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Faced with the shortcomings of conventional dialysis on a long-term basis, as illustrated by the dialysis-related pathology, a need for a new strategy exists to improve the overall quality of treatment in end-stage renal failure (ESRF) patients. On-line haemodiafiltration (HDF) seems to be the best therapeutic option to achieve this goal at the present time. By enhancing convective clearances through highly permeable membranes, HDF offers the greatest solute fluxes both for low and higher molecular weight uraemic toxins. As for example, in our routinely performed HDF programme based on 3 weekly sessions lasting 3-4 h each, double-pool urea Kt/V achieved was 1.55±0.20 and β2-microglobulin Kt/V was 0.91. By producing substitution fluid from fresh dialysate, the technique of HDF is simplified and becomes economically affordable. By improving the haemodynamic tolerance, HDF allows more elderly and high risk cardiovascular patients to be treated more safely. By using bicarbonate-buffered infusate, HDF facilitates the correction of acidosis. Both by using ultrapure bicarbonate dialysate and down-regulating the membrane reactivity via a 'protein cake', HDF introduces the first step for a full haemocompatibility concept. Finally, by giving access to virtually unlimited amounts of sterile and non-pyrogenic fluid, HDF should introduce new therapeutic options such as a totally automated and feed-back-controlled machine. Today's on-line HDF is already a step forward to enhance the overall efficacy of renal replacement therapy and to improve the global care of ESRF patients. [ABSTRACT FROM PUBLISHER]

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Introduction: We report on our experience of using Helical Tomotherapy (HT) in the context of post-mastectomy radiation therapy (PMRT) with or without immediate implant-based breast Reconstruction (IBR)., Material and Methods: The study included a total of 173 patients who underwent PMRT with HT between 2013 and 2015 in our institution (87 immediate breast reconstructions with retropectoral implants (IBR + ), 86 without reconstructions (IBR-)). The chest wall target volume included subcutaneous tissue and pectoralis muscle and excluded the posterior region of the implant as well as the ribs., Results: Median time to initiation of the first adjuvant treatment from mastectomy was similar between the two groups (p = 0.134). Dose coverage to the chest wall was significantly improved for the IBR + group (V95% = 95.1 % versus 92.0 %; p < 0.0001). The irradiated volume of the ipsilateral lung was significantly decreased in the IBR + group with a median V20Gy of 11.6 %, compared to 15.2 % for the control group (p < 0.0001). The median heart V15Gy was also significantly lower in the IBR + group than in the control group (1.7 vs 2.5 %; p = 0.0280). The reconstruction failure rate was 14.9% (n = 13). After a median follow-up of 65 months, loco regional recurrence rate was low in both groups: 3 patients (3.4%) in the IBR + group and 5 patients (5.8%) in the control group, without any local recurrence in the posterior part of the implant., Conclusions: The presence of a breast implant reduces cardiac and pulmonary doses during Tomotherapy irradiation, without compromising oncological outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Competing Interests: Competing interests: GF reports personal fees from Olympus outside of the submitted work.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: GF reports personal fees from Olympus outside of the submitted work.

Competing Interests: Competing interests: GF reports personal fees from Olympus outside of the submitted work.

