Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver.

Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1+/2+ (CXCR1+/CXCR2+) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.

Static cold storage compared with normothermic machine perfusion of the liver and effect on ischaemic-type biliary lesions after transplantation: a propensity score-matched study.

BACKGROUND: Given the susceptibility of organs to ischaemic injury, alternative preservation methods to static cold storage (SCS), such as normothermic machine perfusion (NMP) are emerging. The aim of this study was to perform a comparison between NMP and SCS in liver transplantation with particular attention to bile duct lesions. METHODS: The outcomes of 59 consecutive NMP-preserved donor livers were compared in a 1 : 1 propensity score-matched fashion to SCS control livers. Postoperative complications, patient survival, graft survival and bile duct lesions were analysed. RESULTS: While patients were matched for cold ischaemia time, the total preservation time was significantly longer in the NMP group (21 h versus 7 h, P < 0.001). Patient and graft survival rates at 1 year were 81 versus 82 per cent (P = 0.347) and 81 versus 79 per cent (P = 0.784) in the NMP and SCS groups, respectively. The postoperative complication rate was comparable (P = 0.086); 37 per cent NMP versus 34 per cent SCS patients had a Clavien-Dindo grade IIIb or above complication. There was no difference in early (30 days or less) (NMP 22 versus SCS 19 per cent, P = 0.647) and late (more than 30 days) (NMP 27 versus SCS 36 per cent, P = 0.321) biliary complications. However, NMP-preserved livers developed significantly fewer ischaemic-type bile duct lesions (NMP 3 versus SCS 14 per cent, P = 0.047). CONCLUSION: The use of NMP allowed for a significantly prolonged organ preservation with a lower rate of observed ischaemic-type bile duct lesions.

[Mentoring and workplace-based assessments for final year medical students : An effective way to increase satisfaction and competence?] / Mentoring und arbeitsplatzbasierte Prüfungen im Praktischen Jahr : Ein effektiver Weg zur Steigerung von Zufriedenheit und Kompetenz?

BACKGROUND: The final year of medical training in Germany is one of the least structured and standardized years of medical school. Medical students often complain about a lack of guidance, supervision and feedback. They are mostly asked to perform delegable nonmedical tasks even though student experiences in this period critically determine future decisions for certain medical specialties. Consequently, right from the beginning many young professionals feel overburdened especially by the time pressure of everyday clinical practice. The planned amendment of the medical licensing regulations will make competence-based training even more important. This article therefore aims to examine the extent to which a mentoring-based curriculum with workplace-based examinations during the final year of medical studies can make a valuable contribution to this. METHODS: After a needs assessment (structured literature search, results evaluation and focus groups with both students and medical specialists), a mentoring-based curriculum for final year medical students was developed following the Kern cycle. In 2 work sessions 10 discipline-specific competencies for the fields of anesthesiology, critical care, emergency and pain medicine were established and prioritized, which had to be mastered by every student independently at the end of the training period. Assessment of these competencies was performed on a regular basis by trained mentors in the form of workplace-based assessments (mini-clinical evaluation exercise, mini-CEX, direct observation of procedural skills, DOPS). Multiperspective evaluation was and is the foundation of continuous program development. By September 2019 a total of 40 students had completed the modified curriculum and were subsequently interviewed online about various aspects of the tertial. RESULTS: The response rate to the survey was 80% (n = 32). The gender ratio was balanced (male = 50%, female = 50%). Prioritization and assessment of 10 competencies by trained mentors enabled a focused, demand-driven and high-quality training of final year medical students. Surveyed students found the section mentoring and feedback to be very positive and it supported their learning success (grade 1.5). Despite firmly established feedback structures, in retrospect almost half (51.6%) wanted more structured feedback. Workplace-based assessments were mostly previously unknown (64.6%) but were experienced as helpful and meaningful (76.7%). Students felt confident and prepared for the final state examination (81.3%) and their career start (71.0%) after being part of the program. These findings were accompanied by a high level of satisfaction (grade 1.7) as well as a high recommendation rate for this institution (as a training program for final year medical students and as a career start for residents, both with 93.7%). Thus, the good evaluation results of the department before the start of the project could again be slightly improved. CONCLUSION: A demand-driven, mentoring-based curriculum with integrated workplace-based assessments not only led to high overall student satisfaction but also promoted the quality of teaching in an effective and resource-saving way. Mentoring promotes learning success mainly through feedback and individual learning support and also supports the communicative and social skills of students and mentors alike.

