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Autophagy and Non-small Cell Lung Carcinomas

Background:

Lung carcinoma has a poor prognosis that is mainly predicted by the stage of the disease. Despite evaluation of various prognostic factors, the role of autophagy, a self-degradative process involved in the turnover of cytoplasmic material, remains unexplored in lung malignancy.

 Methods:

Autophagic activity was investigated in 115 patients with non-small cell lung carcinoma treated with surgery (64 squamous cell carcinomas, 24 adenocarcinomas of mixed subtype, 18 large cell carcinomas, 9 uncommon types). The median overall survival was 32 months (range, 2-102 months). We used the MAP1LC3A antibody and a standard immunohistochemical technique. Autophagic activity was correlated with clinical and pathologic parameters.

 Results:

Immunohistochemical examination revealed three patterns of autophagic activity: diffuse cytoplasmic, cytoplasmic perinuclear, and "stone-like" structures (SLSs), which are dense, rounded cytosolic structures typically enclosed within light-chain 3 (LC3) A-positive vacuoles. A high SLS count was associated with a reduction of the overall median survival from 88 to 15 months and constituted the strongest independent variable in multivariate analysis. Interestingly, a high presence of SLS defined significantly poor prognosis within stage I and II, whereas a similar trend was noted within stage III. The other two patterns of LC3A reactivity were not correlated with prognosis.

 Conclusions:

Exaggerated autophagy, as indicated by the intense presence of SLSs, is strongly correlated with a poor outcome in non-small cell lung carcinoma, suggesting possibly that autophagy functions as a survival tool in cancer cells.

Oxygen Supplementation During Air Travel

Background:

Patients with COPD may need supplemental oxygen during air travel to avoid development of severe hypoxemia. The current study evaluated whether the hypoxia-altitude simulation test (HAST), in which patients breathe 15.1% oxygen simulating aircraft conditions, can be used to establish the optimal dose of supplemental oxygen. Also, the various types of oxygen-delivery equipment allowed for air travel were compared.

 Methods:

In a randomized crossover trial, 16 patients with COPD were exposed to alveolar hypoxia: in a hypobaric chamber (HC) at 2,438 m (8,000 ft) and with a HAST. During both tests, supplemental oxygen was given by nasal cannula (NC) with (1) continuous flow, (2) an oxygen-conserving device, and (3) a portable oxygen concentrator (POC).

 Results:

Pao2 kPa (mm Hg) while in the HC and during the HAST with supplemental oxygen at 2 L/min (pulse setting 2) on devices 1 to 3 was (1) 8.6 ± 1.0 (65 ± 8) vs 12.5 ± 2.4 (94 ± 18) (P < .001), (2) 8.6 ± 1.6 (64 ± 12) vs 9.7 ± 1.5 (73 ± 11) (P < .001), and (3) 7.7 ± 0.9 (58 ± 7) vs 8.2 ± 1.1 (62 ± 8) (P= .003), respectively.

 Conclusions:

The HAST may be used to identify patients needing supplemental oxygen during air travel. However, oxygen titration using an NC during a HAST causes accumulation of oxygen within the facemask and underestimates the oxygen dose required. When comparing the various types of oxygen-delivery equipment in an HC at 2,438 m (8,000 ft), compressed gaseous oxygen with continuous flow or with an oxygen-conserving device resulted in the same Pao2, whereas a POC showed significantly lower Pao2 values.

 Trial registry:

ClinicalTrials.gov; No.: Identifier: NCT01019538; URL: clinicaltrials.gov

Surgical Reinnervation of the Paralyzed Diaphragm

Background:

Unilateral phrenic nerve injury often results in symptomatic hemidiaphragm paralysis, and currently few treatment options exist. Reported etiologies include cardiac surgery, neck surgery, chiropractic manipulation, and interscalene nerve blocks. Although diaphragmatic plication has been an option for treatment, the ideal treatment would be restoration of function to the paralyzed hemidiaphragm. The application of peripheral nerve surgery techniques for phrenic nerve injuries has not been adequately evaluated.

 Methods:

Twelve patients presenting with long-term, symptomatic, unilateral phrenic nerve injuries following surgery, chiropractic manipulation, trauma, or anesthetic blocks underwent a comprehensive evaluation, including radiographic and electrophysiologic assessments. Surgical treatment was offered following a minimum of 6 months of conservative management. Operative planning was based on preoperative and intraoperative testing using one or more established nerve reconstruction techniques (neurolysis, interpositional grafting, or neurotization).

 Results:

Measures of postoperative improvement included pulmonary function testing, fluoroscopic sniff testing, and a standardized quality-of-life survey, from which it was determined that eight of nine patients who could be completely evaluated experienced improvements in diaphragmatic function.

 Conclusions:

Based on the favorable results in this small series, we suggest expanding nerve reconstruction techniques to phrenic nerve injury treatment and propose an algorithm for treatment of unilateral phrenic nerve injury that may expand the current limitations in therapy.

Glycemic Control in the ICU

Hyperglycemia is common in critically ill patients, with approximately 90% of patients treated in an ICU developing blood glucose concentrations > 110 mg/dL (6.1 mmol/L). Landmark trials in Leuven, Belgium, suggested that targeting normoglycemia (a blood glucose concentration of 80-110 mg/dL [4.4-6.1 mmol/L]) reduced mortality and morbidity, but other investigators have not been able to replicate these findings. Recently, the international multicenter Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study reported increased mortality with this approach, and recent meta-analyses do not support intensive glucose control for critically ill patients. Although the initial trials in Leuven produced enthusiasm and recommendations for intensive blood glucose control, the results of the NICE-SUGAR study have resulted in the more moderate recommendation to target a blood glucose concentration between 144 mg/dL and 180 mg/dL (8-10 mmol/L). As critical care practitioners pay greater attention to glycemic control, it has become clear that currently used point-of-care measuring systems are not accurate enough to target tight glucose control. Unresolved issues include whether increased blood glucose variability is inherently harmful and whether even moderate hypoglycemia can be tolerated in the quest for tighter blood glucose control. Future research must first address whether intensive glucose control can be delivered safely, and whether computerized decision support systems and newer technologies that allow accurate and continuous or near-continuous measurement of blood glucose can make this possible. Until such time, clinicians would be well advised to abide by the age-old adage to "first, do no harm."

Role of Allergen Sensitization in Older Adults

Abstract  
There is a common perception among physicians and patients that allergic diseases are not relevant in older adults. There is also recognition that innate and adaptive immune functions decline with aging. It is the function of a variety of immune cells in the form of allergic inflammation that is a hallmark of allergic diseases. In fact, there is a fairly consistent observation that measures of allergic sensitization, such as skin prick testing, specific IgE, or total IgE, decline with age. Nonetheless, the association between allergic sensitization and allergic diseases, particularly asthma and allergic rhinitis, remains robust in the older adult population. Consequently, an appropriate evaluation of allergic sensitivities is warranted and indicated in older asthma and rhinitis patients to provide optimal care for the individual and minimize any resultant morbidity and mortality.
  • Content Type Journal Article
  • Pages 1-7
  • DOI 10.1007/s11882-011-0204-9
  • Authors
    • Ravi K. Viswanathan, Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, K4/952 CSC, 600 Highland Avenue, Madison, WI 53792, USA
    • Sameer K. Mathur, Division of Allergy, Pulmonary and Critical Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health, K4/952 CSC, 600 Highland Avenue, Madison, WI 53792, USA

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