Effect of different ventilation modalities on the early prognosis of patients with sleep apnea after acute ischemic stroke---protocol for a prospective, open-label and randomised controlled trial.

BACKGROUND: Sleep apnea is highly prevalent after acute ischemic stroke (AIS) and has increased stroke-related mortality and morbidity. The conventional sleep apnea treatment is continuous positive airway pressure (CPAP) ventilation. However, it is poorly tolerated by patients and is not used in all stroke patients. This protocol describes the impact of high-flow nasal cannula (HFNC) oxygen therapy compared to nasal continuous positive airway pressure (nCPAP) ventilation or usual care on the early prognosis of patients with sleep apnea after AIS. METHODS: This randomised controlled study will be conducted in the intensive care unit of the Department of Neurology at the Wuhan Union Hospital. According to the study plan, 150 patients with sleep apnea after AIS will be recruited. All patients are randomly allocated in a 1:1:1 ratio to one of three groups: the nasal catheter group (standard oxygen group), the HFNC group, and the nCPAP group. Patients receive different types of ventilation after admission to the group, and their tolerance while using the different ventilation is recorded. Patients will be followed up by telephone three months after discharge, and stroke recovery is recorded. The primary outcomes were 28-day mortality, the incidence of pulmonary infection and endotracheal intubation. DISCUSSION: This study analyses different ventilation modalities for early interventions in patients with sleep apnea after AIS. We will investigate whether nCPAP and HFNC reduce early mortality and endotracheal intubation rates and improve distant neurological recovery in patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05323266; 25 March 2022).

One-year mortality and consequences of COVID-19 in cancer patients: A cohort study.

The 1-year mortality and health consequences of COVID-19 in cancer patients are relatively underexplored. In this multicenter cohort study, 166 COVID-19 patients with cancer were compared with 498 non-cancer COVID-19 patients and 498 non-COVID cancer patients. The 1-year all-cause mortality and hospital mortality rates in Cancer COVID-19 Cohort (30% and 20%) were significantly higher than those in COVID-19 Cohort (9% and 8%, both P < .001) and Cancer Cohort (16% and 2%, both P < 0.001). The 12-month all-cause post-discharge mortality rate in survival discharged Cancer COVID-19 Cohort (8%) was higher than that in COVID-19 Cohort (0.4%, P < .001) but similar to that in Cancer Cohort (15%, P = .084). The incidence of sequelae in Cancer COVID-19 Cohort (23%, 26/114) is similar to that in COVID-19 Cohort (30%, 130/432, P = .13). The 1-year all-cause mortality was high among patients with hematologic malignancies (59%), followed by those who have nasopharyngeal, brain, and skin tumors (45%), digestive system neoplasm (43%), and lung cancers (32%). The rate was moderate among patients with genitourinary (14%), female genital (13%), breast (11%), and thyroid tumors (0). COVID-19 patients with cancer showed a high rate of in-hospital mortality and 1-year all-cause mortality, but the 12-month all-cause post-discharge mortality rate in survival discharged cancer COVID-19 patients was similar to that in Cancer Cohort. Comparing to COVID-19 Cohort, risk stratification showed that hematologic, nasopharyngeal, brain, digestive system, and lung tumors were high risk (44% vs 9%, P < 0.001), while genitourinary, female genital, breast, and thyroid tumors had moderate risk (10% vs 9%, P = .85) in COVID-19 Cancer Cohort. Different tumor subtypes had different effects on COVID-19. But if cancer patients with COVID-19 manage to survive their COVID-19 infections, then long-term mortality appears to be similar to the cancer patients without COVID-19, and their long-term clinical sequelae were similar to the COVID-19 patients without cancer.

Risk factors and in-hospital mortality of postoperative hyperlactatemia in patients after acute type A aortic dissection surgery.