Benefits and limitations of belatacept in 4 hand-transplanted patients.

Belatacept (cytotoxic T-lymphocyte-associated protein 4 Ig) is an emerging treatment in kidney transplantation. Lack of nephrotoxicity and possibly an inhibitory effect on the development of donor-specific antibodies (DSAs) make it an interesting agent in hand transplantation. To reduce calcineurin inhibitor immunosuppression and preserve kidney function, we have added belatacept to the therapeutic regimen of 4 hand-transplanted patients at month 4 and at 6, 9, and 13 years after hand-forearm transplantation. Patients received 5 mg/kg belatacept every 2 weeks, and the dosing interval was extended to 4 weeks after 5 applications. Belatacept was initially well tolerated in all cases. Two patients were weaned to a low-dose tacrolimus monotherapy together with monthly belatacept applications. One patient is taking belatacept with lowered tacrolimus and sirolimus trough levels. A fourth patient had significant levels of DSAs at time of conversion and progressed to a severe necrotizing rejection early despite an unaltered baseline immunosuppression. Finger skin necrosis and histologic signs of severe chronic allograft vasculopathy eventually led to amputation of the graft. Implementation of belatacept can be beneficial in hand transplantation. However, our findings indicated both potential and caution and reflection of the immunologic state at the time of conversion.

First observations of fertilized eggs and preleptocephalus larvae of Rhinomuraena quaesita in the Vienna Zoo.

For the first time worldwide, fertilized eggs of ribbon eels (Rhinomuraena quaesita) hatched into feeding preleptocephali and could be kept alive for a period of seven days in the Vienna Zoo. The study reports on husbandry, behavioral observations and dimensions of eggs and preleptocephalus larvae. Furthermore, body color variations of ribbon eels in captivity do not reflect its sex or sexual maturity.

Significant weight loss and rapid resolution of diabetes and dyslipidemia during short-term follow-up after laparoscopic sleeve gastrectomy.

BACKGROUND: Bariatric surgery has been established as the best option of treatment for morbid obesity. Recently, laparoscopic sleeve gastrectomy (SG) has become very popular because of good postoperative weight loss and low morbidity. The aim of this study was to report our single-center experience with SG regarding feasibility, morbidity, and outcome. METHODS: From January 2006 to December 2011, 93 patients (68 female) with a median age of 46 years underwent laparoscopic SG at our department. Thirteen patients had a history of gastric banding with insufficient weight loss or band-related complications. Clinical outcome and laboratory findings were analyzed. RESULTS: The mean preoperative and postoperative body mass index (BMI) was 44.1 ± 6.9 and 33.4 ± 6.8 kg/m(2), respectively (p < 0.001). The mean excessive body weight loss after a median follow-up of 11.9 months was 55.7 % ± 24.9 %. Three bleedings, two staple line leakages, and a deep wound infection required conversion to laparotomy (n = 1), reoperation (n = 4), or endoscopic stent implantation (n = 2). Resolution of diabetes and dyslipidemia was seen in 85 and 50 % of patients, respectively. Blood test results of HbA1c, cholesterols, triglycerides, and leptin showed significant postoperative improvement. CONCLUSIONS: Laparoscopic SG represents a feasible bariatric procedure with good short-term weight loss, low morbidity rate, and efficient resolution of diabetes and dyslipidemia, especially in patients with lower BMI. The significant decrease of leptin necessitates further studies to understand the ambiguous role of leptin in bariatric surgery.