Changes in physical performance during British Army Junior Entry, British Army Standard Entry and Royal Air Force Basic Training.

INTRODUCTION: The purpose was to quantify physical performance in men and women during British Army Junior Entry (Army-JE), British Army Standard Entry (Army-SE) and Royal Air Force (RAF) basic training (BT). DESIGN: Prospective longitudinal study. METHODS: 381 participants ((339 men and 42 women) n=141 Army-JE, n=132 Army-SE, n=108 RAF) completed a 2 km run, medicine ball throw (MBT) and isometric mid-thigh pull (MTP), pre-BT and post-BT. To examine changes in pre-BT to post-BT physical test performance, for each course, paired Student t-test and Wilcoxon test were applied to normally and non-normally distributed data, respectively, with effect sizes reported as Cohen's D and with rank biserial correlations, respectively. A one-way between-subjects analysis of variance (ANOVA) (or Welch ANOVA for non-normally distributed data) compared performance between quartiles based on test performance pre-BT. Where the main tests statistic, p value and effect sizes identified likely effect of quartile, post hoc comparisons were made using Games-Howell tests with Tukey's p value. Data are presented as mean±SD, with statistical significance set at p<0.05. RESULTS: During BT, 2 km run time improved by 13±46 s (-2.1%±8.1%), 30±64 s (-4.8%±12.3%) and 24±27 s (-4.5%±5.1%) for Army-JE, Army-SE and RAF, respectively (all p<0.005). MBT distance increased by 0.27±0.28 m (6.8%±7.0%) for Army-JE (p<0.001) and 0.07±0.46 m (2.3%±10.9%) for Army-SE (p=0.040), but decreased by 0.08±0.27 m (-1.4%±6.0%) for RAF (p=0.002). MTP force increased by 80±281 n (10.8%±27.6%) for Army-JE (p<0.001) and did not change for Army-SE (-36±295 n, -0.7%±20.6%, p=0.144) or RAF (-9±208 n, 1.0±17.0, p=0.603). For all tests and cohorts, participants in the lowest quartile of pre-BT performance scores demonstrated greater improvements, compared with participants in the highest quartile (except Army-JE MBT, ∆% change similar between all quartiles). CONCLUSIONS: Changes in physical performance were observed for the three fitness tests following the different BT courses, and recruits with the lowest strength and aerobic fitness experienced greatest improvements.

Predictive Value of Supraventricular Short Runs for New-Onset Atrial Fibrillation in Patients with Ischemic Stroke.

Background: The clinical importance of supraventricular run (SVR) is uncertain in the management of patients with previous cerebrovascular events. We aim to evaluate the role of SVRs in the development of future atrial fibrillation (AF) in patients diagnosed with ischemic stroke. Methods: We retrospectively evaluated patients who underwent 24-h Holter monitoring for the evaluation of possible AF after ischemic cerebrovascular events. The presence and duration of SVR were noted. Subsequent diagnosis of AF was searched in patients with sinus rhythm. Results: A total of 694 patients were included in the analysis. SVR was detected in 104 (14.9%) patients in the study group. Seventy-one (10.2%) patients were diagnosed with AF in the follow-up. SVRs were more prevalent among patients with AF (P < 0.001). The median atrial run duration was 5.96 (2.02-17.84) s in the AF absent group vs. 8.76 (3.78-17.62) s in the AF present group (P < 0.001). The best predictive cut-off duration of an atrial run was 8 s (sensitivity = 61.5% and specificity = 74.4%, Area Under Curve (AUC) = 0.708). Cox regression analysis showed that age (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.00-1.060, P = 0.020), presence of short supraventricular run (OR: 2.53, 95% CI 1.40-4.57, P = 0.002), and left atrial diameter (OR: 1.13 95% CI: 1.07-1.19, P < 0.001) were the independent predictors of AF development in the follow-up. Conclusion: Age, left atrial diameter, and the presence of SVRs are associated with an increased risk of future AF after ischemic stroke. SVR duration may be an important parameter in risk stratification.

