Meglumine cyclic adenylate improves cardiovascular hemodynamics and motor-function in a rat model of acute T4 thoracic spinal cord injury.

STUDY DESIGN: Animal experimental study. OBJECTIVES: Spinal cord injury (SCI) at or above the T6 level causes cardiovascular dysfunction. Maintaining cAMP levels with cAMP analogs can facilitate neurological recovery. In the present study, the effects of meglumine cyclic adenylate (MCA), a cAMP analog and approved cardiovascular drug, on cardiovascular and neurological recovery in acute T4-SCI in rats were investigated. SETTING: Hospital in Kunming, China. METHODS: Eighty rats were randomly allocated to five groups, and groups A-D received SCI: (A) a group administered MCA at 2 mg/kg/d iv qd, (B) a group administered dopamine at 2.5 to 5 µg/kg/min iv to maintain mean arterial pressure above 85 mm Hg, (C) a group administered atropine at 1 mg/kg iv bid, (D) a group receiving an equal volume of saline iv qd for 3 weeks after SCI and (E) a group undergoing laminectomy only. The cardiovascular and behavioral parameters of the rats were examined, and spinal cord tissues were processed for hematoxylin and eosin staining, Nissl staining, electron microscopy, and analysis of cAMP levels. RESULTS: Compared with dopamine or atropine, MCA significantly reversed the decrease in cAMP levels in both myocardial cells and the injured spinal cord; improved hypotension, bradycardia and behavioral parameters at 6 weeks; and improved spinal cord blood flow and histological structure at 7 days post-SCI. The regression analysis suggested spinal cord motor-function improved as decreased heart rate and mean arterial pressure were stopped post-SCI. CONCLUSIONS: MCA may be an effective treatment for acute SCI by sustaining cAMP-dependent reparative processes and improving post-SCI cardiovascular dysfunction. SPONSORSHIP: N/A.

Clinical Courses and Outcomes of Patients with Chronic Obstructive Pulmonary Disease During the COVID-19 Epidemic in Hubei, China.

Purpose: In this study, we investigated the acute exacerbation and outcomes of COPD patients during the outbreak of COVID-19 and evaluated the prevalence and mortality of COPD patients with confirmed COVID-19. Methods: A prospectively recruited cohort of 489 COPD patients was retrospectively followed-up for their conditions during the COVID-19 pandemic from December 2019 to March 2020 in Hubei, China. In addition, the features of 821 discharged patients with confirmed COVID-19 were retrospectively analyzed. Results: Of the 489 followed-up enrolled COPD patients, 2 cases were diagnosed as confirmed COVID-19, and 97 cases had exacerbations, 32 cases of which were hospitalized, and 14 cases died. Compared with the 6-month follow-up results collected 1 year ago, in 307 cases of this cohort, the rates of exacerbations and hospitalization of the 489 COPD patients during the last 4 months decreased, while the mortality rate increased significantly (2.86% vs 0.65%, p=0.023). Of the 821 patients with COVID-19, 37 cases (4.5%) had pre-existing COPD. Of 180 confirmed deaths, 19 cases (10.6%) were combined with COPD. Compared to COVID-19 deaths without COPD, COVID-19 deaths with COPD had higher rates of coronary artery disease and/or cerebrovascular diseases. Old age, low BMI and low parameters of lung function were risk factors of all-cause mortality for COVID-19 patients with pre-existing COPD. Conclusion: Our findings imply that acute exacerbations and hospitalizations of COPD patients were infrequent during the COVID-19 pandemic. However, COVID-19 patients with pre-existing COPD had a higher risk of all-cause mortality.

Effect of Body Mass Index on Lung Function in Chinese Patients with Chronic Obstructive Pulmonary Disease: A Multicenter Cross-Sectional Study.

