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Passo Tonale is like total not interesting boy girl , who at your first glance will not amaze.. So check it out!! Anyway there are not so many places in the world where you can find tapped Pilsen, decent snow park and several tens of kilometers freeride lines? Here you have everything at one resort! Passo Tonale is a small village that is located on the border of Lombardy and Trentino , in a mountain pass, nearly two thousand feet above sea level. In fact, Passo Tonale is one of the ugliest Italian villages I've ever seen. Even when you are climbing up by the winding road and staring at the glaciers up there, spoiling a good impression prefabs, whose architect was inspired by old skyscrapes. Tonale is connected to the neighboring resort of Ponte di Legno m by a cabin, and together provide nearly km pistes. Cool thing is that a lot of lifts start directly in the village, so needless to ski bus or car. Everywhere you can go on foot and on skis usually drive to the apartment. Distance from Prague is less than km, with only the last about 80 kilometers in not on the highway. If the forecast reported snowfall without wheel chains do not try this pass over.. Prices are slightly above average. In high season day pass will cost 37e, six days, then it costs Euros. The official website of Passo del Tonale www. Bullshit in the cage. There is only one - Adamello Freestyle Arena. Such a better Italy's average. The park is shaped daily by a snowcat and by shapers hands. Shapers are always at least two and jumps have a clay foundation. Already at the entrance to the park is a kind of a selection - you have to pass old cab from the cable car.. In the PRO zone you can find the following: Lines of three kickers, and every has two platforms. Size 5 to 12 meters. Then there is the spin box, speed rail, cupro box and rainbow. Starting by funbox follows teh rail only part - pipes, boxes, mini rails, wall ride and fun ride. In the middle of the park is a stylish wooden house, a few chairs, music and chicks. All this serves fast fourchair, starting right in the village and ends where it begins Adamello Freestyle Arena. And they do great buns. Sure, but due to the park and Czech beer you will not probably go to Tonale. Now that serve the highest caliber: Powder! NO, at lot of powder!! Rule number one - When it snows in Tonale it is always at least half a meter. It is possible to ride in powder near the slopes, of course, where are snow fields without trees. But the best from the backcountry can be found on the south of the Tonale. Where is the glacier called Presena. Numero uno are skialp tracks Sgualdrina in Italian it means sluts and Cantieri Italian laborer.. The best part is that there is no need to hike.. But you need to have a skipass. A car. The best are two cars. One of them you leave at the parking few miles from Tonale. And then you ride by the first cab to Paradiso , then by ramshackle doubleseat to the glacier and with a T-bar more than three thousand meters above sea level. Stare down towards the Tonale and the right side of the valley begins to parallel valley called Sgualdrina. The first part is a bit steep, and if you are above the first - which can rarely, usually is also already ridden. Then the valley expands, and you can choose which way to go - in the middle of the plain, mini canyon on the left, right drops. The terrain is very various but a bit confusing. Track Cantieri begins where ends and begins the T-bar on the glacier. Again stare towards the Tonale and Cantieri valley, which is parallel to Sgualdrina whore, you have by your right side. Compared to light Deva is shorter, but not exposed to the sun, so the snow is much better. Guys who are not afraid, can hike up a ridge between Sgualdrina and Cantieri and go down right where those two valleys converge. When your skies or board stop and you are at the flat, take a notice!! The valley continues. By a waterfall and sharp ravines down, but it is possible to ride it down with a little of courage. But after that will take you about one and a half hour of hiking back to Tonale. So follow the ridge on the left. Winding path leads through here and by which you can walk around the ridge. Now a surprise is waiting for you. There is a tunnel. When during the winter snows a lot, the entrance to the tunnel can be only a square meter hole carved into the snow. And this tunnel you have to find because there is no another way from there. Well, then you can continue along the path, then a piece of tree riding and you're in the parking, where you previously left the car. Hurray for the next round! For another piece of freeride you do not even need a car. Just skipass. Its name is Canalino di Diavolo. Devil's Pass. It's not so bad