BACKGROUND: Hyperlactatemia may be caused by increased production due to tissue hypoxia or non-hypoxia. The aim of this study was first to identify risk factors for postoperative hyperlactatemia (POHL) after Stanford type A acute aortic dissection surgery (AADS) and construct a predictive model, and second to evaluate the impact of POHL on prognosis. METHODS: This retrospective study involved patients undergoing AADS from January 2016 to December 2019 in Wuhan Union Hospital. Multivariate logistic regression analysis was performed to identify independent risk factors for POHL. A nomogram predicting POHL was established based on these factors and was validated in the original dataset. The receiver operating characteristic curve was drawn to assess the ability of postoperative lactate levels to predict the in-hospital mortality. RESULTS: A total of 188 patients developed POHL after AADS (38.6%). Male gender, surgery history, red blood cell transfusion and cardiopulmonary bypass time were identified as independent predictors. The C-index of the prediction model for POHL was 0.72, indicating reasonable discrimination. The model was well calibrated by visual inspection and goodness-of-fit test (Hosmer-Lemeshow χ2 = 10.25, P = 0.25). Decision and clinical impact curves of the model showed good clinical utility. The overall in-hospital mortality rate was 10.1%. Postoperative lactate levels showed a moderate predictive power for postoperative in-hospital mortality (C-index: 0.72). CONCLUSION: We developed and validated a prediction model for POHL in patients undergoing AADS, which may have clinical utility in personal risk evaluation and preventive interventions. The POHL could be a good predictor for in-hospital mortality.

Evaluating the performance of five scoring systems for prescreening obstructive sleep apnea-hypopnea syndrome.

PURPOSE: A comparison of all scoring systems used for screening for obstructive sleep apnea-hypopnea syndrome (OSAHS) is lacking. The aim of this investigation was to evaluate the performance of five scoring systems for screening for OSAHS, as well as to validate the use of the NoSAS and SACS in the Chinese population. METHODS: Data were retrospectively collected from hospital-based, manned, overnight sleep monitoring studies for 105 consecutive outpatients using a portable monitor (PM) device. RESULTS: The 105 participants had an average age of 46 years and were mostly men (75%). STOP-Bang, SACS, and NoSAS scoring exhibited moderate predictive values at different AHI cutoffs (AUC 0.761-0.853, 0.722-0.854, and 0.724-0.771 respectively), followed by the STOP and Berlin questionnaire (AUC 0.680-0.781vs 0.624-0.724). Both STOP-Bang and SACS showed excellent sensitivity (89.5-100% vs 93.4-94.6%) and negative predictive value (68-100% vs 77.3-90.9%), while STOP-Bang, STOP, and SACS showed low negative likelihood ratios (- LR) (0-0.2). CONCLUSIONS: Our study indicated that the STOP-Bang questionnaire and the SACS both show better predictive value than other scoring systems among the five screening tools for OSAHS. Both scoring systems are simple and easy to implement for screening for OSAHS in the community and in hospitals.

Different profiles of notch signaling in cigarette smoke-induced pulmonary emphysema and bleomycin-induced pulmonary fibrosis.

OBJECTIVE: Different profiles of Notch signaling mediate naive T cell differentiation which might be involved in pulmonary emphysema and fibrosis. METHODS: C57BL/6 mice were randomized into cigarette smoke (CS) exposure, bleomycin (BLM) exposure, and two separate groups of control for sham exposure to CS or BLM. The paratracheal lymph nodes of the animals were analyzed by real-time PCR and immunohistochemistry. Morphometry of the lung parenchyma, measurement of the cytokines, and cytometry of the bronchoalveolar lavage fluid (BALF) were also done accordingly. RESULTS: In comparison with controls, all Notch receptors and ligands were upregulated by chronic CS exposure, especially Notch3 and DLL1 (P < 0.01), and this was in line with emphysema-like morphology and Th1-biased inflammation. While Notch3 and DLL1 were downregulated by BLM exposure (P < 0.01), those was in line with fibrotic lung remodeling and Th2 polarization. CONCLUSIONS: This founding implies that the CS exposure but not the BLM exposure is capable of initiating Notch signaling in lymphoid tissue of the lung, which is likely relevant to the pathogenesis of pulmonary emphysema. Unable to initiate the Th1 response or inhibit it may lead to Th2 polarization and aberrant repair.

Effect of ventilation modalities on the early prognosis of patients with poststroke sleep apnea.