Objective: The aim of this study was to explain "obesity paradox" in chronic obstructive pulmonary disease (COPD) by evaluating the effect of body mass index (BMI) on lung function in Chinese patients with COPD. Methods: A total of 1644 patients diagnosed with COPD were recruited from four Chinese tertiary hospitals and were divided into four groups including underweight, normal weight, overweight and obese according to BMI classification standard. The medical data of these patients were collected and used for the multiple linear regression analyses. Results: After adjustment for age, sex, educational level, economic status, smoking status, alcohol consumption, duration of COPD history, events of acute exacerbation in previous year, hypertension, diabetes mellitus, cardiovascular disease, cerebrovascular disease and osteoporosis, BMI had a curvilinear correlation with the forced expiratory volume in the first second (FEV1) in patients with Global Initiative for Obstructive Lung Disease (GOLD) 1-2 grade (first-order coefficient ß, 0.09; 95% CI, 0.03-0.16; second-order coefficient ß, -0.002; 95% CI, -0.003--0.001; P<0.01). However, BMI had a positive correlation with FEV1 in patients with GOLD 3-4 grade (ß, 0.01; 95% CI, 0.008-0.017; P<0.01) when BMI was used as a quantitative variable. When BMI was used as a qualitative variable, only FEV1 in overweight group with GOLD 1-2 grade was significantly higher than that of normal weight group (P<0.01). Interestingly, both overweight and obese groups had higher FEV1 in GOLD 3-4 grade compared with normal weight group (ß, 0.06; 95% CI, 0.02-0.11; ß, 0.11; 95% CI, 0.04-0.18; P<0.01). The effect of BMI on predicted percentage of FEV1 (FEV1%) was similar to that of FEV1 in different GOLD grades. Conclusion: Obesity only had a protective effect on lung function in COPD patients with GOLD 3-4 grade rather than GOLD 1-2 grade. Trial Registry: ClinicalTrials.gov, No.: NCT03182309, URL: www.clinicaltrials.gov.

Obstructive Sleep Apnea Increases the Prevalence of Hypertension in Patients with Chronic Obstructive Disease.

Whether there are increased rates of chronic diseases associated with the combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlap syndrome (OVS) has not been determined. The purpose of this study was to assess the prevalence of five comorbidities in COPD and OVS patients. A total of 968 patients with confirmed COPD were included in this study. Participants were requested to fill out a questionnaire involving their basic information and medical history. All subjects underwent one overnight polysomnography and were then divided into an OVS group or a COPD only group according to their apnea-hypopnea index. The prevalence of hypertension, diabetes, cardiovascular disease, arrhythmia and cerebrovascular disease were compared and risk factors for comorbidities in COPD patients were identified. Compared with the COPD only group, the prevalence of hypertension was significantly higher in the OVS group, however, the prevalence rates of the other four kinds of diseases were not statistically different between the two groups. In COPD patients, the prevalence of hypertension increased with the severity of OSA and the prevalence of arrhythmia increased with airflow limitation severity. Risk factors for OSA in patients with COPD included BMI, FEV1%, Epworth Sleepiness Scale score and the Sleep Apnea Clinical Score. OSA was an independent risk factor for hypertension. The other risk factors for hypertension in COPD patients included age, BMI, CAT score and alcohol consumption. Age, lower FEV1% may be risk factors for arrhythmia. OVS patients were associated with a high prevalence rate of hypertension, while OSA was an independent risk factor for hypertension.

Effects of the excitation or inhibition of basal forebrain cholinergic neurons on cognitive ability in mice exposed to chronic intermittent hypoxia.

Cognitive impairment of obstructive sleep apnea syndrome (OSAS) patients is related to the basal forebrain (BF) cholinergic neurons. To further investigate the effect of the excitation or inhibition of BF cholinergic neurons on cognitive ability, we employed a chronic intermittent hypoxia (CIH) mice model and implanted microinjection cannulas in the BFs for targeted intervention, finally performed the behavioral experiments and examined immunohistochemistry and biochemical changes in the BFs. The results showed that (1) CIH induced cognitive decline in mice. (2) The excitation of BF cholinergic neurons attenuated cognitive decline, while the inhibition of these neurons aggravated cognitive impairment. (3) Microinjection of adenosine into the BF aggravated cognitive decline, while caffeine improved cognitive ability. (4) CIH induced BF cholinergic neuron injury in mice. (5) The excitation of BF cholinergic neurons alleviated cholinergic neuron injury, while the inhibition of these neurons aggravated this injury. (6) Microinjection of adenosine into the BF aggravated cholinergic neuron injury, while caffeine alleviated this injury. (7) CIH induced endoplasmic reticulum stress, oxidative stress and inflammatory responses in the BFs of mice. (8) The excitation of BF cholinergic neurons mitigated endoplasmic reticulum stress, oxidative stress and inflammatory responses in the BF in mice, while the inhibition of BF cholinergic neurons worsened these responses in the BF. (9) Microinjection of adenosine into the BF aggravated endoplasmic reticulum stress, oxidative stress and the inflammatory response, while caffeine alleviated these responses. This work indicates that CIH induces BF cholinergic neuron injury through multiple pathways, including endoplasmic reticulum stress, oxidative stress and the inflammatory response, thereby leading to cognitive dysfunction in mice. BF cholinergic neurons play a vital role in these pathways, thus reducing cholinergic neuron injury and restoring cognitive function in mice. Adenosine, which is an upstream modifier of acetylcholine, also plays an important role in altering cognitive ability.