when you're on top. But from the bottom of the village looks quite evil. This time you ride a cabin Paradiso. Stare at the Tonale. Look to the right. And there is a ridge that you see from the Tonale. You will keep riding him from the other side and as high as possible. Because you will not have to climb a lot. Once the Devil's pass over you, climb up. And then just drop down and you ride powder towards the Tonale. A bit difficult for physical condition is the exit from the glacier Pisgana or Pisganino which leads to Ponte di Legno. You will take a cabin, doubleseat and lift up and continue up towards the ridge on foot. The first is a view to the valley in front of you when you need to keep right and this will be hard work. Which meters you will go lower, the more you will need to hike up back. To hike up into the Pisgana pass is quite hard hike. And still you have to hike up the glacier. The ride down but worth it. Elevation is about two thousand meters and is over ten miles long freeride line. In Ponte get into the cable car and after a while you are in Tonale pass again. There are obviously many more ways to enjoy powder snow - Il Dito, a steep narrow pass, where you need to hike a lot uphill, then - when there is little snow - you have to run down the rope, and just ecstasy when you are going down. Or go down the slopes Alpino and drive down the valley toward the cabin way station of Ponte di Legno in Tonale. There are many options. And since it really snows in the Tonale, it is more that obvious that you will meet here with powder. And then spend money for the fly ticket to Alaska! Freeride is prohibited in Italy, but in Tonale is tolerated by patrols. Mainly Sgualdrina , Cantieri , Pisgana and a ridge at Alpino are skialpinist tracks. So hiking on them is allowed. If you are unsure which way to go, grab a mountain guide. Although it costs something, but you will not get lost. Or go to El Bait.. Valid CSS!

Extracorporeal Treatment for Methotrexate Poisoning

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Official websites use. Share sensitive information only on official, secure websites. Bunchman, Diane P. Calello, Paul K. Mowry, Marlies E. Walsh, Anselm Wong, and Christopher Yates. Correspondence: Dr. David M. Email: david. Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning EXTRIP methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients 89 with impaired kidney function. Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Overall mortality in these publications was Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: 1 suggested against extracorporeal treatments when glucarpidase is not administered; 2 recommended against extracorporeal treatments when glucarpidase is administered; and 3 recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: 1 extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; 2 extracorporeal treatments remove folinic acid; 3 in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and 4 extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity. Toxicity from methotrexate is commonly described and affects many organs. Treatment is supportive, including folinic acid leucovorin and glucarpidase in specific circumstances. The use of extracorporeal treatments is controversial. Methotrexate inhibits the intracellular folate cycle by competitively inhibiting dihydrofolate reductase, thereby reducing substrates for cell division. Methotrexate is used for various indications including malignancies, rheumatoid arthritis, and inflammatory bowel disease. Oral bioavailability is limited by saturable active drug transporters 13 , 14 , which limit absorption at high doses and can be protective in acute overdose Methotrexate distributes slowly but extensively into erythrocytes 16 — The remainder is eliminated by the kidneys 13 , 23 , correlating with GFR 11 , 24 , 25 , and additionally, methotrexate is both filtered and actively secreted in the tubules 25 , 26 ; although at high concentrations, tubular secretion becomes saturated. Total body clearance and volume of distribution were obtained from intravenous data. If these data were unavailable but reported for oral data, then values were adjusted for bioavailability. Intravenous high-dose methotrexate and oral low-dose methotrexate can result in toxicity even at therapeutic doses. We describe these situations in detail in order to delineate potential indications for extracorporeal treatments. Therapeutic drug monitoring of methotrexate predicts toxicity 46 , 53 — 55 , and the risk of AKI and mucositis increases exponentially as the methotrexate concentration rises 56 , With better monitoring and protocolized therapy urine alkalinization, leucovorin , the incidence of toxicity has decreased considerably Delayed methotrexate