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This study investigated burden of 'not well-controlled' asthma, overall and by Global Initiative for Asthma (GINA) Step, among treated asthma patients in Practice Fusion's research database. Asthma control (Asthma Control Test [ACT]) was stratified by GINA Step; prevalence ratios were estimated using Poisson regression with robust variance controlled for confounders. ACT scores ≤19 reflect not well-controlled; >19 reflect 'well-controlled' asthma. Of 15,579 patients, 30% had not well-controlled asthma at index date. The proportion of patients with not well-controlled asthma increased from GINA Step 1 (29%) to Step 5 (45%). Compared with Step 1, the proportion of patients with not well-controlled asthma was 0.87-times lower in Step 2, 1.10-times greater in Step 4, and 1.37-times greater in Step 5. Results suggest that despite available treatments, patients remain symptomatic across GINA Steps in real-world primary care and specialist outpatient practices, with incremental disease burden and unmet medical need in these populations., (© 2023. The Author(s).)

Background: Due to radical resection, endoprosthetic reconstruction (EPR) is more invasive and increases the risk of dislocation. Therefore, the suitability of EPR for elderly patients with metastatic tumor needs further investigation., Methods: Seventy-one adult patients with isolated proximal femoral bone metastases who underwent EPR were retrospectively analyzed and stratified into two groups: elderly age group (≥60 years, n = 31) and younger age group (<60 years, n = 40). The effect of age on prognosis was analyzed to determine whether EPR is beneficial in elderly patients with proximal femoral metastatic tumor. Cox regression modeling was used to evaluate the effect of different factors on postoperative survival outcomes., Results: Ten (32.26%) and 9 (22.50%) cases of perioperative complications were recorded in the elderly and younger age groups, respectively, with median survival times of 22.00 ± 4.61 months and 23.00 ± 2.85 months, respectively; a log-rank test showed that the difference was not statistically significant (p = 0.657). A Cox regression model was established with patient age as the covariable to evaluate whether it affected postoperative survival. The risk of death due to age was not significant (p = 0.649), but malignancy and femoral metastasis type were significantly associated with postoperative survival (p = 0.001 and p = 0.019)., Conclusion: Although older patients have a slightly higher incidence of postoperative complications than younger patients, they do not experience severe adverse consequences. With rigorous selection and careful preparation, EPR is appropriate for the treatment of proximal femoral metastases in older patients, including those with Harrington type I-II acetabular invasion., (© 2022. Society of Surgical Oncology.)

Background: There is limited information available on the impact of moderate asthma exacerbations, often called "asthma attacks" (i.e., those not requiring hospitalisation or treatment with systemic corticosteroids) on patients' lives. This multi-country qualitative study explored the patient experience of these events., Methods: Semi-structured concept elicitation interviews were conducted in the USA and Germany with adult patients with asthma who had experienced a moderate asthma exacerbation in the prior 30 days. Physicians with experience in managing patients with asthma were also interviewed. Interviews explored patients' experience of symptoms and impact of moderate exacerbations and associated exacerbation triggers and treatment patterns. Physicians were also asked about their interpretation of a clinical definition and treatment of a moderate exacerbation., Results: Twenty-eight patient (n = 20 in the USA, n = 8 in Germany) and six physician (n = 3 in the USA, n = 3 in Germany) interviews were conducted. During their moderate exacerbation, all patients reported experiencing shortness of breath, which many considered to be severe and the most bothersome symptom. Wheezing was also reported by all patients and considered severe by two thirds of patients. Most patients also reported coughing and chest tightness. All or almost all patients reported that moderate exacerbation caused fatigue/tiredness and impacted their physical functioning, emotional functioning, activities of daily living and work/school life. Most patients reported using rescue or maintenance inhalers to alleviate symptoms of the exacerbation. Conceptual saturation (i.e., the point at which no new concepts are likely to emerge with continued data collection) was achieved. Findings were used to develop a patient-focused conceptual model of the experience of moderate asthma exacerbations, outlining concepts related to triggers, symptoms, impact, and treatment from the patient perspective. Physician data was consistent with patient reports and complemented the conceptual model., Conclusions: Findings from concept elicitation interviews highlight the increased frequency, duration and severity of asthma symptoms and increased rescue medication use during moderate asthma exacerbations compared with the typical daily asthma experience, which have a substantial impact on patients' lives., (© 2022. The Author(s).)

