Dyspnea-alleviating and survival-prolonging effects of corticosteroids in patients with terminal cancer

In patients with cancer, dyspnea, which serves as a prognostic factor, increases toward the end of life. Notably, corticosteroid treatment can alleviate dyspnea in this patient population. Therefore, it is important to investigate the effects of corticosteroid responsiveness on patient survival. Accordingly, we retrospectively evaluated these effects and the efficacy of corticosteroids for dyspnea alleviation in patients with terminal cancer. Patients for whom corticosteroid therapy was or was not effective were designated as responders or non-responders, respectively, and survival was compared among patients in both groups. The primary endpoint was patient survival, and the secondary endpoints were the incidence of adverse effects and the effect of combination medicine use on responses to corticosteroids. From January 2012 through December 2015, 52 patients were investigated, and 30 and 22 were classified as responders and non-responders, respectively. Survival significantly increased among responders, compared to that among non-responders (8.5 vs. 5.0 days, P?=?0.0019, Mann–Whitney U-test), although the average corticosteroid daily doses (in prednisolone equivalents) did not differ significantly (28.96 ± 12.83 and 29.13 ± 18.48?mg among responders and non-responders, respectively; P?=?0.75, unpaired t-test). Observed corticosteroid-related side effects included insomnia (15.4%), delirium (11.5%), and hyperglycemia (3.8%). We attribute the survival difference to responsiveness to corticosteroids, as opposed to differences in patient prognosis related to underlying disease processes that resulted in apparent responses to medication. Our results suggest that further research is needed to evaluate the clinical factors related to corticosteroid combination therapy.     

Effectiveness of Corticosteroid Monotherapy for Dyspnea Relief in Patients with Terminal Cancer

Dyspnea is a common symptom in patients with cancer, particularly those with late-stage terminal disease. It markedly affects terminal cancer patients, reducing their quality of life. Reduced quality of life also affects survival; therefore, dyspnea is a prognostic factor. However, the role of corticosteroids, which often are used to alleviate dyspnea, has not been sufficiently validated. In this study, we retrospectively investigated whether corticosteroid monotherapy was effective for dyspnea palliation. The effectiveness rate of corticosteroid therapy was 45% in nine male and two female study subjects (mean age: 74.5 years; range: 64–86 years). No significant differences were found between responders and nonresponders in the first-day corticosteroid doses (25.5 ± 10.86 vs. 36.1 ± 16.39 mg, P = .29) or doses administered on 2 days (47.7 ± 25.99 vs. 72.2 ± 32.78 mg, P = .25). The mean ± standard error assessment score changed significantly from 2.7 ± 0.14 at the beginning of corticosteroid administration to 1.5 ± 0.37 at the time of maximum effect (P = .028); however, the decrease to 2.1 ± 0.25 at the final administration was not significant (P = .068). This indicates that corticosteroid therapy relieved dyspnea and could provide an early-stage treatment option.     

Range of Effective Corticosteroid Doses for Alleviating Dyspnea in Terminal Cancer Patients: A Retrospective Review

This study aimed to determine the range of mean cumulative corticosteroid doses that could effectively palliate dyspnea in opioid-treated patients with terminal cancer and to investigate the demographic or biochemical factors predictive of corticosteroid responsiveness. To this end, responders and nonresponders were compared with regard to corticosteroid dose and whether they had initiated opioid use before or concomitantly with corticosteroid use. A logistic regression analysis was conducted to assess the impacts of demographic and biochemical factors on corticosteroid effectiveness. The final sample comprised 20 patients who satisfied the selection criteria. The responders accounted for 70% of the total sample (n = 14) and experienced the strongest effect with regard to dyspnea palliation at a mean cumulative dose equivalent to 64.4 mg prednisolone. However, no factors predictive of response were identified. In summary, this retrospective study identified effective corticosteroid doses for dyspnea alleviation in terminal cancer patients. Although our study sample was limited in size, the results support further prospective research.     

