Composite Hodgkin lymphoma and mantle cell lymphoma: two clonally unrelated tumors

Association of Hodgkin lymphoma and non-Hodgkin lymphoma is rare and, specifically, the combination of Hodgkin lymphoma and mantle cell lymphoma has not been previously described. Here we describe composite mantle cell lymphoma and Hodgkin lymphoma affecting the spleen in one case and the eyelid and cervical lymph nodes in a second. In both, nodules of classical Hodgkin lymphoma were intermixed with diffuse or nodular areas of typical mantle cell lymphoma. Immunohistochemical and molecular analyses confirmed cyclin D1 overexpression secondary to the translocation t(11;14) in the small mantle cell lymphoma component; with CD30, CD15, and EBV expression in the Hodgkin and Reed-Sternberg cells. Finally, clonal analysis of rearranged immunoglobulin genes performed on microdissected Hodgkin and Reed-Sternberg and mantle cell lymphoma cells provided definite evidence of separate clonal origins of the two tumors in the patients. These EBV-positive, clonally unrelated tumors seem to represent true composite neoplasms, in contrast to cases showing merely clonal progression.     

Risk of gastrointestinal bleeding during anticoagulant treatment

Introduction: Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009.

Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB.

Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.     

Development of a multiplex PCR technique for detection and epidemiological typing of salmonella in human clinical samples

We have developed a multiplex PCR assay for Salmonella detection and epidemiological typing. Six sets of primers were designed to detect the major Salmonella serotypes and phage types in Spain. An internal amplification control was designed in order to detect PCR inhibition. The different amplification profiles obtained allowed us to detect Salmonella bacteria and to distinguish the clinically prevalent Salmonella enterica serotypes Enteritidis, Typhimurium and subspecies I serotype 4,5,12:i:-. Using this method, we could detect a specific band for DT104 and U302 phage types in Salmonella serotype Typhimurium. Salmonella enterica serotype Hadar and other C2 serogroup strains showed two specific band profiles. In the validation stage, the assay was reproducible for all serotypes studied, apart from some C2 serogroup strains. When the technique was applied to clinical stool specimens, the prevalent serotypes Enteritidis and Typhimurium were detected with a sensitivity of 93%, specificity of 100%, and efficiency of 98%. Also, a low PCR inhibition rate (8%) was obtained. The overall agreement of the multiplex PCR with conventional culture-based techniques was 95% for Salmonella typing using Cohen's kappa index.     

Inhibition of COX-2 Impairs Colon Cancer Liver Metastasis through Reduced Stromal Cell Reaction

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE₂ secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE₂ secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.     

Self-Formation Assessed by Cumulative Summation Test Does Not Reach Recommended Thresholds for Optical Diagnosis of Colorectal Polyps ≤ 7 mm

Background and Aims

Accurate optical diagnosis of diminutive polyps would allow implementing a resect and discard strategy. We evaluated the learning curve of a single training session followed by self-education in subjects with no endoscopic experience.

Methods

Learning curves were evaluated in 38 subjects employing learning curve–cumulative summation (LC‐CUSUM) tests, with each participant attending one training session regarding narrow band imaging and optical diagnosis and then individually assessing 100 lesions, receiving feedback after each diagnosis. Diagnostic accuracy was subsequently evaluated in 180 patients with lesions?≤?7 mm. Evaluators predicted each polyp’s histology and recommended a surveillance interval. Determinants of accuracy were explored using regression analysis.

Results

According to the LC‐CUSUM curve, 20 evaluators (52.6%) reached diagnostic competence after 57 lesions (IQR 55–76.5). During the diagnostic performance assessment, 11,666 diagnoses and 6840 follow-up recommendations were generated. Considering high confidence diagnoses, accuracy was 81.3% (80.5–82.1%), negative predictive value (NPV) for rectosigmoid adenomas 78.6% (76.4–80.6%), and sensitivity for adenomas 86.6% (85.8–87.4%). Two (5.3%) evaluators reached a?≥?90% accuracy, 3 (7.9%) presented a NPV for rectosigmoid adenomas?≥?90%, and 18 (47.4%) a sensitivity for adenomas?≥?90%. Multivariable logistic regression showed high confidence and size?≥?5 mm as the strongest predictors of accuracy. Fifteen (39.5%) evaluators recommended a correct or reduced follow-up interval in over 90% of subjects.