Newcastle disease (ND) is an acute, febrile, and highly contagious disease caused by the Newcastle disease virus (NDV), an important pathogen harmful to domestic poultry. Virulent NDV strain infection induces IL-1β expression and along with strong inflammatory response, ultimately results in death. Inhibition or overexpression of S1PR1, an important target for inflammatory disease treatment, regulates IL-1β expression, suggesting that S1PR1 may alter the degree of the inflammatory response induced by NDV infection by regulating pro-inflammatory cytokine expression. However, the molecular mechanism by which S1PR1 regulates IL-1β expression remains unclear. Here, we explore the expression and tissue distribution of S1PR1 after NDV infection and found that S1PR1 expression increased in the lungs, bursa of Fabricius, and DF-1. IL-1β expression induced by NDV was increased following treatment of cells with the S1PR1-specific agonist, SEW2871. In contrast, IL-1β expression induced by NDV was decreased after cells were treated with the S1PR1 inhibitor W146, suggesting that S1PR1 promotes NDV-induced IL-1β expression. Further investigation demonstrated that NDV induced IL-1β expression through p38, JNK/MAPK, and NLRP3/caspase-1 signaling molecules and S1PR1 affected the expression of IL-1β by activating the NLRP3/caspase-1 inflammasome but had no significant effect on p38 and JNK/MAPK. Our study shows that NDV infection promotes S1PR1 expression and induces IL-1β expression through p38, JNK/MAPK, and NLRP3/caspase-1 inflammasomes and that S1PR1 regulates IL-1β expression mainly through the NLRP3/caspase-1 inflammasome., (© 2022. The Author(s).)

It has been reported that the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR), as well as systemic inflammation response index (SIRI), are closely related with overall survival (OS) in breast cancer patients. However, which one is the optimal indicator is vague. This study incorporates 280 breast cancer patients who received NACT. A cut-off value of LMR, PLR, SIRI and NLR is determined by Youden index. The Pearson's X 2 test or Fisher's exact test is applied to compare the correlation of different clinicopathologic characteristics divided by SIRI. The K-M survival curves and log-rank test were applied to determine OS. Univariate and multivariable analysis are explored by the Cox regression model. We apply the Z test to contrast the prognostic capacity of SIRI, LMR, PLR, and NLR. At the meanwhile, we construct the nomogram based on the results of multivariable analysis. All enrolled cases are divided into two parts by pretreatment SIRI (cut-off value = 0.52). Compared to high pre-treatment SIRI, high pre-treatment NLR and clinical T3 + T4 stage, the low pre-treatment SIRI, low pretreatment NLR and clinical T1 + T2 stage had longer OS time. The Z test showed that the SIRI group had bigger AUC than LMR and PLR, and the difference is statistically significant. The ability of nomogram, based on pretreatment SIRI, pre-treatment NLR and clinical T stage, to predict the 3-year, 5-year, and 8-year overall survival rates of breast malignant tumor patients is better than clinical TNM stage. Pre-treatment SIRI was a more crucial and integral prognostic index for breast malignant tumor patients receiving NACT. It could be helpful for doctors to predict the prognosis of breast malignant tumor patients and to evaluate the treatment status of patients., Competing Interests: Disclosures There is no conflict of interest among all authors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hypoxia is a distinguished hallmark of the tumor microenvironment. Hypoxic signaling affects multiple gene expressions, resulting in tumor invasion and metastasis. Quantification of hypoxic status although challenging, can be useful for monitoring tumor development and aggressiveness. However, hypoxia-independent factors such as nonspecific binding and heterogenous probe delivery considerably influence the probe signal thereby disenabling reliable quantitative imaging in vivo. In this study, we designed a self-calibrated activatable nanoprobe Cy7-1/PG5-Cy5@LWHA that specifically detects nitroreductase activity upregulated in hypoxic tumor cells. Dual fluorescence emission of the nanoprobe enables ratiometric calibration and eliminates the target-independent interference. In orthotopic and metastatic breast cancer mouse models, Cy7-1/PG5-Cy5@LWHA demonstrated remarkable hypoxia sensing capability in vivo. Moreover, ratiometric processing provided quantitative hypoxia assessment at different tumor developmental stages and facilitated tumor burden assessment in the metastatic lymph nodes. Therefore, our study demonstrates that ratiometric imaging of Cy7-1/PG5-Cy5@LWHA can be a prospective noninvasive tool to quantitatively monitor tumor hypoxia, which would be beneficial for investigating the fundamental role of hypoxia in tumor progression and for evaluating response to novel anti-hypoxia therapeutics. Furthermore, successful detection of metastatic lymph nodes with the proposed imaging approach illustrates its potential clinical application in assessing lymph node status during surgery., (© 2022. The Author(s).)

