Transforming Growth Factor β1 Regulates Tissue Inhibitor of Metalloproteinases—1 Expression in Differentiated Human Articular Chondrocytes

Objective. To investigate the role of interleukin-6 (IL-6) and transforming growth factor β1 (TGF β1) in the regulation of tissue inhibitor of metalloproteinases—1 (TIMP-1) synthesis in human articular chondrocytes. Methods. Articular cartilage was obtained from human knee joints 24 hours after death. Chondrocytes were isolated by collagenase digestion and embedded in low-gelling-temperature agarose. After stimulation by cytokines, total RNA was isolated and analyzed by Northern blotting. TIMP-1 protein levels were determined using a competitive enzyme-linked immunosorbent assay. Results. Human chondrocytes in agarose culture expressed messenger RNA (mRNA) for the IL-6 receptor (gp80) and its signal-transducing subunit gp130. In contrast to the findings in a previous study, IL-6 did not stimulate TIMP-1 expression in these cells, whereas TGF β1 was an important inducer of TIMP-1 mRNA and protein synthesis. Conclusion. Our findings suggest that TGF β1 has a protective effect on the extracellular matrix of human articular chondrocytes.     

Predicting survival in anaplastic astrocytoma patients in a single-center cohort of 108 patients

Purpose

Stereotactic radiation therapy (SRT) and immune checkpoint inhibitors (ICI) may act synergistically to improve treatment outcomes but may also increase the risk of symptomatic radiation necrosis (RN). The objective of this study was to compare outcomes for patients undergoing SRT with and without concurrent ICI.

Methods and materials

Patients treated for BMs with single or multi-fraction SRT were retrospectively reviewed. Concurrent ICI with SRT (SRT-ICI) was defined as administration within 3 months of SRT. Local control (LC), radiation necrosis (RN) risk and distant brain failure (DBF) were estimated by the Kaplan-Meier method and compared between groups using the log-rank test. Wilcoxon rank sum and Chi-square tests were used to compare covariates. Multivariate cox regression analysis (MVA) was performed.

Results

One hundred seventy-nine patients treated with SRT for 385 brain lesions were included; 36 patients with 99 lesions received SRT-ICI. Median follow up was 10.3 months (SRT alone) and 7.7 months (SRT- ICI) (p = 0.08). Lesions treated with SRT-ICI were more commonly squamous histology (17% vs 8%) melanoma (20% vs 2%) or renal cell carcinoma (8% vs 6%), (p < 0.001). Non-small cell lung cancer (NSCLC) compromised 60% of patients receiving ICI (n = 59). Lesions treated with SRT-ICI had significantly improved 1-year local control compared to SRT alone (98 and 89.5%, respectively (p = 0.0078). On subset analysis of NSCLC patients alone, ICI was also associated with improved 1 year local control (100% vs. 90.1%) (p = 0.018). On MVA, only tumor size ≤2 cm was significantly associated with LC (HR 0.38, p = 0.02), whereas the HR for concurrent ICI with SRS was 0.26 (p = 0.08). One year DBF (41% vs. 53%; p = 0.21), OS (58% vs. 56%; p = 0.79) and RN incidence (7% vs. 4%; p = 0.25) were similar for SRT alone versus SRT-ICI, for the population as a whole and those patients with NSCLC.

Conclusion

These results suggest SRT-ICI may improve local control of brain metastases and is not associated with an increased risk of symptomatic radiation necrosis in a cohort of predominantly NSCLC patients. Larger, prospective studies are necessary to validate these findings and better elucidate the impact of SRT-ICI on other disease outcomes.

     

Do they teach what they need to? An analysis of the impact of curriculum mapping on the learning objectives taught in a lecture series in surgery

Abstract

Introduction: Curriculum mapping shows concordances and differences between the intended and the taught curriculum. To our knowledge, no previous studies describe the effects that this mapping has on the curriculum. The aim of the present study is to map the content of a lecture series in surgery to the National Catalogue of Learning Objectives in Surgery and analyze the effects this mapping has on the content of the following lecture series.

Methods: All lecturers in the lecture series were directly observed by a minimum of two reviewers and learning objectives and the level of competence were documented. After the lecture series, the results were visualized within the catalog of learning objectives and were sent to the lecturers. In the following lecture series, learning objectives were documented correspondingly.

Results: In the first lecture series, 47% of the learning objectives were taught. After the mapping, the number of learning objectives that were taught increased to 59% (p?<?0.001). The increase was found in all surgical disciplines and in all levels of competences without any changes in the average duration of the lectures.

Conclusions: The presented method for mapping a curriculum effectively increased the number of taught learning objectives without requiring longer lecture durations.     

Analysis During Sinus Rhythm of Critical Sites in Reentry Circuits of Postinfarction Ventricular Tachycardia

Background: Critical sites within reentry circuits of postinfarction ventricular tachycardia (VT) were identified during sinus rhythm (SR) and VT to determine whether electrogram characteristics during SR may be helpful in identifying successful ablation sites. Methods: In 33 patients (mean age 67 ± 11 yrs) with prior infarction, mapping and radiofrequency (RF) catheter ablation of 57 hemodynamically-tolerated VT's (cycle length 478 ± 96) were performed. The morphologies of electrograms (EGM) at sites of concealed entrainment (CE) were compared during SR and VT. RF energy was delivered at 94 sites (51 successful and 43 unsuccessful ablation sites). Results: During SR, isolated potentials (IP), but not late potentials (LP) recorded via the mapping catheter, were associated with successful ablation. At 29/39 sites with an IP during sinus rhythm, an isolated diastolic potential (IDP) also was present during VT, whereas at 4 sites IP's were present only during SR (p < 0.001). At 11/29 sites where isolated potentials were present during SR and VT, the morphology of the isolated potential during VT and SR was similar; and all but one of these sites were successful ablation sites (p = 0.01). The EGM amplitude during VT correlated with the amplitude during SR (R = 0.9, p < 0.001). An identical pacemap was present during SR at 33/94 sites; this was not associated with successful ablation. Conclusion: SR mapping may be helpful in identifying critical sites of reentry in postinfarction VT. At sites within the reentry circuit, characteristics of sinus rhythm EGM's that are associated with successful ablation include the presence of IP's, but not the presence of LP's.     

Initial findings concerning a sexual knowledge questionnaire

SUMMARY: The authors describe a 69 item sexual knowledge questionnaire that covers the areas: physiology, pregnancy, the sex act, masturbation, contraception, types of sexuality, and venereal disease. There is also a ‘Belief in Myths’ scale. Mean scores for delinquent boys and young mentally handicapped adults are given, with the latter having lower scores. All areas correlate with total score. The handicapped group showed increased sexual knowledge when re-tested after a human relations course. A control group, tested after the same interval, showed only random changes. Further research is suggested.