A useful mTORC1 signaling-related RiskScore model for the personalized treatment of osteosarcoma patients by using the bulk RNA-seq analysis.

AIMS: This research developed a prognostic model for OS patients based on the Mechanistic Target of Rapamycin Complex 1 (mTORC1) signature. BACKGROUND: The mTORC1 signaling pathway has a critical role in the maintenance of cellular homeostasis and tumorigenesis and development through the regulation of cell growth, metabolism and autophagy. However, the mechanism of action of this signaling pathway in Osteosarcoma (OS) remains unclear. OBJECTIVE: The datasets including the TARGET-OS and GSE39058, and 200 mTORC1 genes were collected. METHODS: The mTORC1 signaling-related genes were obtained based on the Molecular Signatures Database (MSigDB) database, and the single sample gene set enrichment analysis (ssGSEA) algorithm was utilized in order to calculate the mTORC1 score. Then, the WGCNA were performed for the mTORC1-correlated gene module, the un/multivariate and lasso Cox regression analysis were conducted for the RiskScore model. The immune infiltration analysis was performed by using the ssGSEA method, ESTIMATE tool and MCP-Count algorithm. KM survival and Receiver Operating Characteristic (ROC) Curve analysis were performed by using the survival and timeROC package. RESULTS: The mTORC1 score and WGCNA with ß = 5 screened the mTORC1 positively correlated skyblue2 module that included 67 genes, which are also associated with the metabolism and hypoxia pathways. Further narrowing of candidate genes and calculating the regression coefficient, we developed a useful and reliable RiskScore model, which can classify the patients in the training and validation set into high and low-risk groups based on the median value of RiskScore as an independent and robust prognostic factor. High-risk patients had a significantly poor prognosis, lower immune infiltration level of multiple immune cells and prone to cancer metastasis. Finally, we a nomogram model incorporating the metastasis features and RiskScore showed excellent prediction accuracy and clinical practicability. CONCLUSION: We developed a useful and reliable risk prognosis model based on the mTORC1 signaling signature.

CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status.

Chaperonin-containing TCP1 (CCT) is a multi-subunit complex, known to participate the correct folding of many proteins. Currently, the mechanism underlying CCT subunits in cancer progression is incompletely understood. Based on data analysis, the expression of CCT subunit 6 A (CCT6A) is found higher than the other subunits of CCT and correlated with an unfavorable prognosis in colon cancer. Here, we find CCT6A silencing suppresses colon cancer proliferation and survival phenotype in vitro and in vivo. CCT6A plays a role in cellular process, including the cell cycle, p53, and apoptosis signaling pathways. Further investigations have shown direct binding between CCT6A and both Wtp53 and Mutp53, and BIRC5 is found to act downstream of CCT6A. The highlight is that CCT6A inhibition significantly reduces BIRC5 expression independent of Wtp53 levels in Wtp53 cells. Conversely, in Mutp53 cells, downregulation of BIRC5 by CCT6A inhibition mainly depends on Mutp53 levels. Additionally, combined CCT6A inhibition and Wtp53 overexpression in Mutp53 cell lines effectively suppresses cell proliferation. It is concluded CCT6A is a potential oncogene that influences BIRC5 through distinct pathways in Wtp53 and Mutp53 cells.

Pirfenidone ameliorates liver steatosis by targeting the STAT3-SCD1 axis.