Combined Effect of Opioids and Corticosteroids for Alleviating Dyspnea in Terminal Cancer Patients: A Retrospective Review

Dyspnea is a prognostic factor that affects the quality of life of terminal cancer patients, and many reports have described opioid treatment for dyspnea alleviation. Here, we retrospectively evaluated differences in the effects of various opioids administered concomitantly with corticosteroids on dyspnea in 20 terminal-stage cancer patients (13 men, 7 women; mean age [range]: 71 [49–94] years) who received opioids concomitantly with corticosteroids. Effectiveness was assessed throughout administration using the Support Team Assessment Schedule, Japanese version (STAS-J), particularly the subscale indicating how strongly a patient is affected by symptoms. The effectiveness of combined opioid and corticosteroid therapy against dyspnea and the opioid dose comprised the primary and secondary foci, respectively. Among concomitantly treated patients, STAS-J scores at initiation (mean ± SD: 3.1 ± 0.24) and lowest recorded STAS-J scores (1.4 ± 0.22) differed significantly (P = .0034) among those receiving morphine, but not among those receiving oxycodone (P = .068) or fentanyl (P = .18). Concomitant opioid and corticosteroid treatment was associated with a ≥2-point STAS-J score improvement in 14/20 patients (effectiveness: 70%). The opioid dose did not significantly affect dyspnea alleviation. We conclude that concomitant opioid and corticosteroid treatment can effectively alleviate dyspnea in terminal cancer patients.     

The effect of fluid resuscitation on the effective circulating volume in patients undergoing liver surgery: a post-hoc analysis of a randomized controlled trial

To assess the significance of an analogue of the mean systemic filling pressure (Pmsa) and its derived variables, in providing a physiology based discrimination between responders and non-responders to fluid resuscitation during liver surgery. A post-hoc analysis of data from 30 patients undergoing major hepatic surgery was performed. Patients received 15 ml kg^?1 fluid in 30 min. Fluid responsiveness (FR) was defined as an increase of 20% or greater in cardiac index, measured by FloTrac-Vigileo^®. Dynamic preload variables (pulse pressure variation and stroke volume variation: PPV, SVV) were recorded additionally. Pvr, the driving pressure for venous return (=Pmsa–central venous pressure) and heart performance (E_H; Pvr/Pmsa) were calculated according to standard formula. Pmsa increased following fluid administration in responders (n?=?18; from 13?±?3 to 17?±?4 mmHg, p?<?0.01) and in non-responders (n?=?12; from 14?±?4 to 17?±?4 mmHg, p?<?0.01). Pvr, which was lower in responders before fluid administration (6?±?1 vs. 7?±?1 mmHg; p?=?0.02), increased after fluid administration only in responders (from 6?±?1 to 8?±?1 mmHg; p?<?0.01). E_H only decreased in non-responders (from 0.56?±?0.17 to 0.45?±?0.12; p?<?0.05). The area under the receiver operating characteristics curve of Pvr, PPV and SVV for predicting FR was 0.75, 0.73 and 0.72, respectively. Changes in Pmsa, Pvr and E_H reflect changes in effective circulating volume and heart performance following fluid resuscitation, providing a physiologic discrimination between responders and non-responders. Also, Pvr predicts FR equivalently compared to PPV and SVV, and might therefore aid in predicting FR in case dynamic preload variables cannot be used.     

