[The National German Transplantation Certification : Interdisciplinary and innovative]. / Zusatzweiterbildung Transplantationsmedizin : Interdisziplinär und innovativ.

The interdisciplinary additional advanced training in transplantation medicine (ZWB) has been passed with the (Model) Advanced Training Regulation 2018 and is now implemented in all federal states. It includes joint interdisciplinary contents that must be mastered by all disciplines and special skills that are specific to the individual disciplines. An organ-specific training is also possible. With its interdisciplinary approach the ZWB transplantation certification is pioneering the structure of modern transplantation centers and will thus further improve the quality of treatment for patients on the waiting lists for organ transplantation and for patients with transplanted organs.

Elderly Patients with Hepatocellular Carcinoma Benefit from Liver Transplantation as Much as Younger Ones.

Introduction: The literature on liver transplantation (LT) for cirrhosis-associated hepatocellular carcinoma (cirr-HCC) in elderly patients (≥65 years of age) is scarce. The aim of this study was therefore to analyze the outcome after LT for cirr-HCC in elderly patients in our single-center experience. Methods: All consecutive patients who underwent LT for cirr-HCC at our center were identified from our prospectively collected LT database and stratified into an elderly (≥65 years) and a younger (<65 years) cohort. Perioperative mortality as well as Kaplan-Meier estimations of overall (OS) and recurrence-free survival (RFS) were compared between age strata. A subgroup analysis was performed for patients with HCC only inside Milan criteria. For further oncological comparison, outcome in the subgroup of elderly LT recipients with HCC inside Milan was also compared to a group of elderly patients undergoing liver resection for cirr-HCC inside Milan extracted from our institutional liver resection database. Results: Out of 369 consecutive patients with cirr-HCC who underwent LT between 1998 and 2022 at our center, we identified 97 elderly (with a subgroup of 14 septuagenarians) and 272 younger LT patients. 5- and 10-year OS in elderly compared to younger LT patients was 63% and 52% versus 63% and 46% (p = 0.67), respectively, while 5- and 10-year RFS was 58% and 49% versus 58% and 44% (p = 0.69). 5-/10-year OS and RFS in 50 elderly LT recipients with HCC inside Milan were 68%/55% and 62%/54%, respectively, which compared to 46%/38% (p = 0.07) and 26%/14% (p < 0.0001) in elderly patients after liver resection for cirr-HCC inside Milan. Conclusion: Our results in almost 100 elderly patients after LT for cirr-HCC show that older age per se should not be considered a contraindication to LT and that selected elderly patients older than 65 and even 70 years benefit from LT as much as younger ones.

[Surgical Education of Medical Students in Times of COVID-19 - Necessary Adjustments are Chances for the Future]. / Chirurgische Lehre in Zeiten von COVID-19: Aus notwendigen Kompromissen werden Chancen für die Zukunft.

BACKGROUND: Education of medical students in surgery not only consists of knowledge about diseases and their treatment but also of practical skills like i.e. suturing. In the clinical training of medical students, professional interaction and communication with patients is a key component. Due to the circumstances of distancing and reduced exposure to patients during the COVID-19 pandemic, clinical training of medical students has been challenging. To combat these restrictions, digital modern teaching concepts had to be implemented. MATERIAL AND METHODS: Surgical education of medical students was reorganised during the summer semester 2020 and winter semester 2020/2021 and the necessary adjustments, as well as their evaluation by students, were analysed. Results were compared to the pre-COVID evaluations of the summer semester 2019. Furthermore a survey of all university surgical departments in Germany (n = 39) was conducted to compare the different approaches to handling this very new situation. RESULTS: All participating centres were performing surgical education with medical students during the COVID-19 pandemic. Overall, digital teaching methods were well accepted by students and teachers, even though short-term changes were necessary during the second wave of the pandemic. Both students and teachers missed the direct mutual interaction as well as with patients (summer semester 2020 36%, winter semester 2020/2021 40%). Modern and digital teaching concepts were assessed positively (summer semester 2020 45%, winter semester 2020/2021 40%) and long term implementation was desired by students and teachers (winter semester 2020/2021 60%). CONCLUSION: Training of practical surgical skills, as well as communication skills, can only be taught in presence. Digital learning concepts can support, but not replace, surgical courses held in presence, including contact to patients and manual training. Blended learning concepts facilitate a leap towards modern teaching concepts and increase the quality of classes spent in presence.