OBJECTIVE: Previous studies reported that pirfenidone (PFD) is associated with liver disease. However, the effects of pirfenidone on energy metabolism and hepatic lipid accumulation are still poorly understood. METHODS: In this study, C57BL/6J mice were randomly divided into two groups, and fed a normal chow diet (NCD) or a high-fat diet (HFD) for 16 weeks. At the end of the eighth week, half of the mice fed on both diets were treated with PFD. Biochemical and lipid metabolism-related indices were analyzed. Furthermore, Hepa 1-6 cells and mouse primary hepatocytes (MPHs) were incubated with PFD with or without free fatty acid (FFA) treatment. Then, stattic (a p-STAT3 inhibitor) or Ad-shSTAT3 was used to further elucidate the effects of Signal Transducer and Activator of Transcription 3 (STAT3) signaling on PFD regulation of hepatic steatosis. RESULTS: PFD ameliorated obesity and hepatic lipid deposition in HFD mice by decreasing stearoyl-CoA desaturase 1 (SCD1) expression and upregulating p-STAT3 in the liver. In Hepa 1-6 cells and MPHs, PFD also down-regulated the expression of SCD1. STAT3 inhibition treatment eliminated the benefits of PFD on both SCD1 and hepatic steatosis. CONCLUSION: In summary, our data reveal that PFD may play an important role in mitigating hepatic steatosis in a STAT3-SCD1-dependent manner.

Temporal changes in biomarkers in individuals with and without acute mountain sickness following rapid ascent.

BACKGROUND: Field studies have reported conflicting results regarding changes in biomarkers at high altitude. This study measured temporal changes in biomarkers and compared the differences between individuals with and without acute mountain sickness (AMS). MATERIALS AND METHODS: This study included 34 nonacclimatized healthy participants. Ten-milliliters of blood were collected at four time points: 3 days before ascent (T0), on two successive nights at 3150 m (T1 and T2), and 2 days after descent (T3). Participants were transported by bus from 555 m to 3150 m within 3 hours. AMS was diagnosed using the self-reported Lake Louise Scoring (LLS) questionnaire. RESULTS: Compared with T0, significant increases in E-selectin and decreases in vascular endothelial growth factor (VEGF) levels were observed at high altitude. Significantly increased C-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and S100 calcium-binding protein B (S100B) levels were observed at T2, and significantly decreased vascular cell adhesion molecule-1 (VCAM-1) levels were observed at T3. Eighteen (53%) participants developed AMS. Changes in E-selectin, CRP, MCP-1, and S100B levels were independent of AMS. Relative to individuals without AMS, those with AMS had significantly higher atrial natriuretic peptide (ANP) and VCAM-1 levels and lower plasminogen activator inhibitor-1 (PAI-1) levels at T1 and higher brain natriuretic peptide and lower VEGF and PAI-1 levels at T3. LLSs were positively correlated with ANP and VCAM-1 levels and negatively correlated with PAI-1 levels measured at T1. CONCLUSIONS: After acute ascent, individuals with and without AMS exhibited different trends in biomarkers associated with endothelial cell activation and natriuretic peptides.

Mouth opening/breathing is common in sleep apnea and linked to more nocturnal water loss.

BACKGROUND: Mouth opening/breathing during sleep is common in patients with obstructive sleep apnea (OSA), which is probably associated with more water loss and higher risk for nocturnal ischemic heart attack. This study aimed to evaluate nocturnal changes in hematocrit/hemoglobin levels and estimated plasma volume loss in OSA patients and its relation to their OSA severity and mouth open/breathing. METHODS: Sixty OSA patients and fifteen healthy controls were enrolled and underwent overnight polysomnography. Mouth status was evaluated via an infrared camera and nasal/mouth airflow. Hematocrit and hemoglobin levels in peripheral venous blood were measured before and after sleep to estimate the change of plasma volume. RESULTS: Compared to controls, OSA patients had a greater nocturnal increase in hematocrit (1.35% vs. 1.0%, p = 0.013), hemoglobin (0.50% vs. 0.30%, p = 0.002) and more estimated water loss (5.5% vs 3.7% of plasma volume, p < 0.013). The extent of increase was correlated to apnea-hypopnea index (AHI)_the marker of OSA severity (Spearman's ρ = 0.332, p = 0.004; ρ = 0.367, p = 0.001 for hematocrit, hemoglobin, respectively), which remained significant after serial multivariate adjustment. OSA patients had more sleep time with mouth open (96.7% vs 26.7% of total sleep time, p < 0.001) and time with complete mouth breathing (14.1% vs 2.7%, p < 0.001). The extent of mouth breathing was correlated to AHI (ρ=0.487, p < 0.001), nocturnal increase in hematocrit/hemoglobin levels (ρ = 0.236, p = 0.042; ρ = 0.304, p = 0.008, respectively) and estimated plasma volume loss (ρ = 0.262, p = 0.023). CONCLUSION: OSA patients had a greater increase in hematocrit/hemoglobin levels after sleep, which is probably linked to more water loss and more sleep time with mouth open/breathing.

