FoxP3 T cells and the pathophysiologic effects of brain death and warm ischemia in donor kidneys

Background and objectives Forkhead box P3 regulatory T cells control inflammatory responses, but it remains unclear whether they inhibit brain death-initiated inflammation and tissue injury in deceased kidney donors. Design, setting, participants, & measurement To study the actions of regulatory T cells at various stages of the donation and transplantation procedure, forkhead box P3, regulatory and inflammatory cytokine expression, and tissue injury markers were determined in time 0 kidney biopsies from deceased and living donors. Additionally, the interaction between forkhead box P3+ T cells and kidney injury molecule-1 by activated primary tubular epithelial cells was studied. Results After cold storage, the deceased donor kidneys expressed the higher mRNA levels of kidney injury molecule-1 and CD3ε. In these samples, the inflammatory cytokines IL-8 and IFN-γ and markers associated with regulation (forkhead box P3, TGF-β, and IL-10) were highly expressed compared with living donor kidneys. Correlations were found between mRNA expression levels of forkhead box P3 and kidney injury molecule-1 and forkhead box P3 and IFN-γ. Immunohistochemical analysis confirmed the presence of forkhead box P3+ T cells in donor kidneys. Renal function (analyzed by serum creatinine levels) at the first week posttransplantation correlated with kidney injury molecule-1 and forkhead box P3 mRNA levels. In vitro studies showed that kidney injury molecule-1 expression by primary tubular epithelial cells was 63% (mean) lower when cocultured with regulatory T cells compared with control T cells. Conclusions These results show that donor forkhead box P3+ T cells infiltrate the deceased donor kidney, where they may control inflammatory and injury responses

Low skeletal muscle mass as a risk factor for postoperative delirium in elderly patients undergoing colorectal cancer surgery

Background: Both low skeletal muscle mass (LSMM) and delirium are frequently seen in elderly patients. This study aimed to investigate the association between preoperative LSMM and postoperative delirium (POD) in elderly patients undergoing colorectal cancer (CRC) surgery and to design a model to predict POD. Patients and methods: This is a retrospective observational cohort study. Patients aged 70 years or older undergoing CRC surgery from January 2013 to October 2015 were included in this study. The cross-sectional skeletal muscle area at the level of the third lumbar vertebra using computed tomography was adjusted for patients' height, resulting in the skeletal muscle index. The lowest quartile per sex was defined as LSMM. Short Nutritional Assessment Questionnaire for Residential Care and KATZ-Activities of Daily Living were used to define malnourishment and physical dependency, respectively. POD was diagnosed using the Delirium Observational Screening Scale and geriatricians' notes. Results: Median age of the 251 included patients was 76 years (IQR, 73-80 years), of whom 56% of patients were males, 24% malnourished, and 15% physically impaired. LSMM and POD were diagnosed in 65 and 33 (13%) patients, respectively. POD occurred significantly more in patients with LSMM (25%) compared with patients without LSMM (10%), P=0.006. In the multivariate analysis, age, history of delirium, and LSMM were significantly associated with POD. In addition, this effect increased in patients with LSMM and malnourishment (P=0.019) or physical dependency (P=0.017). Conclusion: Age, history of delirium, LSMM, and malnourishment or physical dependency were independen

Evidence-based guideline on management of colorectal liver metastases in the Netherlands.

A dutch national evidence-based guideline on the diagnosis and treatment of patients with colorectal liver metastases has been developed. The most important recommendations are as follows. For synchronous liver metastases, spiral computed tomography (CT) or magnetic resonance imaging (MRI) should be used as imaging. For evaluation of lung metastases, imaging can be limited to chest radiography. For detection of metachronous liver metastases, ultrasonography could be performed as initial modality if the entire liver is adequately visualised. In doubtful cases or potential candidates for surgery, CT or MRI should be performed as additional imaging. For evaluation of extrahepatic disease, abdominal and chest CT could be performed. Fluorodeoxyglucose positron emission tomography could be valuable in patients selected for surgery based on CT (liver/abdomen/chest), for identifying additional extrahepatic disease. Surgical resection is the treatment of choice with a five-year survival of 30 to 40%. Variation in selection criteria for surgery is caused by inconclusive data in the literature concerning surgical margins

