Frozen section analysis of sentinel lymph nodes in patients with breast cancer does not impair the probability to detect lymph node metastases

Intra-operative frozen section analysis (FS analysis) of sentinel lymph nodes (SLNs) in patients with breast cancer can prevent a second operation for axillary lymph node dissection. In contrast, loss of tissue during FS analysis may impair the probability to detect lymph node metastases. To determine the effect of tissue loss on the probability of detection of metastases, dimensions and tissue loss resulting from intra-operative frozen section analysis were measured for 21 SLNs. In a mathematical model, the influence of tissue loss on the probability to detect metastases was calculated in relation to SLN size for various pathology protocols: an American, a widely used European, the extensive ‘Milan’ and the Dutch protocol. For median-sized SLN 11 × 8 × 5 mm (length × width × height), FS analysis led to a median loss of 680 μm (13.6%) of the height of the SLN. Irrespective of SLN size or used pathology protocol, the probability of detecting 2 mm metastases remained unchanged or even increased (0–12.8%). Moreover, the probability to detect 0.2 mm metastases increased for the majority of tested combinations of SLN size, tissue loss and used protocol. Only when combining maximum tissue loss and smallest SLN size in the Dutch protocol, or when applying the extensive Milan protocol on a median-sized SLN, the probability to detect 0.2 mm metastases decreased by 2.7% and 14.3%, respectively. Contrary to ‘common knowledge’, doing FS analysis of SLNs does not impair the probability to detect lymph node metastases

The multiplex bead array approach to identifying serum biomarkers associated with breast cancer