Point-of-care application of diaphragmatic ultrasonography in the emergency department for the prediction of development of respiratory failure in community-acquired pneumonia: A pilot study.

Background: Early recognition of patients with community-acquired pneumonia (CAP) at risk of poor outcomes is crucial. However, there is no effective assessment tool for predicting the development of respiratory failure in patients with CAP. Diaphragmatic ultrasonography (DUS) is a novel technique developed for evaluating diaphragmatic function via measurements of the diaphragm thickening fraction (DTF) and diaphragm excursion (DE). This study evaluated the accuracy of DUS in predicting the development of respiratory failure in patients with CAP, as well as the feasibility of its use in the emergency department (ED) setting. Materials and methods: This was a single-center prospective cohort study. We invited all patients with ED aged ≥ 20 years who were diagnosed with CAP of pneumonia severity index (PSI) SIe diagnosed with CAP of pneumonia severe with respiratory failure or septic shock were excluded. Two emergency physicians performed DUS to obtain DTF and DE measurements. Data were collected to calculate PSI, CURB-65 score, and Infectious Diseases Society of America/American Thoracic Society severity criteria. Study endpoints were taken at the development of respiratory failure or 30 days post-ED presentation. Continuous variables were analyzed using T-tests, while categorical variables were analyzed using chi-square tests. Further logistic regression and receiver operating characteristic curve analyses were performed to examine the ability to predict the development of respiratory failure. Intra- and inter-rater reliability was examined with intraclass correlation coefficients (ICCs). Results: In this study, 13 of 50 patients with CAP enrolled developed respiratory failure. DTF was found to be an independent predictor (OR: 0.939, p = 0.0416). At the optimal cut-off point of 23.95%, DTF had 69.23% of sensitivity, 83.78% of specificity, 88.57% of negative predictive value, and 80% of accuracy. Intra- and inter-rater analysis demonstrated good consistency (intra-rater ICC 0.817, 0.789; inter-rater ICC 0.774, 0.781). Conclusion: DUS assessment of DTF may reliably predict the development of respiratory failure in patients with CAP presenting to the ED. Patients with DTF > 23.95% may be considered for outpatient management.

The immune regulation of BCL3 in glioblastoma with mutated IDH1.

BACKGROUND: Glioblastoma in the brain is the most malignant solid tumor with a poor prognosis. Screening critical targets and exploring underlying mechanisms will be a benefit for diagnoses and treatment. IDH1 mutation (R132) was used to distinguish glioblastoma grade and predict prognosis as a significant marker. However, the manner of IDH1 mutation regulating glioblastoma development was still unclear. METHODS: To study the function of IDH1 mutation, multi-type sequencing data (transcriptome, methylation and copy number variation) from the GEO and TCGA database were analyzed using bioinformatics techniques. The biological functions of IDH1 mutation (R132) would be comprehensively evaluated from the regulatory networks, tumor immune microenvironment and clinical relevance. Then the analysis result would be validated by experimental techniques. RESULTS: Compared with adjacent tissues, IDH1 was up-regulated in glioblastoma, which also positively correlated with the malignant degree and a poor prognosis. To further study the mechanism of mutated IDH1 (R132) function, 5 correlated genes (FABP5, C1RL, MIR155HG, CSTA and BCL3) were identified by different expression gene screening, enrichment analysis and network construction successively. Among them, the BCL3 was a transcription factor that may induce IDH1expression. Through calculating the correlation coefficient, it was found that in IDH1mut glioblastoma, the dendritic cell infiltration was reduced which may result in a better prognosis. In addition, the level of IDH1, FABP5, C1RL, MIR155HG, CSTA and BCL3 might also influence lymphocytes infiltration (eg. CD4+ T cell) and chemokine expression (CXCL family). CONCLUSIONS: IDH1 may participate in pathological mechanisms of glioblastoma via expression alteration or gene mutation. Furthermore, IDH1 mutation might improve prognosis via suppressing the expression of FABP5, C1RL, MIR155HG, CSTA and BCL3. Meanwhile, it was identified that BCL3 might perform similar immunomodulatory functions with IDH1 as an upstream transcript factor.

