Rambam Health Care Campus

About: Rambam Health Care Campus is a healthcare organization based out in Haifa, Israel. It is known for research contribution in the topics: Population & Cancer. The organization has 2498 authors who have published 3715 publications receiving 104362 citations. The organization is also known as: Rambam Hospital & Bet ha-ḥolim ha-memshalti Rambam.

CPM Test-Retest Reliability: "Standard" vs "Single Test-Stimulus" Protocols.

Abstract: Objectives. Assessment of pain inhibitory mechanisms using conditioned pain modulation (CPM) is relevant clinically in prediction of pain and analgesic efficacy. Our objective is to provide necessary estimates of intersession CPM reliability, to enable transformation of the CPM paradigm into a clinical tool. Design. Two cohorts of young healthy subjects (N = 65) participated in two dual-session studies. In Study I, a Bath-Thermode CPM protocol was used, with hot water immersion and contact heat as conditioning- and test-stimuli, respectively, in a classical parallel CPM design introducing test-stimulus first, and then the conditioning- and repeated test-stimuli in parallel. Study II consisted of two CPM protocols: 1) Two-Thermodes, one for each of the stimuli, in the same parallel design as above, and 2) single test-stimulus (STS) protocol with a single administration of a contact heat test-stimulus, partially overlapped in time by a remote shorter contact heat as conditioning stimulus. Test–retest reliability was assessed within 3–7 days. Results. The STS-CPM had superior reliability intraclass correlation (ICC2 , 1 = 0.59) over Bath-Thermode (ICC2 , 1 = 0.34) or Two-Thermodes (ICC2 , 1 = 0.21) protocols. The hand immersion conditioning pain had higher reliability than thermode pain (ICC2 , 1 = 0.76 vs ICC2 , 1 = 0.16). Conditioned test-stimulus pain scores were of good (ICC2 , 1 = 0.62) or fair (ICC2 , 1 = 0.43) reliability for the Bath-Thermode and the STS, respectively, but not for the Two-Thermodes protocol (ICC2 , 1 = 0.20). Conclusions. The newly developed STS-CPM paradigm was more reliable than other CPM protocols tested here, and should be further investigated for its clinical relevance. It appears that large contact size of the conditioning-stimulus and use of single rather than dual test-stimulus pain contribute to augmentation of CPM reliability.

Heparanase promotes glioma progression via enhancing CD24 expression

Abstract: Heparanase is an endo-β-d-glucuronidase that cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans. Compelling evidence tie heparanase levels with all steps of tumor formation including tumor initiation, growth, metastasis and chemo-resistance, likely involving augmentation of signaling pathways and gene transcription. In order to reveal the molecular mechanism(s) underlying the protumorigenic properties of heparanase, we established an inducible (Tet-on) system in U87 human glioma cells and applied gene array methodology in order to identify genes associated with heparanase induction. We found that CD24, a mucin-like cell adhesion protein, is consistently upregulated by heparanase and by heparanase splice variant devoid of enzymatic activity, whereas heparanase gene silencing was associated with decreased CD24 expression. This finding was further substantiated by a similar pattern of heparanase and CD24 immunostaining in glioma patients (Pearson's correlation; R = 0.66, p = 0.00001). Noteworthy, overexpression of CD24 stimulated glioma cell migration, invasion, colony formation in soft agar and tumor growth in mice suggesting that CD24 functions promote tumor growth. Likewise, anti-CD24 neutralizing monoclonal antibody attenuated glioma tumor growth, and a similar inhibition was observed in mice treated with a neutralizing mAb directed against L1 cell adhesion molecule (L1CAM), a ligand for CD24. Importantly, significant shorter patient survival was found in heparanase-high/CD24-high tumors vs. heparanase-high/CD24-low tumors for both high-grade and low-grade glioma (p = 0.02). Our results thus uncover a novel heparanase-CD24-L1CAM axis that plays a significant role in glioma tumorigenesis.

Metabolic PET/CT-Guided Lung Lesion Biopsies: Impact on Diagnostic Accuracy and Rate of Sampling Error

Abstract: CT-guided fine-needle aspiration (FNA) of lung lesions is subject to sampling errors. The current study assessed whether information provided by 18F-FDG PET/CT will decrease the false-negative (FN) rate and thus improve the accuracy of CT-guided FNA. Methods: Data from 311 consecutive patients with lung nodules who underwent 18F-FDG PET/CT and CT-guided FNA within an interval of less than 30 d were retrospectively assessed. In-house–developed software was used to register CT images performed for the FNA procedure (CT FNA) with corresponding slices of the PET/CT study. The quality of registration was rated on a scale of 1 (excellent) to 5 (misregistration). Only cases scored 1 or 2 were further evaluated. The software provided the highest standardized uptake value (SUV) within the lesion and at the location of the tip of the aspirating needle. The distance between the tip and the area with the highest SUV within the lesion was measured. The mean distance from the tip of the needle to the focus with the highest SUV, as well as the mean difference between the maximum SUV in the whole lesion and at the needle tip, was calculated and compared for cases with true-positive (TP) and FN FNA results. Anatomic and metabolic parameters of lesions included in these 2 groups were also compared. Results: There were 267 patients (86%) with score 1 or 2 registration quality for CT FNA and PET/CT/CT images, including 179 TP (67%), 5 false-positive (FP, 2%), 49 true-negative (TN, 18%), and 34 FN (13%) FNA results. The distance between the location of the needle tip and the focus with the highest SUV in the lesion was significantly greater in the FN group (15.4 ± 14 mm) than in the TP group (5.9 ± 13.4 mm, P