[Freedom in retirement home, facing confinement]. / Les libertés en EHPAD, à l'épreuve du confinement.

The COVID-19 pandemic has limited the freedom of any citizen, further increased constraint for people in EHPAD - the most widespread type of French Residential care for senior citizens with a high level of dependency, often very aged, suffering multiple pathologies and sometimes psycho-behavioral disorders. "Golden" containment rule was 24/7 confinement in their room, with the very restrictive framework - up to NO visiting by relatives - and very often with a total absence of consent as for screening sample decisions. We can then question the fundamentals of such restriction of freedom, which is a constitutional right for everybody, including for residents in EHPAD, especially non-compliance with self-determination and consent. The principal objective has been a collective interest, before the individual right and the benefit for the patient itself. Nothing would have been justifying to create a possible risk to other residents, generated by another resident's behavior or one of his relatives. But these safety measures were taken despite the underlying risk of deteriorating individual situations through social and emotional isolation, and thus to further reduce autonomy capacities. "Luckily" the know-how and creative spirit of EHPAD professionals limited the consequences of this restriction of freedom. Hard lessons should be learned from share experiences if such a context were to occur again. But above all arises the question of the place of these dependent people in our society. It is essential to think collectively about these living spaces including protocols that should reflect people's choice and on-location adapted to be more open to the outside/foreigners visits. Spaces shall be adapted to their vulnerability, designed to reduce isolation, to repeat such extreme restrictive measures in the event if it shall occur. Of course, rigorous confinement rules allowed to limit deaths linked to the COVID infection, but at the risk of dying in loneliness and grief.

Acoustical bubble trapper applied to hemodialysis.

Gaseous microemboli can arise in extracorporeal lines and devices such as dialysis machines. They are associated with severe pulmonary side effects in patients undergoing chronic hemodialysis sessions. The goal of this study was to develop a gaseous emboli trapper using ultrasound waves to remove any air bubble from the tubing system before they reach the patient. A homemade bubble trapper, developed in the laboratory, consists of a Perspex block containing a main channel connected to the tubing of a hemodialysis machine and a second subchannel positioned perpendicularly to the main one, used to trap the air microemboli. The microemboli flowing in the main channel were insonified through an acoustic window with an ultrasound wave, at a frequency of 500 kHz and with a maximal acoustic pressure of 500 kPa, generated by a single-element transducer positioned 3 cm away from the main flow. The radiation force induced by the ultrasound beam acts directly on the flowing air emboli, by pushing them into the subchannel. Two Doppler probes operating both at 2 MHz, connected to a DWL Doppler machine were placed before and after the bubble trapper to count sequentially the number of embolic events. The flow of the machine was varied between 200 mL/min and 500 mL/min. Depending on the flow velocity, the number of microembolic signals (MES) detected by the Doppler probes before and after the trapping system was identical and ranged from 5 to 150 MES/min in absence of the ultrasound irradiation. When the air bubble trapper was activated, a reduction of the number of MES, up to 70%, was achieved. Doppler recordings suggest that the circulating bubbles were either fragmented into smaller bubble fragments or directly got pushed into the second subchannel where they were collected. This simple approach using an ultrasound-based trapping system was shown to operate adequately with the current settings and can be used to filter air microemboli.

Salvage of immature forearm fistulas for haemodialysis by interventional radiology.