BAIAP2L2 promotes the proliferation, migration and invasion of osteosarcoma associated with the Wnt/ß-catenin pathway.

BACKGROUND: Osteosarcoma is the most common bone cancer that significantly affects the quality of life of patients. Studies have shown that overexpression of BAIAP2L2 elevates the proliferation and growth of some types of cancer cells. However, the role of BAIAP2L2 in osteosarcoma is unclear. This study aimed to investigate the functions of BAIAP2L2 in the development of osteosarcoma. METHODS: We used immunohistochemical and Western blot analysis to determine the expression levels of endogenic BAIAP2L2 in osteosarcoma cells. Cell counting kit-8 assay and colony formation assay were performed to investigate cell proliferation of tumor cells. Transwell assay was performed to detect cell migration. Flow cytometry assay was used to analyze cell apoptosis. The role of BAIAP2L2 in tumor growth was further explored in vivo. RESULTS: We found that BAIAP2L2 was significantly upregulated in human osteosarcoma, and inhibition of BAIAP2L2 suppressed the proliferation of osteosarcoma cells. In addition, down-regulation of BAIAP2L2 could lead to osteosarcoma cancer cell apoptosis, inhibit cell migration and invasion, and induce the inactivation of the Wnt/ß-catenin pathway. In addition, down-regulation of BAIAP2L2 inhibited tumor growth in vivo. CONCLUSION: In conclusion, down-regulation of BAIAP2L2 inhibited the proliferation, migration, and invasion of osteosarcoma associated with the Wnt/ß-catenin pathway.

Artificial stone-associated silicosis with concurrent Cryptococcus infection.

Acute silicoproteinosis is a disease that develops in weeks, and lasting for years, after massive exposure to silica dust in relatively closed spaces. It was rare, but the cases have recently increased worldwide due to the development of artificial stone industry. Compared with traditional silicosis, artificial stone-associated silicosis is more rapidly progressive and lethal. Hence, a correct diagnosis and optimal treatment are crucial. Here, we present the clinical course of a 33-year-old artificial stonemason who suffered from acute silicoproteinosis with concurrent Cryptococcus infection resulting in profound respiratory failure. This patient was treated by bronchoscope-assisted therapeutic segmental lung lavage and antifungal agent, under mechanical ventilator and ECMO support and recovered well. A brief review of acute silicoproteinosis and artificial stone-associated silicosis is also presented and highlights the new form of industry exposure to silica.

Clinical usefulness of bronchoalveolar lavage in patients with interstitial lung diseases: a pilot study.

BACKGROUND: Bronchoalveolar lavage (BAL) is a useful tool in the diagnostic work-up of patients with interstitial lung diseases (ILDs). In this prospective study, we investigated the clinical usefulness of BAL in patients with ILD radiographically. METHODS: The enrolled patients were classified into outpatient department (OPD), and inpatients groups who was admitted to general ward (GW) or intensive care unit (ICU) groups based on the time when BAL done. The clinical usefulness of BAL was defined as a new diagnosis established and/or treatment significantly changed. The clinical usefulness of BAL among the three groups of patients and the patients divided by underlying diseases was compared using the χ2 test with or without Fisher's exact test. RESULTS: Among our 184 patients, there were 37 in OPD group, 86 in GW group and 61 in ICU group. The final diagnoses were infectious in 23, non-infectious in 102, mixed etiologies in 19, and non-diagnostic in 40 patients. The diagnostic yields (revised diagnosis after BAL) of BAL among ICU patients, GW patients and OPD patients were 60.6%, 69.7% and 21.6%, respectively (P<0.001), and was 57.1% in total patients. The diagnostic yields of BAL among patients with cancer, organ transplantation and collagen vascular disease were statistically different (P=0.009). CONCLUSIONS: BAL is of use in establishing a diagnosis of ILD and is mandatary especially in the admitted patients with ILD because diagnostic yield was relatively higher in admitted patients than in OPD patients. In addition, BAL should be done more early in the admitted patients with malignancy, stem cell and/or organ transplantation and collagen vascular disease especially when they showed poor response to initial medications.