Organ donation as transition work:Policy discourse and clinical practice in The Netherlands

An increasing number of patients become eligible for organ transplants. In the Netherlands, at the level of policy discourse, growing waiting lists are often referred to as a persistent “shortage” of organs, producing a “public health crisis.” In this way, organ donation is presented as an ethical, social, and medical necessity. Likewise, policy discourse offers a range of seemingly unambiguous solutions: improving logistical infrastructure at the level of hospitals, developing organizational and legal protocols, as well as public information campaigns. Instead of taking these problem and solution definitions as given, we critically examine the relationship between policy discourse and clinical practice. Based on a historical review, first, we trace the key moments of transformation where organ donation became naturalized in Dutch policy discourse, particularly in its altruistic connotation. Second, based on in-depth interviews with medical professionals, we show how those involved in organ donation continue to struggle with the controversial nature of their clinical practice. More specifically, we highlight their use of different forms of knowledge that underlie clinicians’ “transition work”: from losing a patient to “gaining” a donor. Keywords: death dying and bereavement, health policy, profession and professionalization, research methodology, technology in health car

More than a decade after live donor nephrectomy: a prospective cohort study

Item does not contain fulltextPreviously reported short-term results after live kidney donation show no negative consequences for the donor. The incidence of new-onset morbidity takes years to emerge, making it highly likely that this will be missed during short-term follow-up. Therefore, evidence on long-term outcome is essential. A 10-year follow-up on renal function, hypertension, quality of life (QOL), fatigue, and survival was performed of a prospective cohort of 100 donors. After a median follow-up time of 10 years, clinical data were available for 97 donors and QOL data for 74 donors. Nine donors died during follow-up of unrelated causes to donation, and one donor was lost to follow-up. There was a significant decrease in kidney function of 12.9 ml/min (P < 0.001) at follow-up. QOL showed significant clinically relevant decreases of 10-year follow-up scores in SF-36 dimensions of physical function (P < 0.001), bodily pain (P = 0.001), and general health (P < 0.001). MFI-20 scores were significantly higher for general fatigue (P < 0.001), physical fatigue (P < 0.001), reduced activity (P = 0.019), and reduced motivation (P = 0.030). New-onset hypertension was present in 25.6% of the donors. Donor outcomes are excellent 10 years post-donation. Kidney function appears stable, and hypertension does not seem to occur more frequently compared to the general population

Imaging and treatment of patients with colorectal liver metastases in the Netherlands: a survey

BACKGROUND: Clinical experience has highlighted the absence of a uniform approach to the management of patients with colorectal liver metastases in the Netherlands. METHODS: A written survey on the diagnosis and treatment of patients with colorectal liver metastases was sent to all 107 chairmen of oncology committees in each hospital. Questions were asked concerning: specialists involved in decision-making, availability and existence of guidelines and meetings, factors that needed to be improved, information regarding the diagnostic work-up of liver metastases, detailed techniques of ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET), factors influencing resectability, types of surgery performed, the use of (neo)adjuvant chemotherapy, portal vein embolisation performance, considering isolated hepatic perfusion (IHP) or local ablation as treatment options, actual performance of local ablation and the use of systemic as well as regional chemotherapy. RESULTS: Response rate was 68% (73/107). Specialists involved in the management were mostly surgeons (70), medical oncologists (66) and radiologists (42). Factors that needed to be improved, as indicated by responders, were the absence of 1) guidelines; 2) registration of patients and 3) guidelines for radiofrequency ablation (RFA). Diagnostic work-up of synchronous liver metastases occurred in 71 hospitals, (by US in 69 and by CT in 2). For the work-up of metachronous liver metastases, US was used as initial modality in 14, CT in 2 hospitals, and 57 hospitals used one or the other (mainly US). As additional modality, CT was performed (71) and to a lesser extent MRI (38) or PET (22). Diagnostic laparoscopy and biopsy were performed incidentally. The choice for an imaging modality was mostly influenced by the literature, and to a lesser extent by the availability and by costs, personnel and waiting lists. Substantial variation exists in the US, CT, MRI and PET techniques. The absence of extrahepatic disease and the clinical condition were considered as the most important factors influencing resectability. Surgery was performed in 30 hospitals; hemihepatectomy in 25, segment resection in 27, multisegment resection in 23, wedge excision in 27 and combination of resection and RF A in 18 institutions. In 52 hospitals (neo)adjuvant chemotherapy was administrated to improve surgical results, partly (35%) in trials. In nine hospitals portal vein embolisation was performed, with the volume of the remnant liver as the most important factor. Local ablative techniques were considered as a treatment option in 48 hospitals and actually performed in 16 hospitals, without clearly defined indications. Experimental IHP was considered a treatment option by 45 (62%) responders, irrespective whether this treatment was available at their centre. Patients with extensive metastases received systemic chemotherapy in all 73 hospitals and regional chemotherapy in ten hospitals. CONCLUSION: This survey shows substantial variation in the diagnostic and therapeutic work-up of patients with colorectal liver metastases. This variation reflects either under- or over-utilisation of diagnosis and treatment options. Evidence-based guidelines taking into account the available evidence, experience and availability can solve this variation