Introduction: The objective was to evaluate whether hybrid imaging combining single photon emission tomography with computed tomography (SPECT/CT) provides additional clinical value for dectection of sentinel lymph nodes (SLNs) compared with intraoperative combined mapping in uterine and cervical malignancies., Methods: This was a retrospective study of prospectively collected data from patients with stages IA-IB2 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2018) or stage I endometrial cancer, who underwent preoperative SPECT/CT for SLN detection. All included patients had dual injection of technetium-99m ( 99m Tc) with patent blue or indocyanine green., Results: A total of 171 patients were included with 468 SLNs detected during surgery: 146/171 patients (85.4%) had both radiotracer and blue injection whereas 25/171 patients (14.6%) had radiotracer and indocyanine green injected. The overall detection rate was 95.3%. The detection rate of SLN mapping was 74.9% for SPECT/CT, 90.6% for 99m Tc, 91.8% for blue dye, and 100% for indocyanine green. Bilateral drainage was found in 140 patients (81.9%), detected by 99m Tc in 105 patients (61.4%), by blue in 99 patients (67.3%), by indocyanine green in 23 patients (92%), and by SPECT/CT in 62 patients (36.4%). Atypical SLN locations were identified by SPECT/CT in 64 patients (37.4%), by 99mTc in 28 patients (16.4%), by blue in 17 patients (9.9%), and by indocyanine green in 8 patients (4.7%). Sensitivity and negative predictive value of SLN biopsy to detect lymph node metastasis using dual injection of different intraoperative combined techniques were 88.9% and 97.5%, respectively., Conclusion: SPECT/CT enhanced topographic delineation of SLN and more accurately identified drainage to atypical locations. Fluorescent SLN mapping using indocyanine green offered the highest SLN detection rate. When indocyanine green was used, SPECT/CT did not increase SLN detection, and did not add further information to improve lymph node localization and removal., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Gastric perforation after cytoreductive surgery (CRS) is an infrequent complication. There is lack of evidence regarding the risk factors for this postoperative complication. The aim of this study was to assess the prevalence of postoperative gastric perforation in patients undergoing CRS for peritoneal carcinomatosis (PC) and to evaluate risk factors predisposing to this complication., Methods: We designed a unicentric retrospective study to identify all patients who underwent an open upfront or interval CRS after a primary diagnosis of PC of different origins between March 2007 and December 2018 at a French Comprehensive Cancer Center. The main outcome was the occurrence of postoperative gastric perforation., Results: Five hundred thirty-three patients underwent a CRS for PC during the study period and 13 (2.4%) presented a postoperative gastric perforation with a mortality rate of 23% (3/13). Neoadjuvant chemotherapy was administered in 283 (53.1%) patients and 99 (18.6%) received hyperthermic intraperitoneal chemotherapy (HIPEC). In the univariate analysis, body mass index (BMI), peritoneal cancer index, splenectomy, distal pancreatectomy, and histology were significantly associated with postoperative gastric perforation. After multivariate analysis, BMI (OR [95%CI] = 1.13 [1.05-1.22], p = 0.002) and splenectomy (OR [95%CI] = 26.65 [1.39-509.67], p = 0.029) remained significantly related to the primary outcome., Conclusions: Gastric perforation after CRS is a rare event with a high rate of mortality. While splenectomy and increased BMI are risk factors associated with this complication, HIPEC does not seem to be related. Gastric perforation is probably an ischemic complication due to a multifactorial process. Preventive measures such as preservation of the gastroepiploic arcade and prophylactic suture of the greater gastric curvature require further assessment., Competing Interests: The authors have declared that no competing interests exist.

Background: A few studies have examined the characteristics of severe breast cancer-related lymphedema (BCRL). This study aims at analyzing the factors associated with severe lymphedema (LE) across a specific population of patients with BCRL. Methods and Results: Seventy-four patients with BCRL were included and cared for in the Lymphology Unit of Toulouse University Hospital between 2015 and 2016. Characteristics of patients and factors related to severe BCRL were retrospectively assessed. The median age at time of LE was 56 years (30-82). Thirty-five patients (47.3%) had a mastectomy and 72 (97.3%) an axillary lymphadenectomy. Among patients treated with radiation therapy ( n  = 72), 76.3% received lymphatic nodes irradiation. Fifty-five patients (74.3%) received chemotherapy and 52 (70.3%) a hormonal suppression therapy. A high proportion of patients had severe (>400 mL, 64.9%) and premature LE, with a median time of 13 months since onset of surgery (0.1-400.2). Weight gain between surgery and LE management was more prevalent in obese patients ( p  = 0.0164). Body mass index (BMI) at BCRL diagnosis was the only risk factor associated with severe LE ( p  = 0.0132). There was no significant association between LE severity and treatments received for breast cancer. Conclusions: Our study did not show any influence of tumor characteristics and cancer-related treatments on the severity of BCRL. Only BMI at BCRL diagnosis appears as a factor related to severe LE. These results highlight the importance of an education care unit promoting personalized nutritional lifestyle and encouraging physical activity early in the management of breast cancer.

