Lymphocyte percentage and platelet count correlate with the treatment outcome to tyrosine kinase inhibitors in epidermal growth factor receptor-mutated lung adenocarcinoma.

This observational study evaluated the treatment outcomes of clinical factors on the patients with lung adenocarcinoma with epidermal growth factor receptor mutations who received tyrosine kinase inhibitors as first-line treatment.Patients with stage IIIb or IV lung adenocarcinoma with mutated epidermal growth factor receptor were enrolled retrospectively between March 2010 and December 2017. The hematologic markers on progression-free survival (PFS) and overall survival (OS) were analyzed.Totally 190 patients were enrolled. In univariate analysis by hematologic markers, lower lymphocyte percentage and higher platelet count were associated with significantly poor PFS and OS. Multivariate analysis showed lower lymphocyte percentage was independent poor prognostic factors for PFS and OS. Higher platelet count was an independent poor prognostic factor for OS only.Patients with lung adenocarcinoma receiving tyrosine kinase inhibitors with lower lymphocyte percentage and higher platelet count had poorer prognoses compared with other patients.

Adaptive Support Ventilation Attenuates Ventilator Induced Lung Injury: Human and Animal Study.

Adaptive support ventilation (ASV) is a closed-loop ventilation, which can make automatic adjustments in tidal volume (VT) and respiratory rate based on the minimal work of breathing. The purpose of this research was to study whether ASV can provide a protective ventilation pattern to decrease the risk of ventilator-induced lung injury in patients of acute respiratory distress syndrome (ARDS). In the clinical study, 15 ARDS patients were randomly allocated to an ASV group or a pressure-control ventilation (PCV) group. There was no significant difference in the mortality rate and respiratory parameters between these two groups, suggesting the feasible use of ASV in ARDS. In animal experiments of 18 piglets, the ASV group had a lower alveolar strain compared with the volume-control ventilation (VCV) group. The ASV group exhibited less lung injury and greater alveolar fluid clearance compared with the VCV group. Tissue analysis showed lower expression of matrix metalloproteinase 9 and higher expression of claudin-4 and occludin in the ASV group than in the VCV group. In conclusion, the ASV mode is capable of providing ventilation pattern fitting into the lung-protecting strategy; this study suggests that ASV mode may effectively reduce the risk or severity of ventilator-associated lung injury in animal models.

Presence of pleural effusion is associated with a poor prognosis in patients with epidermal growth factor receptor-mutated lung cancer receiving tyrosine kinase inhibitors as first-line treatment.

AIM: This study was conducted to evaluate the effect of clinical factors on the treatment outcomes of lung cancer patients with active epidermal growth factor receptor (EGFR) mutations treated by first-line tyrosine kinase inhibitors (TKIs). METHODS: Patients of stage IIIb or IV lung adenocarcinoma harboring mutated EGFR were enrolled between March 2010 and June 2014 and followed up until December 2015. The effects of various clinical features, such as age, sex, smoking history, EGFR mutation types, TKIs used, presence of pleural effusion, metastatic sites on progression-free survival (PFS) and overall survival (OS), were analyzed retrospectively. RESULTS: A total of 104 patients were included in this study. Patients with pleural effusion at initial diagnosis had significantly shorter PFS and OS than those without pleural effusion (median PFS: 8.2 months vs 15.3 months, P = 0.0004; median OS: 16.3 months vs 28.2 months, P = 0.0003). Univariate analysis revealed that being male or a smoker was associated with short PFS, whereas smoking history, bony metastasis and malignant pleural effusion were associated with poor OS. Stepwise multivariate Cox regression analysis showed that the presence of pleural effusion and different TKI use were independent prognostic factors for PFS [hazard ratio [HR] = 2.50 (95% confidence interval [CI], 1.53-4.10), P = 0.0003 and HR = 0.55 (95% CI, 0.31-0.97), P = 0.0396, respectively], whereas the presence of pleural effusion and liver metastasis were associated with poor OS [HR = 2.79 (95% CI: 1.46-5.30), P = 0.0018 and HR = 2.12 (95% CI, 1.02-4.40), P = 0.0440, respectively]. CONCLUSION: The presence of pleural effusion predicts poor PFS and OS in lung adenocarcinoma patients receiving TKIs as the first-line treatment. Additional studies are warranted to elucidate the underlying mechanisms and determine novel strategies for improving the outcome of these patients.

Sniff nasal inspiratory pressure does not decrease in elderly subjects.

[Purpose] Measurements of inspiratory strength are critical for detecting inspiratory muscle weakness. Sniff nasal inspiratory pressure (SNIP) is a quick, noninvasive measurement of global inspiratory strength; however, it is not clear how many trials are needed for reliable measurements. [Subjects and Methods] One hundred and nineteen subjects (age 39.9±16.5, range 18-69 yrs) completed the study. They were divided into subgroups of different ages and gender. Subjects were asked to take 20 maximal sniffs after normal expiration, with 30 seconds rest in-between. The highest values among the first 10 and last 10 SNIP maneuvers were recorded as SNIP1-10, and SNIP11-20, respectively. The paired t-test was used to compare the differences. Two-way measures ANOVA was used to compare the effects of age and gender on SNIP. [Results] SNIP 11-20 was significantly greater than SNIP1-10, suggesting that 10 trials is not enough to eliminate learning effects. Age did not affect SNIP in either gender, suggesting SNIP is preserved. In stepwise multiple linear regression analysis, the SNIP values were positively related with body mass index in women and positively related with weight in men. [Conclusion] The results suggest that twenty trials are needed for reliable SNIP measurements. The mean value and lower limits of normal SNIP are provided for clinical comparison.