Introduction Breast cancer is the most common type of cancer seen in women in western countries. Thus, diagnostic modalities sensitive to early-stage breast cancer are needed. Antibody-based array platforms of a data-driven type, which are expected to facilitate more rapid and sensitive detection of novel biomarkers, have emerged as a direct, rapid means for profiling cancer-specific signatures using small samples. In line with this concept, our group constructed an antibody bead array panel for 35 analytes that were selected during the discovery step. This study was aimed at testing the performance of this 35-plex array panel in profiling signatures specific for primary non-metastatic breast cancer and validating its diagnostic utility in this independent population. Methods Thirty-five analytes were selected from more than 50 markers through screening steps using a serum bank consisting of 4,500 samples from various types of cancer. An antibody-bead array of 35 markers was constructed using the Luminex (TM) bead array platform. A study population consisting of 98 breast cancer patients and 96 normal subjects was analysed using this panel. Multivariate classification algorithms were used to find discriminating biomarkers and validated with another independent population of 90 breast cancer and 79 healthy controls. Results Serum concentrations of epidermal growth factor, soluble CD40-ligand and proapolipoprotein A1 were increased in breast cancer patients. High-molecular-weight-kininogen, apolipoprotein A1, soluble vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, vitamin-D binding protein and vitronectin were decreased in the cancer group. Multivariate classification algorithms distinguished breast cancer patients from the normal population with high accuracy (91.8% with random forest, 91.5% with support vector machine, 87.6% with linear discriminant analysis). Combinatorial markers also detected breast cancer at an early stage with greater sensitivity. Conclusions The current study demonstrated the usefulness of the antibody-bead array approach in finding signatures specific for primary non-metastatic breast cancer and illustrated the potential for early, high sensitivity detection of breast cancer. Further validation is required before array-based technology is used routinely for early detection of breast cancer.Kenny HA, 2008, J CLIN INVEST, V118, P1367, DOI 10.1172/JCI33775Shah FD, 2008, INTEGR CANCER THER, V7, P33, DOI 10.1177/1534735407313883Carlsson A, 2008, EUR J CANCER, V44, P472, DOI 10.1016/j.ejca.2007.11.025Nolen BM, 2008, BREAST CANCER RES, V10, DOI 10.1186/bcr2096Brogren H, 2008, THROMB RES, V122, P271, DOI 10.1016/j.thromres.2008.04.008Varki A, 2007, BLOOD, V110, P1723, DOI 10.1182/blood-2006-10-053736Madsen CD, 2007, J CELL BIOL, V177, P927, DOI 10.1083/jcb.200612058Levenson VV, 2007, BBA-GEN SUBJECTS, V1770, P847, DOI 10.1016/j.bbagen.2007.01.017VAZQUEZMARTIN A, 2007, EUR J CANCER, V43, P1117GARCIA M, 2007, GLOBAL CANC FACTS FIMoore LE, 2006, CANCER EPIDEM BIOMAR, V15, P1641, DOI 10.1158/1055-9965.EPI-05-0980Borrebaeck CAK, 2006, EXPERT OPIN BIOL TH, V6, P833, DOI 10.1517/14712598.6.8.833Zannis VI, 2006, J MOL MED-JMM, V84, P276, DOI 10.1007/s00109-005-0030-4Jemal A, 2006, CA-CANCER J CLIN, V56, P106Silva HC, 2006, NEOPLASMA, V53, P538Chahed K, 2005, INT J ONCOL, V27, P1425Jain KK, 2005, EXPERT OPIN PHARMACO, V6, P1463, DOI 10.1517/14656566.6.9.1463Abe O, 2005, LANCET, V365, P1687Paradis V, 2005, HEPATOLOGY, V41, P40, DOI 10.1002/hep.20505Molina R, 2005, TUMOR BIOL, V26, P281, DOI 10.1159/000089260Furberg AS, 2005, CANCER EPIDEM BIOMAR, V14, P33Benoy IH, 2004, CLIN CANCER RES, V10, P7157Song JS, 2004, BLOOD, V104, P2065, DOI 10.1182/blood-2004-02-0449Schairer C, 2004, J NATL CANCER I, V96, P1311, DOI 10.1093/jnci/djh253Hellman K, 2004, BRIT J CANCER, V91, P319, DOI 10.1038/sj.bjc.6601944Roselli M, 2004, CLIN CANCER RES, V10, P610Zhou AW, 2003, NAT STRUCT BIOL, V10, P541, DOI 10.1038/nsb943Hapke S, 2003, BIOL CHEM, V384, P1073Miller JC, 2003, PROTEOMICS, V3, P56Amirkhosravi A, 2002, BLOOD COAGUL FIBRIN, V13, P505Bonello N, 2002, HUM REPROD, V17, P2272Li JN, 2002, CLIN CHEM, V48, P1296Louhimo J, 2002, ANTICANCER RES, V22, P1759Knezevic V, 2001, PROTEOMICS, V1, P1271Di Micco P, 2001, DIGEST LIVER DIS, V33, P546Ferrigno D, 2001, EUR RESPIR J, V17, P667Webb DJ, 2001, J CELL BIOL, V152, P741Gion M, 2001, EUR J CANCER, V37, P355Schonbeck U, 2001, CELL MOL LIFE SCI, V58, P4Blackwell K, 2000, J CLIN ONCOL, V18, P600Carriero MV, 1999, CANCER RES, V59, P5307Antman K, 1999, JAMA-J AM MED ASSOC, V281, P1470Loskutoff DJ, 1999, APMIS, V107, P54Molina R, 1998, BREAST CANCER RES TR, V51, P109Bajou K, 1998, NAT MED, V4, P923Chan DW, 1997, J CLIN ONCOL, V15, P2322Chu KC, 1996, J NATL CANCER I, V88, P1571vanDalen A, 1996, ANTICANCER RES, V16, P2345Yamamoto N, 1996, CANCER RES, V56, P2827KOCH AE, 1995, NATURE, V376, P517HADDAD JG, 1995, J STEROID BIOCHEM, V53, P579FOEKENS JA, 1994, J CLIN ONCOL, V12, P1648GEARING AJH, 1993, IMMUNOL TODAY, V14, P506HUTCHENS TW, 1993, RAPID COMMUN MASS SP, V7, P576DECLERCK PJ, 1992, J BIOL CHEM, V267, P11693GABRIJELCIC D, 1992, AGENTS ACTIONS S, V38, P350BIEGLMAYER C, 1991, TUMOR BIOL, V12, P138DNISTRIAN AM, 1991, TUMOR BIOL, V12, P82VANDALEN A, 1990, TUMOR BIOL, V11, P189KARAS M, 1988, ANAL CHEM, V60, P2299, DOI 10.1021/ac00171a028LERNER WA, 1983, INT J CANCER, V31, P463WESTGARD JO, 1981, CLIN CHEM, V27, P493TROUSSEAU A, 1865, CLIN MED HOTEL DIEU, V3, P654*R PROJ, R PROJ STAT COMP1

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial loads, haematological and biochemical parameters and histopathological changes following treatment.

Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Mf counts dropped significantly (p0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans

Left ventricular speckle tracking-derived cardiac strain and cardiac twist mechanics in athletes: a systematic review and meta-analysis of controlled studies

Background: The athlete’s heart is associated with physiological remodeling as a consequence of repetitive cardiac loading. The effect of exercise training on left ventricular (LV) cardiac strain and twist mechanics are equivocal, and no meta-analysis has been conducted to date. Objective: The objective of this systematic review and meta-analysis was to review the literature pertaining to the effect of different forms of athletic training on cardiac strain and twist mechanics and determine the influence of traditional and contemporary sporting classifications on cardiac strain and twist mechanics. Methods: We searched PubMed/MEDLINE, Web of Science, and ScienceDirect for controlled studies of aged-matched male participants aged 18–45 years that used two-dimensional (2D) speckle tracking with a defined athlete sporting discipline and a control group not engaged in training programs. Data were extracted independently by two reviewers. Random-effects meta-analyses, subgroup analyses, and meta-regressions were conducted. Results: Our review included 13 studies with 945 participants (controls n = 355; athletes n = 590). Meta-analyses showed no athlete–control differences in LV strain or twist mechanics. However, moderator analyses showed greater LV twist in high-static low-dynamic athletes (d = –0.76, 95% confidence interval [CI] –1.32 to –0.20; p < 0.01) than in controls. Peak untwisting velocity (PUV) was greater in high-static low-dynamic athletes (d = –0.43, 95% CI –0.84 to –0.03; p < 0.05) but less than controls in high-static high-dynamic athletes (d = 0.79, 95% CI 0.002–1.58; p = 0.05). Elite endurance athletes had significantly less twist and apical rotation than controls (d = 0.68, 95% CI 0.19–1.16, p < 0.01; d = 0.64, 95% CI 0.27–1.00, p = 0.001, respectively) but no differences in basal rotation. Meta-regressions showed LV mass index was positively associated with global longitudinal (b = 0.01, 95% CI 0.002–0.02; p < 0.05), whereas systolic blood pressure was negatively associated with PUV (b = –0.06, 95% CI –0.13 to –0.001; p = 0.05). Conclusion: Echocardiographic 2D speckle tracking can identify subtle physiological differences in adaptations to cardiac strain and twist mechanics between athletes and healthy controls. Differences in speckle tracking echocardiography-derived parameters can be identified using suitable sporting categorizations

Open questions in utility theory

Throughout this paper, our main idea is to explore different classical questions arising in Utility Theory, with a particular attention to those that lean on numerical representations of preference orderings. We intend to present a survey of open questions in that discipline, also showing the state-of-art of the corresponding literature.This work is partially supported by the research projects ECO2015-65031-R, MTM2015-63608-P (MINECO/ AEI-FEDER, UE), and TIN2016-77356-P (MINECO/ AEI-FEDER, UE)

Prevalence of Peptostreptococcus micros morphotypes in patients with adult periodontitis

The prevalence of the smooth and rough colonial morphotypes of Peptostreptococcus micros was examined with culture technique in 123 patients with adult periodontitis (age 24-68 years). Of all subgingival samples, 91% contained the smooth morphotype of P. micros. The smooth morphotype constituted a mean percentage of the total anaerobic viable biota of 6.0%, with a range of 0.02-35.7%. Of these samples, 49% contained colonies of the rough morphotype as well, with a mean percentage of the total anaerobic viable biota of 2.3% (range 0.01-16.2%). None of the samples contained only the rough morphotype. The total percentage of P. micros varied from 0.02-35.71% with a mean of 7.2%. No correlation was found between the prevalence of both morphotypes of P. micros and the age of the subjects or with loss of attachment or pocket depth