A Phase 1 Study Evaluating Rovalpituzumab Tesirine in Frontline Treatment of Patients With Extensive-Stage SCLC.

INTRODUCTION: Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC. METHODS: One cycle of CE pre-enrollment was permitted (later mandated). The following four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, every 6 [q6] wk × 2; cohort 1; n = 4); Rova-T induction (0.3 mg/kg, q6 wk × 2) followed by CE every 21 days (q21) × 4 (cohort 2; n = 5); Rova-T (0.1 or 0.2 mg/kg, q6 wk × 2) overlapping with CE q21 × 4 (cohort 3; n = 14); and Rova-T maintenance (0.3 mg/kg, q6 wk × 2) after CE q21 × 4 (cohort 4; n = 3). RESULTS: A total of 26 patients were dosed (cohort 3: 14; cohorts 1, 2, and 4 combined: 12). Median age was 66 years, and 73% had Eastern Cooperative Oncology Group performance status of 1. In cohort 3, seven patients (50%) had confirmed objective responses, with a median progression-free survival of 5.2 months and median overall survival of 10.3 months. Compared with cohorts 1, 2, and 4 combined, cohort 3 had lower frequency of some Rova-T-related adverse events of special interest, such as pleural effusion (0 versus 33%), pericardial effusion (0 versus 17%), ascites (0 versus 8%), peripheral edema (36% versus 42%), generalized edema (0 versus 8%), pneumonia (7% versus 25%), and hypoalbuminemia (0 versus 17%). CONCLUSIONS: Lower Rova-T doses may be associated with lower incidence of some Rova-T-related adverse events of special interest. Rova-T 0.2 mg/kg plus CE (cohort 3) was tolerable; however, there was no clear efficacy benefit of adding Rova-T to CE.

COVID-19-Importance for Patients on the Waiting List and after Kidney Transplantation-A Single Center Evaluation in 2020-2021.

(1) Background: Dialysis patients and recipients of a kidney allograft are at high risk for infection with SARS-CoV-2. It has been shown that the development of potent neutralizing humoral immunity against SARS CoV-2 leads to an increased probability of survival. However, the question of whether immunocompromised patients develop antibodies has not yet been sufficiently investigated; (2) Methods: SARS-CoV-2 antibodies were examined in hemodialysis patients on the waiting list for kidney transplantation as well as patients after kidney transplantation. Patients were interviewed about symptoms and comorbidities, BMI, and smoking history; (3) Results: SARS-CoV-2 antibodies were found in 16 out of 259 patients (6%). The trend of infections here reflects the general course of infection in Germany with a peak in November/December of 2020. Remarkably, patients on the waiting list experienced only mild disease. In contrast, transplanted patients had to be hospitalized but recovered rapidly from COVID-19. Most interesting is that all immunosuppressed patients developed antibodies against SARS-CoV-2 after infection; (4) Conclusions: Even with extensive hygiene concepts, an above-average number of patients were infected with SARS-CoV-2 during the second wave of infections in Germany. Because SARS-CoV-2 infection triggered the formation of antibodies even in these immunocompromised patients, we expect vaccination to be effective in this group of patients. Thus, dialysis patients and patients after kidney transplantation should be given high priority in vaccination programs.

C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation.

