Bortezomib-containing multimodality treatment for antibody-mediated rejection with anti-HLA and anti-AT1R antibodies after kidney transplantation

For decades, the human leukocyte antigen (HLA) complex has been considered the primary target of antibody-mediated rejection (AMR), and treatment strategies have mainly focused on anti-HLA antibodies. Recently, other antibodies potentially causing organ damage and loss have been discovered. Conclusive evidence on treatment options for these subtypes of AMR is still lacking. After an experience previously reported in this journal,1 we describe a case of late-onset AMR, with mixed anti-HLA and anti-angiotensin II type 1 receptor (AT1R) antibodies, that was successfully treated with a multimodal approach, including the use of the proteasome inhibitor bortezomib

Local symmetry in liquid metals probed by x-ray absorption spectroscopy

The nature of local point symmetry in simple monoatomic liquids has been a fundamental open question for almost 40 years of computational and experimental studies. We present original results of local ordering in different monoatomic liquids obtained by x-ray absorption spectroscopy (XAS), exploiting its high sensitivity to short-range ordering. We used Reverse Monte Carlo (RMC) analysis (RMC-GNXAS package) for obtaining structural models compatible with XAS experimental data (and diffraction techniques for long-range ordering). Pair, bond-angle distributions and suitable indicators for point symmetry are calculated for different liquid metals

Impact of remnant vital tissue after locoregional treatment and liver transplant in hepatocellular cancer patients. A multicentre cohort study

The role of pathological findings after locoregional treatments as predictors of hepatocellular cancer recurrence after liver transplantation has been poorly addressed. The aim of the study was to identify the role of remnant vital tissue (RVT) of the target lesion in predicting hepatocellular cancer recurrence. Two hundred and seventy-six patients firstly undergoing locoregional treatment and then transplanted between January 2010 and December 2015 in four European Transplant Centres (i.e. Rome Tor Vergata, Birmingham, Brussels and Ancona) were enrolled in the study to investigate the role of pathological response at upfront locoregional treatment. At multivariable Cox regression analysis, RVT ≥2 cm was a strong independent risk factor for post-LT recurrence (HR = 5.6; P < 0.0001). Five-year disease-free survival rates were 60.8%, 80.9% and 95.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. When only Milan Criteria-IN patients were analysed, similar results were reported, with 5-year disease-free survival rates of 58.1%, 79.0% and 94.0% in patients presenting a RVT ≥2 cm vs. 0.1-1.9 vs. no RVT, respectively. RVT is an important determinant of tumour recurrence after liver transplantation performed for hepatocellular cancer. Its discriminative power looks to be evident also in a Milan-IN setting, suggesting to more liberally use locoregional treatments also in these patients

HLA-G14bp ins/del polymorphism and post-transplant weight gain in kidney transplantation. Potential implications beyond tolerance

Background: Human leukocyte antigen (HLA)-G is a non-classical HLA molecule with immunomodulant and immunosuppressive functions, involved in transplantation tolerance. HLA-G14bp ins/del polymorphism in exon 8 has been associated with allograft rejection and kidney transplant outcome, with controversial results. We investigated associations of HLA-G14bp ins/del polymorphism on onset of some of the main post-transplant risk factors, like excess body weight, lipid abnormalities, increased fasting plasma glucose. Polymorphisms of cytokines with both immunosuppressive and metabolic effects were also assessed for comparisons and associated analysis. Methods: The present study involved kidney transplant recipients (n = 173) in which body mass index, cholesterol, triglycerides, fasting plasma glucose were registered in the first years after transplantation and analyzed in association with genotypes. Presence of hypertension and smoking habits, demographic, transplant-related and therapeutic data of patients were also recorded. Polymerase chain reaction, sequence-specific primer amplification and Taqman allelic discrimination techniques were used for genotyping of HLA-G14bp ins/del, interleukin (IL)-10(-1082G &gt; A,-819 T &gt; C,-592A &gt; C), transforming growth factor-β(+ 869 T &gt; C,+915C &gt; G), IL-6(-174G &gt; C), tumor necrosis factor-α(-308G &gt; A) and IL-18(-137G &gt; C,-607C &gt; A). Effects of genotypes on clinical markers at each time point (pre-transplant and 1 to 5 years after transplant) were analyzed using a repeated-measures general linear model analysis; adjustment for potential confounders was performed. Results: Results showed that HLA-G14bp ins/ins was significantly associated with obesity, in particular after transplantation (3 years, p = 0.002, OR = 4.48, 95% CI:1.76-11.41). Post-transplant body mass index was significantly increased in HLA-G14bp ins/ins carriers (3 and 4 years, p = 0.033 and p = 0.044); effects of HLA-G14bp genotypes on post-transplant BMI were confirmed by using repeated-measures analysis and after controlling for confounding variables. Cytokine genotypes did not associate with the examined factors. Conclusions: The study of transplanted patients allowed to evidence a potential relationship between post-transplant weight gain and HLA-G14bp ins/del polymorphism, previously involved in rejection for its immunosuppressive/tolerogenic activity. This novel association could widen the knowledge of the role and functions of HLA-G molecules in diseases and transplantation