BACKGROUND: The goal of this article is to assess the value of endovascular techniques for the salvage of fistulas that fail to mature. METHODS: Over a 6-year period, 52 dysfunctional and 17 thrombosed immature forearm fistulas (mean age 10 weeks) were treated by interventional radiology. Angiography was performed by puncture of the brachial artery but dilation of underlying stenoses was performed after cannulation of the fistula itself, whenever possible, with a balloon never smaller than 5 mm. Embolization or ligation of any type of vein was never indicated and never performed. For thrombosed fistulas, significant clots were removed by manual catheter-directed aspiration. A covered stent (Passager) was used in cases of dilation-induced rupture not controlled by balloon tamponade. RESULTS: An underlying stenosis was diagnosed in 100% of cases. Half of them were located in the anastomotic area. The initial success rate of interventional radiology was 97%. Dilation-induced rupture occurred in nine cases (13%) but stents were necessary in only two cases. The rate of significant clinical complications was 2.8% (bacteraemia, pseudoaneurysm). Primary and secondary patency rates at 1 year were 39 and 79%, respectively. CONCLUSIONS: Delayed maturation of native fistulas should lead systematically to imaging as an underlying stenosis is diagnosed in all cases. Interventional radiology can treat the majority of cases and achieve a 97% success rate but early recurrence of stenoses can occur. Multidisciplinary re-evaluation of the patient must, therefore, be performed after radiological salvage of the fistula.

Increased glomerular cell heparan sulfates in vitro by ciclosporin A: a Possible explanation of Its beneficial effect in idiopathic nephrotic syndrome.

BACKGROUND/AIM: In idiopathic nephrotic syndrome (INS), ciclosporin A (CsA) was shown to decrease proteinuria, an effect explained by its immunologic and hemodynamic actions. In order to determine whether CsA could have a direct action on glomerular cells, we studied the effect of CsA on glomerular cells in vitro, particularly on glycosaminoglcycans (GAG) and heparan sulfates (HS) which are decreased in INS patients. METHODS: Human glomerular epithelial cells and rat mesangial cells were cultured at various concentrations of CsA. HS were quantified using a cationic membrane after metabolic labeling. RESULTS: Mesangial cell GAG and HS and epithelial cell HS increased significantly when cells were cultured with CsA. For both cell types this increase was prevailing on the secreted fraction of HS in comparison with the cellular fraction. CsA induced also an increase in cellular cAMP levels, but the effect of CsA was not transduced via a cAMP pathway. CONCLUSIONS: CsA is able to increase glomerular GAG and HS in vitro. As this effect of CsA was the opposite effect on glomerular cells to the effect of plasma from INS patients, we conclude that this direct action of CsA on glomerular cells could explain in part the effect of this drug in decreasing proteinuria in INS.

In vitro decrease of glomerular heparan sulfate by lymphocytes from idiopathic nephrotic syndrome patients.

BACKGROUND: Lymphocytes are involved in the physiopathologic mechanism of idiopathic nephrotic syndrome (INS). We have recently demonstrated that plasma from patients with INS decreases human glomerular epithelial cell (GEC) glycosaminoglycans (GAGs), particularly heparan sulfates (HS) in vitro. In this study we investigate the effect of peripheral blood lymphocytes (PBL) from INS patients on glomerular cell GAG and HS. METHODS: Human GECs were cultured with total peripheral blood mononuclear cells (PBMCs), PBL, and monocytes from patients and controls. The amounts of GAG and HS were assessed using a cationic membrane after metabolic labeling. RESULTS: In coculture with GECs, mononuclear cells from controls decreased total epithelial cell GAG (-30% with PBMC, P < 0.05; -25% with PBL, P < 0.02; -19% with monocytes, P < 0.05). Particularly HSs were decreased (-36% with PBMC, P < 0.05; -27% with PBL, P < 0.02; and -19% with monocytes, P < 0.05). When GECs were in coculture with PBL from INS patients, the decrease in GAG and HS was significantly greater in comparison to control PBL (-10%, P < 0.02; -10%, P < 0.02, respectively, for GAG and HS). Moreover, supernatants of stimulated PBMCs from patients decreased also GAG and HS in comparison with controls (-13%, P < 0.02; -15%, P < 0.02, respectively, for GAG and HS). CONCLUSION: These data provide direct evidence that PBLs from INS patients are able to decrease GEC HS as previously shown with plasma from patients. This might be instrumental in the onset of albuminuria.

Role of cyclic AMP in idiopathic nephrotic syndrome: a pathway involving a decrease in glomerular cell heparan sulfates?