Objective: Few prognostic factors likely to influence therapeutic management of early-stage cervical cancer are currently recognized. The objective of this study was to determine the prognostic value of lymphovascular space invasion (LVSI) in overall survival of patients with early-stage cervical cancer., Methods: This is a retrospective study of patients treated for early-stage cervical cancer between January 1996 and December 2013 at Toulouse University Hospital and the Cancer Center Claudius Regaud Institute. Patients were included if they had FIGO 2018 stage IA1, IA2, IB1/2, or IIA1 cervical cancer. All patients had to have had surgery (conization, radical hysterectomy, or radical trachelectomy). The presence of LVSI was evaluated in the initial anatomic pathology reports of the excised tissue. The presence of LVSI was defined by the presence of epithelial tumor cells in the lumen of vessels, lined by endothelial cells. If the data were missing, the slides were reviewed by an expert pathologist. Comparative analyses of patient populations with and without LVSI invasion were performed, as well as analyses of overall and disease-free survival., Results: A total of 158 patients were included in the analysis. Seventy-two (45.6%) patients had LVSI. More patients with LVSI received external radiotherapy in addition to standard treatment than patients without LVSI (53% vs 14%, p<0.0001). The overall survival of patients with LVSI (89.8%) was similar to that of patients without LVSI (91.5%) (p=0.39). For patients without lymph node involvement but with LVSI, disease-free survival at 5 years tended to be higher among those treated with external radiotherapy in addition to standard treatments (92.6% vs 79.8%, difference not tested due to the small number of events)., Conclusion: Patients with early-stage cervical cancer with LVSI received external radiotherapy more often, and therefore had an overall survival at 5 years identical to patients without LVSI., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Our objective was to use 18 F-FDG PET/CT to identify a high-risk subgroup requiring therapeutic intensification among patients with locally advanced cervical cancer (LACC) and paraaortic lymph node (PALN) involvement. Methods: In this retrospective multicentric study, patients with LACC and PALN involvement concurrently treated with chemoradiotherapy and extended-field radiotherapy between 2006 and 2016 were included. A senior nuclear medicine specialist in PET for gynecologic oncology reviewed all 18 F-FDG PET/CT scans. Metabolic parameters including SUV max , metabolic tumor volume, and total lesion glycolysis (TLG) were determined for the primary tumor, pelvic lymph nodes, and PALNs. Associations between these parameters and overall survival (OS) were assessed with the Cox proportional hazards model. Results: Sixty-eight patients were enrolled in the study. Three-year OS was 55.5% (95% confidence interval, 40.8-68.0). When adjusted for age, stage, and histology, pelvic lymph node TLG, PALN TLG, and PALN SUV max were significantly associated with OS ( P < 0.005). Conclusion: 18 F-FDG PET/CT was able to identify predictors of survival in the homogeneous subgroup of patients with LACC and PALN involvement, thus allowing therapeutic intensification to be proposed., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Competing Interests: Competing interests: GF reports personal fees from Olympus outside of the submitted work.

