Frequency of the acquired resistant mutation T790 M in non-small cell lung cancer patients with active exon 19Del and exon 21 L858R: a systematic review and meta-analysis.

BACKGROUND: Although EGFR-TKI is the preferred treatment for NSCLC patients with sensitive mutations, subsequent drug resistance is almost inevitable. The specific mechanisms of EGFR-TKI drug resistance can be identified through repeat biopsy. METHODS: To better understand the clinical characteristics of TKI resistance in NSCLC patients, we retrospectively reviewed studies of acquired TKI drug resistance using repeat biopsy from the last decade. The relevant literature was retrieved from January 2005 to August 2015 in the databases Medline and Embase. The search terms were NSCLC or non-small cell lung cancer and T790 M. RESULTS: A total of 478 patients with NSCLC tested by repeated biopsy were confirmed to have acquired TKI resistance. Analysis indicated that 240 patients (50.21%) of the 478 patients with acquired TKI drug resistance had the T790 M mutation. The detection rate of T790 M in different repeat biopsy sites was also different, with the highest positive rate in the lymph nodes (60%) and the lowest detection rate in cerebrospinal fluid (less than 5%). In addition, patients with T790 M had longer overall survival compared to those without the mutation (P < 0.05). Of the 240 patients with T790 M mutations, 213 patients showed results consistent with the mutation analysis before TKI treatment, and the rate of patients with the L858R point mutation along with the T790 M mutation was lower than that of patients with the exon 19 deletion (36.42% to 58.30%). CONCLUSIONS: T790 M occurred more frequently in patients with the exon 19 deletion than in those with exon 21 L858R, which gave the survival benefit of the T790 M mutation and may explain why patients with the exon 19 deletion had an improved overall survival.

The efficacy and tolerance of prone positioning in non-intubation patients with acute hypoxemic respiratory failure and ARDS: a meta-analysis.

BACKGROUND AND AIMS: The application of prone positioning with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) in non-intubation patients is increasing gradually, applying prone positioning for more high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) patients. This meta-analysis evaluates the efficacy and tolerance of prone positioning combined with non-invasive respiratory support in patients with AHRF or ARDS. METHODS: We searched randomized controlled trials (RCTs) (prospective or retrospective cohort studies, RCTs and case series) published in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 1 July 2020. We included studies that compared prone and supine positioning with non-invasive respiratory support in awake patients with AHRF or ARDS. The meta-analyses used random effects models. The methodological quality of the RCTs was evaluated using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 16 studies fulfilled selection criteria and included 243 patients. The aggregated intubation rate and mortality rate were 33% [95% confidence interval (CI): 0.26-0.42, I2 = 25%], 4% (95% CI: 0.01-0.07, I2 = 0%), respectively, and the intolerance rate was 7% (95% CI: 0.01-0.12, I2 = 5%). Prone positioning increased PaO2/FiO2 [mean difference (MD) = 47.89, 95% CI: 28.12-67.66; p < 0.00001, I2 = 67%] and SpO2 (MD = 4.58, 95% CI: 1.35-7.80, p = 0.005, I2 = 97%), whereas it reduced respiratory rate (MD = -5.01, 95% CI: -8.49 to -1.52, p = 0.005, I2 = 85%). Subgroup analyses demonstrated that the intubation rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 34% and 21%, respectively; and the mortality rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 6% and 0%, respectively. PaO2/FiO2 and SpO2 were significantly improved in COVID-19 patients and non-COVID-19 patients. CONCLUSION: Prone positioning could improve the oxygenation and reduce respiratory rate in both COVID-19 patients and non-COVID-19 patients with non-intubated AHRF or ARDS.The reviews of this paper are available via the supplemental material section.

[Risk factors of novel severe influenza A(H1N1) with concurrent adult respiratory distress syndrome].

OBJECTIVE: To analyze the risk factors of novel severe influenza A (H1N1) with concurrent adult respiratory distress syndrome (ARDS). METHODS: A multivariable Logistic regression analysis was conducted for ARDS risk factors in controlled clinical trials for comparing the clinical features between the ARDS and non-ARDS groups and comparing ARDS patients' lymphocyte counts and T lymphocyte subsets between the smoking and non-smoking groups through a retrospective analysis of 92 novel influenza A (H1N1) patients who admitted to our hospital from October 2009 to January 2010. RESULTS: Through a single factor analysis between ARDS and non-ARDS groups, the comparisons in the factors including smoking (17 cases vs 11 cases), T lymphocyte subsets, lactate dehydrogenase (LDH), initial treatment point of oseltamivir and initial oxygen flow greater than 2 L/min (28 cases vs 18 cases) had statistically significant differences (all P<0.05). The comparison in T lymphocyte subsets had statistically significant difference between the smoking and non-smoking groups in ARDS patients (all P<0.05). The multivariable Logistic regression analysis showed that smoking (P=0.027, OR=8.05, 95%CI: 1.28-50.80) and initial oxygen flow greater than 2 L/min (P=0.010, OR=16.70, 95%CI: 3.29-84.84) were relevant to the incidence of ARDS in novel influenza A (H1N1) patients. CONCLUSION: Smoking and initial oxygen flow greater than 2 L/min were the risk factors of novel severe influenza A (H1N1) with concurrent ARDS.