OBJECTIVE: Continuous positive airway pressure (CPAP) is the primary modality for treating sleep apnea after acute ischemic stroke (AIS). However, not all patients are well adherent to CPAP. Finding an alternative modality of ventilation to CPAP is essential. METHODS: This prospective randomized clinical trial was conducted from 1 May 2022 to 8 January 2023 at the Department of Neurology, Wuhan Union Hospital. Participants diagnosed with sleep apnea after AIS were grouped according to block randomization principles into the usual care group (nasal cannula and facemask), nasal continuous positive airway pressure (nCPAP) group, and high-flow nasal cannula (HFNC) group. Rates of pulmonary infection and endotracheal intubation within 1 week of hospitalization and 28-day mortality (poststroke) were the primary outcomes (early prognosis). RESULTS: In the trial, 178 patients (119 males [66.85%]; mean [SD] age, 61.04 [11.78] years) were eventually enrolled in the usual care group (n = 63), the nCPAP group (n = 55), and the HFNC group (n = 60). After ventilation, the nCPAP and HFNC groups were more effective than the usual care group in reducing the rate of pulmonary infection, endotracheal intubation, and improving neurological function and sleep apnea severity. However, there was no difference in 28-day mortality. Additionally, the improvement in prognosis was consistent between nCPAP and HFNC. In the comparison of comfort, the HFNC group was superior to nCPAP. INTERPRETATION: nCPAP and HFNC reduced early pulmonary infection rates and endotracheal intubation rates. For patients with poor compliance with nCPAP, HFNC may be the best alternative.

A risk-predictive model for obstructive sleep apnea in patients with chronic obstructive pulmonary disease.

Background: Obstructive sleep apnea syndrome (OSA) is increasingly reported in patients with chronic obstructive pulmonary disease (COPD). Our research aimed to analyze the clinical characteristics of patients with overlap syndrome (OS) and develop a nomogram for predicting OSA in patients with COPD. Methods: We retroactively collected data on 330 patients with COPD treated at Wuhan Union Hospital (Wuhan, China) from March 2017 to March 2022. Multivariate logistic regression was used to select predictors applied to develop a simple nomogram. The area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the value of the model. Results: A total of 330 consecutive patients with COPD were enrolled in this study, with 96 patients (29.1%) confirmed with OSA. Patients were randomly divided into the training group (70%, n = 230) and the validation group (30%, n = 100). Age [odds ratio (OR): 1.062, 1.003-1.124], type 2 diabetes (OR: 3.166, 1.263-7.939), neck circumference (NC) (OR: 1.370, 1.098-1,709), modified Medical Research Council (mMRC) dyspnea scale (OR: 0.503, 0.325-0.777), Sleep Apnea Clinical Score (SACS) (OR: 1.083, 1.004-1.168), and C-reactive protein (CRP) (OR: 0.977, 0.962-0.993) were identified as valuable predictors used for developing a nomogram. The prediction model performed good discrimination [AUC: 0.928, 95% confidence interval (CI): 0.873-0.984] and calibration in the validation group. The DCA showed excellent clinical practicability. Conclusion: We established a concise and practical nomogram that will benefit the advanced diagnosis of OSA in patients with COPD.