clearance refers to methotrexate concentrations predictive of complications Supplemental Table 7 46 , 59 , 60 including AKI 21 , 37 , 57 , 58 , 61 — 65 , mucositis 56 , 66 — 68 , myelosuppression 63 , 66 , 69 , 70 , hepatotoxicity 63 , infections 61 , and mortality 71 — AKI reduces methotrexate clearance, prolonging the exposure to high methotrexate concentrations. AKI also prevents administration of further methotrexate doses, compromising treatment of the underlying malignancy. The mechanism of AKI is tubular precipitation of methotrexate and metabolites especially at acidic pH and direct tubular toxicity. In contemporary cohorts, AKI occurs in 0. AKI is usually nonoliguric, and serum creatinine concentration peaks 2—7 days after infusion 59 , 71 , 85 — Long-term dialysis after methotrexate-induced AKI is extremely uncommon 59 , Toxicity from oral, subcutaneous, or intravenous low-dose methotrexate can occur after therapeutic error in the setting of kidney impairment and unintentional mis-dosing: for example, a weekly dose of methotrexate erroneously taken daily. Preexisting CKD , , , , kidney failure even after a single dose of 2. Other risk factors include length of exposure, weekly dosing, cumulative dose , , , , , and lack of folate supplementation Factors associated with a poorer prognosis include lower white blood cell counts , and low serum albumin concentration In contrast to high-dose methotrexate, therapeutic drug monitoring has little value in low-dose methotrexate toxicity , as no correlation exists between toxicity and methotrexate concentrations, and morbidity is reported at undetectable concentrations 68 , , , Acute single oral ingestions, either unintentional or with intended self-harm, usually carry little risk because of saturable absorption kinetics limiting bioavailability , — , , — , except when impaired kidney function is present. Standard care of methotrexate toxicity includes methotrexate cessation and intravenous hydration Supplemental Table 1. Methotrexate is a weak acid pKa of approximately 5. Leucovorin mitigates the risk of toxicity of high-dose methotrexate by bypassing dihydrofolate reductase to restart the intracellular folate cycle. In patients with toxicity from low-dose methotrexate, leucovorin is also used If intravenous leucovorin is unavailable, the oral form is an acceptable alternative Folic acid is ineffective as an antidote. Glucarpidase carboxypeptidase-G2 is a recently approved methotrexate antidote. It is a recombinant enzyme that hydrolyzes methotrexate to inactive metabolites 4-deoxyamino-methylpteroic acid DAMPA and glutamate. The catalytic effect of glucarpidase persists for 48—72 hours 46 , Some workgroups have proposed that glucarpidase be used when the methotrexate concentration is above specific thresholds in the setting of AKI Supplemental Table 7 46 with the rationale that prolonged leucovorin rescue could decrease the cure rate of malignancy leucovorin overrescue , Glucarpidase is not indicated for low-dose methotrexate toxicity. Three studies comparing the clinical benefit of glucarpidase with standard care have not clearly demonstrated a benefit with regard to mortality, length of stay, extrarenal complications, or incidence and severity of AKI 71 , 85 , Median time to kidney function recovery in cohorts receiving glucarpidase is between 10 and 23 days 59 , 71 , 75 , 86 , 87 , 91 , , , , but this took months in a subset of patients 71 , 79 , ; although groups are not directly comparable, time to kidney recovery is similar in historical cohorts 70 , 97 , In summary, although the kinetic effect of glucarpidase at lowering plasma methotrexate concentrations is indisputable, data confirming clinical benefits are lacking. The workgroup performed systematic reviews of the literature and developed clinical recommendations following published EXTRIP methodology 2 with modifications, updates, and clarifications. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations Supplemental Figure 2. The full methods are presented in the online supplement Supplemental Tables 3—6. Results of the literature search first performed on March 1, and last updated November 18, are presented in Supplemental Figure 3. A total of articles were identified after removal of duplicates. In the final analysis, 92 articles were included, including two in vitro experiments , , four animal experiments — , 84 case reports and case series 24 , 35 , 88 , 90 , , , , , — , one pharmacokinetic modeling study , and one observational study Although several articles were designed as pharmacokinetic studies in kidney failure patients , , , , , many participants in these studies developed methotrexate-associated toxicity and were included in case reports. Methotrexate has a low molecular weight and moderate