Biophysical interplay between extracellular matrix remodeling and hypoxia signaling in regulating cancer metastasis.

Mechanical properties of the tumor microenvironment play a critical role in cancer progression by activation of cancer mechano-responses. The biophysical interactions between cancer cells and their dynamic microenvironment are attributed to force-dependent alterations in molecular pathways that trigger the structural reorganization of intracellular organelles and their associated genetic modifications. Recent studies underscore the role of oxygen concentration in cancer metastasis. Suppressed oxygen levels promote the development of invasive phenotypes and aggressive proliferation of cancer cells, accompanied by remodeling of tumor microenvironment encompassing the modulation of physical settings of extracellular matrix. This review summarizes the role of biophysical interactions between cancer cells and their surroundings in determining cancer progression. Biophysical interpretation of the tumor microenvironment and cancer progression could provide further insights into the development of novel biomedical technologies for therapeutic cancer treatment.

Interobserver Reproducibility in Sonographic Measurement of Diameter and Volume of Papillary Thyroid Microcarcinoma.

Background: Active surveillance is recommended as an alternative to immediate surgery for low-risk papillary thyroid microcarcinoma (PTMC), and determining meaningful changes in diameter and volume on ultrasonography (US) is critical. However, interobserver reproducibility of the sonographic measurement of maximum diameter and volume of PTMC has not been well established. We aimed to determine the reproducibility in the measurement of maximum diameter and volume of PTMC on US. Methods: Consecutive patients who underwent US for pathologically proven PTMC between December 2018 and December 2019 were retrospectively reviewed. Two observers independently performed sonographic measurement of each nodule using standardized measurement methods. Each observer measured maximum transverse, anteroposterior, and longitudinal nodule diameters, and using these, nodule volume was calculated using the ellipsoid formula. Interobserver reproducibility in the measurement of the maximum diameter and volume was assessed using percentage reproducibility coefficient (RC). Z-tests of the intraclass correlation coefficients (ICCs) were used to compare the interobserver reproducibility in subgroups defined according to sonographic characteristics, such as the presence of microcalcification, nodule size, and parenchymal heterogeneity. Results: A total of 197 thyroid nodules from 188 patients were included in the study series. The percentage RCs were 71.8% [95% confidence interval, CI 65.4-79.7%] and 23.7% [CI 21.6-26.3%] for volume and maximum diameter measurements, respectively. There were no significant differences noted in the ICC values according to nodule orientation, presence of calcifications, size, or parenchymal heterogeneity. Conclusion: For PTMC, a difference of up to 24% in the maximum diameter and 72% in the volume may be considered to be within measurement error on US. This value may be used to determine the cutoff for defining meaningful change in the maximum diameter and volume for PTMC during active surveillance.

Magnesium Supplementation Shortens Hemodialysis-Associated Prolonged QT.

Hemodialysis affects myocardial depolarization and repolarization notably lengthening the QT interval. Prolonged QT, in turn, has been a reliable surrogate for higher risk of potentially lethal ventricular arrhythmias. We present an adolescent girl with end-stage kidney disease who consistently developed prolonged QT following hemodialysis sessions. Interestingly, her QT intervals were inversely correlated with her serum magnesium levels. Magnesium supplementation appeared to help reduce the QT prolongation after hemodialysis. Our case shows the potential utility of magnesium as a cardioprotective agent in hemodialysis patients. We recommend that patients undergoing hemodialysis receive frequent electrocardiograms and electrolytes monitoring for tailored electrolytes management to reduce the risk of developing potentially lethal cardiac arrhythmias.

Improved prognostic stratification using NCCN- and GELTAMO-international prognostic index in patients with diffuse large B-cell lymphoma.