The physiopathological mechanisms of idiopathic nephrotic syndrome involve a circulating plasma factor and a decrease in HS in the glomerular basement membrane. Previous studies have demonstrated that plasma from patients with INS decreases glomerular cell HS in vitro. We examined the involvement of cyclic adenosine monophosphate (cAMP) in this interaction. We studied the effect of plasma from patients with INS on mesangial cell cAMP. We also determined mesangial cell HS when cAMP levels were modified using a cationic membrane after metabolic labeling. Cellular cAMP levels increased significantly when mesangial cells were incubated with plasma from patients with INS in comparison with control plasma (+77%, P = 0.01). Forskolin and IBMX, which increased cellular cAMP, decreased HS levels (-21 +/- 9% and -15 +/- 6% respectively, P < 0.05 for both), whereas dideoxyadenosine, which decreased cellular cAMP, increased HS levels (+24 +/- 7%, P < 0.05). Plasma from patients with INS decreased glomerular cell HS in comparison with control plasma (-34 +/- 8%, P < 0,05). This effect was abolished when cells were preincubated with ddAdo to prevent an increase in cAMP levels. We conclude that in mesangial cells, plasma from patients with INS increases cAMP levels, and that cAMP mediates a decrease in HS levels. Moreover, the action of plasma from patients on HS was inhibited when an increase in cAMP was prevented. cAMP may therefore be instrumental in the negative effect of the plasma factor on mesangial cell HS.

Transplant renal artery stenosis: potential role of ischemia/reperfusion injury and long-term outcome following angioplasty.

PURPOSE: We assess long-term arterial pressure, renal function, and patient and graft survival in recipients of cadaveric kidney transplant with or without transplant renal artery stenosis. We also evaluate the risk factors for transplant renal artery stenosis. MATERIALS AND METHODS: We reviewed and analyzed baseline clinical, immunological and outcome data for 26 patients with transplant renal artery stenosis before and after angioplasty, and 72 without stenosis on angiography. We also analyzed graft and patient survival in 304 cases in which angiography was not performed. RESULTS: The incidence of transplant renal artery stenosis was 6.6% (26 of 402 patients). Acute rejection episodes (42 versus 22%, p <0.05) and delayed graft function (50 versus 32%, p <0.10) were more frequent, and mean cold ischemia time plus or minus standard error (29.2+/-1.7 versus 24.8+/-1.3 hours, p <0.01) was longer in patients with than without transplant renal artery stenosis. The technical success of angioplasty was 92.3%. Restenosis was documented in 6 of 26 patients (23.1%). Revascularization resulted in a decrease in arterial pressure and better renal function. The 8-year patient (100, 98.6 and 95.7%, respectively) and graft (88.1, 88.9 and 89.3%, respectively) actuarial survival rates were similar among patients with or without transplant renal artery stenosis, and those who did not undergo angiography. CONCLUSIONS: Transplant renal artery stenosis had no detectable influence on long-term arterial pressure control, renal function, and patient and graft survival rates, which were similar to those in patients without stenosis. Long cold ischemia time may have a role in the development of transplant renal artery stenosis through ischemia/reperfusion injury.

[Transplant renal artery stenosis: long term effect of angioplasty on arterial pressure control and renal function]. / Sténose de l'artère rénale du greffon: effet à long terme de l'angioplastie sur le contrôle de la pression artérielle et la fonction rénale.