Pre-exposure to Aerosolized Polyvalent Bacterial Lysates Protects Against Bleomycin-Induced Pulmonary Fibrosis in Mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. No therapeutic modalities can reverse or stop its ever-deteriorating course. The stimulation of lung innate immunity using bacterial lysates was found to protect against lethal pulmonary infection. Hence, this study aimed to explore whether the immune-stimulating enhancement by pretreatment with bacterial lysates led to protection against bleomycin-induced pulmonary fibrosis. C57BL/6 mice were randomly divided into 4 groups with 20 mice in each group. The mice were exposed to an aerosolized mixture of polyvalent bacterial lysates (PVBL) or phosphate-buffered saline (PBS) three times on separate days. Twenty-four hours after the last exposure, the lungs were intratracheally infused with bleomycin (BLM) or normal saline (NS). The pulmonary morphology, Ashcroft's scale of pulmonary fibrosis, and levels of pro-inflammatory cytokines such as interferon (IFN)-γ and interleukin (IL)-4 were evaluated 14 days after the intratracheal infusion. The exposure to PVBL did not induce any discernible structural abnormalities in the lungs, while the IFN-γ/IL-4 ratio increased. BLM-induced pulmonary fibrosis was associated with an overwhelming downregulation of IFN-γ and IL-4 expression. Pre-exposure to PVBL protected against BLM-induced pulmonary fibrosis, which was demonstrated by a greater reduction of Ashcroft's fibrotic score and a greater decrease in the hydroxyproline level in the lungs. Although the PVBL pre-exposure did not restore the BLM-induced downregulation of IL-4 and IFN-γ levels, the IFN-γ/IL-4 ratio was still maintained greater than the animals with BLM infusion. BLM-induced murine pulmonary fibrosis is associated with downregulation of IFN-γ and IL-4 levels. Pre-exposure to the aerosolized PVBL protects against BLM-induced pulmonary fibrosis.

A trial of arbidol hydrochloride in adults with COVID-19.

BACKGROUND: To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. METHODS: This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. RESULTS: A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P  = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. CONCLUSIONS: SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week anas, accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. TRIAL REGISTRATION: Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1.

Development and validation of a nomogram model for early postoperative hyperlactatemia in patients undergoing cardiac surgery.

BACKGROUND: Postoperative hyperlactatemia (POHL) is common in patients undergoing cardiac surgery, associated with adverse outcomes. The aim of this study was to identify predictors for POHL after cardiac surgery and to develop and validate a predictive model. METHODS: Adult patients who underwent open heart surgery at our institution between 2016 and 2019 were retrospectively included. The patients were randomly divided into training and validation groups at a 2:1 ratio. Multivariate logistic regression was performed to identify independent predictors for POHL in the training set. A nomogram was then constructed and was validated in the validation set. RESULTS: POHL developed in 713 of the 5,323 patients (13.4%). The mortality rate was higher in patients with POHL compared with patients without that (9.5% vs. 2.1%, P<0.001). Age, white blood cell (WBC) count, left ventricular ejection fraction, renal insufficiency, cardiac surgery history, red blood cell (RBC) transfusion, and cardiopulmonary bypass (CPB) time were identified as independent risk factors. The nomogram based on these predictors indicated good discrimination in both the training (c-index: 0.787) and validation (c-index: 0.820) sets. The calibration was reasonable by both visual inspection and goodness-of-fit test. The decision and clinical impact curves demonstrated good clinical utility. CONCLUSIONS: We identified 7 independent risk factors and derived a prediction model for POHL in patients undergoing cardiac surgery. The model may contribute significantly to early risk assessment and clinical intervention.

Impacts of anti-inflammatory phosphodiesterase inhibitors on a murine model of chronic pulmonary inflammation.

Chronic obstructive pulmonary disease (COPD) often tends to respond poorly to glucocorticoid (GC) therapy. Reduced Histone deacetylase-2 (HDAC-2) activity is an important mechanism behind this GC insensitivity. In this study, we investigated the effects of three phosphodiesterase inhibitors (PDEIs), with an anti-inflammatory propensity, on cigarette smoke (CS)-induced pulmonary inflammation and HDAC-2 activity. Male C57BL/6 mice were exposed to cigarette smoke (CS) over the course of 30 weeks. Administration of the PDEIs commenced from the 29th week and followed a schedule of once daily treatments, 5 days a week, for 2 weeks. Roflumilast (ROF) was administered intragastrically (5 mg·kg-1 ), while pentoxifylline (PTX) (10 mg·kg-1 ) and theophylline (THEO) (10 mg·kg-1 ) were administered intraperitoneally, either alone or in combination with a GC (triamcinolone acetonide or TRI, 5 mg·kg-1 , i.m., single injection). Lung morphometry, as well as the activity of HDAC-2, pro-inflammatory cytokines and reactive oxygen species (ROS) were assessed at the end of the 30-week course. CS exposure was associated with a reduction in HDAC-2 activity and the up-regulation of ROS expression. PTX, ROF, and THEO administration led to the partial restoration of HDAC-2 activity, which was favorably associated with the reduction of ROS expression. However, combining TRI to any of these PDEIs did not synergistically augment HDAC-2 activity. Inactivation of HDAC-2 due to long-term CS exposure is closely related to exaggerated oxidative stress, and this reduced HDAC-2 activity could partially be restored through the use of PDEIs. This finding provides a potential novel approach for further clinical research.