Abscopal Effect of Radiotherapy in the Immunotherapy Era: Systematic Review of Reported Cases.

Mounting evidence suggests that radiation stimulates the immune system and this contributes to the abscopal effect, which is defined as "response at a distance from the irradiated volume." Though identified more than 50 years ago, the abscopal effect is revisited today. One rationale is that the abscopal effect is often observed with efficient immunotherapy. Here, we give an overview of the clinical data on the abscopal effect, generated by a combination of immunotherapy and radiotherapy (RT). Only papers that included RT in combination with immunotherapy were evaluated according to four main categories including RT parameters, sequencing of therapies, the definition of the abscopal effect, and patient selection. Twenty-four cases in 15 reports were reviewed. The results varied. Patient ages ranged from 24 to 74. RT dose (median total dose 18-58 Gy) varied. Biologically effective dose (BED) 10 was calculated to be a median 49.65 Gy (28-151 Gy). The time to a documented abscopal response ranged from less than a month to 12 months. The large variation concerning fractionation and sequencing of therapies indicates that these conflicting points need to be resolved, to generate for the abscopal effect to be clinically significant.

1.5mile run time and body mass predict 8mile loaded march performance, irrespective of sex.

OBJECTIVES: To develop a statistical model to predict 8mile Loaded March (LM) performance and quantify differences in physical characteristics for men and women British Army Personnel. DESIGN: 135 trained soldiers (87 men; 48 women) completed two sessions, seven days apart. METHODS: Session 1: Participants' stature, body mass, Fat Free Mass (FFM) [by dual-energy X-ray absorptiometry], Single Lift (SL), Water Can Carry (WCC), and 1.5mile run performance were measured. Session 2: Participants completed an 8mile LM, carrying 25kg (4miles paced and 4miles individual best effort). Sex differences were compared using independent samples t-tests and 8mile LM performance time was predicted using various multiple linear regression analysis: hierarchical forced entry multiple ordinary least squares, principal component and ordinary least products. RESULTS: A combination of 1.5mile run time and body mass were the strongest predictors of 8mile LM time (R2=0.71; SEE=4.17min; p<0.001). Including stature, FFM, sex, SL score, or WCC score did not further improve predictions (p>0.05). Compared to women, men had faster mean 1.5mile run and LM times, greater body mass and total FFM and higher SL and WCC scores (p<0.001), however some women outperformed men. CONCLUSION: 1.5mile run time and body mass predict 8mile LM performance with no further improvement gained in the model by including sex as a variable.

Characterizing the acute heat stress response in gilts: I. Thermoregulatory and production variables.

Identifying traits associated with susceptibility or tolerance to heat stress (HS) is a prerequisite for developing strategies to improve efficient pork production during the summer months. Study objectives were to determine the relationship between the thermoregulatory and production responses to acute HS in pigs. Prepubertal gilts (n = 235; 77.9 ± 1.2 kg BW) were exposed to a thermoneutral (TN) period (P1, 24 h; 21.9 ± 0.5 °C, 62 ± 13% RH; fed ad libitum) followed immediately by a subsequent acute HS period (P2, 24 h; 29.7 ± 1.3 °C, 49 ± 8% RH; fed ad libitum). Rectal temperature (TR), skin temperature (TS), and respiration rate (RR) were monitored and BW and feed intake (FI) were determined. All pigs had increased TR, TS, and RR (0.80 °C, 5.65 °C, and 61.2 bpm, respectively; P < 0.01) and decreased FI and BW (29% and 1.10 kg, respectively; P < 0.01) during P2 compared to P1. Interestingly, body temperature indices did not explain variation in FI during P2 (R2 ≤ 0.02). Further, the percent change in BW during P2 was only marginally explained by each body temperature index (R2 ≤ 0.06) or percent change in FI (R2 = 0.14). During HS, TR was strongly correlated with P1 TR (r = 0.72, P < 0.01), indicating a pig's body temperature during TN conditions predicts the severity of hyperthermia during HS. Additionally, the change in TR (ΔTR, HS TR - TN TR) was larger in pigs retrospectively classified as susceptible (SUS) as compared to tolerant (TOL) pigs (1.05 vs. 0.51 °C, respectively; P < 0.01). In summary, thermoregulatory responses and production variables during acute HS are only marginally related. Further, changes in BW and FI were unexpectedly poorly correlated during acute HS (r = 0.34; P < 0.01). Collectively, suboptimal growth is largely independent on the thermoregulatory response and hypophagia during acute HS. Consequently, incorporating solely body temperature indices into a genetic index is likely insufficient for substantial progress in selecting HS tolerant pigs.

