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Non-Tuberculous Mycobacteria: Classification, Diagnostics, and Therapy.

Adv Exp Med Biol. 2016 Sep 20;

Authors: Porvaznik I, Solovič I, Mokrý J

Abstract
Non-tuberculous mycobacteria (NTM) are species other than those belonging to the Mycobacterium tuberculosis complex and do not cause leprosy. NTM are generally free-living organisms that are ubiquitous in the environment. There have been more than 140 NTM species identified to-date. They can cause a wide range of infections, with pulmonary infections being the most frequent (65-90 %). There is growing evidence that the incidence of NTM lung diseases and associated hospitalizations are on the rise, mainly in regions with a low prevalence of tuberculosis. A crucial clinical problem remains the evaluation of NTM significance in relation to the disease, especially in regard to the colonization of the respiratory tract in patients with residual lesions after tuberculosis or bronchiectasis. Clinical and radiographic pictures of mycobacteriosis, as well as therapy, have often similarities to those of tuberculosis. The treatment regimen should be individualized. In addition to antituberculotics, antibiotics are used more frequently. The most common mycobacteria causing lung disease in Slovakia are Mycobacterium avium and Mycobacterium abscessus.

PMID: 27645543 [PubMed - as supplied by publisher]

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Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine.

Chest. 2016 Sep 16;

Authors: Dunham-Snary KJ, Danchen Wu, Sykes EA, Thakrar A, Parlow LR, Mewburn JD, Parlow JL, Archer SL

Abstract
Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation-perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in PASMC. This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction. Sustained hypoxia activates rho kinase, reinforcing vasoconstriction, and HIF-1α, leading to adverse pulmonary vascular remodelling and pulmonary hypertension (PH). In the non-ventilated fetal lung, HPV diverts blood to the systemic vasculature. After birth, HPV commonly occurs as a localized homeostatic response to focal pneumonia or atelectasis that optimizes systemic PO2 without altering pulmonary artery pressure. In single-lung anesthesia, HPV reduces blood flow to the non-ventilated lung thereby facilitating thoracic surgery. At altitude, global hypoxia causes diffuse HPV, increases PA pressure and initiates PH. Exaggerated or heterogeneous HPV contributes to high altitude pulmonary edema. Conversely, impaired HPV, whether due to diseases (COPD, sepsis) or vasodilator drugs, promotes systemic hypoxemia. Genetic and epigenetic abnormalities of this oxygen-sensing pathway can trigger normoxic activation of HIF-1α and can promote abnormal metabolism and cell proliferation. The resulting pseudo-hypoxic state underlies the Warburg metabolic shift and contributes to the neoplasia-like phenotype of PH. HPV and oxygen-sensing are important in human health and disease.

PMID: 27645688 [PubMed - as supplied by publisher]

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The Mucus Barrier to Inhaled Gene Therapy.

Mol Ther. 2016 Sep 20;

Authors: Duncan GA, Jung J, Hanes J, Soo Suk J

Abstract
Recent evidence suggests that the airway mucus gel layer may be impermeable to the viral and synthetic gene vectors used in past inhaled gene therapy clinical trials for diseases like cystic fibrosis. These findings support the logic that inhaled gene vectors that are incapable of penetrating the mucus barrier are unlikely to provide meaningful benefit to patients. In this review, we discuss the biochemical and biophysical features of mucus that contribute its barrier function, and how these barrier properties may be reinforced in patients with lung disease. We next review biophysical techniques used to assess the potential ability of gene vectors to penetrate airway mucus. Finally, we provide new data that suggest that fresh human airway mucus should be used to test the penetration rates of gene vectors. The physiological barrier properties of spontaneously expectorated CF sputum remained intact up to 24 hours after collection when refrigerated at 4ºC. Conversely, the barrier properties were significanctly altered after freezing and thawing of sputum samples. Gene vectors capable of overcoming the airway mucus barrier hold promise as a means to provide the widespread gene transfer throughout the airway epithelium required to achieve meaningful patient outcomes in inhaled gene therapy clinical trials.

PMID: 27646604 [PubMed - as supplied by publisher]

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Recent clinical innovations in thoracic surgery in Hong Kong.

J Thorac Dis. 2016 Aug;8(Suppl 8):S618-26

Authors: Zhao ZR, Li Z, Situ DR, Ng CS

Abstract
The concept of personalized medicine, which aims to provide patients with targeted therapies while greatly reducing surgical trauma, is gaining popularity among Asian clinicians. Single port video-assisted thoracic surgery (VATS) has rapidly gained popularity in Hong Kong for major lung resections, despite bringing new challenges such as interference between surgical instruments and insertion of the optical source through a single incision. Novel types of endocutters and thoracoscopes can help reduce the difficulties commonly encountered during single-port VATS. Our region has been the testing ground and has led the development of many of these innovations. Performing VATS, in particular single-port VATS in hybrid operating theatre helps to localise small pulmonary lesions with real-time images, thus increasing surgical accuracy and pushes the boundaries in treating subcentimeter diseases. Such approach may be assisted by use of electromagnetic navigational bronchoscopy in the same setting. In addition, sublobar resection can also be more individualised according to pathologic tumour subtype that require rapid intraoperative diagnostic test to guide appropriate surgical therapy. A focus on technology and innovation for large tumours that require chest wall resection and reconstructions have also been on going, with new materials and prostheses that may be tailored to each individual needs. The current paper reviews the literature pertaining to the above topics and discusses recent related innovations in Hong Kong, highlighting the study results and future perspectives.

PMID: 27651937 [PubMed]