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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]

Objective: To assess seizure and developmental outcomes, their predictors, and complications in 160 children who, between 1998 and 2022, underwent surgery for lesional epilepsy with curative intent before the age of 3 years. To compare trends in epilepsy surgery in this age group before and after the year 2014., Methods: Retrospective multicenter study. Descriptive and univariate analyses, and multivariable models for all outcomes., Results: These 160 patients (76 F; 47.5%) underwent 169 surgeries (age at surgery 20.4 ± 9.4 months). At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were in Engel class I, 106 (66.2%) of whom were in Engel class Ia. Antiseizure medications were stopped in 84 patients (52.5%). Complications requiring reoperations were observed in 16 patients (10%; 9.5% of surgeries) and unexpected permanent deficits in 12 (7.5%; 7.1% of surgeries). Postoperative cognitive functions remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Multivariable analyses showed that the probability of achieving Engel class Ia was lower when the duration of epilepsy was longer, patients underwent preoperative video-EEG, and unexpected postoperative permanent deficits occurred. Cognitive improvement after surgery was associated with lower preoperative seizure frequency, better preoperative developmental level, and a longer postoperative follow-up. FCDII and tumors were the histopathologies carrying a higher probability of achieving seizure freedom, while polymicrogyria was associated with a lower probability of cognitive improvement. The number of patients operated on after 2014 was higher than before (61.3% vs. 38.7%), with stable outcomes., Significance: Epilepsy surgery is effective and safe in infants and toddlers, although the complication rate is higher than seen in older patients. Shorter duration of epilepsy, lower seizure frequency, no need for video-EEG, tumors, and some malformations of cortical development are robust predictors of seizure and cognitive outcome that may be exploited to increase earlier referral., Plain Language Summary: This study analyzed the results of epilepsy surgery in 160 children who had been operated on before the age of 3 years at four Italian centers between 1998 and 2022. At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were free from disabling seizures, of which 106 (66.2%) were completely seizure-free since surgery. Major surgical complications occurred in 28 patients (17.5%), which is higher than observed with epilepsy surgery in general, but similar to hemispheric/multilobar surgery. Postoperative cognitive function remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Epilepsy surgery is effective and safe in infants and toddlers., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Italy was the first country to largely experience the COVID-19 epidemic among other Western countries during the so-called first wave of the COVID-19 pandemic. Proper management of an increasing number of home-quarantined individuals created a significant challenge for health care authorities and professionals. This was especially true when considering the importance of remote surveillance to detect signs of disease progression and consequently regulate access to hospitals and intensive care units on a priority basis., Objective: In this paper, we report on an initiative promoted to cope with the first wave of the COVID-19 epidemic in the Spring/Summer of 2020, in the Autonomous Province of Trento, Italy. A purposefully built app named TreCovid19 was designed to provide dedicated health care staff with a ready-to-use tool for remotely monitoring patients with progressive symptoms of COVID-19, who were home-quarantined during the first wave of the epidemic, and to focus on those patients who, based on their self-reported clinical data, required a quick response from health care professionals., Methods: TreCovid19 was rapidly developed to facilitate the monitoring of a selected number of home-quarantined patients with COVID-19 during the very first epidemic wave. The app was built on top of an existing eHealth platform, already in use by the local health authority to provide home care, with the following functionalities: (1) to securely collect and link demographic and clinical information related to the patients and (2) to provide a two-way communication between a multidisciplinary health care team and home-quarantined patients. The system supported patients to self-assess their condition and update the multidisciplinary team on their health status. The system was used between March and June 2020 in the province of Trento., Results: A dedicated multidisciplinary group of health care professionals adopted the platform over a period of approximately 3 months (from March-end to June 2020) to monitor a total of 170 patients with confirmed COVID-19 during home quarantine. All patients used the system until the end of the initiative. The TreCovid19 system has provided useful insights of possible viability and impact of a technological-organizational asset to manage a potentially critical workload for the health care staff involved in the periodic monitoring of a relevant number of quarantined patients, notwithstanding its limitations given the rapid implementation of the whole initiative., Conclusions: The technological and organizational model adopted in response to the COVID-19 pandemic was developed and finalized in a relatively short period during the initial few weeks of the epidemic. The system successfully supported the health care staff involved in the periodic monitoring of an increasing number of home-quarantined patients and provided valuable data in terms of disease surveillance., (©Lorenzo Gios, Giulia Crema Falceri, Stefano Micocci, Luigi Patil, Sara Testa, Simona Sforzin, Ettore Turra, Diego Conforti, Giulia Malfatti, Monica Moz, Andrea Nicolini, Paolo Guarda, Alessandro Bacchiega, Carlo Mion, Michele Marchesoni, Rosa Maimone, Pietro Benedetto Molini, Alberto Zanella, Venet Osmani, Oscar Mayora-Ibarra, Stefano Forti. Originally published in JMIR Formative Research (https://formative.jmir.org), 31.05.2021.)