Background: Besides the interest of an early detection of ovarian cancer, there is an urgent need for new predictive and prognostic biomarkers of tumor development and cancer treatment. In healthy patients, circulating blood monocytes are typically subdivided into classical (85%), intermediate (5%) and non-classical (10%) populations. Although these circulating monocyte subsets have been suggested as biomarkers in several diseases, few studies have investigate their potential as a predictive signature for tumor immune status,tumor growth and treatment adaptation., Methods: In this study, we used a homogeneous cohort of 28 chemotherapy-naïve patients with ovarian cancer to evaluate monocyte subsets as biomarkers of the ascites immunological status. We evaluated the correlations between circulating monocyte subsets and immune cells and tumor burden in peritoneal ascites. Moreover, to validate the use of circulating monocyte subsets tofollow tumor progression and treatment response, we characterized blood monocytes from ovarian cancer patients included in a phase 1 clinical trial at baseline and following murlentamab treatment., Results: We demonstrate here a robust expansion of the intermediate blood monocytes (IBMs) in ovarian cancer patients. We establish a significant positive correlation between IBM percentage and tumor-associate macrophages with a CCR2 high /CD163 high /CD206 high /CD86 low profile. Moreover, IBM expansion is associated with a decreased effector/regulatory T-cell ratio in ascites and with the presence of soluble immunosuppressive mediators. We also establish that IBM proportion positively correlates with the peritoneum tumor burden. Finally, the study of IBMs in patients with ovarian cancer under immunotherapy during the phase clinical trial supports IBMs to follow the evolution of tumor development and the treatment adaptation., Conclusions: This study, which links IBM level with immunosuppression and tumor burden in peritoneum, identifies IBMs as apotential predictive signature of ascites immune status and as a biomarker ofovarian cancer development and treatment response., Trial Registration Number: EudraCT: 2015-004252-22 NCT02978755., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. In this study, we characterize the mechanisms by which naïve mesenchymal stromal cells (MSCs) can acquire a CA-MSCs phenotype. Ovarian tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells, resulting in the secretion of high levels of CXC chemokine receptors 1 and 2 (CXCR1/2) ligands such as chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and interleukin 8 (IL-8). CXCR1/2 ligands can also inhibit the immune response against ovarian tumor cells. Indeed, through their released factors, CA-MSCs promote the differentiation of monocytes towards M2 macrophages, which favors tumor progression. When CXCR1/2 receptors are inhibited, these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral phenotype. Both ex vivo and in vivo, we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of CA-MSCs. Since high concentrations of CXCR1/2 ligands in patients' blood are associated with chemoresistance, CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance., (© The Author(s) (2019). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.)

Objectives: In hemodialysis, diminution of muscle strength constitutes a major prognostic factor of mortality. Currently, measurement of quadriceps isometric maximal voluntary force (MVF) represents the reference method to investigate muscle strength. However, reduction of MVF is rarely detected in these patients due to the absence of portative bedside tools in clinical practice. The purposes of this study were therefore to assess the agreement of a belt-stabilized handheld dynamometer (HHD) with the dynamometer chair (reference method) and to determine intratester and intertester reliability of the quadriceps MVF measurements using belt-stabilized HHD in healthy subjects and in hemodialysis patients., Design: Repeated-measures cross-sectional study., Setting: Clinical and academic hospital., Participants: Fifty-three healthy adult subjects (23 males, 36.5 + 12.5 y.o.) and 21 hemodialysis patients (14 males, 72.4 + 13.3 y.o., dialysis vintage 30 + 75.1 months)., Intervention: Not applicable., Main Outcome Measure: MVF measurements were assessed with belt-stabilized HHD and dynamometer chair, by two independent investigators. The agreement between the two devices would be quantified using the Bland-Altman 95% limits of agreement (LOA) method and the Spearman correlation., Results: For healthy subjects and hemodialysis patients, Spearman coefficients between belt-stabilized HHD and dynamometer chair were 0.63 and 0.75, respectively (P < .05). In hemodialysis group, reliability was excellent for both the intratester and intertester reliability R 2  = 0.85 (P < .01) and R 2  = 0.90 (P < .01), respectively. In all individuals, the mean difference between the dynamometer chair and the belt-stabilized HHD was -13.07 ± 21.77 N.m. (P < .001). The LOA for the upper and the lower was 29.59 and -55.73 N.m., respectively., Conclusion: In healthy subjects and in hemodialysis patients, the belt-stabilized HHD dynamometer appears as a valid and reliable method to measure in clinical practice isometric MVF of quadriceps in hemodialysis patients. Therefore, the belt-stabilized HHD appears as a suitable and a relevant diagnostic tool for the identification of muscle dysfunction in hemodialysis patients., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

New highly sensitive (hs) assays have challenged the interpretation of cardiac troponins (cTn) as markers of injury while natriuretic peptides remain the markers of choice for myocardial dysfunction. However, variability extracardiac factors such as age, gender and renal function may alter circulating levels. In chronic kidney disease (CKD), the increase in circulating levels of these biomarkers in the absence of cardiac disease underlines the problem of discriminative value for diagnosis as well as the need to redefine the thresholds. In addition, these biomarkers are of potential interest to stratify cardiovascular risk, the leading cause of death in CKD. The aim of this work is to clarify the effect of age and renal function on circulating levels of high-sensitivity troponins and natriuretic peptides.