Coinfection of SARS-CoV-2 and Other Respiratory Pathogens.

PURPOSE: To differentiate between respiratory infections caused by SARS-CoV-2 and other respiratory pathogens during the COVID-19 outbreak in Wuhan, we simultaneously tested for SARS-CoV-2 and pathogens associated with CAP to determine the incidence and impact of respiratory coinfections in COVID-19 patients. PATIENTS AND METHODS: We included 250 patients who were diagnosed with COVID-19. RT-PCR was used to detect influenza A, influenza B and respiratory syncytial viruses. Chemiluminescence immunoassays were used to detect IgM antibodies for adenovirus, Chlamydia pneumoniae and Mycoplasma pneumoniae in the serum of patients. Based on these results, we divided the patients into two groups, the simple SARS-CoV-2-infected group and the coinfected SARS-COV-2 group. Coinfected patients were then further categorized as having a coinfection of viral pathogen (CoIV) or coinfection of atypical bacterial pathogen (CoIaB). RESULTS: No statistically significant differences were found in age, gender, the time taken to return negative SARS-CoV-2 nucleic acid test results, length of hospital stays, and mortality between the simple SARS-CoV-2 infection group and the coinfection group. Of the 250 hospitalized COVID-19 patients, 39 (15.6%) tested positive for at least one respiratory pathogen in addition to SARS-CoV-2. A third of these pathogens were detected as early as the 1st week after symptom onset and another third were identified after more than three weeks. The most detected CAP pathogen was C. pneumoniae (5.2%), followed by the respiratory syncytial virus (4.8%), M. pneumoniae (4.4%) and adenovirus (2.8%). Patients coinfected with viral pathogens (CoIV) (n=18) had longer hospital stays when compared to patients coinfected with atypical bacterial pathogens (CoIaB) (n=21). Except for one fatality, the remaining 38 coinfected patients all recovered with favourable outcomes. CONCLUSION: Coinfections in COVID-19 patients are common. The coinfecting pathogens can be detected at variable intervals during COVID-19 disease course and remain an important consideration in targeted treatment strategies for COVID-19 patients.

Potential of Arbidol for Post-exposure Prophylaxis of COVID-19 Transmission: A Preliminary Report of a Retrospective Cohort Study.

The efficient transmission of severe acute respiratory syndrome-2 coronavirus (SARS-CoV-2) from patients to health care workers or family members has been a worrisome and prominent feature of the ongoing outbreak. On the basis of clinical practice and in-vitro studies, we postulated that post-exposure prophylaxis (PEP) using Arbidol is associated with decreased infection among individuals exposed to confirmed cases of COVID-19 infection. We conducted a retrospective cohort study on family members and health care workers who were exposed to patients confirmed to have SARS-CoV-2 infection by real-time RT-PCR and chest computed tomography (CT) from January 1 to January 16, 2020. The last follow-up date was Feb. 26, 2020. The emergence of fever and/or respiratory symptoms after exposure to the primary case was collected. The correlations between post-exposure prophylaxis and infection in household contacts and health care workers were respectively analyzed. A total of 66 members in 27 families and 124 health care workers had evidence of close exposure to patients with confirmed COVID-19. The Cox regression based on the data of the family members and health care workers with Arbidol or not showed that Arbidol PEP was a protective factor against the development of COVID-19 (HR 0.025, 95% CI 0.003-0.209, P=0.0006 for family members and HR 0.056, 95% CI 0.005-0.662, P=0.0221 for health care workers). Our findings suggest Arbidol could reduce the infection risk of the novel coronavirus in hospital and family settings. This treatment should be promoted for PEP use and should be the subject of further investigation.

[Relevance of sleep apnea-associated heart rate variability to morning blood pressure].