The National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and GELTAMO (Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea)-IPI were developed to enable better risk prediction of patients with diffuse large B-cell lymphoma (DLBCL). The present study compared the effectiveness of risk prediction between IPI, NCCN-IPI, and GELTAMO-IPI in patients with DLBCL particularly in terms of determining high-risk patients. Among 439 patients who were enrolled to a prospective DLBCL cohort treated with R-CHOP immunochemotherapy, risk groups were classified according to the three IPIs and the prognostic significance of individual IPI factors and IPI models were analyzed and compared. All three IPI effectively separated the analyzed patients into four risk groups according to overall survival (OS). Estimated 5-year OS of patients classified as high-risk according to the IPI was 45.7%, suggesting that the IPI is limited in the selection of patients who are expected to have a poor outcome. In contrast, the 5-year OS of patients stratified as high-risk according to NCCN- and GELTAMO-IPI was 31.4% and 21.9%, respectively. The results indicate that NCCN- and GELTAMO-IPI are better than the IPI in predicting patients with poor prognosis, suggesting the superiority of enhanced, next-generation IPIs for DLBCL.

Highly elevated serum lactate dehydrogenase is associated with central nervous system relapse in patients with diffuse large B-cell lymphoma: Results of a multicenter prospective cohort study.

Central nervous system involvement remains a challenging issue in the treatment of patients with diffuse large B-cell lymphoma. We conducted a prospective cohort study with newly diagnosed diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone to identify incidence and risk factors for central nervous system involvement. Among 595 patients, 279 patients received pre-treatment central nervous system evaluation, and 14 patients had central nervous system involvement at diagnosis (2.3% out of entire patients and 5.0% out of the 279 patients). For those patients, median follow-up duration was 38.2 months and some of them achieved long-term survival. Out of 581 patients who did not have central nervous system involvement at diagnosis, 26 patients underwent secondary central nervous system relapse with a median follow-up of 35 months, and the median time to central nervous system involvement was 10.4 months (range: 3.4-29.2). Serum lactate dehydrogenase > ×3 upper limit of normal range, the Eastern Cooperative Oncology Group performance status ≥ 2, and involvement of sinonasal tract or testis, were independent risk factors for central nervous system relapse in multivariate analysis. Our study suggests that enhanced stratification of serum lactate dehydrogenase according to the National Comprehensive Cancer Network-International Prognostic Index may contribute to better prediction for central nervous system relapse in patients with diffuse large B-cell lymphoma. This trial was registered at clinicaltrials.gov identifier: 01202448.

Endobronchial Primitive Neuroectodermal Tumor With Pneumothorax Ex Vacuo.

We experienced a rare case of an endobronchial primitive neuroectodermal tumor of the left main bronchus. Initially we suspected pneumothorax caused by a collapsed left upper lobe and an air-entrapped lower lobe. After tube thoracostomy, the pneumothorax persisted without air leakage. A tumor was detected at the left main bronchus on computed tomography and bronchoscopy, and diagnosed pathologically as small cell lung cancer. Under the presumed diagnosis of limited-stage small cell lung cancer, we performed a left pneumonectomy. The tumor was eventually identified pathologically as a primitive neuroectodermal tumor. Although adjuvant chemoradiotherapy was not performed, no recurrence was observed.

Gastric Fluid and Heat Stress Response of Listeria monocytogenes Inoculated on Frankfurters Formulated with 10%, 20%, and 30% Fat Content.

This study evaluated the effects of frankfurter fat content on Listeria monocytogenes resistance to heat stress and gastric fluid, and the Caco-2 cell invasion efficiency of the pathogen. A 10-strain mixture of L. monocytogenes was inoculated on frankfurters formulated with 10%, 20%, and 30% fat content (10%: F10, 20%: F20, 30%: F30) and stored at 10℃ for 30 d. The samples were analyzed for L. monocytogenes resistance to heat stress and a simulated gastric fluid challenge. The total bacteria and L. monocytogenes survival rates were measured on tryptic soy agar plus 0.6% yeast extract and Palcam agar, respectively. L. monocytogenes colonies inoculated on F10, F20, and F30 samples were used for a Caco-2 cell invasion assay. In general, no obvious differences were observed between the survival rates of total bacteria and L. monocytogenes grown on different fat contents under heat stress and gastric fluid challenge. However, L. monocytogenes obtained from the F30 samples had a significantly higher Caco-2 cell invasion efficiency than those in the F10 and F20 samples (p<0.05). These results indicate that although high fat content in food may not be related to L. monocytogenes resistance to heat stress and gastric fluid, it may increase the Caco-2 cell invasion efficiency of the pathogen.

