Formation of de novo donor-specific antibodies (dn-DSAs) has been associated with longterm immunologic complications after liver transplantation (LT). We hypothesized that human leukocyte antigen (HLA) epitope/eplet mismatch (MM) is a marker of immunogenicity and a risk factor for dn-DSA formation. Sera from 80 LT recipients were prospectively screened for dn-DSA by a Luminex single-antigen test (One Lambda, Inc., Canoga Park, CA) at 1, 2, 3, 6, 12, 18, 24, and 36 months after LT. HLA typing of the recipients and donors was performed using polymerase chain reaction (PCR)-SSP and PCR-SSOP Luminex low-resolution methods (One Lambda, Inc.). The HLAMatchmaker computer algorithm was used for identification of MM eplets at HLA-DRB1 and -DQA1/B1 loci. Luminex single-antigen bead solid phase assay was used for antibody analysis. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus maintenance. There were 27 (34%) patients who developed dn-DSA. There were no episodes of antibody-mediated rejection, and 9 (11%) developed acute cellular rejection (ACR). A positive crossmatch status and a higher number of HLA-A, -B, -DR, and -ABDR MMs were not associated with dn-DSA formation. Patients developing dn-DSA had a significantly higher number of total (38 ± 2.7 versus 28 ± 2.3; P = 0.01) and antibody-verified (AbVer; 14 ± 1.1 versus 10 ± 1; P = 0.015) class II MM eplets. By a multivariate regression analysis, the number of class II MM eplets was strongly associated with risk of class II dn-DSA formation (odds ratio [OR], 1.2; P < 0.01). Patients with ACR had a significantly higher number of total (20.2 ± 1.3 versus 13.9 ± 0.9; P < 0.01) as well as AbVer (10.7 ± 1.1 versus 7.5 ± 0.6; P = 0.03) class I MM eplets. In conclusion, donor-recipient HLA epitope MM is associated with a risk of dn-DSA formation and rejection after LT. However, further studies are required to evaluate the clinical utility of epitope matching in LT.
Background Acute liver rejection (ALR), a significant complication of liver transplantation, burdens patients, healthcare payers, and the healthcare providers due to an increase in morbidity, cost, and resources. Despite clinical resolution, ALR is associated with an increased risk of graft loss. A unique protocol of delayed immunosuppression used in our institute provided a model to characterize metabolomic profiles in human ALR. Material/Methods Twenty liver allograft biopsies obtained 48 hours after liver transplantation in the absence of immunosuppression were studied. Hepatic metabolites were quantitated in these biopsies by liquid chromatography and mass spectroscopy (LC/MS). Metabolite profiles were compared among: 1) biopsies with reperfusion injury but no histological evidence of rejection (n=7), 2) biopsies with histological evidence of moderate or severe rejection (n=5), and 3) biopsies with histological evidence of mild rejection (n=8). Results There were 133 metabolites consistently detected by LC/MS and these were prioritized using variable importance to projection (VIP) analysis, comparing moderate or severe rejection vs. no rejection or mild rejection using partial least squares discriminant statistical analysis (PLS-DA). Twenty metabolites were identified as progressively different. Further PLS-DA using these metabolites identified 3 metabolites (linoleic acid, γ-linolenic acid, and citrulline) which are associated with either cyclooxygenase or nitric oxide synthase functionality. Conclusions Hepatic metabolic aberrancies associated with cyclooxygenase and nitric oxide synthase function occur contemporaneous with ALR. Additional studies are required to better characterize the role of these metabolic pathways to enhance utility of the metabolomics approach in diagnosis and outcomes of ALR.