Background: There are limited published data on the burden of moderate/severe uncontrolled asthma., Methods: We conducted a systematic literature review to better understand the impact of moderate-to-severe asthma in the US, the UK, Germany, France, Italy, Spain, Canada, Japan, and Australia in terms of prevalence, clinical measures, health-related quality of life (HRQoL) and economic burden, for patients whose asthma is uncontrolled despite inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA) therapy., Results: The prevalence of uncontrolled asthma among patients with moderate/severe disease varied but was as high as 100% in some subgroups. Patients with uncontrolled asthma generally had poor lung function (mean/median pre-bronchodilator forced expiratory volume in 1 second [FEV 1 ]: 1.69-2.45 L; mean/median pre-bronchodilator percent predicted FEV 1 : 57.2-79.7). There was also a substantial but variable exacerbation burden associated with uncontrolled asthma, with the annualised rate of exacerbations ranging from 1.30 to 7.30 when considering various patient subgroups. Furthermore, the annualised rate of severe exacerbations ranged from 1.66 to 3.60. The HRQoL burden measured using disease-specific and generic instruments consistently demonstrated substantial impairment of HRQoL for those with uncontrolled asthma; Asthma Quality of Life Questionnaire scores ranged from 3.00 to 5.20, whilst EurQol-5 Dimensions index scores ranged from 0.53 to 0.59. Direct, indirect and total costs together with consumption of other healthcare resources associated with managing uncontrolled asthma were also substantial in the population studied; no caregiver burden was identified., Conclusions: Our findings suggest that significant unmet needs exist for patients with uncontrolled asthma despite the availability of ICS/LABA therapy. Novel treatments are needed to help reduce the burden to patients, healthcare systems and society., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the efficacies of neuronavigation-guided pure endoscopic endonasal transsphenoidal approach for removing pituitary adenomas., Methods: Retrospective analyses were conducted for the clinical data of 139 patients undergoing pure endoscopic endonasal transsphenoidal surgery for pituitary adenomas between July 2011 and July 2014. There were 55 males and 84 females with a mean age of 48. 9 (21 - 73) years. The classifications of Hardy-Wilson were I (n =16), II (n = 39), III (n = 48) and IV (n = 36). Neuronavigation was used in all patients. And neuro-ophthalmological, neuroimaging and endocrinological follow-ups were conducted postoperatively., Results: Total (n = 95, 68. 3%), subtotal (n = 33, 23. 7%) and partial (n = 11, 7. 9%) removals were achieved. For Hardy-Wilson I, gross total removal was achieved (n = 16, 100%); Hardy-Wilson II (n = 35, 89. 7%), Hardy-Wilson III (n = 34, 70. 8%) and Hardy-Wilson IV (n = 10, 27. 8%). Postoperative visual acuity improved (92. 1%, 70/76) and endocrine remission was observed (59. 6%, 53/89). The postoperative complications included cerebrospinal fluid (CSF) leakage (n = 8, 5. 8%), meningitis (n = 3), sellar hematoma (n = 5) and delayed carotid artery rupture (n = 1). And the patient of hemorrhagic shock underwent emergency interventional procedures and was discharged successfully., Conclusion: Pure endoscopic endonasal transsphenoidal approach for removing pituitary adenoma is both safe and effective. And its efficacies may further increased through combined neuronavigation.

Objective: To explore the outcomes of surgery for the treatment of small acoustic neuroma by the neuroendoscope-assisted microsurgery and microscope., Methods: From 2008 to 2013, 42 patients with small acoustic neuroma underwent neuroendoscope-assisted microsurgery (n = 20) and microscopic tumoural resection (n = 22). Neurophysiological monitoring, 30-degree rigid neuroendoscope and microscope were employed intra-operatively. For the endoscope group, facial nerve and inner acoustic meatus could be visualized distinctly in each aspect, as for the microscope group, microscopic operation could be accomplished directly. The damage extents of facial nerve and inner acoustic meatus were compared between two groups., Results: Total removal of acoustic neuroma and conservation of facial nerve were achieved in all patients. For the neuroendoscope-assisted group, the postoperative facial functions were Grade I (n = 6), Grade II (n = 10) and Grade III (n = 4). Internal acoustic canal was drilled 2-3 mm in 4 patients and no drilling in others. For the microscope group, Grade I (n = 5), Grade II (n = 6), Grade III (n = 8) and Grade III-IV (n = 3). Internal acoustic canal was drilled at least 3 mm in 12 patients and no drilling in others. No complication such as cerebrospinal fluid leakage occurred during the follow-ups., Conclusion: Endosocopic operation of acoustic neuroma surgery is superior to microscopic operation in terms of magnification, illumination, wide-angel and angulation. And the former procedure may yield better outcomes through alleviating the damage of facial nerve and decreasing the drilling degree of inner acoustic meatus.