Portable Optical Fiber Probe-Based Spectroscopic Scanner for Rapid Cancer Diagnosis: A New Tool for Intraoperative Margin Assessment

There continues to be a significant clinical need for rapid and reliable intraoperative margin assessment during cancer surgery. Here we describe a portable, quantitative, optical fiber probe-based, spectroscopic tissue scanner designed for intraoperative diagnostic imaging of surgical margins, which we tested in a proof of concept study in human tissue for breast cancer diagnosis. The tissue scanner combines both diffuse reflectance spectroscopy (DRS) and intrinsic fluorescence spectroscopy (IFS), and has hyperspectral imaging capability, acquiring full DRS and IFS spectra for each scanned image pixel. Modeling of the DRS and IFS spectra yields quantitative parameters that reflect the metabolic, biochemical and morphological state of tissue, which are translated into disease diagnosis. The tissue scanner has high spatial resolution (0.25 mm) over a wide field of view (10 cm×10 cm), and both high spectral resolution (2 nm) and high spectral contrast, readily distinguishing tissues with widely varying optical properties (bone, skeletal muscle, fat and connective tissue). Tissue-simulating phantom experiments confirm that the tissue scanner can quantitatively measure spectral parameters, such as hemoglobin concentration, in a physiologically relevant range with a high degree of accuracy (<5% error). Finally, studies using human breast tissues showed that the tissue scanner can detect small foci of breast cancer in a background of normal breast tissue. This tissue scanner is simpler in design, images a larger field of view at higher resolution and provides a more physically meaningful tissue diagnosis than other spectroscopic imaging systems currently reported in literatures. We believe this spectroscopic tissue scanner can provide real-time, comprehensive diagnostic imaging of surgical margins in excised tissues, overcoming the sampling limitation in current histopathology margin assessment. As such it is a significant step in the development of a platform technology for intraoperative management of cancer, a clinical problem that has been inadequately addressed to date.Case Comprehensive Cancer Center. Tissue Procurement, Histology and Immunohistochemistry Core Facility (P30 CA43703)National Cancer Institute (U.S.) (R01-CA140288)National Cancer Institute (U.S.) (R01-CA97966)National Center for Research Resources (U.S.) (S10-RR031845)National Center for Research Resources (U.S.) (P41-RR02594

Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.</p> <p>Material</p> <p>Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).</p> <p>Treatment</p> <p>Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m²: 56 pts (standard).</p> <p>Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m²d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.</p> <p>Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.</p> <p>Results</p> <p>The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.</p> <p>At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.</p> <p>Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.</p> <p>Conclusion</p> <p>In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.</p

The role of host genetic factors in respiratory tract infectious diseases:systematic review, meta-analyses and field synopsis

Host genetic factors have frequently been implicated in respiratory infectious diseases, often with inconsistent results in replication studies. We identified 386 studies from the total of 24,823 studies identified in a systematic search of four bibliographic databases. We performed meta-analyses of studies on tuberculosis, influenza, respiratory syncytial virus, SARS-Coronavirus and pneumonia. One single-nucleotide polymorphism from IL4 gene was significant for pooled respiratory infections (rs2070874; 1.66 [1.29-2.14]). We also detected an association of TLR2 gene with tuberculosis (rs5743708; 3.19 [2.03-5.02]). Subset analyses identified CCL2 as an additional risk factor for tuberculosis (rs1024611; OR = 0.79 [0.72-0.88]). The IL4-TLR2-CCL2 axis could be a highly interesting target for translation towards clinical use. However, this conclusion is based on low credibility of evidence - almost 95% of all identified studies had strong risk of bias or confounding. Future studies must build upon larger-scale collaborations, but also strictly adhere to the highest evidence-based principles in study design, in order to reduce research waste and provide clinically translatable evidenc

International Society of Sports Nutrition Position Stand: Nutritional recommendations for single-stage ultra-marathon; training and racing

Background. In this Position Statement, the International Society of Sports Nutrition (ISSN) provides an objective and critical review of the literature pertinent to nutritional considerations for training and racing in single-stage ultra-marathon. Recommendations for Training. i) Ultra-marathon runners should aim to meet the caloric demands of training by following an individualized and periodized strategy, comprising a varied, food-first approach; ii) Athletes should plan and implement their nutrition strategy with sufficient time to permit adaptations that enhance fat oxidative capacity; iii) The evidence overwhelmingly supports the inclusion of a moderate-to-high carbohydrate diet (i.e., ~60% of energy intake, 5 – 8 g⸱kg−1·d−1) to mitigate the negative effects of chronic, training-induced glycogen depletion; iv) Limiting carbohydrate intake before selected low-intensity sessions, and/or moderating daily carbohydrate intake, may enhance mitochondrial function and fat oxidative capacity. Nevertheless, this approach may compromise performance during high-intensity efforts; v) Protein intakes of ~1.6 g·kg−1·d−1 are necessary to maintain lean mass and support recovery from training, but amounts up to 2.5 g⸱kg−1·d−1 may be warranted during demanding training when calorie requirements are greater; Recommendations for Racing. vi) To attenuate caloric deficits, runners should aim to consume 150 - 400 kcal⸱h−1 (carbohydrate, 30 – 50 g⸱h−1; protein, 5 – 10 g⸱h−1) from a variety of calorie-dense foods. Consideration must be given to food palatability, individual tolerance, and the increased preference for savory foods in longer races; vii) Fluid volumes of 450 – 750 mL⸱h−1 (~150 – 250 mL every 20 min) are recommended during racing. To minimize the likelihood of hyponatraemia, electrolytes (mainly sodium) may be needed in concentrations greater than that provided by most commercial products (i.e., >575 mg·L−1 sodium). Fluid and electrolyte requirements will be elevated when running in hot and/or humid conditions; viii) Evidence supports progressive gut-training and/or low-FODMAP diets (fermentable oligosaccharide, disaccharide, monosaccharide and polyol) to alleviate symptoms of gastrointestinal distress during racing; ix) The evidence in support of ketogenic diets and/or ketone esters to improve ultra-marathon performance is lacking, with further research warranted; x) Evidence supports the strategic use of caffeine to sustain performance in the latter stages of racing, particularly when sleep deprivation may compromise athlete safety