Outcome and prognostic factors of interstitial lung disease patients with acute respiratory failure in the intensive care unit.

BACKGROUND: There are few studies reporting the clinical characteristics and outcomes of interstitial lung disease (ILD) patients with acute respiratory failure (ARF). The goal of this study is to investigate the clinical features, management, mortality, and associated factors in ILD patients with ARF requiring mechanical ventilation (MV). METHODS: This was a retrospective, observational study conducted in a 24-bed intensive care unit (ICU) of a medical center in Taiwan during a 3-year period. Patients admitted to the ICU with a diagnosis of ILD with ARF needing MV were included for analysis. Patient characteristics, including demographics, critical-illness factors, and outcome data, were collected and analyzed. RESULTS: A total of 82 patients with ILD who developed ARF were admitted to the ICU during the study period. At the onset of ARF, 38 patients received invasive MV, while 44 patients were treated with noninvasive MV. Overall in-hospital mortality was 65.9%, and 90-day and 1-year mortality were 69.5% and 76.8%, respectively. The independent risk factors for in-hospital mortality were worse oxygenation on days 5 and 7 after the onset of ARF. Invasive MV patients had significantly lower albumin levels, had higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the onset of ARF, and received more vasopressors, sedatives, and corticosteroid pulse therapy during hospitalization compared with noninvasive MV patients. CONCLUSION: High in-hospital and long-term mortality rates were observed in ILD patients with ARF requiring MV. Poor oxygenation during hospitalization could serve as a predictive factor of poor prognosis. The reviews of this paper are available via the supplemental material section.

Impact of Intermittent Hypoxia on Sepsis Outcomes in a Murine Model.

Sleep apnea has been associated with a variety of diseases, but its impact on sepsis outcome remains unclear. This study investigated the effect of intermittent hypoxia [IH]-the principal feature of sleep apnea-on murine sepsis. 5-week-old male C57BL6 mice were assigned to groups receiving severe IH (O2 fluctuating from room air to an O2 nadir of 5.7% with a cycle length of 90 seconds), mild IH (room air to 12%, 4 minutes/cycle), or room air for 3 weeks. Sepsis was induced by cecal ligation and puncture and survival was monitored. Sepsis severity was evaluated by murine sepsis scores, blood bacterial load, plasma tumor necrosis factor-α [TNF-α]/interleukin-6 [IL-6] levels and histopathology of vital organs. Compared with normoxic controls, mice subjected to severe IH had earlier mortality, a lower leukocyte count, higher blood bacterial load, higher plasma TNF-α and IL-6 levels, more severe inflammatory changes in the lung, spleen and small intestine. Mice subjected to mild IH did not differ from normoxic controls, except a higher IL-6 level after sepsis induced. The adverse impact of severe IH was reversed following a 10-day normoxic recovery. In conclusion, severe IH, not mild IH, contributed to poorer outcomes in a murine sepsis model.

Pulmonary tuberculous cavities in diabetic patients: Glycemic control is still the dominant factor despite the emerging role of metformin.