In most human cancers, a large number of proteins with driver mutations are involved in tumor development, implying that multiple fine tuners are involved in cancer formation and/or maintenance. A useful strategy for cancer therapy may therefore be to target multiple cancer type-specific fine tuners. Furthermore, genome-wide association studies of tumor samples have identified a large number of long noncoding (lnc)RNA associated with various types of tumor. In this context we have previously found that C20orf204 (a splice variant of Linc00176) RNA contains a 189 amino acid (AA) long open reading frame (C20orf204-189AA) that is expressed predominantly in hepatocellular carcinoma (HCC). We report here that a protein, C20orf204-189AA, was detected in the nucleus of 14 out of 20 primary HCC, but not in control livers. Strikingly, overexpression of C20orf204-189AA enhanced cell proliferation and ribosomal RNA transcription. C20orf204-189AA is co-localized, and interacted with nucleolin via the C-terminal and with ribosomal RNA via the N-terminal domain. Furthermore, the expression of C20orf204-189AA upregulates the protein level of nucleolin. Nucleolin and C20orf204 mRNA levels in HCC are correlated with tumor differentiation grade and patient survival, suggesting that C20orf204-189AA is a cancer type-specific fine tuner in some HCC that presents itself for potential targeting therapy and cancer biomarker. Thus, cancer cells exhibit remarkable transcriptome alterations partly by adopting cancer-specific splicing isoforms of noncoding RNAs and may participate in tumor development.

Comparison of Cytomegalovirus-Specific Immune Cell Response to Proteins versus Peptides Using an IFN-γ ELISpot Assay after Hematopoietic Stem Cell Transplantation.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Measuring CMV-specific cellular immunity may improve the risk stratification and management of patients. IFN-γ ELISpot assays, based on the stimulation of peripheral blood mononuclear cells with CMV pp65 and IE-1 proteins or peptides, have been validated in clinical settings. However, it remains unclear to which extend the T-cell response to synthetic peptides reflect that mediated by full-length proteins processed by antigen-presenting cells. We compared the stimulating ability of pp65 and IE-1 proteins and corresponding overlapping peptides in 16 HSCT recipients using a standardized IFN-γ ELISpot assay. Paired qualitative test results showed an overall 74.4% concordance. Discordant results were mainly due to low-response tests, with one exception. One patient with early CMV reactivation and graft-versus-host disease, sustained CMV DNAemia and high CD8+ counts showed successive negative protein-based ELISpot results but a high and sustained response to IE-1 peptides. Our results suggest that the response to exogenous proteins, which involves their uptake and processing by antigen-presenting cells, more closely reflects the physiological response to CMV infection, while the response to exogenous peptides may lead to artificial in vitro T-cell responses, especially in strongly immunosuppressed patients.

Standardized monitoring of cytomegalovirus-specific immunity can improve risk stratification of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation.

Recurrence of cytomegalovirus reactivation remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Monitoring cytomegalovirus-specific cellular immunity using a standardized assay might improve the risk stratification of patients. A prospective multicenter study was conducted in 175 intermediate- and high-risk allogeneic hematopoietic stem cell transplant recipients under preemptive antiviral therapy. Cytomegalovirus-specific cellular immunity was measured using a standardized IFN-γ ELISpot assay (T-Track® CMV). Primary aim was to evaluate the suitability of measuring cytomegalovirus-specific immunity after end of treatment for a first cytomegalovirus reactivation to predict recurrent reactivation. 40/101 (39.6%) patients with a first cytomegalovirus reactivation experienced recurrent reactivations, mainly in the high-risk group (cytomegalovirus-seronegative donor/cytomegalovirus-seropositive recipient). The positive predictive value of T-Track® CMV (patients with a negative test after the first reactivation experienced at least one recurrent reactivation) was 84.2% in high-risk patients. Kaplan-Meier analysis revealed a higher probability of recurrent cytomegalovirus reactivation in high-risk patients with a negative test after the first reactivation (hazard ratio 2.73; p=0.007). Interestingly, a post-hoc analysis considering T-Track® CMV measurements at day 100 post-transplantation, a time point highly relevant for outpatient care, showed a positive predictive value of 90.0% in high-risk patients. Our results indicate that standardized cytomegalovirus-specific cellular immunity monitoring may allow improved risk stratification and management of recurrent cytomegalovirus reactivation after hematopoietic stem cell transplantation. This study was registered at www.clinicaltrials.gov as #NCT02156479.

Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small-Cell Lung Cancer.