OBJECTIVE: To explore the role of vagal nerve in obstructive sleep apnea hypopnea syndrome (OSAHS) associated hypertension. METHODS: A total of 104 patients were diagnosed OSAHS via polysomnography for at least 7 hours. Their blood pressures were measured before and after sleep. Pearson's and Spearman's correlation test were applied to analyze the relevance of body mass index (BMI), apnea-hypopnea index (AHI), nocturnal minimum of arterial oxygen saturation (nSaO2% min), percentage of dwell time of arterial oxygen saturation lower than 90% (DT90%), deviation between minimal heart rate and maximal heart rate during apnea (DHR) to systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MAP) before and after sleep. Logistic regression was performed to examine the risk factors of morning diastolic hypertension and systolic hypertension. Moreover, odds ratio (OR) and 95% confidence interval (CI) of each risk factor were calculated. RESULTS: Morning SBP, DBP and MAP in 104 subjects were (128.3 +/- 17. 9), (88.6 +/- 10.6) and (101.8 +/- 12.3) mm Hg respectively. They were significantly elevated as compared with their pre-sleep levels [(123.5 +/- 17.8), (82.0 +/- 9.6) and (95.8 +/- 11.5) mm Hg respectively, all P < 0.01]. Thirty-seven cases (35.6%) met the diagnostic criteria of hypertension (SBP > or = 140 and/or DBP > or = 90 mm Hg) in their blood pressures before sleep while 49 cases (47.1%) in their morning blood pressures. Spearman's correlation analysis shows that DBP after sleep was correlated with DHR (r = 0.214, P < 0.05). DHR in OSAHS patients with diastolic hypertension increased as compared with those without diastolic hypertension (P < 0.05). After adjusting for age, BMI, AHI, nSaO2% min and DT90%, DHR was a predictor for the morning systolic hypertension (OR = 1.253, 95% CI: 1. 057 - 1.486, P < 0.01). CONCLUSIONS: Sleep apnea-associated heart rate variability is correlated with morning DBP in OSAHS patients. And it is also an independent predictive factor for morning systolic hypertension. This suggests that vagal regulation may be involved in OSAHS associated hypertension.

Spreading of extended-spectrum ß-lactamase-producing Escherichia coli ST131 and Klebsiella pneumoniae ST11 in patients with pneumonia: a molecular epidemiological study.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) are the important pathogens causing pneumonia. This study aimed to investigate the clinical characteristics and molecular epidemiology of ESBL-producing E. coli and K. pneumoniae causing pneumonia at a large teaching hospital in China. METHODS: We collected patient's clinical data and ESBL-producing E. coli and K. pneumoniae strains causing pneumonia (from December 2015 to June 2016) at a hospital in Wuhan. The susceptibilities, multi-locus sequence typing, homologous analysis, ESBL genes by polymerase chain reaction and sequencing were determined. RESULTS: A total of 59 ESBL-producing strains (31 E. coli and 28 K. pneumoniae) isolated from patients with pneumonia were analyzed. The majority of strains were isolated from patients were with hospital-acquired pneumonia (37/59, 62.7%), followed by community-acquired pneumonia (13/59, 22.0%), and ventilator-related pneumonia (9/59, 15.3%). The E. coli ST131 (9 isolates, 29.0%) and K. pneumoniae ST11 (5 isolates, 17.9%) were the predominant sub-types. The most prevalent ESBL gene was CTX-M-14, followed by SHV-77, CTX-M-3, SHV-11, and CTX-M-27. At least 33 (55.9%) of the ESBL-producing strains carried two or more ESBL genes. The ISEcp1 and IS26 were found upstream of all blaCTX-M (CTX-Ms) and of most blaSHV (SHVs) (57.6%), respectively. Moreover, three ESBL-producing K. pneumoniae ST11 strains which were resistant to carbapenems carried the blaNDM-1 and blaKPC-2, two of which also bearing blaOXA-48 were resistant to all antibiotics (including Tigecycline). CONCLUSIONS: Hospital-acquired pneumonia is more likely correlated with ESBL-producing E. coli and K. pneumoniae. ESBL-producing E. coli ST131 and multi-drug resistance ESBL-producing, as well as New Delhi metallo-ß-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemases-2 (KPC-2) bearing K. pneumoniae ST11 are spreading in patients with pneumonia in hospital.