Complex interactions existing between cardiac and renal diseases led to define 5 types of so-called cardiorenal syndromes. This classification is based on the organ primarily involved and the acute or chronic failure. The mutual impact of renal and cardiac functions makes it difficult to evaluate and manage patients with cardiorenal syndromes and worsen morbidity and mortality. This review seeks to discuss the place of biomarkers in diagnosis, management and follow-up of patients with cardiorenal syndromes. Biomarkers can be classified as functional (creatinine, cystatin C…) or lesional (neutrophil gelatinase-associated lipocalin, urinary cystatin C…) renal markers and functional (natriuretic peptides…) or lesional (troponin, fatty acid binding protein) cardiac markers. A last kind of biomarkers reflects the dialogue between heart and kidney (renin-angiotensin-aldosteron-system, indicators of activation of arginine vasopressin system) or the systemic impact (inflammation, oxidative stress…). In order to evaluate accurately the complex interactions that are the basis of cardiorenal syndromes, a multi-marker approach seems nowadays necessary.

The safety of online hemodiafiltration (ol-HDF) relies on very strict rules of use. The use of ultrapure water to feed an ol-HDF machine is a basic requirement for ol-HDF. Technical aspects and microbial monitoring have been precisely described in the European Best Practice Guidelines. Specifically designed and certified ol-HDF machines are needed. All these machines share the production of substitution fluid by the cold sterilization process of fresh dialysate based on ultrafilters. Hygiene handling is a crucial measure to ensure permanent safety of the ol-HDF system. Frequent disinfection of the water treatment system and dialysis machine, destruction of biofilm by chemical agents and/or thermochemical disinfection, change of filters at regular intervals, and maintenance of a permanent circulation of water are among the basic measures required to ensure ultra-purity of water and dialysis fluid. Optimal performances of ol-HDF require the use of high blood flow (300-400 ml/min), highly permeable and adequately sized hemodiafilters, a high volume of substitution (5-6 l/h) and high dialysate flow (500 ml/min). The site and type of substitution (pre-, post-, mixed, and mid-dilution) should be customized to each patient according to its blood hemorheology and its filtration fraction limitation (transmembrane pressure). All attempts should be made to maximize the fluid volume exchange per session (convective dose) in any cases. The treatment schedule in terms of session duration and weekly frequency need to be adjusted individually to improve hemodynamic tolerance, to facilitate correction of fluid overload and to increase dialysis dose (for middle-sized solutes) in order to reduce circulating levels of major uremic toxins. ol-HDF is the more advanced form of renal replacement therapy offering high efficiency over a large spectrum of toxins, high biocompatibility profile and high flexible modality. ol-HDF may help to improve global care of chronic kidney disease patients and may be considered the renal replacement therapy of the future., (Copyright © 2011 S. Karger AG, Basel.)

Background: Inflammation and malnutrition are recognized as important risk factors for cardiovascular disease (CVD) in hemodialysis (HD) patients. Owing to substantial short-term variability of serum C-reactive protein (CRP), more reliable markers of malnutrition-inflammation complex syndrome should be sought with stronger associations with the risk of CVD in HD patients. We therefore explored the clinical relevance of a composite inflammatory index (prognostic inflammatory and nutritional index [PINI]) and of muscle protein mass indicators, derived from creatinine kinetics., Methods: This cross-sectional study included 177 HD patients (89 women and 88 men; median age, 67.73 years). CVD and risk factors were assessed using medical charts, clinical examination, and biochemical measurements performed at inclusion. Lean body mass (LBM) was derived from creatinine kinetic modeling, whereas PINI was calculated as the ratio (CRP xalpha1-acid-glycoprotein)/(albumin x transthyretin). Patients were divided according to the presence or absence of established CVD., Results: The traditional risk factors diabetes (odds ratio [OR], 5.83; p = 0.0045) and smoking (OR, 3.50; p < 0.02) were associated with an increase in prevalent CVD. Low transthyretin (OR, 3.79; p < 0.02) and high levels of CRP (OR, 2.70; p < 0.05), PINI (OR, 3.44; p < 0.02), observed LBM (OR, 3.01; p < 0.05), and the ratio of observed/expected LBM (OR, 4.24; p < 0.01) were associated with CVD after adjustment for age, sex, dialysis center, and dialysis vintage. After additional adjustment for diabetes and smoking, only PINI (OR, 2.85; p = 0.0446) and observed/expected LBM (OR, 2.96; p = 0.0361) were still significant., Conclusion: PINI and LBM are associated with increased relative risk for having CVD and could be used routinely to examine the degree of severity of malnutrition inflammation complex syndrome.