Modeling to predict growth/no growth boundaries and kinetic behavior of Salmonella on cutting board surfaces.

This study developed models to predict the growth probabilities and kinetic behavior of Salmonella enterica strains on cutting boards. Polyethylene coupons (3 by 5 cm) were rubbed with pork belly, and pork purge was then sprayed on the coupon surface, followed by inoculation of a five-strain Salmonella mixture onto the surface of the coupons. These coupons were stored at 13 to 35°C for 12 h, and total bacterial and Salmonella cell counts were enumerated on tryptic soy agar and xylose lysine deoxycholate (XLD) agar, respectively, every 2 h, which produced 56 combinations. The combinations that had growth of ≥0.5 log CFU/cm(2) of Salmonella bacteria recovered on XLD agar were given the value 1 (growth), and the combinations that had growth of <0.5 log CFU/cm(2) were assigned the value 0 (no growth). These growth response data from XLD agar were analyzed by logistic regression for producing growth/no growth interfaces of Salmonella bacteria. In addition, a linear model was fitted to the Salmonella cell counts to calculate the growth rate (log CFU per square centimeter per hour) and initial cell count (log CFU per square centimeter), following secondary modeling with the square root model. All of the models developed were validated with observed data, which were not used for model development. Growth of total bacteria and Salmonella cells was observed at 28, 30, 33, and 35°C, but there was no growth detected below 20°C within the time frame investigated. Moreover, various indices indicated that the performance of the developed models was acceptable. The results suggest that the models developed in this study may be useful in predicting the growth/no growth interface and kinetic behavior of Salmonella bacteria on polyethylene cutting boards.

A facile synthesis of highly functionalized 4-arylcoumarins via Kostanecki reactions mediated by DBU.

An efficient synthesis of 4-arylcoumarins has been accomplished via Kostanecki reactions of 2-hydroxybenzophenones with acetic anhydride employing DBU at ambient temperature. Using the same strategy, several 2-acyloxybenzophenone derivatives were readily converted to 3,4-difunctionalized coumarins. This protocol offers a notable improvement in reaction conditions for coumarin synthesis and takes advantage of its synthetic capability, especially for highly functionalized 4-arylcoumarins with structural diversity.

Daily multidisciplinary discharge rounds in a trauma center: a little time, well spent.

BACKGROUND: Patient flow in a trauma center can be improved by multidisciplinary discharge rounds (MDR), but the content and logistics of MDR discussions have not been well quantified for purposes of improvement and adoption. We characterized the discussion content and time spent during MDRs and measured success rates in implementing communicated plans. METHODS: Bedside MDRs in seven patient care units were observed during consecutive working days in a major academic trauma center. PATIENT: Discussions were timed and their content coded. Coding reliability was assessed with kappa statistics. Implementations of communicated plans were assessed during sequential working days. RESULTS: MDRs over 23 days comprising 1,769 patient-discussions were observed. MDRs lasted a median of 34 minutes for a median of 78 patients. Kappa statistics for the discussions were 0.63 to 0.96. Each patient-discussion lasted a median of 13 seconds (range, 2 seconds-233 seconds), and 96% lasted less than a minute. Clinical topics were presented in 71.5%, new complications in 12%, discharge plans in 67%, surgical plans in 19%, and care advancement in 8% of them. Discussions >30 seconds duration were likely to contain exploration of care advancement, systems related, and clinical topics (p < 0.05). Advancement of care exploration correlated moderately with census of the trauma center (r = 0.53, p = 0.01). Ninety-four percent of the communicated plans were implemented with most delays caused by systems factors (82%). CONCLUSIONS: The short duration and goal-focused communication may have made MDRs sustainable. Given the benefits of successful implementation of communicated plans and previously demonstrated improved patient outcomes, time for MDRs is well spent.