Respiratory-inductive-plethysmography-derived flow can be a useful clinical tool to detect patients with obstructive sleep apnea syndrome.

BACKGROUND/PURPOSE: Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of a complete or partial collapse of the upper airway during sleep. The disease is traditionally diagnosed by overnight polysomnography with detection flow limitation by nasal pressure cannulas. The aim of this study was to evaluate the accuracy of flow (X flow) from calibrated respiratory inductive plethysmography. METHODS: We studied 60 male and 26 female patients who came to our sleep center in 2007. All the participants received overnight polysomnography and data were graded blindly and randomly by two experienced technicians. RESULTS: Patients with OSA were predominantly male, with higher body mass index, higher percentage of snorers, and more events of oxygen desaturation and arousal than those without OSA. There was a good correlation of X flow and flow from nasal pressure cannulas, regardless of total apnea-hypopnea, apnea or hypopnea events. The correlation was especially strong in severe OSA patients. The sensitivity and specificity to find OSA (apnea-hypopnea index ≥5) from X flow versus standard polysomnography was 98% and 100%, respectively. Positive predictive value was 100% and negative predictive value was 97%. CONCLUSION: X flow could be a good clinical tool to be used instead of flow from nasal pressure cannulas in OSA patients.

Comparison of inspiratory muscle strength training effects between older subjects with and without chronic obstructive pulmonary disease.

BACKGROUND/PURPOSE: Inspiratory muscle strength training (IMST) has been traditionally recommended for patients with chronic obstructive pulmonary disease (COPD) to improve respiratory strength. Respiratory strength is reduced as age increases. However, few studies have focused on the effects of IMST on older adults without COPD. METHODS: Subjects were divided into training non-COPD (TNC, n = 24) and training COPD (TC, n = 12) according to their forced expiratory volume in 1 second (% predicted). Both groups received 6 weeks of IMST, with training at 75-80% of maximal inspiratory pressure using pressure threshold trainers. A second group of COPD subjects served as controls (CC, n = 24), which received no training. Dyspnea was measured using the basic dyspnea index. Health-related quality of life was measured using the SF-36. The SF-36 subcategories, physical component summary and mental component summary were compared. A 6-minute walk test was performed to determine functional status. Two-way repeated measures analysis of variance was used to compare group effects and training effects of IMST. RESULTS: Maximal inspiratory pressure was increased in both training groups (TNC: 59.1 cmH(2)O pre-IMST to 82.5 cmH(2)O post-IMST; TC: 53.2 to 72.6), but not in the CC group. Therefore, the basic dyspnea index was improved in both training groups (TNC: 9.6 to 10.8; TC: 6.2 to 7.3). Functional status was improved in the TNC group (TNC: 392.1 m to 436.3 m), but not in the TC or CC groups. Quality of life was improved in the physical component summary in both training groups. CONCLUSION: IMST increases maximal inspiratory pressure, relieves dyspnea and improves health-related quality of life in older adults. IMST especially improves functional status in subjects without COPD. IMST benefits subjects with COPD and those without COPD. Therefore, IMST as a treatment tool is not confined to patients with COPD.

Thyroid storm and lymphocytic myocarditis.

Cardiac failure is the leading cause of mortality in patients with thyroid storm. But the underlying cardiac pathology is unclear. Here, we report a 46-year-old woman who presented with hyperpyrexia and sinus tachycardia subsequent to accidental neck contusion. Her hyperthyroidism was verified by abnormal biochemical changes. Despite vigorous antithyroid treatment including a beta-blocker, glucocorticoid and potassium iodide, the patient eventually succumbed to refractory congestive heart failure in 4 days. Autopsy revealed lymphocytic myocarditis. We propose that lymphocytic myocarditis played a prominent role in her demise.

Hypoglycemia in a patient with a huge malignant solitary fibrous tumor of the pleura.

Solitary fibrous tumor of the pleura (SFTP) is rare. A 73-year-old man, without past history of diabetes mellitus, was admitted to hospital with profound hypoglycemia, loss of consciousness and respiratory failure. CT indicated a huge heterogenous mass lesion (12 x 12 x 17 cm) at the right thoracic cavity with total atelectasis of the right lower lung. He underwent a standard thoracotomy with complete excision of the tumor. Pathology indicated malignant SFTP with insulin-like growth factor-binding protein-2 production. There were no further incidences of hypoglycemia or respiratory failure after excision of the tumor. Hypoglycemia resulting from a solitary fibrous tumor is uncommon. Standard thoracotomy and complete resection of this giant tumor provided a good result for the present patient.

Nitric oxide production and immunoglobulin deposition in leptospiral hemorrhagic respiratory failure.

Diffuse pulmonary hemorrhage leading to death is a syndrome which may develop in leptospirosis, but its pathophysiology is not well documented. We report an autopsy case of leptospirosis. A healthy 41-year-old man presented with low back myalgia, dry cough and fever for 4 days and a normal chest X-ray on admission. Acute respiratory failure developed hours later. Profuse bloody fluid appeared in the endotracheal tube immediately after intubation. Chest X-ray showed whiteness across all lung fields. He died of persistent shock 16 h after the onset of acute respiratory failure. Autopsy revealed diffuse pulmonary hemorrhage with hyaline-membrane formation, myocarditis, interstitial nephritis and hepatitis. Silver stain of lung and kidney tissue demonstrated leptospires. Immunohistochemical staining showed inducible nitric oxide synthase in alveolar macrophages. Immunofluorescein staining showed immunoglobulin in alveolar septum and alveolar space. This case suggests that hemorrhagic diffuse alveolar damage with persistent shock is related to over-production of nitric oxide and immunoglobulin deposition in fatal leptospirosis.