protein binding, so it passes easily through modern dialyzers and hemofilters, which is confirmed by in vitro and animal experiments Activated charcoal adsorbs methotrexate better than resins , , although both are limited by cartridge saturation In one porcine study, resin hemoperfusion provided a two- to three-fold greater initial clearance than hemodialysis, which was negated at 3 hours because of saturated adsorption Toxicokinetic data related to extracorporeal treatments were available on 90 patients. Because of the inherent complexity of methotrexate toxicokinetics detailed above, determination of the ability of extracorporeal treatments to remove methotrexate is challenging. Most of the publications were dated and did not use modern dialytic technologies that are expected to provide even better clearances. Hemoperfusion was efficient but had decreased efficacy after 2 hours Other techniques, including continuous KRTs CKRTs , therapeutic plasma exchange, and peritoneal dialysis, had inferior effects on methotrexate removal. To compare the relative efficacy of extracorporeal treatments, many publications used the percentage decrease in methotrexate concentrations 44 , , , , , , , However, this metric has little value unless it is adjusted for kidney function and duration of the extracorporeal treatment because serum concentrations are expected to decrease spontaneously due to endogenous processes. Again, hemodialysis with or without hemoperfusion provided the greatest percentage of methotrexate body content removed per period of time. In rare cases when the extracorporeal treatment was initiated rapidly after a single dose of methotrexate before distribution into cells and tissues , the effect was considerable , , , Kidney function affects the grading of dialyzability because the contribution of extracorporeal clearance to total clearance increases as kidney function declines. Final dialyzability grading on the basis of the number of patients with impaired kidney function according to EXtracorporeal TReatments In Poisoning criteria. Grading of dialyzability is defined in Supplemental Table 4 , and level of evidence for dialyzability is defined in Supplemental Table 5. One additional patient had normal kidney function and methotrexate was assessed as dialyzable with CKRT Few articles compare the kinetics of extracorporeal treatments with that of glucarpidase. This was confirmed in all studies in which both glucarpidase and extracorporeal treatments were given 58 , , , , , , , , , Some reports noted that dialysis clearance is concentration dependent , , , , although this is surprising in the absence of saturation of protein binding or membrane adsorption; this may have been caused by detection sensitivity of the assay at low concentration, or redistribution of methotrexate from red blood cells in the outlet, inflating that methotrexate concentration. Extracorporeal treatments appear to accelerate elimination of methotrexate metabolites 7-hydroxymethotrexate and 5-methyltetrahydrofolate in blood In 62 patients in whom it could be evaluated, methotrexate concentration rose after extracorporeal treatments in 42 patients. The magnitude of rebound was greater after more efficient techniques such as intermittent hemodialysis or hemoperfusion compared with CKRT or peritoneal dialysis. Of note, rebound is also reported post glucarpidase, and extracorporeal treatments have been used to minimize this effect in some cases. No data exist. However, glucarpidase has a molecular mass of 83 kDa and is only expected to be removed by therapeutic plasma exchange or exchange transfusion. One retrospective single-center study of patients with cancer with methotrexate toxicity — was identified Compared with the nonglucarpidase group, the glucarpidase group had statistically shorter hospital stay and lower day mortality. Conclusions from these results are severely limited by selection bias, confounding-by-indication, residual confounding, and insufficient data to adjust for clinical and demographic differences between groups. The remainder of the evidence is on the basis of case reports spanning 40 years, during which treatment has changed greatly, especially leucovorin rescue. The clinical summary of included cases is presented in Table 4. All survivors were weaned off KRT, and in all but six patients , , , , , , kidney function returned to baseline in a median time of The overall mortality was Data are median with interquartile range when applicable. Historical cohorts treated solely with standard care are difficult to compare with the cohort receiving extracorporeal treatment because of their lower index of severity. Also, in all glucarpidase studies, concurrent dialysis was allowed. Time to administration of next chemotherapy cycle was