Short message service (SMS) texting as a method of communication during on call: prevalence and experience of medical staff in a large acute NHS Trust in the UK.

With the widespread use of smartphones, text messaging has become an accepted form of communication for both social and professional use in medicine. To our knowledge no published studies have assessed the prevalence and use of short message service (SMS) texting by doctors on call. We have used an online questionnaire to seek information from doctors in a large NHS Trust in the UK about their use of texting while on call, what they use it for, and whether they send images relevant to patients' care. We received 302 responses (43% response rate), of whom 166 (55%) used SMS while on call. There was a significant association between SMS and age group (p=0.005), with the 20-30-year-old group using it much more than the other age groups. Doctors in the surgical specialties used it significantly less than those in other speciality groups (p<0 .001). Texting while on call was deemed to be safe and reliable (p<0.001). Eighteen clinicians (11%) admitted to routinely sending images of patients by text, despite some being identifiable. Texting was mainly used to update colleagues on patients' progress and give information about times of ward rounds and meetings. With the increasing use of texting in healthcare, much of which seems to be unregulated, further work and detailed guidance is required on what information may be given to ensure confidentiality and that SMS is a safe and acceptable method of communication to use when on call.

Low serum 25-hydroxyvitamin D is associated with increased risk of stress fracture during Royal Marine recruit training.

UNLABELLED: The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training. Poor vitamin D status was associated with an increased risk of stress fracture. Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status. INTRODUCTION: Stress fracture is a common overuse injury in military recruits, including Royal Marine (RM) training in the UK. RM training is recognised as one of the most arduous basic training programmes in the world. Associations have been reported between serum 25-hydroxyvitamin D (25(OH)D) and risk of stress fracture, but the threshold of 25(OH)D for this effect remains unclear. We aimed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training. METHODS: We prospectively followed 1082 RM recruits (males aged 16-32 years) through the 32-week RM training programme. Troops started training between September and July. Height, body weight and aerobic fitness were assessed at week 1. Venous blood samples were drawn at weeks 1, 15 and 32. Serum samples were analysed for 25(OH)D and parathyroid hormone (PTH). RESULTS: Seventy-eight recruits (7.2 %) suffered a total of 92 stress fractures. Recruits with a baseline serum 25(OH)D concentration below 50 nmol L(-1) had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold (χ(2) (1) = 3.564, p = 0.042; odds ratio 1.6 (95 % confidence interval (CI) 1.0-2.6)). Baseline serum 25(OH)D varied from 47.0 ± 23.7 nmol L(-1) in February, to 97.3 ± 24.6 nmol L(-1) in July (overall mean 69.2 ± 29.2 nmol L(-1), n = 1016). There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 (r = -0.209, p < 0.001) and week 32 (r = -0.214, p < 0.001), but not at baseline. CONCLUSION: Baseline serum 25(OH)D concentration below 50 nmol L(-1) was associated with an increased risk of stress fracture. Further studies into the effects of vitamin D supplementation on stress fracture risk are certainly warranted.

Anesthetic management of super-morbidly obese parturients for cesarean delivery with a double neuraxial catheter technique: a case series.

