Lea Rath-Wolfson

The PI3K–NF-κB signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant-induced arthritis

The anti-inflammatory effect of adenosine was previously found to be mediated via activation of the A3 adenosine receptor (A3AR). The aim of the present study was to decipher the molecular mechanism involved with the inhibitory effect of IB-MECA, an A3AR agonist, on adjuvant-induced arthritis.The adjuvant-induced arthritis rats responded to IB-MECA treatment with a decrease in the clinical score and the pathological score of the disease. The response to IB-MECA was neutralized by the antagonist MRS 1220, confirming that the efficacy of the synthetic agonist was A3AR mediated.The A3AR protein expression level was highly expressed in the synovia, in the peripheral blood mononuclear cells and in the drain lymph node (DLN) tissues of adjuvant-induced arthritis rats in comparison with naïve animals. Downregulation of A3AR expression was noted upon treatment with IB-MECA. Analysis of synovia and DLN protein extracts revealed a decreased expression level of PI3K, PKB/Akt, IKK, NF-κB and tumor necrosis factor alpha, known to affect survival and apoptosis of inflammatory cells, whereas the caspase-3 level was upregulated.Taken together, high A3AR expression is found in the synovia, in the immune cells in the DLN and in peripheral blood mononuclear cells. IB-MECA, an orally bioavailable molecule, activates the A3AR, inducing receptor downregulation and the initiation of a molecular mechanism that involves de-regulation of the PI3K–NF-κB signaling pathway. As a result, a potent anti-inflammatory effect manifested in the improvement of the disease clinical score and pathological score occurs. The finding that the A3AR expression level in the peripheral blood mononuclear cells and in the DLN reflects the receptor status in the remote inflammatory site suggests use of the A3AR as a follow-up biomarker.

An improved technique for mitosis counting.

Mitosis counting remains one of the most valuable prognostic indicators in tumor pathology; however, as currently carried out it is time consuming and not reproducible. In this study, 6 different pathologists, using different microscopes, arrived at widely different mitotic counts on the same slide, ranging from 4 to 16. These differences were mainly due to the different field areas of the various microscopes used and the method used for counting and recording. In evaluating the most active 10 HPF, the count ranged from 10 to 19. Instead, when an average of 40 fields was recorded, the range was 4-11. Using the mitosis/volume index, which expresses the number of mitotic figures per mm2 of viable tumor, the counts ranged from 8 to 10, a marked improvement. However, this method is complicated and not “user-friendly.” We suggest a variation of the technique by which a 2 mm2 rectangle is drawn on a cover slip and mounted under the microscope, centered on the most mitotically active area of the tumor. The mitoses in that area are counted (=n) and the percent of viable tumor (=x%) is estimated under low magnification. The number of mitoses per mm2 of viable tumor (cs-MAI) is then calculated according to the formula Cs-MAI=100n/2x. Using this modified method, the range of mitoses counted by the different observers was very narrow (9 to 11), and the time required for the counting was only 5-10 minutes.

Talc Inhalation is a Life-Threatening Condition

A case of rapidly progressive disease and pulmonary hypertension due to chronic cosmetic talc inhalation is presented. Although an uncommon cause of pulmonary hypertension, talc, especially through intravenous administration, should be included in the etiology of parenchymal pulmonary hypertension. In our case talc inhalation was inadvertent, causing fulminant disease leading to the patient’s death. To our knowledge, this is the first case of inadvertent talc inhalation causing death in adult patient.

