Reducing the toll of inflammatory lung disease

Toll-like receptors (TLRs) are pivotal in human response to microbial stimuli. Their activation and signaling underpin much of the observed epidemiologic data generated by the hygiene hypothesis, and their contribution to infectious exacerbations of airways disease is likely to be highly important. Our growing knowledge in this field will have a significant impact on the understanding of the pathogenesis of inflammatory diseases, and TLR-based therapies are already in early clinical trials to modify atopic disease severity.     

Discrepant results between pyrazinamide susceptibility testing by the reference BACTEC 460TB method and pncA DNA sequencing in patients infected with multidrug-resistant W-Beijing Mycobacterium tuberculosis strains

BACKGROUND: Mycobacterium tuberculosis strains belonging to the W-Beijing family have received broad clinical and public health attention because of their rapid worldwide spread and their frequent association with outbreaks, multidrug resistance, and treatment failures and relapses. METHODS: The present study examined a large number of multidrug-resistant strain-W isolates (isolates of 29 patients) by susceptibility testing for pyrazinamide (PZA) using the reference BACTEC 460TB method (Becton Dickinson Diagnostic Instrument Systems; Sparks, MD) and also by DNA sequencing of the pncA gene. RESULTS: We found that despite of the presence of a strain W-specific Thr47Ala in the pncA gene, all strains showed susceptibility to PZA in the reference BACTEC 460TB system due to their higher minimum inhibitory concentrations (relative to BACTEC 460TB PZA-susceptible strains). CONCLUSIONS: Our results suggest that the current radiometric reference method cannot reproducibly detect PZA resistance in patients infected with W-Beijing strains. Therefore, PZA susceptibility testing should instead be based on analysis of the pncA gene for resistance-associated mutations.     

Occult traumatic pneumothorax: diagnostic accuracy of lung ultrasonography in the emergency department

BACKGROUND: The role of chest ultrasonography (US) in the diagnosis of pneumothorax (PTX) has been established, but how it compares with lung CT scanning in the diagnosis of radiooccult PTX and in the determination of its topographic extension has not yet been completely evaluated. OBJECTIVE: To determine the diagnostic accuracy of chest US in the emergency department (ED) in the diagnosis of occult PTX in trauma patients and to define its ability to determine PTX extension. DESIGN: An 18-month prospective study. PATIENTS: A total of 109 conscious, spontaneously breathing patients who had been admitted to the ED for chest trauma or polytrauma. METHODS: All eligible patients underwent a standard anteroposterior supine chest radiograph (Rx) and a spiral CT lung scan within 1 h of ED admission. Lung US was carried out by an operator who was unaware of the other examination results, both for diagnosis and for the quantitative delimitation of the PTX. RESULTS: Twenty-five traumatic PTXs were detected in the 218 hemithoraxes (109 patients; 2 patients had a bilateral PTX) evaluated by spiral CT scan; of these, only 13 of 25 PTXs (52%) were revealed by chest Rx (sensitivity, 52%; specificity, 100%), while 23 of 25 PTXs (92%) were identified by lung US with one false-positive result (sensitivity, 92%; specificity, 99.4%). In 20 of 25 cases, there was agreement on the extension of the PTX between CT lung scan and lung US with a mean difference of 1.9 cm (range, 0 to 4.5 cm) in the localization of retroparietal air extension; chest Rx was not able to give quantitative results. CONCLUSIONS: Lung US scans carried out in the ED detect occult PTX and its extension with an accuracy that is almost as high as the reference standard (CT scanning).     

Prevention of acute renal failure

Acute renal failure (ARF) comprises a family of syndromes that is characterized by an abrupt and sustained decrease in the glomerular filtration rate. In the ICU, ARF is most often due to sepsis and other systemic inflammatory states. ARF is common among the critically ill and injured and significantly adds to morbidity and mortality of these patients. Despite many advances in medical technology, the mortality and morbidity of ARF in the ICU continue to remain high and have not improved significantly over the past 2 decades. Primary strategies to prevent ARF still include adequate hydration, maintenance of mean arterial pressure, and minimizing nephrotoxin exposure. Diuretics and dopamine have been shown to be ineffective in the prevention of ARF or improving outcomes once ARF occurs. Increasing insight into mechanisms leading to ARF and the importance of facilitating renal recovery has prompted investigators to evaluate the role of newer therapeutic agents in the prevention of ARF.     

Obstructive sleep apnea and type 2 diabetes: interacting epidemics

Type 2 diabetes is a major public health concern with high morbidity, mortality, and health-care costs. Recent reports have indicated that the majority of patients with type 2 diabetes also have obstructive sleep apnea (OSA). There is compelling evidence that OSA is a significant risk factor for cardiovascular disease and mortality. Rapidly accumulating data from both epidemiologic and clinical studies suggest that OSA is also independently associated with alterations in glucose metabolism and places patients at an increased risk of the development of type 2 diabetes. Experimental studies in humans and animals have demonstrated that intermittent hypoxia and reduced sleep duration due to sleep fragmentation, as occur in OSA, exert adverse effects on glucose metabolism. Based on the current evidence, clinicians need to address the risk of OSA in patients with type 2 diabetes and, conversely, evaluate the presence of type 2 diabetes in patients with OSA. Clearly, there is a need for further research, using well-designed studies and long-term follow-up, to fully demonstrate a causal role for OSA in the development and severity of type 2 diabetes. In particular, future studies must carefully consider the confounding effects of central obesity in examining the link between OSA and alterations in glucose metabolism. The interactions among the rising epidemics of obesity, OSA, and type 2 diabetes are likely to be complex and involve multiple pathways. A better understanding of the relationship between OSA and type 2 diabetes may have important public health implications.