Introduction and Objectives. In recent years, there has been increasing utilization of single-use ureteroscopes albeit with few studies comparing the performance characteristics between these devices. We compared two commonly utilized single-use ureteroscopes in a porcine model. Methods. A female pig was placed under general anesthesia and positioned supine, and retrograde access to the renal collecting system was obtained. The LithoVue (Boston Scientific) and Uscope (Pusen Medical) were evaluated by three experienced surgeons, and each surgeon started with a new scope. The following parameters were compared between each ureteroscope: time for navigation to upper and lower pole calyces with and without implements (1.9 F basket, 200 μm laser fiber, and 365 μm laser fiber for upper only) in the working channel and subjective evaluations of maneuverability, irrigant flow through the scope, lever force, ergonomics, and scope optics. Results. Navigation to the lower pole calyx was significantly faster with LithoVue compared to Uscope when the working channel was empty (24.3 vs. 49.4 seconds, p<0.01) and with a 200 μm fiber (63.6 vs. 94.4 seconds, p=0.04), but not with the 1.9 F basket. Navigation to the upper pole calyx was similar for all categories except faster with LithoVue containing the 365 μm fiber (67.1 vs. 99.7 seconds, p=0.02). Subjective assessments of scope maneuverability to upper and lower pole calyces when the scope was empty and with implements favored LithoVue in all categories, as did assessments of irrigant flow, illumination, image quality, and field of view. Both scopes had similar scores of lever force and ergonomics. Conclusions. In an in vivo porcine model, the type of single-use ureteroscope employed affected the navigation times and subjective assessments of maneuverability and visualization. In all cases, LithoVue provided either equivalent or superior metrics than Uscope. Further clinical studies are necessary to determine the implications of these findings.
Introduction Surgeries that affirm a person's gender identity can be the ultimate end to the distress associated with the discordance between one's gender identity and sex assigned at birth. Gender-affirming vaginoplasty (GAV) is increasingly being performed as a critical component of gender transition for individuals assigned male at birth transitioning to female. As GAV becomes offered at more centers around the United States (US), it is important to understand and consider surgical outcomes that are unique to this operation without losing sight of the larger context of surgical care in the US. In this vain, it is known that post-surgery prescriptions for opioids are a catalyst for opioid addiction in nearly 1 in 16 surgery patients; furthermore, individuals with gender dysphoria are twice as likely to abuse prescription opioids. Regional anesthetic blocks have been adopted in many urologic surgeries to reduce opioid consumption both during and after surgery. The sacral erector spinae plane block (ESP) is a novel block that can block the S2-S4 pain levels in addition to some of the lumbar plexus with benefits over a neuraxial/epidural block including being a superficial block, no significant motor weakness, reduced risk of epidural hematoma, and less risk of intraoperative hemodynamic lability. Objective We sought to review complications and opioid usage after a novel sacral erector spinae plane block as an adjunct for pain control in the perioperative period in patients undergoing robotic-assisted penile inversion vaginoplasty. Methods We reviewed all charts of patients undergoing robotic-assisted penile inversion vaginoplasty or vulvoplasty at our institution. On the morning of surgery, patients were placed in a prone position and administered midazolam and fentanyl for sedation. Median sacral crests and the erector spinae muscle/plane (ESP) were identified using ultrasound guidance, and 0.2% ropivacaine was injected at the S4 and S2 sacral crest. Results A total of 13 patients received the ESP block. There were no complications either in the immediate post-block period or after surgery related to the block. Mean opioid consumption in the first 24 hours after surgery, 24-48hr, 48-72hr, 72-96hr, and 96-120 hours after surgery were 29.1, 50.9, 46.0, 36.5, and 38.7 oral morphine equivalents (OMEs), respectively. There was a significantly reduced amount of OME consumption in the 24 hours after surgery compared to the 24-48 hour period (p=0.017). Conclusions Sacral erector spinae plane block is a safe and efficacious way to reduce opioid consumption in the postoperative period after gender-affirming robotic-assisted penile inversion vaginoplasty or vulvoplasty. Disclosure No
Purpose of reviewTo review the current literature and guidelines regarding salvage therapy for local and regional recurrence of primary penile cancer. Recent findingsWhile invasive surgical management has not significantly changed, penile sparing treatments (PSTs) may have a promising role in the management of local recurrence. Penile sparing surgeries do appear to have higher rates of recurrence. However, the overall survival rate is comparable to that of partial and total penectomies. Additionally, a combination of therapies may have a more profound effect on management of penile cancer. SummaryClinicians must discuss the role of each type of therapy for penile cancer with their patients, and tailor their management to the extent of disease in each patient. While it is important to discuss the balance between quality of life and rates of relapse, one must also emphasize the rates of overall survival in patients with local recurrence who are treated with PSTs.
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