Efficacy of patients' preferred exercise modalities in chronic obstructive pulmonary disease: A parallel-group, randomized, clinical trial.

INTRODUCTION: Physical exercise effectively improves health-related quality of life in patients with chronic obstructive pulmonary disease (COPD). However, application of this medical intervention is problematic, due to poor adherence to the exercise program or unawareness of the significance of this intervention. OBJECTIVE: To determine whether COPD patients who adopted personal-preferred exercise modalities (PPEMs) for daily training would demonstrate sustained benefits due to improved adherence. METHODS: Stable COPD patients were randomly assigned to the daily PPEMs group or the control group (without extra exercise apart from daily life activities). All other treatments were similar. The primary outcome was the health-related quality of life (HRQoL), measured with St. George's Respiratory Questionnaire (SGRQ) score at 12 months. Other measures included the Borg dyspnea score, 6-min walking distance (6MWD) and lung function variables. RESULTS: The intention-to-treat (ITT) population included 94 patients, 68 of them completed the study protocol over 12 months (the PP-population). A greater decline of SGRQ score (improvement of HRQoL) in the PPEMs group than that in the controls was demonstrated over 12 months (-19.1 vs -9.0 in the ITT population and -19.1 vs -8.7 in the PP population, P ≤ .001 for all comparisons), the reduction exceeded the minimal clinically important difference of ≥ 4 points. The PPEMs group also showed a greater reduction than the control group in Borg score at 12 months in the ITT and the PP population as well (P < .01). No significant improvement was found in 6MWD or in lung function variables. CONCLUSIONS: COPD patients could benefit from extra daily PPEMs, and the gain may sustain at least for 1 year.

Dynamic expression of tumor necrosis factor-alpha and vascular endothelial growth factor in rat model of pulmonary emphysema induced by smoke exposure.

In order to explore the roles of tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) in the pathogenesis of pulmonary emphysema, male Wistar rats were randomized into group A(1), group A(2.5) and group A(4), each with smoke exposure for 1 month, 2.5 months or 4 months, respectively. Group B(1), group B(2.5) and group B(4) were used as non smoking controls at corresponding time points. TNF-alpha in bronchoalveolar lavage fluid (BALF) and expression of VEGF in lung tissue was determined by ELISA or by SABC immunohistochemistry assay either. Lung slices were stained with hematoxylin and eosin (HE). Results showed that in animal with smoke exposure the mean linear interceptor (Lm), an index of pulmonary emphysema and the content of TNF-alpha in BALF increased gradually, on contrary, the expression of VEGF in lung tissue decreased (P<0.05). This phenomenon was not obvious in animals without smoke exposure. Lm was negatively correlated to the VEGF expression (gamma=-0.81, P<0.01) and positively correlated to TNF-alpha concentration (gamma = 0.52, P<0.004), which implies that smoke exposure decreased the expression of VEGF and increased the expression of TNF-alpha. It is plausible to speculate that the imbalance of TNF-alpha and VEGF may play an important role in the pathogenesis of smoke-induced pulmonary emphysema.

Long-term administration of angiotension-converting enzyme inhibitor improves the outcome of chronic heart failure in senile patients.

One hundred and sixteen senile patients (older than 65 years) with chronic heart failure (CHF) were analyzed retrospectively in order to verify if old patients with CHF would benefit from long-term (one year) angiotension-converting enzyme inhibitor (ACEI) treatment. The frequency of drugs (including ACEI, digitalis and diuretic) used was stratified into four degrees accordingly. Development of the CHF was scored with regard to relapse rate and severity of this disease. Stepwise regression analysis was applied to explore the relationship between the scored outcome of CHF and the frequency of individual drug administration. A significant relationship of the scored outcome of CHF to the frequency of ACEI usage but not to digitalis nor to diuretics was found (partial coefficient of the correlation r = 0.42, P = 0.002). It was concluded that the long-term administration of ACEI improves the outcome of CHF in senile patients.