We describe 7 cases of renal tubular injury in HIV-infected patients receiving an antiretroviral regimen containing tenofovir. Our patients (5 women and 2 men) developed renal tubular dysfunction, with hypophosphatemia, normoglycemic glycosuria, proteinuria, and decrease of creatinine clearance. The first biologic signs of renal toxicity were observed after duration of tenofovir treatment from 5 weeks to 16 months, and they resolved less than 4 months after discontinuation of tenofovir. Six patients had a low body weight (<60 kg). Five patients received low doses of ritonavir, and 1 received didanosine. In 5 patients, the signs resolved with the discontinuation of only the tenofovir. A renal biopsy performed in 1 patient was consistent with tubulointerstitial injury. Proximal tubulopathy appears to be a rare adverse effect of long-term tenofovir therapy. In patients with low weight or mild preexisting renal impairment, regular monitoring of tubulopathy markers could lead to early detection of this dysfunction.

C-reactive protein (CRP) is the prototype of acute-phase protein which is secreted by the liver in response to a variety of inflammatory cytokines. Levels of CRP can increase up to 1000-fold very rapidly after the onset of inflammation and decrease just as rapidly with the resolution of aggression. CRP is a member of the ancient highly conserved pentraxin family of proteins and it is arranged in a cyclic homopentameric structure. The important role of CRP in innate immunity is largely due to its opsonizing abilities, its capability to activate human complement and to bind to immunoglobulin G receptors. CRP can bind phosphocholine largely present in bacterial membranes, cell membrane and lipoproteins, in addition CRP can recognize nuclear constituent in damaged cells. CRP can activate C3 convertase through the classical pathway but not C5 convertase resulting in generation of opsonic complement fragments. Interactions of CRP with Fc receptors lead to the generation of proinflammatory cytokines and reactive oxygen species by monocyte/macrophage while inhibit neutrophiles functions. Recently, CRP was demonstrated to play an active role in atherogenesis and it has been largely proven that a microinflammatory state as defined by a moderate increase in CRP (up to 3 mg/l), is associated with an increased risk for arterial disease. Moreover it has been postulated that CRP may be a useful tool for monitoring drug therapy.

Dialysate purity has become a major concern in hemodialysis since it has been shown that microbial-derived products were stimulating the production and the release of proinflammatory cytokines in hemodialysis patients. This chronic microinflammatory state induced by hemodialysis has been putatively implicated in the development of dialysis-related pathology. In order to prevent risk related to these offenders and to reduce patient/dialysis interaction, it appears highly desirable to use ultrapure dialysis fluid aiming at sterility and apyrogenicity on a regular basis. Ultrapure dialysate results from a complex chain of production where purity grade relies on the weaker link of this chain. Technical aspects and pitfalls in the production of ultrapure dialysate are summarized in this paper. Production of ultrapure dialysate may be achieved on a routine basis, provided adequate components are used, and hygienic handling is regularly ensured. It includes the use of ultrapure water, clean and or sterile electrolytic concentrates (liquid or powder), implementation of ultrafilters on hemodialysis machines, microbiologic monitoring and hygienic handling of the chain with frequent disinfection. Safety and reliability of ultrapure dialysate production relies on a continuous quality assurance process, where results are coupled to corrective action in a feedback loop process., (Copyright 2000 S. Karger AG, Basel)