considered an important patient-important outcome because more chemotherapy offers longer cancer survival but could not be assessed in the intervention group. Includes one retrospective cohort study comparing glucarpidase versus nonglucarpidase groups. Judged at high risk of bias due to various potential selection information biases due to asymmetry in methods to select participants, confounding-by-indication, and information retrospectively derived from Medicare databases. Confounding at baseline was uncontrolled and unadjusted for confounders such as severity of toxicity, coingestions, supportive and standard care, and cointerventions especially between the ECTR and glucarpidase groups. Case reports published on effect of ECTR. Uncontrolled and unadjusted for confounders such as severity of toxicity, supportive and standard care, and cointerventions. Confounding-by-indication is inevitable because ECTR was usually attempted when other therapies failed. Our cohort spans 40 years with very heterogenous treatments, whereas these are protocolized today. ECTR and standard care are not directly compared in the same cohort of patients. For venous catheter insertion, serious complications include hemothorax, pneumothorax, hemomediastinum, hydromediastinum, hydrothorax, subcutaneous emphysema, retroperitoneal hemorrhage, embolism, nerve injury, arteriovenous fistula, tamponade, and death. Hematoma and arterial puncture were judged not serious and thus excluded from this composite outcome. Deep vein thrombosis and infection complications were not included considering the short duration of catheter use. On the basis of five single-arm observational studies, two meta-analyses comparing serious mechanical complications associated with catheterization using or not an ultrasound, which included six randomized controlled trials in subclavian veins and 11 in internal jugular veins ; two randomized controlled trials comparing major mechanical complications of different sites of catheterization , ; one large multicenter cohort study reporting all mechanical complications associated with catheterization Rare events were reported from case series and case reports. Not rated down for inconsistency because heterogeneity was mainly explained by variation in site of insertion, use of ultrasound, experience of the operator, populations adults and pediatric , urgency of catheter insertion, practice patterns, and methodologic quality of studies. Not rated down for indirectness because cannulation and catheter insertion were judged similar to the procedures for other indications. Not rated down for imprecision because wide range reported was explained by inconsistency. The events in the control group are assumed to be zero because no catheter is installed for ECTR ; therefore, the magnitude of effect is at least expected to be large, which increases the confidence in the estimate of effect. Minor bleeding from heparin, transient hypotension, and electrolytes imbalance were judged not serious. For HP, serious complications include severe thrombocytopenia, major bleeding, and hemolysis. Transient hypotension, hypoglycemia, hypocalcemia, and thrombocytopenia were judged not serious. All nonserious complications were excluded from this composite outcome. HP: on the basis of two small single-arm studies in poisoned patients , Rare events were reported in case series and case reports. Assuming that patients in the control group would not receive any form of ECTR, the events in the control group would be zero; therefore, the magnitude of effect is at least expected to be large, which increases the confidence in the estimate of effect. Despite heterogeneity in groups at baseline, no benefit was observed from extracorporeal treatment when compared with standard care regarding other important outcomes. Finally, the time required for recovery from AKI was comparable in all groups, although this analysis is limited by different definitions used for AKI and different criteria for kidney recovery. We identified 21 cases where extracorporeal treatment was added to glucarpidase; although these numbers are low and descriptions limited, no incremental clinical benefit can be deduced from extracorporeal treatment in that scenario. The times for recovery of pancytopenia and mucositis were also comparable in all groups. Compared with the cohort of high-dose methotrexate, most of these patients had preexisting kidney failure Table 4. Plasma concentrations were also considerably lower than in the cohort receiving high-dose methotrexate. Overall mortality was Again, no benefit was observed from extracorporeal treatment compared with standard care alone in historical controls with regard to mortality, length of stay, time of recovery of pancytopenia, or time of recovery