Physician-reported corticosteroid therapy practices in certified palliative care units in Japan: a nationwide survey

Abstract Background: Although corticosteroids are commonly used for symptom relief in the treatment of patients with advanced cancer, few studies have addressed nationwide physician-reported practices and attitudes toward corticosteroid therapy in palliative care settings. Design and Subjects: To clarify physician-reported practices and attitudes toward corticosteroid therapy for anorexia, fatigue, and dyspnea, a 15-item questionnaire was mailed to all 178 certified palliative care units in Japan. Results: In total, 124 physicians returned questionnaires (response rate of 70%). The median percentage receiving corticosteroids among all terminally ill cancer inpatients was 80% (fatigue, 80%; anorexia, 80%; dyspnea, 80%). Physicians reported varying methods and attitudes regarding corticosteroid use in palliative care settings. Regarding withdrawal when patient death was imminent, 46% of respondents usually abruptly ceased corticosteroid use, while 33% reduced but did not stop administration, and 21% neither stopped nor reduced corticosteroids. As for dosage, 47% of physicians selected a minimum daily dose for fatigue <2?mg, while 51% chose 2-4?mg. As for administration period, 50% started administering corticosteroids for dyspnea regardless of the prognosis, while 30% regarded a predicted survival of less than 3 months to be an indication for corticosteroid treatment. For side effect management, 48% did not principally prescribe corticosteroids for patients with hyperactive delirium, while 44% cautiously prescribed corticosteroids. Conclusion: The use of corticosteroids is very common in Japanese palliative care units, but physicians reported varying practices and attitudes regarding administration protocols. Future studies are needed to determine the standard treatment protocol for corticosteroid use in the terminally ill.     

Effect of administered corticosteroids for alleviating dyspnea in patients with terminal cancer: a prospective observational approach

Our primary objective was to prospectively evaluate the effects of corticosteroids on dyspnea in terminal cancer patients at Kasugai Municipal Hospital using the Japanese version of the Support Team Assessment Schedule (STAS-J). Our secondary objective was to report the side effects of corticosteroid use in these patients. The prospective investigation included two female patients with terminal breast cancer (Patients 1 and 2, ages 53 and 57 years, respectively) who satisfied the consecutive selection criteria and were hospitalized at Kasugai Municipal Hospital between January 2016 and March 2017. We used both interviews and a review of clinical records to evaluate these patients’ responses to oral or intravenous corticosteroid therapy for dyspnea. Patient 1 had an initial STAS-J dyspnea scale score of 4 before the commencement of corticosteroid administration, which decreased to scores of 2 (day 1) and 1 (day 2 and day 3) after corticosteroid administration. Patient 2 had an initial STAS-J scale score of 3, which decreased to 1 on day 1 and was maintained at this level until death occurred on day 15. Both patients experienced rapid relief of dyspnea (within 24 hours), indicating that corticosteroids may be used to effectively treat early dyspnea experienced by terminal cancer patients.     

Effect of cardiac resynchronization therapy on mitral valve geometry: a novel aspect as &quot;reversed mitral remodeling&quot;

Amelioration of the valvular geometry is a possible mechanism for mitral regurgitation (MR) improvement in patients receiving cardiac resynchronization therapy (CRT). We aimed to establish the precise definition, incidence, and predictors of reversed mitral remodeling (RMR), as well as the association with MR improvement and short-term CRT outcome. Ninety-five CRT recipients were retrospectively evaluated for the end-point of “MR response” defined as the absolute reduction in regurgitant volume (RegV) at 6 months. To identify RMR, changes in mitral deformation indices were tested for correlation with MR response and further analyzed for functional and echocardiographic CRT outcomes. Overall, MR response was observed in 50 patients (53%). Among the echocardiographic indices, the change in tenting area (TA) had the highest correlation with the change in RegV (r?=?0.653, p?<?0.001). The mean TA significantly decreased in MR responders (4.15?±?1.05 to 3.67?±?1.01 cm² at 6 months, p?<?0.001) and increased in non-responders (3.68?±?1.04 to 3.98?±?0.97 cm², p?=?0.014). The absolute TA reduction was used to identify patients with RMR (47%) which was found to be associated with higher rates of functional improvement (p?=?0.03) and volumetric CRT response (p?=?0.036) compared to those without RMR. Non-ischemic etiology and the presence of LBBB independently predicted RMR at multivariate analysis. In conclusion, reduction in TA is a reliable index of RMR, which relates to MR response, and functional and echocardiographic improvement with CRT. LBBB and non-ischemic etiology are independent predictors of RMR.     

