Ustekinumab and Vedolizumab Dual Biologic Therapy in the Treatment of Crohn's Disease.

We present a case of refractory ileocolonic Crohn's disease in a 27-year-old female treated with dual ustekinumab and vedolizumab biologic therapy. She had mucosal healing for the first time in 13 years after a 10-month treatment of ustekinumab overlapped with 6 months of vedolizumab. No side effects were observed during the 6 months of dual biologic therapy. Short-term dual biologic therapy may be considered as a treatment option for induction of remission in refractory cases of Crohn's disease.

Hemothorax due to Ruptured Mycotic Aneurysm of Intercostal Arteries Associated with Infective Endocarditis.

We present a case of hemothorax due to ruptured mycotic aneurysm in three intercostal arteries in a 40-year-old male with methicillin-resistant Staphylococcus aureus infective endocarditis (IE) due to intravenous drug use. Microcoil embolization and thoracotomy successfully achieved hemostasis. Mycotic aneurysm is a rare complication of IE and is usually found in the intracranial vessels. Ruptured mycotic aneurysm in the intercostal arteries can be associated with IE and can present as acute hemothorax.

Canadian ophthalmic microsurgery course: an innovative spin on wet lab-based surgical education.

Wet lab and surgical simulation can reduce the learning curve of difficult surgical techniques, accelerate the rate for trainees to achieve surgical competency, and improve patient safety. To provide the most up-to-date information and hands-on experiences with novel ophthalmic surgical techniques and instruments, the Department of Ophthalmology at Western University has created a wet lab-based, multilevel microsurgery skills transfer course through collaboration with various industry partners. Several elements in the course goal and design differentiate this type of surgical course from typical wet labs: the format is multileveled surgical training, with a beginner level targeting undergraduate medical students, an intermediate level for ophthalmology residents, and an advanced level for trained ophthalmologist. In addition, the level of industry participation allows the development of true partnership and offers a method to introduce awareness and innovation in a cost-effective manner. This article presents the organization, course setup, and feedback from the pilot course.

Macula Densa Nitric Oxide Synthase 1ß Protects against Salt-Sensitive Hypertension.

Nitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses α-, ß-, and γ-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1ß expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1ß expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1ß mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1α in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1α-knockout (NOS1αKO) mice. Compared with control mice, mice with macula densa-specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (P<0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (P<0.01) fed a high-salt diet. These results indicate that NOS1ß is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP.

Testosterone enhances tubuloglomerular feedback by increasing superoxide production in the macula densa.

Males have higher prevalence of hypertension and renal injury than females, which may be attributed in part to androgen-mediated effects on renal hemodynamics. Tubuloglomerular feedback (TGF) is an important mechanism in control of renal microcirculation. The present study examines the role of testosterone in the regulation of TGF responses. TGF was measured by micropuncture (change of stop-flow pressure, ΔPsf) in castrated Sprague-Dawley rats. The addition of testosterone (10(-7) mol/l) into the lumen increased the ΔPsf from 10.1 ± 1.2 to 12.2 ± 1.2 mmHg. To determine whether androgen receptors (AR) are involved, mRNA of AR was measured in the macula dense cells isolated by laser capture microdissection from kidneys, and a macula densa-like cell line (MMDD1). AR mRNA was expressed in the macula densa of rats and in MMDD1 cells. We next examined the effects of the AR blocker, flutamide (10(-5) mol/l) on the TGF response. The addition of flutamide blocked the effects of testosterone on TGF. The addition of Tempol (10(-4) mol/l) or polyethylene glycol-superoxide dismutase (100 U/ml) to scavenge superoxide blocked the effect of testosterone to augment TGF. We then applied apocynin to inhibit NAD(P)H oxidase and oxypurinol to inhibit xanthine oxidase and found the testosterone-induced augmentation of TGF was blocked. In additional experiments in MMDD1 cells, we found that testosterone increased O2(-) generation. Apocynin or oxypurinol blocked the testosterone-induced increases of O2(-), while blockade of COX-2 with NS-398 had no effect. These findings suggest that testosterone enhances TGF response by stimulating O2(-) production in macula densa via an AR-dependent pathway.