[Expression and activation of hypoxia inducible factor-1alpha and iNOS in the brain of rats with chronic intermittent hypoxia].

OBJECTIVE: To study the expression of iNOS and hypoxia inducible factor-1 (HIF-1)alpha in the brain of rats under chronic intermittent hypoxia, and therefore to explore the molecular mechanisms of hypoxia induced reactions in the nervous system according to the measure of HIF-1 transcription activity. METHODS: Male Wistar rats were divided into 3 groups: a chronic hypoxia group (n = 8, breathing 10%O2 for 8 h per day), an intermittent hypoxia group (n = 8, breathing 10%O2 and air altered per 90 sec for 8 h per day) and a control group (n = 8, breathing air). Thirty days later, the expression of HIF-1alpha and iNOS was assessed by using immunohistochemical methods and Western blot, and HIF-1alpha and iNOS mRNA was assessed by RT-PCR. The detection of binding activity of HIF-1 to the iNOS promoter gene was assessed by electrophoretic mobility shift assay. RESULTS: The productions of HIF-1alpha (508 +/- 77, 1118 +/- 106 and 1937 +/- 119) and iNOS (673 +/- 82, 1325 +/- 139 and 2088 +/- 130) were the highest in the intermittent hypoxia group. Only weaker binding activity between HIF-1 and iNOS promoter gene was detected in the control group, but the binding activity was increased significantly in the intermittent hypoxia group. CONCLUSIONS: Hypoxia, especially intermittent hypoxia, can cause increased expression of iNOS and HIF-1alpha. HIF-1 may be a key factor in up-regulation of the transcription of iNOS under chronic intermittent hypoxia. HIF-1 promotes the transcription of iNOS though enhanced binding activity.

Association of Obstructive Sleep Apnea with Asthma: A Meta-Analysis.

This study evaluates the relationship between obstructive sleep apnea (OSA) and asthma. Literature search was carried out in several electronic databases and random effects meta-analyses were performed to obtain pooled estimates of the prevalence of OSA, OSA risk and sleep disordered breathing (SDB) in asthma patients and pooled odds ratios of the prevalence between asthma and non-asthma patients. In adult asthma patients, the prevalence [95% confidence interval] of OSA, OSA risk, and SDB was 49.50 [36.39, 62.60] %, 27.50 [19.31, 35.69] %, and 19.65 [14.84, 24.46] % respectively. The odds of having OSA, OS risk and SDB by the asthma patients were 2.64 [1.76, 3.52], 3.73 [2.90, 4.57] and 1.73 [1.11, 2.36] times higher (p < 0.00001 for all) in asthma than in non-asthma patients, respectively. Adult asthma patients with OSA had significantly higher BMI in comparison with asthma patients without OSA. This study reveals that the prevalence of OSA in asthma patients is considerably higher; even higher than OSA risk and SDB. Sleep studies should be performed in asthma patients with symptoms suggestive of OSA/OSA risk/SDB.

[The analysis of risk factors correlated to pulmonary hypertension in obstructive sleep apnea syndrome patients during awake state].

OBJECTIVE: To investigate the development of pulmonary hypertension in obstructive sleep apnea syndrome (OSAS) patients and to analyze the correlated factors. METHODS: Pulmonary arterial pressure was monitored by right cardiac catheterization in 15 OSAS patients, and simultaneously polysomnography was performed. Blood gas analysis and lung function were also measured. RESULTS: Pulmonary arterial pressure at awake state was correlated positively to mean maximal pulmonary pressure during sleep, body mass index (BMI) and hemoglobin (Hb), but negatively to PaO2, the percent predicted forced vital capacity (FVC% pred). Compared with OSAS patients without pulmonary hypertension, the BMI, PaCO2, and Hb of OSAS patients with pulmonary hypertension increased significantly, while FVC% pred and PaO2 decreased. Stepwise linear regression indicated that pulmonary arterial pressure at awake state was closely correlated with mean maximal pressure during sleep (beta = 0.35, standard error 0.10, R(2) = 0.89, P = 0.006) and PaCO2 (beta = 0.72, standard error 0.27, R(2) = 0.94, P = 0.022), and mean maximal pulmonary arterial pressure during sleep was closely correlated to PaCO2, BMI, PaO2 and the ratio of arterial pressure and oxygen concentration during rapid eye movement sleep (RDeltaPAP/DeltaSpO2). The regression equation was y' = -152.70 + 1.92 PaCO2 + 1.37 BMI + 0.67 PaO2 + 16.29 RDeltaPAP/DeltaSpO2. CONCLUSION: Pulmonary arterial pressure increasing in OSAS patients is induced mainly by hypercapnia and hypoxia at day time, and related to forced ventilation capacity, BMI and the ratio of pulmonary arterial pressure and oxygen concentration variation during rapid eye movement sleep. There was no obvious relation between pulmonary arterial pressure and apnea index.