Impact of Insulin Degludec in Hospitalized Patients With and Without Type 2 Diabetes Requiring Parenteral/Enteral Nutrition: An Observational Study

Introduction

Hyperglycemia in inpatients is a major problem, especially when nutritional support is required. This study aims to assess the impact of treatment with insulin degludec (IDeg) on mean blood glucose (BG) and glycemic variability in noncritical hospitalized patients with and without type 2 diabetes (T2DM) receiving enteral and/or parenteral nutrition (EN, PN).

Methods

Mean BG and glycemic variability from admission up to 7 days of hospitalization were evaluated in consecutive cases with and without T2DM. Percentage of coefficient of variation (CV) for glucose was used to express glycemic variability.

Results

Overall, 26 patients (13 with and 13 without T2DM) were admitted to the hospital for any cause. Subjects were 65.4% men and they were mainly elderly (mean age 66.3?±?13.4 years). PN was administered in 88.5% of patients and EN in 19.2%. At admission, mean HbA1c level was 5.9?±?0.7% in patients without diabetes and 9.1?±?2.5% in patients with T2DM. During hospitalization, mean daily BG levels changed from 151?±?47.3 mg/dl (day 1) to 157?±?66.7 mg/dl (day 7) in patients without diabetes and from 210?±?66.5 mg/dl to 192?±?48.6 mg/dl in patients with T2DM. CV decreased from 14% (day 1) to 11% (day 7) in patients without diabetes and from 20% (day 1) to 9% (day 7) in patients with T2DM. No symptomatic or severe hypoglycemia occurred.

Conclusions

Despite the small sample size and the lack of control group, this study represents the first proof-of-concept that IDeg in hospitalized patients with or without T2DM who require nutritional support has the potential to maintain stable levels of BG and reduce glycemic variability.

Funding

Novo Nordisk S.p.A. grant.

     

High Intensity Focused Ultrasound (HIFU) Heating Improves Perfusion and Antimicrobial Efficacy in Mouse Staphylococcus Abscess

Chronic wounds typically require long-duration treatment with a combination of antibiotics administered systemically. This incurs adverse side effects and can require aversive surgical treatments and limb amputations. To improve non-invasive antimicrobial therapy, the objective of this study was to investigate antimicrobial chemotherapy combined with high-intensity focused ultrasound (HIFU) heating (HT). A Staphylococcus aureus abscess (80?±?30?mm³) was generated in the mouse flank region. Once the average temperature (~42?°C–46?°C) in the abscess was reached with HIFU-HT, a broad-spectrum antimicrobial (ciprofloxacin, 10?mg/kg) and perfusion marker (Evans blue dye, 40?mg/kg wt) were administered intravenously via the tail vein. Four hours later, mean abscess perfusion and colony-forming units (CFUs) per gram of abscess were determined. HIFU-HT increased abscess perfusion by ~2.5-fold (4?±?0.6?µg/mL Evans blue) compared with control (1.5?±?0.7?µg/mL), and improved antimicrobial efficacy to decrease percentage average survival of S. aureus by ~20% (46?±?7 CFUs/g of abscess) versus that seen with ciprofloxacin alone (61?±?4?CFU/g). Our in vivo data suggest that HIFU-HT can improve antimicrobial treatment responses against deep-seated bacteria in abscess wounds via enhanced perfusion.     