Small cell lung cancer (SCLC) is a leading cause of cancer death worldwide, with few treatment options. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate that targets delta-like 3 on SCLC cells to deliver a cytotoxic payload directly to tumor cells. In this study, the cardiac safety profile of Rova-T was assessed by evaluating changes in QT interval, electrocardiogram (ECG) waveform, heart rate, and proarrhythmic adverse events (AEs) after treatment with Rova-T in patients with previously treated extensive-stage SCLC. Patients underwent ECG monitoring for 2 weeks after each of 2 i.v. infusions of 0.3 mg/kg Rova-T over 30 minutes, administered 6 weeks apart. Forty-six patients received at least one dose of Rova-T. At the geometric mean Rova-T maximum serum concentration of 7,940 ng/mL, ECG monitoring showed no significant changes in the Fridericia-corrected QT (QTcF) interval; the upper limit of the 2-sided 90% confidence interval did not exceed 10 msec for any time point. There were no clinically significant changes in QRS or PR intervals, ECG waveforms, or heart rate after Rova-T administration. All patients experienced a treatment-emergent AE (TEAE); 78% had a grade ≥ 3 TEAE, 59% had a serious TEAE, and 41% had a cardiac-related TEAE. The TEAEs that might signal proarrhythmia tendencies were uncommon. Confirmed partial responses were observed in 24% of patients. Based on the evaluation of ECG data collected in this study from patients treated with Rova-T at 0.3 mg/kg i.v. administered every 6 weeks, a QTcF effect of clinical concern can be excluded.

Ectonucleoside triphosphate diphosphohydrolase 1 and 5'-nucleotidase ecto gene polymorphisms and acute cellular rejection after liver transplantation.

The single nucleotide polymorphisms (SNPs) rs11188513, rs7071836, rs10748643, rs9450279, rs4458647, and rs6922 map in the genes of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) and 5'-nucleotidase ecto. We investigated whether these SNPs and haplotypes of these SNPs are associated with an acute cellular rejection after liver transplantation. A total of 69 recipients with an acute cellular rejection and 138 recipients without an acute cellular rejection were analyzed. Analyzed individually, no SNP demonstrates an association, but the haplotype rs11188513T-rs7071836G-rs10748643A of the ENTPD1 gene appeared more frequently in recipients without rejection and conversely, the haplotype rs11188513T-rs7071836G-rs10748643G of the ENTPD1 gene was more often represented in recipients with rejection. These two haplotypes seem to be important for the susceptibility of an acute cellular rejection after liver transplantation.

The Transcription Factor Promyelocytic Leukemia Zinc Finger Protein Is Associated With Expression of Liver-Homing Receptors on Human Blood CD56bright Natural Killer Cells.

The transcription factor promyelocytic leukemia zinc finger protein (PLZF) is involved in the development of natural killer (NK) cells and innate lymphoid cells, including liver-resident NK cells in mice. In human NK cells, the role of PLZF in liver residency is still unknown. Expression of PLZF in matched human peripheral blood- and liver-derived NK cells and the association of PLZF expression with surface molecules and transcription factors relevant for tissue residency were investigated using multiparameter flow cytometry and assessing single-cell messenger RNA (mRNA) levels. Intrahepatic cluster of differentiation (CD)56bright NK cells expressed significantly higher levels of PLZF than peripheral blood CD56bright NK cells, which were predominantly PLZFlo. Expression of PLZF was highest within C-X-C motif chemokine receptor 6 (CXCR6)+CD69+ liver-resident NK cells among intrahepatic CD56bright NK cell populations. Association of PLZF with liver-residency markers was also reflected at mRNA levels. A small PLZFhiCD56bright NK cell population was identified in peripheral blood that also expressed the liver-residency markers CXCR6 and CD69 and shared functional characteristics with liver-resident NK cells. Conclusion: PLZF is implicated as part of a transcriptional network that promotes liver residency of human NK cells. Expression of liver-homing markers on peripheral blood PLZFhiCD56bright NK cells identifies an intermediate population potentially contributing to the maintenance of liver-resident NK cells.

De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans.