Parturients with super-morbid obesity, defined as body mass index greater than 50kg/m(2), represent a growing segment of patients who require anesthetic care for labor and delivery. Severe obesity and its comorbid conditions place the parturient and fetus at greater risk for pregnancy complications and cesarean delivery, as well as surgical and anesthetic complications. The surgical approach for cesarean delivery in these patients may require a supra-umbilical vertical midline incision due to a large pannus. The dense T4-level of spinal anesthesia can cause difficulties with ventilation for the obese patient during the procedure, which can be prolonged. Patients also may have respiratory complications in the postoperative period due to pain from the incision. We describe the anesthetic management of three parturients with body mass index ranging from 73 to 95kg/m(2) who had a cesarean delivery via a supra-umbilical vertical midline incision. Continuous lumbar spinal and low thoracic epidural catheters were placed in each patient for intraoperative anesthesia and postoperative analgesia, respectively. Continuous spinal catheters were dosed with incremental bupivacaine boluses to achieve surgical anesthesia. In one case, the patient required respiratory support with non-invasive positive pressure ventilation. Two cases were complicated by intraoperative hemorrhage. All patients had satisfactory postoperative analgesia with a thoracic epidural infusion. None suffered postoperative respiratory complications or postdural puncture headache. The use of a continuous lumbar spinal catheter and a low thoracic epidural provides several advantages in the anesthetic management of super-morbidly obese parturients for cesarean delivery.

Sheehan syndrome: acute presentation with severe headache.

Postpartum headache is a common occurrence with a broad differential diagnosis. Sheehan syndrome, or postpartum pituitary necrosis, is not typically recognized as a cause of postpartum headache. We present a case of Sheehan syndrome that initially presented as severe headache after vaginal delivery complicated by retained placenta and postpartum hemorrhage. The patient was discharged home on postpartum day three but continued to have headaches and returned to hospital on postpartum day six with severe headache, failure to lactate, edema, dizziness, fatigue, nausea and vomiting. Cranial magnetic resonance imaging revealed pituitary infarction consistent with Sheehan syndrome. We discuss the differential diagnosis for postpartum headache, the pathophysiological features of Sheehan syndrome and headache as an atypical acute presentation.

Ion-interactions as driving force in polysaccharide assembly.

The structure of cellulose is characterised by extensive non-covalent interactions. Recent discussions suggest that hydrophobic interactions between polymer chains also play a significant role in governing cellulose solubility. Surprisingly in almost all cellulose shaping processes, chemical systems or solvents are applied, which base on melts or solutions of charged molecules. Ionic interactions play a significant role in the shaping and modification of cellulose based materials. Dependent on the systems used different principles govern the processes and define the results, e.g. formation of associates with alkali hydroxides, ion-exchange reactions to selectively bind multivalent ions at carboxylic groups, adsorption of dissolved polymers through surface charge neutralisation or metal complex formation, where cellulose takes the role of a polymer ligand system. Presence of charged compounds takes a significant role in cellulose swelling and dissolution, but also directs reassembly of polysaccharide material to solid three-dimensional structures.

Distinct lines of chickens express different splenic cytokine profiles in response to Salmonella Enteritidis challenge.

Chicken meat and eggs contaminated with Salmonella result in economic losses in the poultry industry and potential human infection. Intestinal parasites have been shown to lead to a reduction in the utilization of nutrients and performance in poultry. This study provides insight into the immune responses used by hens of 3 genetically distinct chicken lines (broiler, Leghorn, and Fayoumi) in the presence and absence of Salmonella Enteritidis infection. Understanding the range of immune responses used by different lines in response to Salmonella Enteritidis may help the poultry industry genetically select birds that are more pathogen resistant. The splenic mRNA levels of several immune-related genes [IL-6, IL-8, IL-10, IL-18, macrophage inflammatory protein 1ß, interferon (IFN)-γ, transforming growth factor ß1, and regulated upon activation, normal T cell expressed, and secreted (RANTES)] were analyzed by quantitative PCR. Line, challenge, and their interaction were considered fixed effects. Line had a significant effect on the mRNA expression of RANTES (P < 0.02) and IFN-γ (P < 0.03). Broilers expressed significantly more splenic RANTES mRNA than Fayoumis, and significantly more splenic IFN-γ mRNA than Leghorns (P < 0.05). There was a significant interaction of genetic line and challenge on IL-18 (P < 0.02) and IL-6 (P < 0.01) mRNA expression. Although there was a significant interaction of genetic line and challenge for IL-18, Tukey's test analysis only showed differences at a suggestive level (P < 0.1). Bacterial challenge had a significant effect on IL-6 mRNA expression only within the Fayoumi line. Challenged Fayoumis expressed significantly less IL-6 mRNA than nonchallenged Fayoumis (P < 0.05). The observed differences in mRNA expression of selected cytokines support the concept that these distinct genetic lines utilize different immune responses at homeostasis and in response to Salmonella Enteritidis infection.