BACKGROUND: Previous studies have reported an increased risk of cavities in diabetic patients with pulmonary tuberculosis (PTB), which may be associated with poor glycemic control. Cavities have a negative impact on PTB treatment outcomes; however, the possible interaction of other potentially confounding diabetes-related variables regarding pulmonary cavities have not been fully evaluated. METHODS: We conducted a retrospective cohort study of diabetic patients with culture-proven PTB. The patients' chest X-rays (CXRs) and computed tomography (CT) scans were reviewed to assess the effects of clinical factors, glycosylated hemoglobin (HbA1c) levels, and antidiabetic agents on cavitary lesions. RESULTS: Among 128 diabetic PTB patients, those with pulmonary cavities on CXRs and CT scans presented younger ages, lack of metformin treatment, and significantly higher HbA1c levels than those without cavities. Multivariate logistic regression analysis revealed significantly higher HbA1c levels in patients with cavities than in those without cavities on CXRs (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.12-1.61) and CT scans (OR, 1.36; 95% CI, 1.13-1.64). Patients with multiple cavities had significantly higher HbA1c levels than those with a single cavity on CT scans (p = 0.002). No significant differences in other variables, including metformin treatment, were noted between the groups. CONCLUSION: This study suggests that despite multiple potential confounding variables, including metformin use, poor glycemic control is still the dominant risk factor for cavitary lesions in diabetic patients with PTB. Efforts to improve glycemic control in diabetic PTB patients may be of considerable value in facilitating antimycobacterial treatment.

The usefulness of prophylactic use of acetazolamide in subjects with acute mountain sickness.

BACKGROUND: The mechanisms of acetazolamide (ACZ) in the prophylaxis of acute mountain sickness (AMS) remain unclear. This study evaluated the changes in physiological variables of sleep and heart rate variability (HRV) in subjects with earlier history of AMS who underwent prophylactic treatment of ACZ. METHODS: Nonacclimatized healthy subjects were transported using a bus from 555 m to 3150 m within 3 hours. Polysomnography (PSG) was performed 3 days before ascent (T0), for two consecutive nights at 3150 m (T1 and T2), and 2 days after descent (T3). HRV was measured before sleep and after awakening from T0 to T3. AMS was diagnosed using a self-reported Lake Louise score questionnaire. Subjects found confirmed to have AMS were enrolled in this study. The physiological variables and HRV were compared in AMS subjects without (control group) and with prophylactic ACZ (prophylactic ACZ group). RESULTS: Thirteen AMS subjects were enrolled. The PSG results were analyzed in eight and HRV were analyzed in nine of the 13 subjects. The prophylactic use of ACZ in the subjects with a history of AMS significantly improved sleep efficiency (p = 0.012) and awakening percentages (p = 0.017) at T1, significantly higher levels of arterial oxygen saturation (SaO2) and lower values of partial pressure end-tidal carbon dioxide tension (PETCO2) at four time points. Furthermore, they had a higher rapid eye movement sleep percentage (p = 0.05) at T2. Prophylactic ACZ treatment significantly increased the normalized unit of high frequency at T1 after awakening (p = 0.028). CONCLUSION: Significantly higher quality of sleep, higher SaO2 during sleep, and lower PETCO2 at high altitude were found in the subjects with a history of AMS using prophylactic ACZ before rapid ascent. ACZ may accelerate the acclimatization process for rapid ascents to high altitudes by increasing parasympathetic tone based on HRV analyses.

Pilot simulation-based research for evaluation, training and assessment of holistic nursing at four intensive care unit sites.

This article was migrated. The article was marked as recommended. Background: Holistic nursing of intensive care unit (ICU) patients encompasses diverse challenges requiring regular in situ evaluation, training and assessment. Simulation has been adopted as a research and training tool in medicine; however, evidence for its use in enhancing holistic care at multi-sites is limited. Objective: This study aims to conduct a simulation-based research (SBR) at four ICU for standardized training of holistic nursing. Methods: There are stages of evaluating, training+in-training assessment and post-course assessment in this SBR. Specifically, the curriculum-mapped scenarios were developed according to the deficiency of each site after evaluating stage. At the training stage, the first simulation by team was defined as preparation step and the in-training assessment was undertaken at the second simulation. Results: From January 2017 to October 2018, sixty-four ICU nurses (16 teams, 4 teams in each site) at RCU, PICU, NICU and GYN ICU, attend 8 similar courses (2 courses at each site) over 20 months. In comparison with baseline performance, in-training assessments revealed the significant improvement of attendee's skills of holistic nursing. Attendees commented that simulation was a valuable training modality to enhance skills of holistic care including history taking, physical examination, communication and teamwork that are rarely taught among ICU nurses. Post-course workplace assessment by senior nurses revealed the high frequency of clinical application of holistic nursing by attendees. Additionally, post-course self assessment revealed a high attendee's confidence of holistic approaching in ICU. Conclusion: This pilot SBR demonstrated the feasibility of a standardized holistic care simulation program across four ICUs. In situ simulation and post-course workplace assessment affords situational learning without compromising patient safety and is an exciting and novel training of holistic nursing for ICU that could be integrated into regular intervention.