Substantial proliferation of human renal tubular epithelial cell-reactive CD4+CD28null memory T cells, which is resistant to tacrolimus and everolimus

Item does not contain fulltex

Multivariate Analysis of Health-related Quality of Life in Donors After Live Kidney Donation

Item does not contain fulltextBACKGROUND: Live-kidney donation has a low mortality rate. Evidence suggests that live-kidney donors experience a quality of life (QoL) comparable to or even superior to that of the general population. There is limited information on factors associated with a decrease in QoL in particular for baseline factors, which would improve information to the donor, donor selection, and convalescence. METHODS: QoL data on 501 live donors included in three prospective studies between 2001 and 2010 were used. The 36-item short form health survey (SF-36) was used to measure QoL up to 1 year after the procedure. Longitudinal effects on both the mental (MCS) and physical component scales (PCS) were analyzed with multilevel linear regression analyses. Baseline variables were age, gender, body mass index (BMI), pain, operation type, and comorbidity. Other covariates were loss of the graft, glomerular filtration rate, and recipient complications. RESULTS: After 1 year we observed a small decrease in PCS (effect size = -0.24), whereas the MCS increased (effect size = 0.32). Both PCS and MCS were still well above the norm of the general Dutch population. Factors associated with a change in PCS were BMI (Cohen's d = -0.17 for 5 BMI points) and age (d = -0.13 for each 10 years older). CONCLUSIONS: Overall, QoL after live-donor nephrectomy is excellent. A lowered PCS is related to age and body weight. Expectations towards a decreased postoperative QoL at 1 year are unjustified. However, one should keep in mind that older and obese donors may develop a reduced physical QoL after live-kidney donation

Short article: Management of ruptured hepatocellular carcinoma in a European tertiary care center

GOALS AND BACKGROUND: Spontaneous rupture is a rare complication of hepatocellular carcinoma (HCC). Treatment options consist of transcatheter arterial embolization (TAE), hepatic resection, and conservative therapy. The best approach is under debate. STUDY: This study presents a review of clinical data of patients with a ruptured HCC admitted to a European tertiary care center. RESULTS: Eleven patients were included; six (55%) had underlying cirrhosis. The majority of patients (73%) had no previous history of HCC. Spontaneous HCC rupture was diagnosed using abdominal computed tomography with or without a diagnostic paracentesis. Computed tomography showed one or two tumors in eight (73%) patients; the other patients had multiple tumors or diffuse infiltrative HCC. Seven (64%) patients were initially treated by TAE and one (9%) patient underwent hepatic resection. The remaining three (27%) patients, all of whom had liver cirrhosis, received conservative therapy. Two patients initially treated by TAE underwent a delayed resection and ultimately received systemic therapy. Overall, at the end of the follow-up period, three patients were still alive at 84, 991, and 1026 days after the initial presentation. Eight (73%) patients had died after a median of 88 days (range 7-417). One year after presentation, none of the conservatively treated patients was alive compared with three out of seven (43%) patients treated with TAE with or without delayed resection. CONCLUSION: Patients with a spontaneously ruptured HCC have a poor prognosis. In selected patients, however, prolonged survival is possible using TAE as initial therapy with or without a delayed resection and systemic therapy