Dialysate purity has become a major concern in recent years since it was shown that low levels of endotoxin in dialysate were able to induce the production of proinflammatory cytokines, which were putatively implicated in the development of dialysis-related pathology. On-line haemodiafiltration (HDF; or haemofiltration) using the dialysate as the source of substitution fluid magnifies this risk and reinforces the critical role of the dialysate quality to be used. In order to virtually abolish the risk related to dialysate contaminants, it is mandatory to ensure the highest purity of the dialysate used in order that the substitution fluid produced satisfies the quality demands of a sterile and pyrogen-free infusion solution. Ultrapure dialysate production is therefore a common need for all on-line systems where substitution fluid is prepared continuously by sterilizing filtration of the dialysate. However, since dialysate purity plays a role in the complex haemocompatibility interaction which occurs during the haemodialysis session, the use of ultrapure dialysate must be considered as a suitable option for all haemodialysis modalities. To achieve this goal, one must keep in mind that ultrapure dialysate and infusate result from a complex chain of production where ultrapurity and/or sterility of the final solution relies on the weakest or worst component of the chain. Reliable production of ultrapure dialysate and infusate relies on several prerequisites: use of ultrapure water, use of clean electrolytic concentrates, implementation of ultrafilters on specifically designed HDF machines, microbiological monitoring of the chain with adequate and sensitive methods, and hygienic handling of the chain including frequent disinfection to reduce the level of contamination and to prevent biofilm formation. When properly done, the safety and reliability of on-line systems have been confirmed in large clinical studies. It is now time to validate the on-line process in large controlled clinical trials.

An angiosarcoma arising at the site of an arteriovenous fistula in a renal transplant recipient is reported. Only two similar cases have yet been described. This report is documented with an immunohistochemical study and etiopathogenesis is discussed. Immunosuppressive therapy and the arterio-venous fistula might both be involved in the occurrence of this neoplasm. We focus attention on this uncommon complication which should always be entertained when a renal transplant recipient complains about a painful arterio-venous fistula.

Severe skin necrosis of poor prognosis have been rarely reported among chronic renal failure patients. Their clinical outbreak must rapidly lead to search for a secondary hyperparathyroidism. Early parathyroidectomy seems is the only treatment able to stop the progression of the skin lesions. From an original clinical observation we discuss the different mechanisms involved.

Temporary vascular access (TVA) is a basic requirement in clinical nephrology. TVA permits immediate and repeated hemodialysis for all type of ESRD patient. Going from peripheral to central and from temporary to permanent angioaccess are the two main trends observed in TVA in contemporary dialysis. Our experience over the last decade illustrates this TVA changes. On the one hand peripheral arterio-venous shunt has been forsaken in favour of percutaneous implanted central venous catheters. On the other hand, two types of central venous catheters have been used covering up our preferences: catheters for short term use (< 7 days) usually via femoral vein and catheters for long term use (7 days to months) mainly via the internal jugular vein. Due to traumatic and/or long term mechanical risks (venous stenosis and/or thrombosis), the subclavian way has been abandoned in our unit. Performances (blood flow rate 250-350 ml/min, recirculation rate 9-12%) obtained in about 1500 patients warranted dialysis efficiency. Traumatic and/or mechanic lesions were the most frequent complications observed with the femoral catheter, while infection remained the most important one associated with the long term use of jugular vein catheters. Therefore, it is clear that over the last decade temporary vascular access was becoming synonymous with percutaneous central venous catheter. Such an approach has greatly simplified the task of physicians while facilitating the management of large uremia treatment program.

To our knowledge Amanita proxima poisoning has never been reported. Amanita proxima is a mushroom seldomy encountered, similar to a common and edible species: Amanita ovoïdae. During October 1992, we had the opportunity to care for five cases of intoxications with Amanita proxima. In all cases early digestive disorders, cytolytic hepatitis and acute renal failure were noted. Outcome was favourable for all patients within three weeks with total recovery of both renal and hepatic functions with symptomatic treatment. Temporary dialysis was required in four patients.