of mucositis, although the first group was assumed to be sicker Table 5 , , , This analysis contains confounding as a large proportion of these patients were already receiving long-term hemodialysis for kidney failure. There were no cases of intentional overdose treated by extracorporeal treatment. Many complications were reported, although it is unclear if some were related to the procedure, methotrexate, underlying disease, or comorbidities. Because of baseline immunosuppression and cytopenia and because multiple extracorporeal sessions are often performed, the risk of catheter infection is higher Costs are variable but are considerably greater with glucarpidase compared with hemodialysis, although the incidence of serious adverse events is lower. Methotrexate toxicity is a medical emergency and carries serious risks of multisystem disease and mortality. General recommendations for extracorporeal treatments in methotrexate toxicity are presented in Box 1. Although extracorporeal treatments accelerate elimination of plasma methotrexate substantially, the panel did not support their use for severe methotrexate toxicity as an addition to standard care, as an alternative to glucarpidase, or as an addition to glucarpidase in most clinical contexts. In patients with severe methotrexate poisoning receiving standard care treatments including folinic acid rescue therapy:. We suggest AGAINST performing extracorporeal treatments when glucarpidase is not administered weak recommendation; very low—quality evidence median: 2; upper quartile: 5. We recommend AGAINST performing extracorporeal treatments when glucarpidase is administered strong recommendation; very low—quality evidence median: 1; upper quartile: 3; disageement index: 0. We recommend AGAINST performing extracorporeal treatments instead of administering glucarpidase strong recommendation; very low—quality evidence median: 1; upper quartile: 3; disagreement index: 0. Neither the presence of life-threatening toxicity cytopenia, mucositis, AKI nor high hour or hour methotrexate cut-off concentration would constitute an indication for extracorporeal treatment, although they would be indications for more intensive leucovorin rescue. By the time there is bone marrow aplasia or mucositis, the plasma methotrexate concentration will be too low for there to be a meaningful effect of extracorporeal treatments. Acute oral self-poisoning is not an indication for preemptive treatment because toxicity seldom occurs in this scenario. The workgroup notes that all usual indications for KRT, aside from methotrexate removal, remain valid. There are no kinetic or other clinical arguments to add extracorporeal treatments to glucarpidase. The workgroup acknowledged that a benefit from extracorporeal treatments may be expected in very limited and rare circumstances, when a large methotrexate burden is present in plasma. Situations that favor the benefit-risk ratio toward extracorporeal treatments include a short time after methotrexate infusion less than 6 to 12 hours ; an exposure likely to cause toxicity e. In all of these circumstances, glucarpidase would be preferred if available. If an extracorporeal treatment is required, intermittent high-efficiency hemodialysis is preferred. Online hemofiltration would presumably offer comparable clearance, although data are absent. Hemoperfusion will not outperform hemodialysis because of the moderate protein binding of methotrexate and extensive cartridge saturation. Other techniques such as therapeutic plasma exchange, liver support devices, and peritoneal dialysis do not offer adequate clearances and are associated with more complications, especially in a methotrexate-toxic patient. There is little justification in awaiting clinical improvement for cessation, as this may take several weeks, long after which there is no serum methotrexate to remove. Methotrexate rebound is expected after extracorporeal treatment because of redistribution, and a session can be repeated if present. Leucovorin is crucial in restoring the intracellular folate cycle and is removed by extracorporeal treatments; it should be readministered immediately after the procedure. Data are needed on the clinical effects of methotrexate rebound after extracorporeal removal, and how this influences the frequency and duration of intermittent hemodialysis. If subsequent data fail to show a benefit of glucarpidase on clinical outcomes, then extracorporeal removal of methotrexate is unlikely to be beneficial. Data suggest that leucovorin is readily dialyzable by hemodialysis. Data on dosage adjustments of leucovorin during and after extracorporeal treatments are needed. The EXTRIP workgroup assessed that methotrexate was moderately dialyzable but did not support the use of extracorporeal