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An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action.

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An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action.

Nat Med. 2014 Jul 27;

Authors: Gibbs J, Ince L, Matthews L, Mei J, Bell T, Yang N, Saer B, Begley N, Poolman T, Pariollaud M, Farrow S, DeMayo F, Hussell T, Worthen GS, Ray D, Loudon A

Abstract
The circadian system is an important regulator of immune function. Human inflammatory lung diseases frequently show time-of-day variation in symptom severity and lung function, but the mechanisms and cell types underlying these effects remain unclear. We show that pulmonary antibacterial responses are modulated by a circadian clock within epithelial club (Clara) cells. These drive circadian neutrophil recruitment to the lung via the chemokine CXCL5. Genetic ablation of the clock gene Bmal1 (also called Arntl or MOP3) in bronchiolar cells disrupts rhythmic Cxcl5 expression, resulting in exaggerated inflammatory responses to lipopolysaccharide and an impaired host response to Streptococcus pneumoniae infection. Adrenalectomy blocks rhythmic inflammatory responses and the circadian regulation of CXCL5, suggesting a key role for the adrenal axis in driving CXCL5 expression and pulmonary neutrophil recruitment. Glucocorticoid receptor occupancy at the Cxcl5 locus shows circadian oscillations, but this is disrupted in mice with bronchiole-specific ablation of Bmal1, leading to enhanced CXCL5 expression despite normal corticosteroid secretion. The therapeutic effects of the synthetic glucocorticoid dexamethasone depend on intact clock function in the airway. We now define a regulatory mechanism that links the circadian clock and glucocorticoid hormones to control both time-of-day variation and the magnitude of pulmonary inflammation and responses to bacterial infection.

PMID: 25064128 [PubMed - as supplied by publisher]

Dyspnea as an Independent Predictor of Mortality.

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Dyspnea as an Independent Predictor of Mortality.

Clin Respir J. 2014 Jul 28;

Authors: Pesola GR, Ahsan H

Abstract
BACKGROUND: Dyspnea is a common and easily elicited presenting complaint in patients seen by physicians who evaluate and take care of chronic respiratory disorders. Although dyspnea is subjective and tends to increase with age or reduced lung function, it appears to be reproducible as a symptom and often signifies serious underlying disease.
METHODS: Systematic review of longitudinal studies with dyspnea as the exposure and mortality as the outcome; age, smoking, and lung function had to be controlled for to be included in the review. In addition, a minimum sample size at baseline of 500 subjects was required for each study.
RESULTS: From over 3,000 potential references ten longitudinal studies met all criteria and were included. All ten studies suggested that dyspnea was an independent predictor of mortality with point estimates by odds ratio, rate ratio, or hazard ratios ranging from 1.3 up to 2.9-fold greater than baseline. All ten studies had actual or implied 95% confidence interval bands greater than the null value of one.
CONCLUSION: Dyspnea, a symptom, predicts mortality and is a proxy for underlying diseases, most often of heart and lung. Therefore, chronic dyspnea needs to be evaluated as to etiology to allow for treatment to minimize morbidity and mortality when possible.

PMID: 25070878 [PubMed - as supplied by publisher]

Surgical Considerations in Older Adults With Cancer.

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Surgical Considerations in Older Adults With Cancer.

J Clin Oncol. 2014 Jul 28;

Authors: Korc-Grodzicki B, Downey RJ, Shahrokni A, Kingham TP, Patel SG, Audisio RA

Abstract
PURPOSE: The aging of the population is a real concern for surgical oncologists, who are increasingly being asked to treat patients who would not have been considered for surgery in the past. In many cases, decisions are made with relatively little evidence, most of which was derived from trials in which older age was a limiting factor for recruitment.
METHODS: This review focuses on risk assessment and perioperative management. It describes the relationship between age and outcomes for colon, lung, hepatobiliary, and head and neck cancer, which are predominantly diseases of the elderly and are a major cause of morbidity and mortality.
RESULTS: Effective surgery requires safe performance as well as reasonable postoperative life expectancy and maintenance of quality of life. Treatment decisions for potentially vulnerable elderly patients should take into account data obtained from the evaluation of geriatric syndromes, such as frailty, functional and cognitive limitations, malnutrition, comorbidities, and polypharmacy, as well as social support. Postoperative care should include prevention and treatment of complications seen more frequently in the elderly, including postoperative delirium, functional decline, and the need for institutionalization.
CONCLUSION: Surgery remains the best modality for treatment of solid tumors, and chronologic age alone should not be a determinant for treatment decisions. With adequate perioperative risk stratification, functional assessment, and oncologic prognostication, elderly patients with cancer can do as well in terms of morbidity and mortality as their younger counterparts. If surgery is determined to be the appropriate treatment modality, patients should not be denied this option because of their age.

PMID: 25071124 [PubMed - as supplied by publisher]

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Intensive care management of pulmonary hypertension.

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Pulmonary hypertension (PH) in the Intensive Care Unit (ICU) may be due to preexisting pulmonary vascular lung disease, liver disease, or cardiac diseases. PH also may be caused by critical illnesses, such as acute respiratory distress syndrome (ARDS), acute left ventricular dysfunction and pulmonary embolism, or may occur after cardiac or thoracic surgery. Regardless of the underlying cause of PH, the final common pathway for hemodynamic deterioration and death is RV failure, which is the most challenging aspect of patient management.

Therapy is thus aimed at acutely relieving RV overload by decreasing PVR and reversing RV failure with pulmonary vasodilators and inotropes.

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension due to lung diseases and/or hypoxia.

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Chronic lung diseases are common causes of pulmonary hypertension. It ranks second after the left heart disease. Both obstructive and restrictive lung diseases are know to cause pulmonary hypertension. The pathophysiology of the disease is complex, and includes factors affecting the blood vessels, airways, and lung parenchyma. Hypoxia and the inhalation of toxic materials are another contributing factors. Recent guidelines have further clarified the association between pulmonary hypertension and chronic lung disease and made general guidelines concerning the diagnosis and management.

In this article, we will provide a detailed revision about the new classification and give general recommendations about the management of pulmonary hypertension in chronic lung diseases.

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