Lankenau Medical Center

About: Lankenau Medical Center is a healthcare organization based out in Philadelphia, Pennsylvania, United States. It is known for research contribution in the topics: Atrial fibrillation & Medicine. The organization has 436 authors who have published 414 publications receiving 7095 citations. The organization is also known as: Lankenau Hospital.

Intestinal barrier tightening by a cell-penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis

Abstract: Patients afflicted with ulcerative colitis (UC) are at increased risk of colorectal cancer. While its causes are not fully understood, UC is associated with defects in colonic epithelial barriers that sustain inflammation of the colon mucosa caused by recruitment of lymphocytes and neutrophils into the lamina propria. Based on genetic evidence that attenuation of the bridging integrator 1 (Bin1) gene can limit UC pathogenicity in animals, we have explored Bin1 targeting as a therapeutic option. Early feasibility studies in the dextran sodium sulfate mouse model of experimental colitis showed that administration of a cell-penetrating Bin1 monoclonal antibody (Bin1 mAb 99D) could prevent lesion formation in the colon mucosa in part by preventing rupture of lymphoid follicles. In vivo administration of Bin1 mAb altered tight junction protein expression and cecal barrier function. Strikingly, electrophysiology studies in organ cultures showed that Bin1 mAb could elevate resistance and lower 14 C-mannitol leakage across the cecal mucosa, consistent with a direct strengthening of colonic barrier function. Transcriptomic analyses of colitis tissues highlighted altered expression of genes involved in circadian rhythm, lipid metabolism, and inflammation, with a correction of the alterations by Bin1 mAb treatment to patterns characteristic of normal tissues. Overall, our results suggest that Bin1 mAb protects against UC by directly improving colonic epithelial barrier function to limit gene expression and cytokine programs associated with colonic inflammation.

What's a mother to do?

Abstract: In the course of things, clinical trial data, no matter how impressive, are not always able to bring the practitioner to an informed patient-care decision. This is not a revelation to the experienced clinician. We know that all of the things that happen in practice cannot be accounted for within a circumscribed clinical trial. The situation is more complex when a new treatment hits the market. Here, clinical experience is sparse as well, making rational treatment decisions even more difficult. We expect that this problem will be particularly intense with the advent of the new anticoagulants.1 So many kinds of physicians treat so many types of patients and conditions that there are going to be wide gaps between what we know and what we are expected to do. We can take some solace from the fact that contemporary studies register thousands of patients, but the fact is that there are fairly rigid enrollment criteria that homogenize the populations more than trialists and sponsors suspect or care to admit. Thus, when a new drug is released, initial unbridled enthusiasm is followed by sobering disappointment. Harken backs to Osler’s famous reminder, to “use the new drugs now, while they still work.” What is a clinician to do in such a circumstance? The choices are to remain steadfast in the use of old therapies until the question has been addressed in trials or there has been vast clinical experience, or to take a deep breath and jump in. Most of us pursue an intermediate approach of using the new agent selectively for a new indication, taking into account the risks of remaining overly conservative versus being too adventuresome. In the realm of anticoagulation where the stakes are high, most of us tilt toward being circumspect. For example, it seems foolhardy to assume that a new direct thrombin inhibitor would protect patients with prosthetic heart valves when we know that a miscalculation would have grave consequences for the patient. In this issue of the Journal of Cardiovascular Electrophysiology, Winkle et al. relate their clinical experience with dabigatran in patients who had an atrial fibrillation (AF) catheter ablation procedure.2 The investigators are to be applauded

A stratified phase I dose escalation trial of hypofractionated radiotherapy followed by ipilimumab in metastatic melanoma: long-term follow-up and final outcomes

Abstract: We conducted a phase I dose-escalation trial of radiation with ipilimumab in patients with melanoma with ≥2 metastatic lesions. Here, we report the final full clinical analysis. Patients received R...