Corticosteroids for alleviating dyspnea in patients with terminal cancer

Dyspnea is a common symptom in patients with cancer, particularly those with advanced disease. Although corticosteroids can provide effective symptom relief to such patients, the effects of these drugs on dyspnea have not been evaluated. Therefore, we retrospectively evaluated the effect of corticosteroids on dyspnea in patients with terminal cancer through a surrogate third-party evaluation intended to overcome the difficulties of self-evaluation. We investigated the electronic medical records of 693 patients who were hospitalized at Kasugai Municipal Hospital between January and December 2015 and subsequently died. After excluding patients whose deaths were not directly cancer-related and 214 patients remained eligible, 19 of 34 remaining patients with dyspnea were ultimately included in the survey. Eleven patients in the final sample received corticosteroid treatment. Among the 11 patients who received corticosteroids, 9 (81.8%), 1 (9.1%), and 1 (9.1%) received betamethasone, dexamethasone, and prednisolone. The expression of the intended effect was observed in 6 of 11 patients in the steroid group. The median time to effect expression in the steroid group was 2 days. The median durations of effect in the steroid group were 3 days. After eliminating the opioid effect, we confirmed that steroid administration improved patients’ STAS-J scores and possibly alleviated dyspnea.     

Intravenous enalaprilat for treatment of acute hypertensive heart failure in the emergency department

Background

Afterload reduction with bolus enalaprilat is used by some for management of acute hypertensive heart failure (HF) but existing data on the safety and effectiveness of this practice are limited. The purpose of this study was to evaluate the clinical effects of bolus enalaprilat when administered to patients with acute hypertensive heart failure.

Findings

We performed an IRB-approved retrospective cohort study of patients who presented to the emergency department of a large urban academic hospital. Patients were identified by pharmacy record and included if they received enalaprilat intravenous (IV) bolus in the setting of acute hypertensive HF. A total of 103 patients were included. Patients were hypertensive on presentation (systolic blood pressure [SBP]?=?195.2 [SD?±?32.3]?mmHg) with significantly elevated mean NT-proBNP levels (3797.8 [SD?±?6523.2]?pg/ml). The mean dose of enalaprilat was 1.3 [SD?±?0.7]?mg, with most patients (76.7%) receiving a single 1.25 mg bolus. By 3 h post­enalaprilat, SBP had decreased substantially (?30.5 mmHg) with only 2 patients (1.9%) developing hypotension. Renal function was unaffected, with no significant change in serum creatinine by 72 h. In the 30 days post-admission, patients spent an average of 23 [SD?±?7.5]?days alive and out of hospital.

Conclusions

In this retrospective cohort of acute hypertensive HF patients, bolus IV enalaprilat resulted in a substantial reduction in systolic BP without adverse effect.

     

Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children

Background

Mycoplasma pneumoniae pneumonia (MPP) is generally a self-limiting disease, but it may become refractory. It is thought that refractory MPP is linked to the excessive immunologic responses of the host. Consequently, the use of adjunctive systemic corticosteroids may have beneficial effects. In this study, we compared the effects of high- and low-dose corticosteroid therapy in a pediatric population with refractory MPP.

Health-related outcomes of critically ill patients with and without sepsis

Purpose

To determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis.

Methods

We conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years.

Results

We obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p?=?0.86), self-care (24.7% vs. 26.0%, p?=?0.44), usual activities (44.5% vs. 46.8%, p?=?0.28), pain/discomfort (42.4% vs. 41.6%, p?=?0.54) and anxiety/depression (36.9% vs. 37.7%, p?=?0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86–1.18, p?=?0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1?±?11.9 vs. 8.0?±?9.8 days (p?<?0.0001) and 22.8?±?21.2 vs. 19.1?±?19.0 days, (p?=?0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345?±?46,263 (€35,109?±?35,043) versus 34,844?±?38,281 (€28,223?±?31,007), mean difference $8501 (€6885), 95% CI $4342–12,660 (€3517?±?10,254), p?<?0.001 as was the total cost of hospital treatment to 2 years: A$74,120?±?60,750 (€60,037?±?49,207) versus A$65,806?±?59,856 (€53,302?±?48,483), p?=?0.005.

Conclusions

Critically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

     

Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study

Purpose

To determine clinical predictors associated with corticosteroid administration and its association with ICU mortality in critically ill patients with severe influenza pneumonia.