Cytomegaloviral or Pneumocystis Jiroveci Pneumonia Increases Mortality in Systemic Lupus Erythematosus Patients with Pulmonary Hemorrhage: Evidence from Bronchoalveolar Lavage Fluid.

OBJECTIVE: To evaluate the role of cytomegaloviral or Pneumocystis jiroveci pneumonia (CMV/PJP) in systemic lupus erythematosus (SLE) patients with pulmonary hemorrhage (PH). METHODS: We retrospectively examined hospital records for 27 SLE patients with PH who received bronchoalveolar lavage fluid (BALF) analyses. Clinical profile and mortality rates were compared between groups with and without CMV/PJP. Risk factors for PH-related mortality were analyzed. RESULTS: Among 27 SLE patients with PH, 15 had pathogens from BALF samples, and 8 had CMV/PJP. Although CMV/PJP was treated, the RR for 90- and 180-day mortality rates of SLE patients with CMV/PJP were higher than those without these infections (5.94, 95% CI 1.44-24.48; 7.13, 95% CI 1.81-28.06, respectively). Risk factors for 90- and 180-day mortality were presence of CMV/PJP (OR 14.2, 95% CI 1.83-109.9; OR 25.5, 95% CI 2.91-223.3, respectively) and use of pulse methylprednisolone for PH treatment (OR 12.0, 95% CI 1.48-97.2; OR 8.5, 95% CI 1.13-63.9, respectively). Factors increasing the 90-day mortality rate were duration of mechanical ventilation exceeding 14 days (OR 11.1, 95% CI 1.11-112.0) and use of aggressive immunosuppression close to PH onset (OR 7.56, 95% CI 1.09-52.4). Three of the 7 patients receiving aggressive immunosuppression died with the presence of CMV/PJP. CONCLUSION: Owing to the high prevalence of CMV/PJP and its association with mortality, routine BALF analysis is recommended for all suitable SLE patients with PH. Use of aggressive immunosuppression does not benefit SLE patients with opportunistic infections during PH attack.

Glycopyrronium bromide inhibits lung inflammation and small airway remodeling induced by subchronic cigarette smoke exposure in mice.

The effects of long-acting muscarinic receptor antagonists (LAMAs) have not been evaluated in a model with simultaneous lung inflammation and small airway remodeling induced by cigarette smoke (CS). We exposed the mice to CS for four weeks with daily treatment with a LAMA (glycopyrronium bromide, NVA237) or its vehicle. Human bronchial epithelial cells (PBECs) and lung fibroblasts were exposed to CS extract (CSE) or acetylcholine with or without NVA237 treatment. We found that NVA237, but not its vehicle, suppressed elevations in inflammatory score, epithelial thickness, and peribronchial collagen deposition in CS-exposed mice. NVA237 alleviated CS-induced increased levels of chemokines, inflammatory cells, and total protein in the bronchoalveolar lavage fluid. NVA237 suppressed acetylcholine- or CSE-induced elevations in IL-8 production in PBECs and elevations in proliferation and collagen production in lung fibroblasts. These phenomena were also prevented by a p44/42 MAPK inhibitor. In conclusion, NVA237 exerted a potent suppressive effect on lung inflammation and small airway remodeling induced by subchronic CS exposure.

The impact of open to collaborative care model in cardiovascular surgical unit.