The utility of autologous induced pluripotent stem cell (iPSC) therapies for tissue regeneration depends on reliable production of immunologically silent functional iPSC derivatives. However, rejection of autologous iPSC-derived cells has been reported, although the mechanism underlying rejection is largely unknown. We hypothesized that de novo mutations in mitochondrial DNA (mtDNA), which has far less reliable repair mechanisms than chromosomal DNA, might produce neoantigens capable of eliciting immune recognition and rejection. Here we present evidence in mice and humans that nonsynonymous mtDNA mutations can arise and become enriched during reprogramming to the iPSC stage, long-term culture and differentiation into target cells. These mtDNA mutations encode neoantigens that provoke an immune response that is highly specific and dependent on the host major histocompatibility complex genotype. Our results reveal that autologous iPSCs and their derivatives are not inherently immunologically inert for autologous transplantation and suggest that iPSC-derived products should be screened for mtDNA mutations.

Structured introduction of retroperitoneoscopic donor nephrectomy provides a high level of safety and reduces the physical burden for the donor compared to an anterior mini incision: A cohort study.

INTRODUCTION: A major goal in living donor kidney transplantation is to reduce the physical burden for the donor. Key-hole surgery for donor nephrectomy is a safe procedure, but concerns regarding donor safety during the learning phase might be the reason for surgeons' reluctance to change to a minimal invasive approach. MATERIAL AND METHODS: We analyzed the first 100 retroperitoneoscopic donor nephrectomies (RPDN) performed at our institution and compared the results to the last 50 mini incision donor nephrectomies (MIDN) regarding donor and recipient outcome, and analyzed the learning curves of RPDN. RESULTS: The learning phase of RPDN was very short with significantly shorter operative times compared to MIDN (118 vs. 175 min, p < 0.001) and significantly fewer surgical complications (p = 0.03). RPDN patients rated the physical burden (p = 0.01) as lower, and they felt less bothered by the surgical scar (p = 0.03). CONCLUSION: Introducing RPDN is safe, even during the learning phase of the surgeons. Changing surgical technique from MIDN to RPDN reduces the surgical burden of the procedure. Our study might encourage more transplant centres to adopt a minimally invasive approach.

CD49a Expression Identifies a Subset of Intrahepatic Macrophages in Humans.

Macrophages play central roles in inflammatory reactions and initiation of immune responses during infections. More than 80% of total tissue macrophages are described to be located in the liver as liver-resident macrophages, also named Kupffer cells (KCs). While studies in mice have established a central role of liver-resident KCs in regulating liver inflammation, their phenotype and function are not well-characterized in humans. Comparing paired human liver and peripheral blood samples, we observed significant differences in the distribution of macrophage (Mφ) subsets, with lower frequencies of CD14hiCD16lo and higher frequencies of CD14int-hiCD16int Mφ in human livers. Intrahepatic Mφ consisted of diverse subsets with differential expression of CD49a, a liver-residency marker previously described for human and mice NK cells, and VSIG4 and/or MARCO, two recently described human tissue Mφ markers. Furthermore, intrahepatic CD49a+ Mφ expressed significantly higher levels of maturation and activation markers, exhibited higher baseline levels of TNF-α, IL-12, and IL-10 production, but responded less to additional in vitro TLR stimulation. In contrast, intrahepatic CD49a- Mφ were highly responsive to stimulation with TLR ligands, similar to what was observed for CD49a- monocytes (MOs) in peripheral blood. Taken together, these studies identified populations of CD49a+, VSIG4+, and/or MARCO+ Mφ in human livers, and demonstrated that intrahepatic CD49a+ Mφ differed in phenotype and function from intrahepatic CD49a- Mφ as well as from peripheral blood-derived monocytes.

Impact of TBX21, GATA3, and FOXP3 gene polymorphisms on acute cellular rejection after liver transplantation.

The single nucleotide polymorphisms (SNPs) rs4794067, rs2275806, rs2232365, and rs3761548 map in the genes of TBX21, GATA3, and FOXP3 involved in mediating acute cellular rejection. We investigated whether these SNPs are associated with acute cellular liver transplant rejection. The SNPs were analyzed in recipients with early acute cellular rejection (n = 97), recipients with late acute cellular rejection (n = 49), and recipients without rejection (n = 149). There was no association between acute cellular rejection and SNPs rs4794067, rs2275806, and rs2232365. In contrast, the allele -3279A of FOXP3 SNP rs3761548 exhibited a higher frequency in recipients with late acute cellular rejection as compared with recipients without rejection. This result indicates that the allele -3279A of the SNP rs3761548 may predispose to the development of late acute cellular rejection.