Methods

Secondary analysis of a prospective cohort study of critically ill patients with confirmed influenza pneumonia admitted to 148 ICUs in Spain between June 2009 and April 2014. Patients who received corticosteroid treatment for causes other than viral pneumonia (e.g., refractory septic shock and asthma or chronic obstructive pulmonary disease [COPD] exacerbation) were excluded. Patients with corticosteroid therapy were compared with those without corticosteroid therapy. We use a propensity score (PS) matching analysis to reduce confounding factors. The primary outcome was ICU mortality. Cox proportional hazards and competing risks analysis was performed to assess the impact of corticosteroids on ICU mortality.

Results

A total of 1846 patients with primary influenza pneumonia were enrolled. Corticosteroids were administered in 604 (32.7%) patients, with methylprednisolone the most frequently used corticosteroid (578/604 [95.7%]). The median daily dose was equivalent to 80 mg of methylprednisolone (IQR 60–120) for a median duration of 7 days (IQR 5–10). Asthma, COPD, hematological disease, and the need for mechanical ventilation were independently associated with corticosteroid use. Crude ICU mortality was higher in patients who received corticosteroids (27.5%) than in patients who did not receive corticosteroids (18.8%, p?<?0.001). After PS matching, corticosteroid use was associated with ICU mortality in the Cox (HR?=?1.32 [95% CI 1.08–1.60], p?<?0.006) and competing risks analysis (SHR?=?1.37 [95% CI 1.12–1.68], p?=?0.001).

Conclusion

Administration of corticosteroids in patients with severe influenza pneumonia is associated with increased ICU mortality, and these agents should not be used as co-adjuvant therapy.

     

Plasma cytokine levels predict response to corticosteroids in septic shock

Purpose

To investigate if plasma cytokine concentrations predict a beneficial response to corticosteroid treatment in septic shock patients.

Methods

A cohort of septic shock patients in whom a panel of 39 cytokines had been measured at baseline (n = 363) was included. Patients who received corticosteroids were propensity score matched to non-corticosteroid-treated patients. An optimal threshold to identify responders to corticosteroid treatment for each cytokine was defined as the concentration above which the odds ratio for 28-day survival between corticosteroid- and non-corticosteroid-treated patients was highest.

Results

Propensity score matching partitioned 165 patients into 61 sets; each set contained matched corticosteroid- and non-corticosteroid-treated patients. For 13 plasma cytokines threshold concentrations were found where the odds ratio for survival between corticosteroid- and non-corticosteroid-treated patients was significant (P < 0.05). CD40 ligand was associated with the highest odds ratio and identified 21 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. Combinations of triplets of cytokines with a significant odds ratio, using the thresholds identified above, were tested to find a higher proportion of responders. IL3, IL6, and CCL4 identified 50 % of the patients in the propensity score matched cohort as responders to corticosteroid treatment. The odds ratio for 28-day survival was 19 (95 % CI 3.5–140, P = 0.02) with a concentration above threshold for a least one of these cytokines.

Conclusion

Plasma concentration of selected cytokines is a potential predictive biomarker to identify septic shock patients that may benefit from treatment with corticosteroids.

     

Renin levels and spironolactone treatment in general practice: similar blood pressure lowering effect of spironolactone in low and normal renin patients

We examined the predictive value of plasma renin activity (PRA) in ambulatory patients in the selection of hypertensive patients for treatment with spironolactone. The patients were classified as frusemide responders or non-responders according to their PRA response to 80 mg frusemide orally. After an initial 4 weeks placebo period forty-five patients with the clinical diagnosis of benign hypertension (WHO stage I-II) entered a 4 X 4 week double blind treatment period during which they received spironolactone (Aldactone) 400, 300, 200 and 100 mg/day, respectively. Five out of the forty-five patients who started the trial were withdrawn on account of side-effects and five patients for other reasons. Of the thirty-five patients who completed the study eighteen belonged to the group of non-responders to frusemide, seventeen to the responders. A gradual and significant decrease in mean blood pressure occurred during the period with the high doses of spironolactone, without any significant difference between the groups. The blood pressure lowering effect obtained with the initial high doses was maintained during the consecutive periods when the doses was reduced to a half or even a fourth, in both groups. We conclude that PRA measurement in ambulatory patients is of little, if any, value for the selection of hypertensives for spironolactone treatment; this in contrast to similar selections performed on hospitalized patients.     

