MHC Tetramers Specifically Identify High- and Low-avidity Donor-specific B Cells in Transplantation Tolerance and Rejection.

BACKGROUND: Although donor-specific antibody pre- and posttransplantation is routinely assessed, accurate quantification of memory alloreactive B cells that mediate recall antibody response remains challenging. Major histocompatibility complex (MHC) tetramers have been used to identify alloreactive B cells in mice and humans, but the specificity of this approach has not been rigorously assessed. METHODS: B-cell receptors from MHC tetramer-binding single B cells were expressed as mouse recombinant immunoglobulin G1 (rIgG1) monoclonal antibodies, and the specificity was assessed with a multiplex bead assay. Relative binding avidity of rIgG1 was measured by modified dilution series technique and surface plasmon resonance. Additionally, immunoglobulin heavy chain variable regions of 50 individual B-cell receptors were sequenced to analyze the rate of somatic hypermutation. RESULTS: The multiplex bead assay confirmed that expressed rIgG1 monoclonal antibodies were preferentially bound to bait MHC class II I-E d over control I-A d and I-A b tetramers. Furthermore, the dissociation constant 50 binding avidities of the rIgG1 ranged from 10 mM to 7 nM. The majority of tetramer-binding B cells were low avidity, and ~12.8% to 15.2% from naive and tolerant mice and 30.9% from acute rejecting mice were higher avidity (dissociation constant 50 <1 mM). CONCLUSIONS: Collectively, these studies demonstrate that donor MHC tetramers, under stringent binding conditions with decoy self-MHC tetramers, can specifically identify a broad repertoire of donor-specific B cells under conditions of rejection and tolerance.

A Call to Evaluate Manual Dexterity of Prospective Surgical Trainees.

INTRODUCTION: This study assesses the correlation between academic grades and gross and fine motor skills in prospective surgical trainees. METHODS: Forty-seven General Surgery Residency applicants and 32 medical students with prospective surgical interests were recruited. Manual dexterity (MD) was assessed through six tasks: O'Connor Tweezer Dexterity Test and Minnesota Manual Dexterity Test; Peg Transfer Test Fundamentals of Laparoscopic Surgery (box); Ring and Rail, Thread the Ring and Suture Sponge (da Vinci Surgical Simulator). RESULTS: Medical students with higher academic scores had longer completion times for the peg transfer test (P = 0.013). Individuals who played musical instruments and perceived themselves to have "Excellent" MD and motor coordination (MC) were more likely to score higher on the Thread the Ring test (P = 0.007; P = 0.009 ,respectively). Those who perceived themselves to have "Mediocre" MD and MC performed the worst on the: O'Connor Tweezer Dexterity Test (P = 0.023). CONCLUSIONS: Preliminary data suggest that MD ability correlates with neither high United States Medical Licensing Examination scores nor high academic grades; however, previous experience playing a musical instrument and high self-ratings of MD/MC may be associated with better test performance.

Toward an understanding of allogeneic conflict in pregnancy and transplantation.

Pregnancy is recognized as a spontaneously acquired state of immunological tolerance by the mother to her semi-allogeneic fetus, but it is a major cause of allosensitization in candidates for organ transplantation. This sensitization, assessed by the presence of anti-HLA IgG, contributes to sex disparity in access to transplantation and increases the risk for rejection and graft loss. Understanding this dual tolerance/sensitization conundrum may lead to new strategies for equalizing access to transplantation among sexes and improving transplant outcomes in parous women. Here, we review the clinical evidence that pregnancy results in humoral sensitization and query whether T cell responses are sensitized. Furthermore, we summarize preclinical evidence on the effects of pregnancy on fetus-specific CD4+ conventional, regulatory, and CD8+ T cells, and humoral responses. We end with a discussion on the impact of the divergent effects that pregnancy has upon alloantigen re-encounter in the context of solid organ transplantation, and how these insights point to a therapeutic roadmap for controlling pregnancy-dependent allosensitization.

Comparison of Different Techniques of Pancreatic Stump Management in Robot-Assisted Pancreaticoduodenectomy.

BACKGROUND: Various technical improvements have decreased the morbidity and mortality after pancreaticoduodenectomy. However, postoperative pancreatic fistula (POPF) is the most feared complication, and the ideal technique for pancreatic reconstruction is undetermined. The aim of this study was to identify the risk factors and incidence of POPF with different types of pancreatic stump management after robot-assisted pancreaticoduodenectomy (RAPD). MATERIALS AND METHODS: This study is a retrospective review of consecutive patients who underwent RAPD at the University of Illinois Hospital and Health Sciences System between September 2007 and January 2016. The cohort was divided based on the type of pancreatic stump management: pancreatic duct occlusion with cyanoacrylate glue (CG), pancreaticojejunostomy (PJ), posterior pancreaticogastrostomy (PPG), and transgastric pancreaticogastrostomy (TPG). RESULTS: The cohort included 69 patients: pancreatic duct occlusion with CG (n = 18), PJ (n = 12), PPG (n = 11), and TPG (n = 28). Pancreatic duct diameter < 3 mm and duct occlusion with CG were identified as risk factors for POPF (p < 0.05). The incidence of POPF was lower when TPG and PJ were performed (p < 0.001). CONCLUSIONS: Reconstruction with PJ and TPG had better results compared to pancreatic duct occlusion with CG and PPG. However, TPG was the technique of choice and showed comparable results to PJ.