treatments for severe methotrexate toxicity in most clinical contexts when standard care including leucovorin is administered. In rare cases where fast removal of methotrexate is required, glucarpidase will outperform extracorporeal treatments. All prospective members were required to disclose any actual, potential, or perceived conflict of interest before inclusion in the workgroup. The disclosures were used to categorize the members as cleared for full participation, allowed to participate with recusal from certain aspects of guideline development, or disqualified from participation. The cochairs remained free of any financial conflict of interest during the entire guideline development process, meaning avoidance of interests and relationships with pharmaceutic or device companies pertaining to the topic of poisoning. Members were required to disclose to the cochairs any new activities that had the potential to be viewed as a conflict of interest before engaging in the activity, at the beginning of face-to-face meeting, and before submission of the manuscript. Cochairs determined if specific activities were allowed under the conflict of interest rules. All conflicts of interest deemed as potential appearance of a conflict of interest were required to be included in the manuscript. Arnies, Inc. Hoffman reports honoraria from UpToDate. Lavergne reports employment with the Infectious Diseases Society of America. Ostermann has received speaker honoraria and research funding from Baxter and Fresenius Medical and has had consulting functions for Baxter and Nxstage. Roberts acknowledges support of St. All remaining authors have nothing to disclose. Ghannoum solely for the reimbursement of travel expenses for the in-person guideline meeting and payment to dedicated translators for retrieval and translation of foreign language articles. We would like to acknowledge the valuable help of our dedicated translators, librarian, data extractors, and meeting secretary. Official translators were Mrs. Alexandra Angulo, Mrs. Alla Abbott, Mr. Anant Vipat, Mr. Andreas Betz, Mrs. Angelina Kovaleva, Mrs. Denise Gemmellaro, Mrs. Ewa Brodziuk, Mrs. Helen Johnson, Mr. Junzheng Peng, Dr. Marcela Covic, Mrs. Nathalie Eeckhout, Mrs. Rosie Finnegan, Mr. Salih Topal, and Mrs. Vilma Etchard. The librarian was Mrs. Elena Guadagno. Maria Rif, Dr. Karine Mardini, Dr. Tudor Botnaru, Dr. Elizabeth Koo, and Mrs. Gabrielle Wilson. The meeting secretary was Ms. Brenda Gallant. Published online ahead of print. Publication date available at www. Supplemental Table 1. Represented societies. Supplemental Table 2. Standard care. Supplemental Table 3. Supplemental Table 4. Supplemental Table 5. Quality of individual studies for toxicokinetic outcomes. Supplemental Table 6. Quality of evidence for toxicokinetic outcomes. Supplemental Table 7. Methotrexate concentrations associated with increased risk of complications. Supplemental Table 8. Quantification of methotrexate mass removal during ECTR. Supplemental Figure 1. Approach to and implications of rating the quality of the evidence and strength of recommendations using the GRADE methodology. Supplemental Figure 2. Voting process for recommendations. Supplemental Figure 3. Result of literature search. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. Clin J Am Soc Nephrol. Find articles by Marc Ghannoum. Find articles by Darren M Roberts. Find articles by David S Goldfarb. Find articles by Jesper Heldrup. Find articles by Kurt Anseeuw. Find articles by Tais F Galvao. Find articles by Thomas D Nolin. Find articles by Robert S Hoffman. Find articles by Valery Lavergne. Find articles by Paul Meyers. Find articles by Sophie Gosselin. Find articles by Tudor Botnaru. Find articles by Karine Mardini. Issue date Apr. Open in a new tab. Effect of ECTRs in patients severely poisoned with methotrexate receiving standard care. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. Serious d. Serious e. Very serious g. Serious h. Serious i. Publication bias strongly suspected j. No formal statistical comparison possible due to reporting of aggregate data, but reported median time to recovery of kidney function seems comparable between the ECTR group and both control groups. No formal statistical comparison possible due to reporting of aggregate data, but reported mean length of stay seems comparable between groups. Serious complications of catheter insertion s , t. Not serious v. Not serious w. Not serious x. Strong association y. Rate of serious complications of catheter insertion varies 0. Absolute effect is estimated to be varying from 1 to 21 more serious complications per patients in the ECTR group. Serious complications of ECTR z. Strong association bb.

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