Humans coexist with a vast bacterial, fungal and viral microbiome with which we have coevolved for millions of years. Several long recognized epidemiological associations between particular bacteria and cancer are now understood at the molecular level. At the same time, the arrival of next-generation sequencing technology has permitted a thorough exploration of microbiomes such as that of the human gut, enabling observation of taxonomic and metabolomic relationships between the microbiome and cancer. These studies have revealed causal mechanisms for both microbes within tumours and microbes in other host niches separated from tumours, mediated through direct and immunological mechanisms.

We examined the neurocirculatory and ventilatory responses to intermittent asphyxia (arterial O(2) saturation = 79-85%, end-tidal PCO(2) =3-5 Torr above eupnea) in seven healthy humans during wakefulness. The intermittent asphyxia intervention consisted of 20-s asphyxic exposures alternating with 40-s periods of room-air breathing for a total of 20 min. Minute ventilation increased during the intermittent asphyxia period (14.2 +/- 2.0 l/min in the final 5 min of asphyxia vs. 7.5 +/- 0.4 l/min in baseline) but returned to the baseline level within 2 min after completion of the series of asphyxic exposures. Muscle sympathetic nerve activity increased progressively, reaching 175 +/- 12% of baseline in the final 5 min of the intervention. Unlike ventilation, sympathetic activity remained elevated for at least 20 min after removal of the chemical stimuli (150 +/- 10% of baseline in the last 5 min of the recovery period). Intermittent asphyxia caused a small, but statistically significant, increase in heart rate (64 +/- 4 beats/min in the final 5 min of asphyxia vs. 61 +/- 4 beats/min in baseline); however, this increase was not sustained after the return to room-air breathing. These data demonstrate that relatively short-term exposure to intermittent asphyxia causes sympathetic activation that persists after removal of the chemical stimuli. This carryover effect provides a potential mechanism whereby intermittent asphyxia during sleep could lead to chronic sympathetic activation in patients with sleep apnea syndrome.

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Objective We have previously described patterns of failure after extrapleural pneumonectomy and multimodality therapy for malignant pleural mesothelioma and sought to update our results with a larger cohort of recent patients. Methods A total of 169 patients underwent extrapleural pneumonectomy without preoperative chemotherapy between 2001 and 2010. Data for treatment, recurrence, and survival were determined from medical records. A thoracic radiologist reviewed postoperative computed tomography or positron emission tomography computed tomography scans to determine sites of recurrence. Time to recurrence was estimated by the Kaplan–Meier method. Rates were compared using the Fisher exact test. Results The median age of patients was 62 years. Histology on final pathology was epithelial for 104 patients (62%) and nonepithelial for 65 patients (38%). A total of 132 patients (78%) received heated intraoperative chemotherapy; 77 patients (45%) received adjuvant chemotherapy, and 71 patients (42%) received adjuvant radiation therapy. Most chemotherapy regimens included platinum or pemetrexed. Median radiation therapy dose was 54 Gy. Among 158 evaluable patients, a recurrence developed in 118 (75%). Median follow-up was 83 months, median time to recurrence was 13.1 months, and median survival was 15 months. Sites of first recurrence were in the ipsilateral hemithorax or mediastinum for 54% of patients, in the abdomen for 39% of patients, in the contralateral hemithorax for 28% of patients, and in other distant sites for 5% of patients. Some patients had simultaneous recurrences in multiple sites. Conclusions The most common site of recurrence after extrapleural pneumonectomy and planned multimodality therapy remains the ipsilateral hemithorax (including mediastinum), and true distant failure (other than the abdomen or contralateral hemithorax) remains unusual. The distribution of recurrences is strikingly similar to our prior report.

IntroductionProlonged intensive care unit lengths of stay (ICU LOS) for critical illness can have acceptable mortality rates and quality of life despite significant costs. Only a few studies have specifically addressed prolonged ICU LOS after trauma. Our goals were to examine characteristics and outcomes of trauma patients with LOS ≥ 30 days, predictors of prolonged stay and mortality.MethodsAll trauma ICU admissions over a seven-year period in a level 1 trauma center were analyzed. Admission characteristics, pre-existing conditions and acquired complications in the ICU were recorded. Logistic regression was used to identify independent predictors of prolonged LOS and predictors of mortality among those with prolonged LOS after univariate analyses.ResultsOf 4920 ICU admissions, 205 (4%) had ICU LOS >30 days. These patients were older and more severely injured. Age and injury severity score (ISS) were associated with prolonged LOS. After logistic regression analysis, sepsis, acute respiratory distress syndrome, and several infectious complications were important independent predictors of prolonged LOS. Within the group with ICU LOS >30 days, predictors of mortality were age, pre-existing renal disease as well as the development of renal failure requiring dialysis. Overall mortality was 12%.ConclusionsThe majority of patients with ICU LOS ≥ 30 days will survive their hospitalization. Infectious and pulmonary complications were predictors of prolonged stay. Further efforts targeting prevention of these complications are warranted.