Background: Dialysis efficacy is mostly influenced by dialyzer clearance. Urea clearance may be estimated in vitro by total ion clearance, which can be obtained by conductivity measurements. We have previously used this approach to assess in vitro clearances in a system mimicking predilutional and postdilutional online hemodiafiltration with a wide range of QD, QB, and ultrafiltration rates. Our current study elaborates on a formula that allows the prediction of the influence of ultrafiltration on small molecule clearances, and validates the mathematical approach both experimentally in vitro and clinically in vivo data., Methods: Two conductivimeters in the dialysate side of an E-2008 Fresenius machine were used. HF80 and HF40 polysulfone dialyzers were used; reverse osmosis water and dialysate were used for blood and dialysate compartments, respectively. Study conditions included QB of 300 and 400 mL/min and QD of 500 and 590 mL/min, with a range of ultrafiltration rate from 0 to 400 mL/min in postdilutional hemodiafiltration and to 590 mL/min in predilutional hemodiafiltration. Urea clearances were determined in the in vivo studies, which included 0, 50, 100, and 150 mL/min ultrafiltration rates., Results: The ultrafiltration rate and clearance were significantly correlated (R > 0.9, P < 0.001) and fitted a linear model (P < 0.001) in all of the experimental conditions. The following formula fitted the experimental points with an error <2% for both postdilutional and predilutional online diafiltration in vitro, respectively. K = K0 + [(QB - K0)/(QB)] x ultrafiltration rateK = K0 + [((QD x QB)/(QB + QD) - K0)/QD] x ultrafiltration rate where K is the clearance; K0 is the clearance with nil ultrafiltration rate; QD is the total dialysate produced (in commercial HDF, QD = QDi + Qinf). Since weight loss was maintained at 0, ultrafiltration rate = infusion flow. QB is the "blood" line flow. The formula was also verified in vivo in clinical postdilutional hemodiafiltration with a QB taking into account the cellular and water compartments., Discussion: In vitro, by simply determining the clearance in conventional dialysis, the total clearance for any ultrafiltration rate may be estimated in both predilutional and postdilutional online diafiltration with an error of less than 2%. The same applies to in vivo postdilutional hemodiafiltration when the formula takes into account the cellular and water composition of blood.

The "gold standard" method to evaluate the mass balances achieved during dialysis for a given solute remains total dialysate collection (TDC). However, since handling over 100 liter volumes is unfeasible in our current dialysis units, alternative methods have been proposed, including urea kinetic modeling, partial dialysate collection (PDC) and more recently, monitoring of dialysate urea by on-line devices. Concerned by the complexity and costs generated by these devices, we aimed to adapt the simple "gold standard" TDC method to clinical practice by diminishing the total volumes to be handled. We describe a new system based on partial dialysate collection, the continuous spent sampling of dialysate (CSSD), and present its technical validation. Further, and for the first time, we report a long-term assessment of dialysis dosage in a dialysis clinic using both the classical PDC and the new CSSD system in a group of six stable dialysis patients who were followed for a period of three years. For the CSSD technique, spent dialysate was continuously sampled by a reversed automatic infusion pump at a rate of 10 ml/hr. The piston was automatically driven by the dialysis machine: switched on when dialysis started, off when dialysis terminated and held during the by pass periods. At the same time the number of production cycles of dialysate was monitored and the total volume of dialysate was calculated by multiplying the volume of the production chamber by the number of cycles. Urea and creatinine concentrations were measured in the syringe and the masses were obtained by multiplying this concentration by the total volume. CSSD and TDC were simultaneously performed in 20 dialysis sessions. The total mass of urea removed was calculated as 58038 and 60442 mmol/session (CSSD and TDC respectively; 3.1 +/- 1.2% variation; r = 0.99; y = 0.92x -28.9; P < 0.001). The total mass of creatinine removed was 146,941,143 and 150,071,195 mumol/session (2.2 +/- 0.9% variation; r = 0.99; y = 0.99x + 263; P < 0.001). To determine the long-term clinical use of PDC and CSSD, all the dialysis sessions monitored during three consecutive summers with PDC (during 1993 and 1994) and with CSSD (1995) in six stable dialysis patients were included. The clinical study comparing PDC and CSSD showed similar urea removal: 510 +/- 59 during the first year with PDC and 516 +/- 46 mmol/dialysis session during the third year, using CSSD. Protein catabolic rate (PCR) could be calculated from total urea removal and was 1.05 +/- 0.11 and 1.05 +/- 0.09 g/kg/day with PDC and CSSD for the same periods. PCR values were clearly more stable when calculated from the daily dialysate collections than when obtained with urea kinetic modeling performed once monthly. We found that CSSD is a simple and accurate method to monitor mass balances of urea or any other solute of clinical interest. With CSSD, dialysis efficacy can be monitored at every dialysis session without the need for bleeding a patient. As it is external to the dialysis machine, it can be attached to any type of machine with a very low cost. The sample of dialysate is easy to handle, since it is already taken in a syringe that is sent directly to the laboratory. The CSSD system is currently in routine use in our unit and has demonstrated its feasibility, low cost and high clinical interest in monitoring dialysis patients.

