Effects of prophylactic use of sirolimus on bronchiolitis obliterans syndrome development in lung transplant recipients.

BACKGROUND: Sirolimus (SIR) has been shown to stabilize the lung function in lung transplant recipients with bronchiolitis obliterans syndrome (BOS). However, there is no long-term data on the prophylactic use of SIR in lung transplant recipients. This retrospective study examines the effects of SIR in the prevention of BOS. METHODS: From 1999 to 2009, 24 lung transplant recipients whose maintenance immunosuppression regimen consisted of tacrolimus (Tac), mycophenolate mofetil (MMF) or azathioprine (AZA), and prednisone (Pred), were switched to Tac, SIR, and Pred at 1 year after transplantation. From these 24 patients, 5 developed side effects that necessitated the cessation of SIR within 1 year, while 19 patients tolerated long-term use of SIR. The clinical outcomes of these 19 patients (SIR group) were compared with 22 lung transplant recipients whose immunosuppression regimen consisted of Tac, MMF or AZA, and Pred from the time of transplant (MMF group). Survival rates and freedom from BOS were calculated by the Kaplan-Meier method. RESULTS: The SIR group had a lower incidence of BOS and viral infection (p = 0.05), and higher survival rates (p = 0.004). The SIR group had lower levels of Tac and received less Pred. The incidences of acute rejection, carcinoma, hypertension, and diabetes were similar between both groups. CONCLUSIONS: Results from this study suggest that conversion to SIR 1 year after lung transplantation improves survival and decreases the development of BOS. Randomized studies with higher number of patients are needed to determine the prophylactic efficacy of sirolimus in preventing the development of BOS.

Role of magnetic resonance cholangiopancreatography in diagnosing choledochal cysts: Case series and review.

AIM: To determine the merits of magnetic resonance cholangiopancreatography (MRCP) as the primary diagnostic test for choledochal cysts (CC's). METHODS: Between 2009 and 2012, patients who underwent MRCP for perioperative diagnosis were identified. Demographic information, clinical characteristics, and radiographic findings were recorded. MRCP results were compared with intraoperative findings. A PubMed search identified studies published between 1996-2012, employing MRCP as the primary preoperative imaging and comparing results with either endoscopic retrograde cholangiopancreatography (ERCP) or operative findings. Detection rates for CC's and abnormal pancreaticobiliary junction (APBJ) were calculated. In addition detection rates for clinically related biliary pathology like choledocholithiasis and cholangiocarcinomas in patients diagnosed with CC's were also evaluated. RESULTS: Eight patients were identified with CC's. Six patients out of them had type IV CC's, 1 had type I and 1 had a new variant of choledochal cyst with confluent dilatation of the common bile duct (CBD) and cystic duct. Seven patients had an APBJ and 3 of those had a long common-channel. Gallstones were found in 2 patients, 1 had a CBD stone, and 1 pancreatic-duct stone was also detected. In all cases, MRCP successfully identified the type of CC's, as well as APBJ with ductal stones. From analyzing the literature, we found that MRCP has 96%-100% detection rate for CC's. Additionally, we found that the range for sensitivity, specificity, and diagnostic accuracy was 53%-100%, 90%-100% and 56%-100% in diagnosing APBJ. MRCP's detection rate was 100% for choledocholithiasis and 87% for cholangiocarcinomas with concurrent CC's. CONCLUSION: After initial ultrasound and computed tomography scan, MRCP should be the next diagnostic test in both adult and pediatric patients. ERCP should be reserved for patients where therapeutic intervention is needed.

Multifactorial Model and Treatment Approaches of Refractory Hypotension in a Patient Who Took an ACE Inhibitor the Day of Surgery.

In the field of anesthesiology, there is wide debate on discontinuing angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy the day of noncardiac surgery. Although there have been many studies attributing perioperative hypotension to same-day ACEI and ARB use, there are many additional variables that play a role in perioperative hypotension. Additionally, restoring blood pressure in these patients presents a unique challenge to anesthesiologists. A case report is presented in which a patient took her ACEI the day of surgery and developed refractory hypotension during surgery. The evidence of ACEI use on the day of surgery and development of hypotension is reviewed, and additional variables that contributed to this hypotensive episode are discussed. Lastly, current challenges in restoring blood pressure are presented, and a basic model on treatment approaches for refractory hypotension in the setting of perioperative ACEI use is proposed.

Intracardial embryonic delivery of developmental modifiers in utero.

Our knowledge of organ ontogeny is largely based on loss-of-function (knockout) or gain-of-function (transgenesis) approaches. However, developmental modulators such as proteins, mRNAs, microRNAs(miRNAs), small interfering RNAs, and other small molecules may complement the above DNA-modifying technologies in a much more direct way. Unfortunately, their use is often limited by the ability of these compounds to cross the placenta and reach physiologically relevant concentrations when administered systemically to the mother. The design of safe and effective techniques to deliver these compounds into the embryo is therefore an area of great scientific potential. In this article we report a new method for introducing developmental modulators into murine embryos by means of direct injection into the heart. Unlike other reported methods that require surgical exposure of the uterus, our percutaneous ultrasound-guided approach allows for the intracardial injection of mouse embryos as early as embryonic day 10.5 (e10.5) and throughout gestation in a minimally invasive manner that largely preserves embryo viability. This system offers a critical advantage over in vitro settings because the effects of any given treatment can be observed without disturbing the native environment of the developing organ. Procedures are described for the delivery and detection of transducible proteins as well as morpholinos designed to block the expression of specific miRNAs within the living embryo.