The Screening Value Of ESS, SACS, BQ, And SBQ On Obstructive Sleep Apnea In Patients With Chronic Obstructive Pulmonary Disease.

Objective: To compare the performance of Epworth sleepiness scale (ESS), sleep apnea clinical score (SACS), Berlin questionnaire (BQ), and STOP-BANG questionnaire (SBQ) in screening for obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 431 patients were analyzed. All subjects completed lung function test, ESS, SACS, BQ, and SBQ survey and overnight polysomnography (PSG). According to lung function and PSG results, participants were divided into COPD with OSA group (OVS, AHI ≥5) and without OSA group (AHI <5). The value of ESS, SACS, BQ, and SBQ was compared in predicting OSA in patients with COPD by receiver-operating characteristic (ROC) curve statistics. Results: Of the 431 subjects, there were 96 cases in COPD without OSA group, and 335 cases in OVS group including 183, 96, and 56 cases of COPD combined with mild, moderate or severe OSA. In predicting different degrees of severity of OSA in patients with COPD, the value of ESS was poor with all the values of area under the curve (AUC) < 0.7. SACS and BQ had moderate predictive value in screening for severe OSA with the value of AUC of 0.750, 0.735 respectively. However, the SBQ performed best in predicting various degrees of OSA. For screening mild OSA (AHI ≥5), the ROC statistics recommended the cut-off score of SBQ >2 was considered high risk of OSA; the sensitivity, specificity, and AUC were 92.8%, 40.6%, and 0.723 respectively, the odds ratio (OR) was 2.161. When AHI ≥15, AUC for SBQ was 0.737. In predicting severe OSA (AHI ≥30), the ROC curve showed cut-off point, sensitivity, specificity, and AUC for SBQ was >4, 66.1%, 82.1%, and 0.824 respectively; the positive and negative likelihood ratio was 3.70, 0.41 separately, the OR was 2.977. Conclusion: SBQ performed better than ESS, SACS, and BQ in predicting OSA in patients with COPD.

Recurrent, late-onset pleural effusions in elderly patients receiving pacemaker therapy.

Late-onset pacemaker-related pleural effusions (PEs) are rare and are often misdiagnosed with other entities. Our study aimed to detail the clinical features and management of PEs long after pacemaker insertion.We conducted a review of 6 consecutive elderly patients with PEs, who had undergone a new pacemaker insertion from September 2014 to January 2017. Also, the clinical characteristics and therapeutic courses of PEs were summarized.Two cases involved fluids after the first implantations, with pacing durations of 3 and 7 months. Two other cases developed PEs 3 or 4 months after the first replacement, with pacing durations of 6 and 11 years. Another 2 cases developed PEs 3 or 5 months following the second replacement, with total pacing durations of 16 and 18 years, respectively. The average interval was 4.17 months for the 6 cases from the time of the new pacemaker insertion to the occurrence of PEs. During the course, they had to be hospitalized repeatedly for thoracenteses because conventional treatments had only short-term effects. After the pacing settings were adjusted, PEs in all cases disappeared gradually. No patients were readmitted for PEs during the median follow-up period of 13 months.For elderly patients following implantation of a new pacemaker, PEs should be considered due to improper pacing settings, and corresponding adjustments to the device should be made.