呼出气一氧化氮测定对吸入糖皮质激素治疗慢性阻塞性肺疾病疗效的预测价值

目的探讨呼出气一氧化氮（fraction of exhaled nitric oxide,FENO）测定预测慢性阻塞性肺疾病（chronicobstructive pulmonary disease,COPD）患者吸入糖皮质激素（inhaled corticosteroid,ICS）治疗疗效的价值。方法 31例戒烟的重度COPD患者（第1s用力呼气容积（forced expiratory volume in one second,FEV1）占预计值百分比〈50%）,试验前进行无ICS的洗脱期后,给予沙美特罗替卡松吸入剂500μg,2次/d,连用4周,测定试验前FENO和试验后肺功能变化。结果基线FENO与使用ICS后FEV1变化无相关性;对ICS有反应者（FEV1增加≥200mL）较对ICS无反应者FENO基线值明显增高（P=0.028）,利用FENO诊断有反应者与无反应者的AUC为0.767。结论对已戒烟的重度COPD患者,FENO是一个较好的预测ICS治疗疗效的指标。     

Effect of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome

OBJECTIVE: We investigated the efficacy of low doses of corticosteroids in septic shock patients with or without early acute respiratory distress syndrome (ARDS) by post hoc analysis of a previously completed clinical trial. DESIGN: Retrospective analysis of a placebo-controlled, randomized, double-blind trial of low doses of corticosteroids in septic shock. SETTING: Nineteen intensive care units in France. PATIENTS: Among the 300 septic shock patients enrolled, we selected those meeting standard criteria for ARDS at inclusion. INTERVENTIONS: Seven-day treatment with 50 mg of hydrocortisone every 6 hrs and 50 microg of 9-alpha-fludrocortisone once a day. MEASUREMENTS AND MAIN RESULTS: There were 177 patients with ARDS (placebo, n = 92; corticosteroids, n = 85) including 129 (placebo, n = 67; corticosteroids, n = 62) nonresponders and 48 (placebo, n = 25; corticosteroids, n = 23) responders. In nonresponders, there were 50 deaths (75%) in the placebo group and 33 deaths (53%) in the steroid group (hazard ratio 0.57, 95% confidence interval 0.36-0.89, p = .013; relative risk 0.71, 95% confidence interval 0.54-0.94, p = .011). The number of days alive and off the ventilator was 2.6 +/- 6.6 in the placebo group and 5.7 +/- 8.6 in the steroid group (p = .006). There was no significant difference between groups in responders. There was no significant difference between groups in the two subsets of patients without ARDS. Adverse events rates were similar in the two groups. CONCLUSIONS: This post hoc analysis shows that a 7-day treatment with low doses of corticosteroids was associated with better outcomes in septic shock-associated early ARDS nonresponders, but not in responders and not in septic shock patients without ARDS.     

Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47?±?7 years, 30?% female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5?±?15 years; LVEF 63.5?±?7?%). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3?±?11?%) with higher LV mass relative to age-matched healthy volunteers (114?±?27 vs. 85.8?±?18 g; p?<?0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τ_ic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39?±?0.06 vs. 0.28?±?0.03, p?<?0.0001; τ_ic: 0.12?±?0.08 vs. 0.08?±?0.03, p?<?0.001). ECV was associated with LV mass (r?=?0.74, p?<?0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35?±?0.02 for 0R vs. 0.45?±?0, p?<?0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τ_ic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.