[Endothelium-dependent vasodilation in patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To evaluate the endothelial function in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) by measuring the brachial artery diameter during reactive hyperemia. METHODS: Thirty patients with OSAHS (8 with mild and 22 with moderate/severe OSAHS) and 10 control subjects were studied. Brachial artery diameter was measured with Doppler ultrasound under baseline conditions, during reactive hyperemia (an endothelium-dependent dilatation) and after sublingual administration of nitroglycerin (an endothelium-independent vasodilator). The dilative rate of brachial artery in different conditions was calculated to evaluate the endothelial function. RESULTS: The dilative rate of brachial artery in the control group, the mild OSAHS group and the moderate/severe OSAHS group were (15.2 +/- 2.6)%, (14.3 +/- 3.2)% and (9.8 +/- 4.9)%, respectively. There was a significant decrease of endothelium-dependent flow-mediated dilation in the moderate/severe OSAHS group compared to the control group and the mild OSAHS group. No significant difference in endothelium-independent vasodilator after sublingual administration of nitroglycerin was found among the three groups. CONCLUSION: Patients with moderate/severe OSAHS have impaired endothelium-dependent vasodilatation, and OSAHS itself maybe a risk factor for endothelial dysfunction.

[Regulation of hypothalamus-pituitary-adrenal axis and growth hormone axis in obstructive sleep apnea-hypopnea syndrome patients].

OBJECTIVE: To explore the regulation of hypothalamus-pituitary-adrenal (HPA) axis and growth hormone (GH) axis in obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: OSAHS patients (OSAHS group) and subjects with obesity alone (control group) were monitored by polysomnography (PSG). The corticotropin-releasing hormone (CRH), growth hormone releasing hormone (GHRH), corticotropin (ACTH), cortisol and growth hormone levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay before and after sleep. Their correlation were analyzed. RESULTS: The CRH concentration [(1.66 +/- 0.34), (4.96 +/- 0.98) mmol/L before and after sleep] and cortisol content [(152.93 +/- 136.15), (445.53 +/- 123.09) microg/L before and after sleep] in the OSAHS group were significantly higher than those of the control group [CRH was (0.67 +/- 0.42), (2.27 +/- 1.10) mmol/L, cortisol concentration was (68.94 +/- 20.13), (146.05 +/- 30.48) microg/L, before and after sleep, respectively, all P < 0.01]; GHRH significantly decreased in the OSAHS group [(1.42 +/- 0.07), (1.01 +/- 0.05) mmol/L before and after sleep] compared with the control group [(1.99 +/- 0.34), (1.58 +/- 0.15) mmol/L, respectively; all P < 0.01]; but there was no difference in growth hormone. The ratio of the variation of CRH, GHRH level (DeltaCRH/DeltaGHRH) was significantly higher in the OSAHS group (285.02 +/- 143.32) than that in the control group (71.15 +/- 15.37, P < 0.01). The bivariate correlation analysis of the OSAHS group indicated that DeltaCRH/DeltaGHRH was correlated positively with average awake duration (r = 0.882), but negatively with average blood oxygen concentration (r = -0.696). The average blood oxygen concentration was negatively correlated with average awake duration (r = -0.729). CONCLUSIONS: There are abnormal changes of HPA axis and GH axis in OSAHS patients, and the feedback regulation is disordered. These abnormalities are related to sleep structure variation and hypoxia during sleep.

[The effect of chronic intermittent hypoxia to hypothalamus-pituitary-adrenal axis and growth hormone level in rats during sleep].

AIM: To research the effect of intermittent hypoxia during sleep on hypothalamus-pituitary-adrenal (HPA) axis and growth hormone (GH) level. METHODS: Rats were respectively exposed to intermittent hypoxia, room air and continuous hypoxia, after 1 day, 3 days, 7 days and 30 days, mRNA levels of corticotropin-releasing hormone (CRH) and growth hormone releasing hormone (GHRH) in hypothalamus of rats were detected using RT-PCR, and the levels of CRH, GHRH, corticotropin(ACTH), cortex ketone, and growth hormone in plasma were measured. RESULTS: After 30 days, the CRH mRNA levels in rats hypothalamus which exposed to intermittent hypoxia were increased significantly than those exposed to continuous hypoxia as well as normal control but GHRH decreased, there was no difference between continuous hypoxia and normal control. After 1 day, 3 days, and 7 days, there was no difference between continuous hypoxia and intermittent hypoxia. After 30 days, the plasmic level of CRH,ACTH and cortex ketone increased, GHRH decreased and GH had no obvious change. CONCLUSION: The rats' HPA axis level increases and GHRH restrained with chronic intermittent hypoxia during sleep, feedback regulation disorders.