BACKGROUND: When compared with open care model, a closed one improves patient care in intensive care units (ICUs), mixed ICUs, surgical ICUs and trauma centers. We wanted to evaluate the benefit of a collaborative care model in highly specialized cardiovascular care unit. METHODS: This study was a retrospective, observational study conducted in the cardiovascular care unit of a teaching hospital. All patients who were above 20 years old and had received cardiovascular operation were enrolled for data collection and analysis. RESULTS: A total of 270 subjects were enrolled for analysis during the 2-year study period. In the collaborative care model, the CVSU length of stay (p = 0.001) and CVSU-free days (p = 0.0008) were significantly better than those in an open care model. DISCUSSION: The collaborative care model improved postoperative outcome in the cardiovascular surgical unit for those needing prolonged ICU care.

Comparison of right ventricular measurements by perioperative transesophageal echocardiography as a predictor of hemodynamic instability following cardiac surgery.

BACKGROUND: The relationship between perioperative right ventricular (RV) performance and hemodynamic instability after cardiac surgery seemed less portrayed. Therefore, we sought to elucidate this relationship and compare the accuracy of different RV systolic indices in predicting outcome of cardiac surgery. METHODS: This study enrolled consecutive patients referred for cardiac surgeries. Exclusion criteria were non-sinus rhythm or contraindications to transesophageal echocardiography (TEE). TEE exam and simultaneous pulmonary hemodynamics were recorded in two stages: after induction of anesthesia and before sternotomy (stage 1), and after sternal closure (stage 2). RV measurements performed offline included fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), peak systolic tricuspid annular velocity (RVS'), myocardial performance index (RVMPI), and global longitudinal strain (RVGLS). The end point was defined as prolonged use (>24 h) of postoperative inotropic agent in the intensive care unit (ICU). RESULTS: The study population included 68 patients (mean age 61 ± 11 y; 49 men). Twenty-two of these patients (32%) were administered inotropic agents for a prolonged period with a mean duration of 63.9 ± 5.3 h, accompanied with significantly longer ventilator use (p = 0.006) and longer ICU stay (p = 0.001) than patients without a prolonged inotropic agent use. Multivariable analysis demonstrated that only RVGLS in either stage 1 (odds ratio [OR] 1.11, p = 0.048) or stage 2 (OR 1.15, p = 0.018) was significantly associated with the outcome, especially a RVGLS > -13.5% in stage 2 demonstrating high risk of prolonged inotropic agent use after cardiac surgery (OR 7.37, p = 0.016). CONCLUSION: RVGLSs performed using perioperative TEE are reliably associated with hemodynamic instability following cardiac surgery. This finding adds substantial information to postoperative critical care.

α-melanocyte stimulating hormone modulates the central acyl ghrelin-induced stimulation of feeding, gastrointestinal motility, and colonic secretion.

BACKGROUND: Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect. OBJECTIVE: This study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats. METHODS AND PROCEDURES: We examined the effects of α-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters. RESULTS: ICV injection of O-n-octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h (P<0.01), enhanced non-nutrient semi-liquid gastric emptying (P<0.001), increased the geometric center and running percentage of small intestinal transit (P<0.001), accelerated colonic transit time (P<0.05), and increased fecal pellet output (P<0.01) and total fecal weight (P<0.01). Pretreatment with ICV injection of α-MSH (1.0 and 2.0 nmol/rat) attenuated the acyl ghrelin-induced hyperphagic effect, fecal pellet output, and total fecal weight, while higher dose of α-MSH (2.0 nmol/rat) attenuated the increase in the geometric center of small intestinal transit (P<0.01). However, neither dose of α-MSH altered acyl ghrelin-stimulated gastroprokinetic effect, increase in the running percentage of small intestinal transit, nor accelerated colonic transit time. CONCLUSION: α-MSH is involved in central acyl ghrelin-elicited feeding, small intestinal transit, fecal pellet output, and fecal weight. α-MSH does not affect central acyl ghrelin-induced acceleration of gastric emptying and colonic transit time in rats.