Conclusions

Self‐formation after a single training session did not allow most evaluators to reach the required accuracy. LC-CUSUM tests did not identify competent evaluators. Despite these results, 86.7% of follow-up intervals would have been corrected or reduced.

     

Anatomical map of the cranial vasculature and sensory ganglia

There is growing evidence of a direct influence of vasculature on the development of neurons in the brain. The development of the cranial vasculature has been well described in zebrafish but its anatomical relationship with the adjacent developing sensory ganglia has not been addressed. Here, by 3D imaging of fluorescently labelled blood vessels and sensory ganglia, we describe for the first time the spatial organization of the cranial vasculature in relation to the cranial ganglia during zebrafish development. We show that from 24 h post‐fertilization (hpf) onwards, the statoacoustic ganglion (SAG) develops in direct contact with two main blood vessels, the primordial hindbrain channel and the lateral dorsal aortae (LDA). At 48 hpf, the LDA is displaced medially, losing direct contact with the SAG. The relationship of the other cranial ganglia with the vasculature is evident for the medial lateral line ganglion and for the vagal ganglia that grow along the primary head sinus (PHS). We also observed that the innervation of the anterior macula runs over the PHS vessel. Our spatiotemporal anatomical map of the cranial ganglia and the head vasculature indicates physical interactions between both systems and suggests a possible functional interaction during development.     

Combined Effects of Citrulline Plus Nitrate-Rich Beetroot Extract Co-Supplementation on Maximal and Endurance-Strength and Aerobic Power in Trained Male Triathletes: A Randomized Double-Blind,Placebo-Controlled Trial

Citrulline (CIT) and nitrate-rich beetroot extract (BR) are ergogenic aids and nitric oxide (NO) precursors. In addition, both supplements seem to have other actions at the level of muscle metabolism that can benefit strength and aerobic power performance. Both supplements have been studied in numerous investigations in isolation. However, scientific evidence combining both supplements is scarce, and to the best of the authors’ knowledge, there is no current study of endurance athletes. Therefore, the main purpose of this study was to determine the effect of 9 weeks of CIT plus BR supplementation on maximal and endurance-strength performance and aerobic power in male triathletes. This study was a randomized double-blind, placebo-controlled trial where participants (n = 32) were randomized into four different groups: placebo group (PLG; n = 8), CIT plus BR group (CIT- BRG; 3 g/kg/day of CIT plus 3 mg/kg/day of nitrates (NO₃⁻); n = 8), CIT group (CITG; 3 g/kg/day; n = 8) and BR group (BRG; 3 mg/kg/day of NO₃⁻; n = 8). Before (T1) and after 9 weeks (T2), four physical condition tests were carried out in order to assess sport performance: the horizontal jump test (HJUMP), handgrip dynamometer test, 1-min abdominal tests (1-MAT) and finally, the Cooper test. Although, no significant interactions (time × supplementation groups) were found for the strength tests (p > 0.05), the CIT- BRG supplementation presented a trend on HJUMP and 1-MAT tests confirmed by significant increase between two study moments in CIT-BRG. Likewise, CIT-BRG presented significant interactions in the aerobic power test confirmed by this group’s improve estimated VO_2max during the study with respect to the other study groups (p = 0.002; η²p = 0.418). In summary, supplementing with 3 g/day of CIT and 2.1 g/day of BR (300 mg/day of NO₃⁻) for 9 weeks could increase maximal and endurance strength. Furthermore, when compared to CIT or BR supplementation alone, this combination improved performance in tests related to aerobic power.