Can Hyperpolarized Helium MRI add to radiation planning and follow-up in lung cancer?

Locally advanced non-small-cell lung cancer (NSCLC) is a common disease with a low overall survival even with aggressive treatments. Standard imaging (CT and PET/CT) provide no information about normal lung function. We therefore, sought to pilot HeMRI in patients with non-small-cell lung cancer before and after definitive radiotherapy (RT). Five patients with NSCLC receiving RT were enrolled on a prospective IRB approved study. Patients underwent CT, FDG-PET and HeMRI before and (within 10 days) following RT. All images (CT, FDG-PET and HeMRI) were co-registered. The CT and PET GTVs were contoured, as well as the ventilation defects on HeMRI caused by the tumor. Patients also underwent pulmonary function tests (PFTs). Correlations between the images and PFTs were evaluated by linear regression. CT and FDG-PET tumor volumes were highly correlated (r² = 0.91 before treatment and 0.99 following RT). There was less correlation between HeMRI and CT or PET (r² = 0.67 (CT) and 0.38 (PET)) prior to treatment and 0.27 following RT). However, HeMRI volumes correlated very well with FEV1, both prior to and following RT. (r² = 0.89 and 0.83, respectively). ³Helium MRI scanning is feasible in NSCLC before and after treatment. HeMRI provides important functional information in addition to CT and CT/PET scanning.

Efficacy of protracted dose-dense temozolomide in patients with recurrent high-grade glioma.

The current standard therapy for newly diagnosed glioblastoma is multimodal, comprising surgical resection plus radiotherapy and concurrent temozolomide, then adjuvant temozolomide for 6 months. This has been shown to provide survival benefits; however, the prognosis for these patients remains poor, and most relapse. The objective of this prospective Phase II study was to evaluate the efficacy and tolerability of protracted, dose-dense temozolomide therapy (100 mg/m(2) for 21 consecutive days of a 28-day cycle) in patients with recurrent glioblastoma or grade 3 gliomas who had previously received standard therapy. Of the 25 patients included (median age 50 years), 20 were evaluable for radiologic response. Two patients had partial responses and 10 had stable disease (60% overall clinical benefit); 8 patients (40%) progressed after the first treatment cycle. Five patients were not assessed for radiologic response due to early clinical progression but were included in the progression-free survival (PFS) and overall survival (OS) analyses. The median follow-up time was 7 months (range, 1-14 months). The median PFS was 3 months (95% confidence interval, CI, 1.8-4.2) and the median OS was 7 months (95% CI 5.1-8.9). The 6-month PFS rate (primary endpoint) was 17.3% (95% CI 1.7-32.2) and the 1-year OS rate was 12% (95% CI -1-25). This regimen was well tolerated. The most frequent adverse event was lymphopenia (grade 3-4 in 20 patients); no opportunistic infections were reported. Treatment was discontinued due to toxicity in 2 patients (grade 4 hepatic toxicity and thrombocytopenia). These data suggest that protracted, dose-dense temozolomide had modest activity with manageable toxicity in patients with recurrent high-grade glioma previously treated with temozolomide.

Clinical outcome of breast cancer patients with N3a (≥10 positive lymph nodes) disease: has it changed over years?