We assessed the long-term (M +/- SE: 68 +/- 3 months) arterial pressure and renal function of cadaveric kidney transplant recipients with and without significant (> 70% diameter reduction) transplant renal artery stenosis (TRAS) at angiography. Baseline clinical, immunological and outcome data for 26 patients with TRAS (incidence of TRAS: 6.6%) before and following angioplasty and 72 patients without stenosis at angiography were reviewed and analyzed. The 2 groups were similar with respect to recipient sex ratio and age (45 vs 46), duration of transplantation (7 months), cause of renal failure, donor sex and age, HLA-antigen mismatches and titers of anti-HLA antibodies, CMV infection and anti-CMV antibodies in donors and recipients. The technical success of angioplasty was 92.3%. Restenosis was documented in 6/26 patients (23.1%). Revascularization resulted in a decrease of arterial pressure and number of antihypertensive medications and a lower serum creatinine compared to baseline values. The long-term arterial pressure and serum creatinine levels were similar in patients with and without stenosis. In conclusion, TRAS after revascularization had no detectable influence on the long-term arterial pressure control and renal function within a follow-up period of 68 +/- 3 months.

Effect of plasma from patients with idiopathic nephrotic syndrome on proteoglycan synthesis by human and rat glomerular cells.

In vivo and in vitro findings have shown that plasma of patients with idiopathic nephrotic syndrome (INS) contain factors that increase glomerular permeability to proteins. The effects of these factors on proteoglycan synthesis by glomerular cells are unknown. To investigate the effect of plasma from patients with INS (n = 23) and other glomerulopathies (n = 12) on the amount of proteoglycans synthesized by cultured rat mesangial cells and human glomerular epithelial cells, glomerular cells were cultured for 24 h with plasma from patients or control subjects, and incorporation of Na2(35)SO4 in chondroitin dermatan sulfate and heparan sulfate was assessed using a cationic nylon membrane. The mean ratio of glycosaminoglycan produced by rat mesangial cells when in contact with plasma (5%) from INS patients to the amount produced when in contact with control plasma was 0.70+/-0.06. The mean ratio of heparan sulfate was 0.58+/-0.08. The decrease of heparan sulfate production was present in the cellular and in the extracellular fraction. It was observed when the cells were in contact with plasma from patients in relapse but not when in remission. No decrease of heparan sulfate production was observed with four of the five patients with membranous glomerulonephritis (ratio of 1.27+/-0.03), IgA nephropathy (n = 5, ratio of 1.27+/-0.03), and membranoproliferative glomerulonephritis (n = 2, ratio of 1.39+/-0.34). When human glomerular epithelial cells were exposed to 5% plasma from INS patients in relapse (n = 9), the mean ratio of heparan sulfate was 0.62+/-0.06 in the cellular fraction and 0.72+/-0.08 in the medium. When in contact with plasma from patients in remission, no difference of glycosaminoglycan production was observed. A factor present in plasma from patients with INS during initial episodes or relapses is able to decrease the proteoglycan production of glomerular cells.

Human lymphocyte adhesion to xenogeneic porcine endothelial cells: modulation by human TNF-alpha and involvement of VLA-4 and LFA-1.

Considering that in the allogeneic situation the adhesion of recipient lymphocytes to donor endothelial cells initiates the cellular rejection, we questioned the possible occurrence of a similar process in the xenogeneic situation. The adhesion of human peripheral blood lymphocytes (PBL) to porcine aortic endothelial cells (PAEC) was thus studied in an in vitro porcine-to-human xenogeneic model. It was found that 25.9% of human PBL adhered to resting PAEC. Furthermore, this adhesion increased significantly when the PAEC were stimulated by the human cytokine TNF-alpha (tumor necrosis factor-alpha). The effect of human TNF-alpha was concentration- and time-dependent and was maximal (from 25.9% to 35.6%) with 100 U/ml during 6 h. Moreover, blocking experiments with monoclonal antibody (mAb) demonstrated the role of the PBL adhesion molecules LFA-1 and especially VLA-4. Indeed, an anti-CD11a mAb decreased PBL adhesion to resting PAEC by 17.1% and to TNF-alpha stimulated PAEC by 16.9%, whereas an anti-CD49d mAb decreased dramatically PBL adhesion to resting PAEC by 53.1% and to TNF-alpha stimulated PAEC by 41.0%. Finally, phenotypic analysis of the adherent PBL showed that 50.5% of adherent cells to resting PAEC were NK (natural killer) cells, whereas 50.7% of adherent cells to TNF-alpha stimulated PAEC were T lymphocytes, showing the preferential adhesion of NK cells to resting PAEC, and that the stimulation of the PAEC with human TNF-alpha affects predominantly T lymphocyte adhesion. These results indicate that human PBL could bind to xenogeneic PAEC and that this interaction could be a first step of a xenogeneic cellular rejection.