Coupled Plasma Filtration Adsorption in Patients with a History of Kidney Transplantation: Report of Two Cases

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Spectrometer for X-ray emission experiments at FERMI free-electron-laser

A portable and compact photon spectrometer to be used for photon in-photon out experiments, in particular x-ray emission spectroscopy, is presented. The instrument operates in the 25\u2013800 eV energy range to cover the full emissions of the FEL1 and FEL2 stages of FERMI. The optical design consists of two interchangeable spherical varied-lined-spaced gratings and a CCD detector. Different input sections can be accommodated, with/without an entrance slit and with/without an additional relay mirror, that allow to mount the spectrometer in different end-stations and at variable distances from the target area both at synchrotron and at free-electron-laser beamlines. The characterization on the Gas Phase beamline at ELETTRA Synchrotron (Italy) is presented

Impact of Donor Age on Clinical Outcomes of Primary Single Kidney Transplantation From Maastricht Category-III Donors After Circulatory Death

Background. Standard-criteria donation after circulatory death (DCD) kidney transplants (KTx) have higher primary nonfunction, delayed graft function (DGF), and rejection rates than age-matched donation after brain death (DBD) but similar graft survival. Data on expanded-criteria DCD are conflicting and many centers remain concerned regarding their use. Methods. In this single-center observational study with 5-year follow-up, we analyzed data from 112 primary DCD Maastricht category-III single KTx receiving similar organ preservation and maintenance immunosuppression. Patients were sorted as young DCD (donor = 60 years, 40 recipients). Old DCD outcomes were compared with young DCD and to a DBD control group (old DBD, donor >= 60 years, 40 recipients). Results. After 5 years, old DCD showed lower patient survival (66% vs 85%; P = 0.014), death-censored graft survival (63% vs 83%; P = 0.001), and Modification of Diet in Renal Disease estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m(2) vs 45.0, 33.0-58.0 mL/min per 1.73 m(2); P = 0.021) than young DCD with higher DGF (70% vs 47.2%; P = 0.029) and graft thrombosis (12.5% vs 1.4%; P = 0.021). Comparison between old DCD and old DBD showed similar 5-year patient survival (66% vs 67%; P = 0.394) and death-censored graft survival (63% vs 69%; P = 0.518) but higher DGF (70% vs 37.5%; P = 0.007) and lower estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73m(2) vs 41, 40.0-42.0 mL/min per 1.73m(2); P = 0.029). Multivariate Cox regression analysis showed that donor 60 years or older (hazard ratio, 3.135; 95% confidence interval, 1.716-5.729; P < 0.001) and induction with anti-IL2-receptor-alpha monoclonal antibody (hazard ratio, 0.503; 95% confidence interval, 0.269-0.940, P = 0.031 in favor of induction with rabbit antithymocyte globulin) are independent predictors of transplant loss. Conclusions. Overall, single KTx from DCD Maastricht category-III donors 60 years or older have inferior outcomes than KTx from donors younger than 60 years. Comparison with age-matched DBD showed similar patient and graft survivals. However, the discrepancy in graft function between DCD and DBD deserves further investigation

Global management of a common, underrated surgical task during the COVID-19 pandemic. Gallstone disease. An international survery

Background: Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic. Methods: A Web-based survey was conducted among 36 Hepato-Prancreato-Biliary surgeons from 14 Countries. Through a 17-item questionnaire, participants were asked about the local management of patients with GD since the start of the COVID-19 pandemic. Results: The majority (n = 26,72.2%) of surgeons reported an alarming decrease in the cholecystectomy rate for GD since the start of the pandemic, regardless of the Country: 19(52.7%) didn't operate any GD, 7(19.4%) reduced their surgical activity by 50–75%, 10(27.8%) by 25–50%, 1(2.8%) maintained regular activity. Currently, only patients with GD complications are operated. Thirty-two (88.9%) participants expect these changes to last for at least 3 months. In 15(41.6%) Centers, patients are currently being screened for SARS-CoV-2 infection before cholecystectomy [in 10(27.8%) Centers only in the presence of suspected infection, in 5(13.9%) routinely]. The majority of surgeons (n = 29,80.6%) have adopted a laparoscopic approach as standard surgery, 5(13.9%) perform open cholecystectomy in patients with known/suspected SARS-CoV-2 infection, and 2(5.6%) in all patients. Conclusion: In the ongoing COVID-19 emergency, the surgical treatment of GD is postponed, resulting in a huge number of untreated patients who could develop severe morbidity. Updated guidelines and dedicated pathways for patients with benign disease awaiting elective surgery are mandatory to prevent further aggravation of the overloaded healthcare systems