It has been shown that breast cancer patients with N3a (10 positive lymph nodes) had a poor prognosis. We planned to investigate the clinical outcome BC patients who presented with N3a disease and had no evidence of systemic metastasis at the time of diagnosis. We made a retrospective chart review of breast cancer patients who had ≥10 positive lymph nodes and received adjuvant systemic therapy in Marmara University Hospital between 1998 and 2008. We recorded clinical, pathologic and treatment characteristics of the patients and analyzed the survival outcome. We identified 73 patients with N3a disease who were treated in Marmara University Hospital between 1998 and 2008. The median age was 52. Most (75%) of the patients had invasive ductal histology, 75% had T2/T3 tumors, 36% had grade 3 tumors. The median number of metastatic lymph nodes was 15. Estrogen and progesterone receptors were both positive in 61% and both negative in 16+ tumors. Her-2/neu status was assessed in 68% of the tumors; 18% of patients had 3+ and 50% had negative scores. Six patients had triple negative tumors. All patients except one received adjuvant chemotherapy and radiotherapy. Seventy-four percent of patients received anthracycline/taxane-based chemotherapy. Fifty-nine patients received adjuvant endocrine therapy, 42% them received aromatase inhibitors. Five of the 13 Her-2 positive patients received adjuvant trastuzumab. With a median follow-up of 47 months, 5-year disease and overall survival rates were 66 and 81%, respectively. Twenty-four patients had relapsed and 14 patients died. Her-2 status and the number of lymph nodes (<20 vs. ≥20) had significant impact on disease-free survival in the univariate analysis (P=0.03 and 0.05, respectively) and Her-2 retained its significant impact on disease-free survival in the multivariate analysis (P=0.05). The prognosis of BC patients with N3a disease has changed favorably in the past decade with the current standards of care.

Tumor volume is a prognostic factor in non-small-cell lung cancer treated with chemoradiotherapy.

PURPOSE: To investigate whether primary tumor and nodal volumes defined on radiotherapy planning scans are correlated with outcome (survival and recurrence) after combined-modality treatment. METHODS AND MATERIALS: A retrospective review of patients with Stage III non-small-cell lung cancer treated with chemoradiation at Brigham and Women's Hospital/Dana-Farber Cancer Institute from 2000 to 2006 was performed. Tumor and nodal volume measurements, as computed by Eclipse (Varian, Palo Alto, CA), were used as independent variables, along with existing clinical factors, in univariate and multivariate analyses for association with outcomes. RESULTS: For patients treated with definitive chemoradiotherapy, both nodal volume (hazard ratio [HR], 1.09; p < 0.01) and tumor volume (HR, 1.03; p < 0.01) were associated with overall survival on multivariate analysis. Both nodal volume (HR, 1.10; p < 0.01) and tumor volume (HR, 1.04; p < 0.01) were also associated with local control but not distant metastases. CONCLUSIONS: In addition to traditional surgical staging variables, disease burden, measured by primary tumor and nodal metastases volume, provides information that may be helpful in determining prognosis and identifying groups of patients for which more aggressive local therapy is warranted.

Esophagus in-field: a new predictor for esophagitis.

PURPOSE: To define optimization parameters for limiting esophageal toxicity with concurrent chemoradiation (CRT) for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A retrospective analysis of patients treated with concurrent chemoradiation at the Dana-Farber/Brigham and Women's Hospital Cancer Center was done with IRB approval. All patients were treated with concurrent CRT. All patients underwent 3-D conformal radiotherapy planned with ECLIPSE (Varian, Palo Alto, CA) treatment planning system. Patients had their esophagus contoured in two ways: the entire esophagus (Esoph) and esophagus in-field (Esoph(in)). Together with clinical variables, dose volume metrics including mean dose, V5-V60 of both structures (Esoph and Esoph(in)) were analyzed for correlation with acute esophagitis (≥ grade 3) and late esophageal stricture. The analyses and graphics were completed using R (R Development Core Team, 2006). Logistic regression analysis was used to assess the relationships between dosimetric factors and swallowing complications while controlling for non-dosimetric variables. RESULTS: 109 patients were studied between 2000 and 2006. 25% of patients had grade 3 or greater acute esophagitis. 5/109 (5.5%) had late esophageal stricture with a six-month actuarial risk of stricture of 6.5% (95% CI=1-11%). Mean dose and V45-V60 for both Esoph and Esoph(in) significantly correlated with development of acute esophagitis. V55 and V60 for both Esoph and Esoph(in) significantly correlated with development of stricture. On Multivariate analysis V55 of the Esoph and Esoph(in) was most predictive of toxicity. Limiting the V55 Esoph(in) to 50% was the best cut-point for acute esophagitis. CONCLUSIONS: In the setting of concurrent CRT, V55 of the Esoph or Esoph(in) is the best predictor of acute esophagitis.