The optimal dialysate calcium (Ca) content for hemodialysis has been classically fixed at 1.75 mM. However, this dialysate Ca concentration (dCa) with its positive intradialytic Ca balance combined with the use of CaCO3 as a phosphate binder may result in hypercalcemia. To prevent or treat hypercalcemia, a decrease in dCa has been proposed. In the present study both the acute and the long-term effects of lowering dCa were assessed. Additionally, given the results obtained after one year with low dCa the effectiveness of i.v. 1 alpha vitamin D3 in lowering PTH serum levels in two groups of patients dialyzed with different dCa was also studied. (a) Ca kinetics during hemodialysis (HD) and on line hemodiafiltration (HDF) were studied in a group of nine stable patients who were sequentially treated with 1.75, 1.5 and 1.25 mM dCa. Dialysate was the same but for the dCa which was lowered stepwise. Na, K, tCa, ionized Ca (iCa), proteins, phosphate and pH were measured from blood inlet and outlet and dialysate outlet at the start, one hour, two hours and after the treatments. At the same time weight, blood pressure and heart rate were recorded. The sieving of iCa was significantly different in HDF versus HD (F = 6.73; P < 0.01); intravenous infusion of 18 liters of filtered ultrapure dialysate compensated the Ca loss due to the convective component of HDF, as iCa was similar at the blood inlet in HD and HDF in the three dCa tested (F = 2.59; NS). Intradialytic iCa kinetics measured in the blood inlet were significantly different with different dCa (P < 0.001 for 1.75 mM vs. 1.5 mm and P < 0.001 for 1.5 mM vs. 1.25 mM). A significant increase in post-dialysis iCa was observed with dCa of 1.75 and 1.5 while no modification was observed with 1.25 mM dCa. (b) Regarding long-term effects of lowering dCa, seven of the nine patients acutely studied were followed for a one year period after changing from dCa = 1.5 to dCa = 1.25 mM. A control group of six patients was maintained with dCa = 1.5 for the same period of time and with the same treatment schedule but for dCa. Total Ca, phosphate and alkaline phosphatase were assessed monthly, and phosphate binders and oral vitamin D derivative doses were adapted accordingly. Intact PTH was determined quarterly. CaCO3 oral intake was more than doubled in the low dCa group. Total Ca, phosphate and ALP were similar in both groups over the assessed year.(ABSTRACT TRUNCATED AT 400 WORDS)

Although hemodiafiltration is purported to provide better cardiovascular stability for dialysis patients; other possible benefits of this therapy have not been well defined. We have compared treatment with hemodialysis (HD) and hemodiafiltration (HDF) in 20 stable patients over a period of 18 months. Dialysis parameters (dialysate composition and flow, duration, dialyzer) were the same in the two periods except for the added convection of HDF and a higher tolerated blood flow in HDF. Cardiovascular parameters were remarkably similar in the two treatment periods, indicating that stable patients do not benefit further from this therapy in terms of these factors. The clearance of urea was significantly improved with HDF, which was reflected in a higher Kt/V and lower TACurea. We observed a significant correlation between Kt/V and PRU in both HD and HDF modes. This correlation was linear and the regression line was similar in both modes. The clearance of beta 2-microglobulin was also significantly improved by HDF compared to HD. Thus the benefit of HDF in stable dialysis patients is the improved clearance of small molecules and beta 2-microglobulin without increasing dialysis time. Further clinical benefits due to the improved clearance may only become apparent with longer follow-up.

Renal function was monitored in 20, living-related kidney donors before and after uninephrectomy. Urinary protein excretion and retinoid metabolism respectively were studied in 10 and 6 of these donors. The functional adaptation was characterized by an increase in glomerular filtration rate and tubular function, which began in the first two days after uninephrectomy. Changes in tubular function were also demonstrated by significant increases in the urinary excretion of beta 2 microglobulin (beta 2M), retinol binding protein (RBP), kappa and lambda light chains of immunoglobulins. In addition, a protein identical to or homologous to cellular retinoic acid binding protein (CRABP), appeared in the urine after nephrectomy. We did not find CRABP in serum samples either before or after nephrectomy, suggesting that urinary CRABP was synthesized by the remaining kidney. Increases in serum levels of Vitamin A and RBP were also observed in the post-nephrectomy period. These modifications in retinol metabolism suggest that these substances could have a role as renotropic growth factors in compensatory hypertrophy.

We blind-tested a method that in earlier studies had shown increased leucine uptake in muscle fibers of biopsy specimens from three obligate carriers and seven of 11 putative carriers of the gene for Duchenne muscular dystrophy. Here, muscle samples obtained at biopsy in seven obligate carriers and nine control subjects from Brazil were examined in Canada without knowledge of the carrier status or serum enzyme concentrations. Leucine uptake was increased in four controls and within normal range in four carriers, a rate of false-positives and -negatives that underscores the need for blind-testing methods for detecting carriers of this disease.