[Lymphocyte adhesion of human peripheral blood to aortic endothelial cells of a porcine xenograft: preferential adhesion to NK CD3-CD16+ cells]. / L'adhésion de lymphocytes de sang périphérique humain à des cellules endothéliales aortiques de porc xénogéniques: adhésion préférentielle de cellules NK CD3- CD16+.

Xenotransplantation, the transplantation of tissues or organs between species find renewal interest because of human organ shortage. As the xenogeneic transplantation leads immediately to an humoral mediated rejection with graft necrosis, the study of the cellular response is not possible in vivo. So we developed an in vitro model to study the adhesion of human peripheral blood lymphocytes (PBL) to porcine aortic endothelial cells (PAEC). We showed that PBL were able to bind to PAEC, and that this adhesion was increased when PAEC were stimulated with human recombinant TNF-alpha. The action of TNF-alpha is maximal when PAEC were stimulated during 6 hours with 100 U/ml TNF-alpha. This adhesion involved preferentially CD3-CD16+ NK cells compared with CD3+CD16- T lymphocytes. Finally monoclonal antibodies directed against PBL adhesion molecules decreased PBL adhesion to PAEC. PBL adhesion to PAEC would be a first step in a cellular mediated rejection in xenotransplantation.

Insufficient dialysis shunts: improved long-term patency rates with close hemodynamic monitoring, repeated percutaneous balloon angioplasty, and stent placement.

Over 54 months, 70 short stenoses of 63 shunts (32 Brescia-Cimino fistulas, 31 grafts) in 59 patients necessitated a first percutaneous transluminal angioplasty (PTA). Restenosis led to 63 redilations in 38 lesions. Nine stents were inserted in seven grafts and two proximal veins in seven patients, the indication being that stenosis had recurred twice in 6 months. In three of these stenoses, five delayed intrastent redilations were necessary. Three previously dilated occluded grafts were recovered with local thrombolysis. Morbidity was 4.08%, with one immediate rupture, four delayed pseudoaneurysms (1-28 months), and two periprocedural bacteremias. Half (15 of 29) of graft stenoses and only 14% (four of 27) of Brescia-Cimino fistula stenoses had a mean restenosis interval of less than 6 months. The mean restenosis interval increased from 3.6 months +/- 0.5 (standard deviation) before stent placement to 15.2 months +/- 0.4 after stent placement (P < .001). Insertion of a stent can be advised when stenoses of graft venous anastomoses have recurred twice in less than 6 months. The combination of all interventional radiologic procedures allowed a significant improvement in secondary patency rates after PTA, with 82% at 1 year, 79% at 2 years, and 71% at 3 years.

Solute equilibration curves, crossing time for urea and glucose during peritoneal dialysis: a function of age in children.

Glucose is absorbed from the dialysate more rapidly in younger than in older children on CAPD leading to a relatively early loss of ultrafiltration during dwell time. In order to assess peritoneal permeability and in term to prescribe optimal management of CAPD, we tested peritoneal equilibration curves (EC) for urea and glucose, especially the crossing time point of these two ECs. Baseline values were obtained from 8 patients divided in two groups by age at start of CAPD: group I (N = 4) mean age 1 year 6 months, mean body weight 8.25 +/- 3.17 kg, group II (N = 4) mean age 12 years 6 months, mean body weight 33.5 +/- 1.5 kg. The crossing time point is earlier in group I (49 +/- 14 min) than in group II (101 +/- 20 min) (p less than 0.001). Followup of each patient, during a mean time of 20 months in group I and 23 months in group II, establishes that the curves crossing time point for each patient remains stable.