Removable Sinus Stent for Endoscopic Sinus Surgery: An Animal Trial

Background The goal of endoscopic sinus surgery in chronic sinusitis is to create good drainage of the paranasal sinuses. Metal stents used to prevent lateralization of the middle concha are associated with adverse effects. Objective The aim of this experimental study was to evaluate the feasibility and safety of a newly developed composite removable stent. Methods The composite removable stent was implanted in nine sheep (18 stents) in the ethmoid cavity after performing an ethmoidectomy and was examined for stability, ease of removal, and adverse effects. Histologic findings were compared between implantation and nonimplantation sites at several time points after stent deployment and removal. Results None of the stents migrated or fell out of the nose. After 4 weeks, there was no infection in the nose or around the stents, and there was no damage to the mucosa. An histologic study showed only mild-to-moderate inflammatory cell infiltration relative to control sites, with no damage to the mucosal epithelium and no necrosis at distant sites. At 2 weeks after stent removal, slight-to-moderate fibroplasia was noted in the deep nasal tissue, with slight-to-moderate osteocartilaginous metaplasia and bone remodeling but no necrotic or inflammatory changes in surrounding tissues. At 4 weeks after stent removal, the middle meatus remained open. Conclusion The promising results of the composite removable stent in a sheep model justify further studies in patients undergoing endoscopic sinus surgery for chromic sinusitis.

CD1a-positive dendritic cell density predicts disease-free survival in papillary thyroid carcinoma.

OBJECTIVES Dendritic cells are common in inflammatory processes and in papillary thyroid carcinoma (PTC). Previous studies of the predictive value of S100-positive dendritic cell density for PTC outcome yielded inconsistent results. This study investigated the association of dendritic cell density and PTC recurrence based on CD1a expression. METHODS Representative slides from 56 consecutive specimens of PTC were immunostained with anti-CD1a antibodies, and dendritic cell density was analyzed by disease-free survival. RESULTS Dendritic cells were abundant in the tumoral tissue and sparse in the normal peritumoral tissue. Peritumoral dendritic cell density >1.1 cells/HPF was inversely associated with the risk of recurrence. Similar results were obtained with tumoral dendritic cell density (>12 cells/HPF), although the statistical significance was marginal. CONCLUSIONS High CD1a-positive dendritic cell density is associated with improved disease-free survival in PTC. The specificity of anti-CD1a immunostain for activated dendritic cells may explain the better outcome prediction in this study than in studies using S100 protein.

Modified Doppler-guided laser procedure for the treatment of second- and third-degree hemorrhoids

Background Hemorrhoids are a common anorectal condition with a major medical and socioeconomic impact. Owing to the high incidence of symptomatic hemorrhoids in the adult population together with the risk of complications of traditional surgery, researchers are seeking less invasive methods of hemorrhoidal treatment.The aim of this study was to present our experience with the mini-invasive Doppler guided hemorrhoidal laser procedure (HeLP) in symptomatic 2nd and 3rd degree hemorrhoids with absent or minimal mucosal prolapse. Methods The cohort included 62 patients with symptomatic hemorrhoids who underwent the HeLP at a tertiary medical center in 2014-2016. Data were collected on clinical and perioperative characteristics and outcome. Findings were compared between patients with second- and third-degree hemorrhoids. Results The cohort included 41 male and 21 female patients of mean age 41.5 years. Fifty-one had bleeding and 11 had hemorrhoidal syndrome. Mean operative time was 16.6 ± 3.7 minutes. A total of 8-12 arterial branches were treated. Patients were discharged home within a mean of 91.95 ± 20.48 minutes and allowed to resume normal activities. Compared to patients with second-degree hemorrhoids, patients with third-degree hemorrhoids had a significantly higher rate of recto-anal repair (18.2% vs 0, p < 0.05), intraoperative bleeding (11.3% vs 5%, p < 0.05), and thrombus formation in the hemorrhoids (11.3 % vs 0, p < 0.01). At the six-month follow-up, no complications were reported, and there was significant improvement in symptoms.Using the visual analog scale, no pain was reported by 82.3% of patients at one week after surgery and 95.2% of patients at one month after surgery. Conclusion Patients with hemorrhoids treated with Doppler-guided laser had an excellent outcome in terms of resolution of symptoms and postoperative pain. Only Minor short-term complications were noted. Doppler-guided laser seems to be an effective and painless technique for the treatment of symptomatic second- to third grade hemorrhoids with minimal mucosal prolapse.