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 µmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 µmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.

Venous anastomosis by piggyback technique to avoid twisting of the pediatric en bloc kidney grafts.

This is the first report of using piggyback technique for the venous anastomosis in two pediatric recipients of small en bloc kidneys, which was found to be effective to avoid twisting of the grafts and vessels. The donors were aged 2 and 3 years with a body weight of 17 and 20 kg. The recipient age was 14 and 16 years with a body weight of 42 and 54 kg. The implantation was done extraperitoneally in the right iliac fossa. The donor's inferior vena cava was anastomosed to the recipient's distal caval vein side-to-side using 6-0 polydioxanone running suture as the piggyback technique, initially dealing with the short vena cava graft in the first case. At the end of the operation, the kidneys were positioned allowing the lateral aspect of each renal unit to face anteriorly as "closing the book." The cold ischemia time was 895 and 820 minutes, respectively. No vascular complication was observed postoperatively. The patients were discharged on POD 16 and POD 21 with an eGFR of 94 and 102 mL/min/1.73 m², respectively. The graft function is stable during the 5- and 7-month follow-up.

Obstruction of peritoneal dialysis catheter is associated with catheter type and independent of omentectomy: A comparative data analysis from a transplant surgical and a pediatric surgical department.

BACKGROUND: Peritoneal dialysis (PD) catheter occlusion is a common complication with up to 36% of catheter obstructions described in the literature. We present a comparison of complications and outcome after implantation of PD catheters in a transplant surgical and a pediatric surgical department. METHODS: We retrospectively analyzed 154 PD catheters, which were implanted during 2009-2015 by transplant surgeons (TS, University Medical Center Hamburg-Eppendorf, Germany, n=85 catheters) and pediatric surgeons (PS, Charité University Medicine Berlin, Germany, n=69 catheters) in 122 children (median (range) age 3.0 (0.01-17.1) years) for acute (n=65) or chronic (n=89) renal failure. All catheters were one-cuffed or double-cuffed curled catheters, except that straight catheters were implanted into smaller children (n=19) by TS in Hamburg. RESULTS: Patient characteristics and operation technique did not differ between the departments. Peritonitis was the most common complication (33 catheters, 21.4%). Leakage (n=18 catheters, 11.7%) occurred more often in children weighing <10kg (p<0.001). The incidence of obstruction and dysfunction was significantly higher in catheters used in PS than catheters used in TS (30.4% vs. 11.8%, p=0.004). Omentectomy did not reduce the incidence of catheter obstruction (p=1.0). Perforation at the catheter tips was larger and appeared to be rougher in catheters used in PS than the catheters in TS. CONCLUSIONS: The type of catheter and presumably the type of perforation at the catheter tip may influence the incidence of peritoneal dialysis catheter obstruction.

Proliferative capacity exhibited by human liver-resident CD49a+CD25+ NK cells.

The recruitment and retention of Natural Killer (NK) cells in the liver are thought to play an important role during hepatotropic infections and liver cirrhosis. The aims of this study were to determine differences between liver-derived and peripheral blood-derived NK cells in the context of liver inflammation and cirrhosis. We conducted a prospective dual-center cross-sectional study in patients undergoing liver transplantation or tumor-free liver resections, in which both liver tissue and peripheral blood samples were obtained from each consenting study participants. Intrahepatic lymphocytes and PBMCs were stained, fixed and analyzed by flow cytometry. Our results showed that, within cirrhotic liver samples, intrahepatic NK cells were particularly enriched for CD49a+ NK cells when compared to tumor-free liver resection samples. CD49a+ liver-derived NK cells included populations of cells expressing CD25, CD34 and CXCR3. Moreover, CD49a+CD25+ liver-derived NK cells exhibited high proliferative capacity in vitro in response to low doses of IL-2. Our study identified a specific subset of CD49a+CD25+ NK cells in cirrhotic livers bearing functional features of proliferation.