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Endometriosis associated with episiotomy surgical mark: an instance report.
BACKGROUND Late antibody-mediated rejection (AMR) is a major cause of transplant failure. Potential therapeutic targets are plasma cells (PC) and/or natural killer (NK) cells, both expressing high levels of CD38. METHODS Here, we report the use of CD38 monoclonal antibody daratumumab (9-month course) in a kidney allograft recipient diagnosed with smoldering myeloma and anti-HLA class II donor-specific antibody (DSA)-positive chronic active AMR 13 years after transplantation. Patient monitoring included serial HLA single antigen testing, peripheral blood immune cell phenotyping, as well as follow-up allograft and bone marrow biopsies at 3 and 9 months, including analyses of rejection-related gene expression patterns. RESULTS Daratumumab led to persistent CD138 cell depletion in the bone marrow and blood, and substantially decreased NK cells counts in blood and graft tissue. At the same time, DSA in serum disappeared, and in vitro alloantibody production by CD138 cells enriched from bone marrow aspirates was abrogated. A 3-month follow-up biopsy revealed a complete resolution of microcirculation inflammation (g+ptc 3 to 0) and molecular AMR activity (AMR score 0.79 to less then 0.2). The same biopsy showed (subclinical) tubulo-interstitial inflammation, which prompted steroid treatment. Over an observation period of 12 months, graft function stabilized. CONCLUSIONS Targeting CD38 for PC and NK cell depletion may be an effective strategy to counteract AMR. Our results may encourage the design of future trials to clarify the role of this innovative treatment concept in organ transplantation.BACKGROUND Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remain unknown. METHODS We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to SRTR for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences, and to identify any center-level characteristics associated with improved post-ILDKT outcomes. https://www.selleckchem.com/products/Irinotecan-cpt-11.html RESULTS After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (p less then 0.01) and 4.4% of the differences in graft loss (p less then 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSION Unlike most aspects of transplantation where center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.BACKGROUND The use of elderly donors (≥60 years) in living-donor liver transplantation (LDLT) remains controversial. In this study, we aimed to determine the safety of surgery for elderly donors and the impact of donor age on LDLT outcomes. METHODS We retrospectively reviewed 470 cases of LDLT at Kumamoto University Hospital from December 1998 to March 2017. RESULTS Donors were divided into 5 groups according to age 20-29 (n=109), 30-39 (n=157), 40-49 (n = 87), 50-59 (n = 81), and ≥60 (n = 36). At our institution, elderly donor candidates required additional preoperative work-up. There were no significant differences in the incidence of postoperative complications and duration of postoperative hospital stay among the 5 donor groups. Regardless of graft type, elderly donors were comparable to younger donor groups ( less then 30 years) in postoperative recovery of liver function. Risk-adjusted overall survival rates of recipients among donor groups were not significantly different. Additionally, donor age was not significantly associated with 6-month graft survival of adult and pediatric recipients. CONCLUSIONS Elderly candidates ≥60 years of age can safely be selected as LDLT donors after meticulous preoperative work-up.Interleukin 6 (IL-6) is a cytokine with critical innate and adaptive immunity functions. It's diverse immunologic and physiologic actions include direction of immune cell differentiation, initial response to invading pathogens and ischemic injury, sustained plasma cell growth, and immunoglobulin production. IL-6 transcriptional dysregulation is commonly seen in patients with autoimmune or inflammatory disorders. Emerging information suggests IL-6 transcription is upregulated in patients with kidney and heart transplant rejection and may account for perpetuation of inflammatory responses in the allograft, leading to allograft rejection and vasculopathy. link2 IL-6 directed therapeutics include monoclonal antibodies directed at IL-6, the IL-6 receptor (IL-6R) and Janus Kinase (JAK) inhibitors. IL-6 mediated signaling to cell targets is unique, involving classic signaling (IL-6->IL-6R) cell membrane receptors, trans signaling (IL-6->soluble IL-6R->gp130) which activates any cell, and the recently discovered IL-6/IL-6R transpresentation where antigen presenting cells (APC) synthesize and express IL-6/IL-6R complexes which are transported through the cell membrane subsequently interacting with gp130 to costimulate T-cells. Currently, there are new trials in autoimmunity and heart and kidney transplantation to determine effectiveness of inhibiting IL-6/IL-6R to ameliorate chronic allograft rejection and coronary allograft vasculopathy. Therapeutic trials aimed at prevention of ischemia/reperfusion injury (IRI) to allografts based on animal data should be considered.PURPOSE OF REVIEW Retinal detachment initiates a series of events that lead to degenerative changes in retinal synaptic