60.6 ± 3.2  BMI (kg/m2) 24.2 ± 2.8 23.9 ± 2.1  Specific IgE (kU/L) 15.3 ± 21.6 <0.35 12.5 ± 18.2 <0.35 <0.35 Regulatory T cells (%) 2.14 ± 2.06 5.95 ± 5.14 2.28 ± 2.35 6.28 ± 7.29 6.68 ± 6.26 Serum IL-4 (pg/mL) 45.8 ± 25.9 12.6 ± 18.6 39.5 ± 31.3 9.8 ± 15.4 10.5 ± 8.6 SPT diameter (mm) 6.58 ± 4.87 2.11 ± 1.14 5.74 ± 3.85 1.86 ± 1.47 1.17 ± 1.08 1-2 5 5.8 3-4 70 81.4 5-6 9 10.5 >7 1 1.2 Table I Clinical features of human subjects Some patients were allergic to more than 1 allergen.
Primary small cell carcinoma of the esophagus (SCCE) is characterized as highly aggressive with a poor prognosis. To identify potential prognostic factors and to assess the role of surgical ...procedures, chemotherapy, and radiotherapy for SCCE, we retrospectively analyzed patients with SCCE from three large institutions in China.
All of the SCCE patients between 1998 and 2012 were identified from three clinical databases of the Sun Yat-Sen University Cancer Center, Peking Union Cancer Hospital and Shantou Cancer Hospital. Potential prognostic factors were analyzed with univariate analysis and a Cox regression model. Subgroup analysis based on the 2002 American Joint Committee on Cancer staging system for esophageal cancer was applied to examine the effect of treatment on survival.
In patients with stage I/II SCCE, 85% underwent operations and showed improved survival (median survival time MST 29 vs 17.4 months, p = 0.082). However, chemotherapy did not further improve survival. In patients with stage IIB/III SCCE, chemotherapy, instead of operation, improved survival (MST 13.0 vs 6.1 months, p = 0.003), and radiotherapy resulted in improved survival. In stage IV patients, chemotherapy improved survival (MST 12.5 vs 4.0 months, p < 0.001), and chemotherapy combined with radiotherapy was superior to chemotherapy alone (MST 13.2 vs 8.9 months, p = 0.014).
Surgical procedures alone can be recommended for stage I/IIA patients. In patients with stage IIB disease or above, chemotherapy should be the main treatment approach, and chemotherapy combined with radiotherapy tended to improve survival.
The study aimed to introduce a rib and costal cartilage harvesting surgery by transumbilical single-incision laparoscopy and evaluate its efficiency and safety.
Patients who underwent rib and costal ...cartilage harvest under different approaches (direct open approach and transumbilical) were collected in this retrospective study. The differences in the pain scores visual analog scale (VAS), postoperative appearance, and complications were compared between the two groups at 1, 2, 3, and 7 days after surgery. In addition, based on the minimal clinically important difference and the generalized estimating equation, the differences were compared between the two groups in terms of the VAS score.
On postoperative day 1, the VAS scores of the direct open approach group and the transumbilical group were significantly different, that is, 7.29 and 6.10, respectively (
< 0.001). Also, the generalized estimating equation results were different (
< 0.001). An interaction was observed between different groups and days, that is, a statistical difference was observed in the VAS score between the two groups (
< 0.001). In terms of aesthetics and complications, patients from the transumbilical group had no scars on the chest wall and no obvious postoperative complications.
Transumbilical single-incision laparoscopic surgery is an innovative surgical approach for harvesting ribs and costal cartilage, which leaves no scars on the skin of the chest wall and has the advantages of slight postoperative pain, quick recovery, and fewer complications. This novel surgery is beneficial to patients with higher aesthetic requirements.
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