Reconstruction/Repair of Iatrogenic Biliary Injuries: Is the Robot Offering a New Option? Short Clinical Report.

OBJECTIVE: The aim of this study is to analyze perioperative outcomes of robotic reconstruction of iatrogenic biliary injuries and describe the surgical technique in detail. BACKGROUND: Iatrogenic bile duct injuries (BDIs) continue to be a major concern in open and laparoscopic cholecystectomy. In the past decade, robotic surgery has been applied to many different procedures showing technical advantages, especially in microsurgical fields. Few cases of robotic BDI reconstructions have been described in the literature so far. This is the first clinical series of consecutive patients undergoing robotic BDI reconstructions. METHODS: This study is a single-surgeon retrospective review of a prospectively maintained database including 14 patients who underwent robot-assisted biliary reconstruction due to iatrogenic BDIs. RESULTS: In all, 14 patients underwent robot-assisted BDI reconstructions. The mean operative time, blood loss, and length of hospitalization were 280.6 min (SD = 132.0), 135.0 mL (SD = 169.7), and 8.4 days (SD = 6.7), respectively. The conversion rate to open surgery was 0%. Long-term follow-up was available in 85.7% (12 out of 14 patients) with a mean follow-up of 36.1 months (SD = 28.1). The >30-day complication rate was 14.3% (n = 2). These 2 patients presented with recurrent episodes of cholangitis due to hepatico-jejunostomy mild stenosis, which were successfully treated with transhepatic percutaneous biliary drainage and multiple dilatations. CONCLUSIONS: Robot-assisted BDI reconstruction is feasible, safe, and may represent an interesting option in expert hands. It maintains all the benefits of minimally invasive surgery and seems to have technical advantages in fine dissection and microsuturing in the liver hilum (magnified microsuturing). In this series, 14 patients with major BDIs were repaired with the robotic approach, with conversion and reoperation rates of 0%. Long-term outcome evaluation requires a longer follow up and larger series, but the initial results are promising.

Primary Pulmonary Vein Leiomyosarcoma With Left Atrial Extension.

Leiomyosarcoma (LMS) is a mesenchymal tumor originating from the smooth muscle cells. LMS of the great vessels accounts for 60% of cases, with inferior vena cava being the most common site. Pulmonary vein LMS is an extremely rare subset that was first reported in 1939. LMS is an aggressive tumor, making surgical resection the treatment of choice. Herein, we present a rare case of pulmonary vein LMS extending into the left atrium, which was resected.

Left Atrial and Carotid Body Paraganglioma.

We report a rare case of left atrial paraganglioma with a synchronous carotid body paraganglioma in a 30-year-old man with succinate dehydrogenase B gene mutation. The patient initially presented with a neck mass and palpitations. Laboratory test results showed elevated catecholamine levels. A cardiac paraganglioma was identified by computed tomography, meta-iodobenzylguanidine scintigraphy, and magnetic resonance imaging. Surgical resection of both paragangliomas were performed on two separate occasions. Serum and urine catecholamine levels returned to normal range. On follow-up, there was no recurrence of the cardiac paraganglioma. Radiotherapy was subsequently initiated for recurrence in the carotid body paraganglioma.

Surgical Correction of Aberrant Right Coronary Anomalies Stranding an Aortic Commissure with and Without Unroofing.

The technique for successful surgical correction of an anomalous origin of the right coronary artery from the opposite aortic cusp with an aberrant course between the aorta and pulmonary artery is illustrated in a symptomatic 62-year-old woman. The intramural course of the right coronary artery traversed the tip of the commissure between the anterior and posterior leaflets, and its repair entailed unroofing of the intramural segment from inside the aortic intima. This technique required resuspension of the overlying commissure to maintain optimal aortic valve leaflet coaptation and prevent aortic insufficiency. Modifications of this technique have been utilized by us whenever the intramural segment traversed behind the commissure. In these cases, partial or subtotal unroofing of the intramural segment was performed to preserve the integrity of the intima behind the overlying commissure. More recently, we have performed the surgical correction by probing the intramural segment within the aortic wall to its most anterior location and then performing a wide anterior unroofing in the aortic intima, and marsupializing the aortic and coronary intima to avoid dissection or intimal flap development. We favor utilizing these techniques of anatomic correction of the anomalous coronary to other techniques involving coronary artery bypass grafting of the anomalous coronary, especially in adult patients, as unroofing provides more lasting results.