architecture as well as the well-known phenomena of gliosis and photoreceptor apoptosis. Retinal reattachment does not always result in complete visual recovery, even if the fovea is not directly involved in the detachment. Rho-kinase (ROCK) inhibitors may mitigate some of these deleterious changes including disruption of synaptic architecture, photoreceptor apoptosis, and initiation of the epithelial-mesenchymal transition that characterizes proliferative vitreoretinopathy (PVR). This review focuses on the use of ROCK inhibitors to modulate synaptic disjunction. RECENT FINDINGS ROCK inhibition prevents retinal detachment-induced photoreceptor synaptic terminal retraction (i.e., synaptic disjunction), thereby diminishing the damage of the first synapse in the visual pathway. ROCK inhibition also reduces retinal detachment-induced photoreceptor apoptosis and suppresses PVR progression in preclinical models. SUMMARY Inhibition of ROCK may help to optimize visual recovery after retinal detachment surgery or iatrogenic detachments during cell transplantation or viral subretinal injection and might play a role in reducing the risk of PVR after retinal detachment surgery.PURPOSE OF REVIEW To compare outcomes of 27-gauge and 23-gauge pars plana vitrectomy (PPV) for treatment of vitreoretinal diseases. RECENT FINDINGS Sixty-eight patients undergoing microincisional PPV for treatment of vitreoretinal diseases were randomized 1  1 to 27-gauge or 23-gauge surgery with a 7500 cuts-per-minute vitrectomy probe. The most common reasons for vitrectomy were epiretinal membrane (49%) and vitreous hemorrhage (24%). link3 Mean ± standard deviation (SD) changes from immediate preoperative to immediate postoperative intraocular pressure were -0.40 ± 6.60 mmHg in the 27-gauge and -3.05 ± 7.64 mmHg in the 23-gauge group (adjusted mean difference 2.42 mmHg, 95% lower confidence limit 0.64, P = 0.013), but these changes were not associated with primary reason for vitrectomy (P = 0.065). Mean ± SD conjunctival edema grades in the 27-gauge and 23-gauge groups 1 week after surgery were 0.02 ± 0.124 and 0.10 ± 0.246, respectively (least squares mean difference -0.09, 95% upper confidence limit -0.03, P = 0.004), and were 0.01 ± 0.122 and 0.12 ± 0.338, respectively, at the probe incision site. Conjunctival edema grades were similar in both groups at 1 and 3 months. Mean ± SD pain ratings on postoperative day 1 - an indicator of patient comfort - were similar in the two groups. SUMMARY Smaller diameter vitrectomy instruments are associated with smaller reductions in immediate postoperative intraocular pressure.PURPOSE OF REVIEW A variety of techniques exist for secondary intraocular lens (IOL) implantation. Of note, scleral fixated intraocular lenses have become more popular with a variety of techniques, both with and without use of sutures. Herein, we focus on reviewing recently published studies describing the long-term outcomes of scleral fixation techniques. RECENT FINDINGS Although initial papers describing novel techniques often report short-term outcomes, several studies have recently described intermediate and long-term outcomes for scleral fixated IOLs, albeit all being retrospective case series. Suture fixation methods with long-term follow-up, up to a minimum of 50 months, report dislocation rates between 0 and 15%. Sutureless scleral fixation techniques have increased in popularity the past several years. Although they appear to have a lower rate of IOL dislocation several studies have reported 0% and one study 8%. The follow-up period for sutureless scleral fixation technique studies, however, is shorter with most studies reporting follow-up of less than a year. Rates of retinal detachment vary between individual studies, but are similar for both suture fixation and sutureless with the majority of studies reporting a rate between 0 and 5%. These studies show that long-term outcomes are important considerations in surgical decision-making. SUMMARY Scleral fixation techniques have shown long-term durability and safety in recent retrospective studies. Comparison of techniques has been limited, and more robust studies may be required to provide stronger anatomic, functional, and comparative data.BACKGROUND Immunocompromised children are at increased risk for respiratory syncytial virus (RSV) infection with associated morbidity and mortality. Prophylaxis is usually provided to these children on a case-by-case basis. METHODS Immunocompromised children who received ≥1 injection of palivizumab were prospectively enrolled across 32 Canadian sites, between 2005 and 2017, during the RSV season. We assessed respiratory illness hospitalization (RIH) and RSV-related hospitalization (RSVH) hazard ratios (HRs) in immunocompromised children versus infants' prophylaxed for standard indications (SI prematurity ≤35 weeks' gestation, bronchopulmonary dysplasia, and congenital heart disease) and complex medical disorders (CMD). Data were analyzed using t-tests, χ and Cox proportional hazards adjusted for confounders. RESULTS A total of 25,003 infants were recruited; 214 immunocompromised, 4283 CMD, 20,506 SI. On average, children received 4.4 ± 1.3 injections. A total of 16,231 children were perfectly adherent (58.4% immunodeficiency, 68.
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