Outcomes of patients with stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery.

BACKGROUND: The objective of this study was to identify the factors associated with improved outcome after treatment for stage III nonsmall cell lung cancer (NSCLC). METHODS: A retrospective review of stage III NSCLC patients treated at who were treated at the Dana-Farber Cancer Institute/Brigham and Women's Cancer Center was done with institutional review board approval. Patients were followed for toxicity, local and distant failure, and overall survival. Multivariate Cox logistic regression analysis was used to determine the factors associated with treatment outcome. RESULTS: Between August 2000 and November 2006, 144 patients received concurrent chemoradiation (CRT) for stage III NSCLC. Eighty of 144 patients were men (56%), and the median age was 61 years (range, 33-81 years). Sixty-two patients (43%) had stage IIIA NSCLC, and 82 patients (57%) had stage IIIB NSCLC. Radiotherapy (RT) was given concurrently with chemotherapy to all patients; 100 patients (69%) received CRT without surgery, and 44 patients (31%) received with neoadjuvant CRT followed by surgical resection. The median RT dose was 60 grays (Gy) (range, 46-70 Gy). The median follow-up was 15 months (range, 3-64 months), the median potential follow-up was 37 months (range, 12-84 months), and the median overall survival was 22 months (95% confidence interval, 15-28 months). The 1-year and 2-year survival rates were 68% and 47%, respectively. Among the 44 patients who underwent resection, the median survival was 61 months, and the 2-year survival rate was 73%. On multivariate analysis, stage at the time of treatment (stage IIIA vs stage IIIB) and use of surgery were the only factors associated with improved outcome (P=.01 and P=.001, respectively). CONCLUSIONS: In this retrospective series, those patients who were able to undergo resection appeared to have improved outcome after induction CRT.

Cation currents in human airway epithelial cells induced by infection with influenza A virus.

Influenza A viruses cause lung disease via an incompletely understood mechanism that involves the accumulation of liquid within the lungs. The accumulation of lung liquid is normally prevented by epithelial Na(+) absorption, a transport process regulated via several pathways including phosphoinositide-3-kinase (PI3K). Since the influenza A virus encodes a non-structural protein (NS1) that can activate this kinase, we now explore the effects of NS1 upon the biophysical properties of human airway epithelial cells. Transient expression of NS1 depolarized electrically isolated cells maintained in glucocorticoid-free medium by activating a cation conductance identical to the glucocorticoid-induced conductance seen in single cells. This response involved PI3K-independent and PI3K-dependent mechanisms. Infecting glucocorticoid-deprived cells with influenza A virus disrupted the normal electrical coupling between neighbouring cells, but also activated a conductance identical to that induced by NS1. This response to virus infection was only partially dependent upon NS1-mediated activation of PI3K. The presence of NS1 allows influenza A to modify the biophysical properties of infected cells by activating a Na(+)-permeable conductance. Whilst the activation of Na(+)-permeable channels may be expected to increase the rate of Na(+) absorption and thus reduce the volume of liquid in the lung, liquid does normally accumulate in influenza A-infected lungs. The overall effect of influenza A on lung liquid volume may therefore reflect a balance between the activation and inhibition of Na(+)-permeable channels.