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Record W2618595923 · doi:10.1093/ndt/gfx141.sp149

SP149ECULIZUMAB TREATMENT OF SHIGA TOXIN ESCHERICHIA COLI HEMOLYTIC UREMIC SYNDROME

2017· article· en· W2618595923 on OpenAlexaff
Dorothy Thomas, Christoph Licht, Anne‐Laure Lapeyraque, Marina Noris, Arnaud Bonnefoy, Jocelyn S. Garland

Bibliographic record

VenueNephrology Dialysis Transplantation · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicPorphyrin Metabolism and Disorders
Canadian institutionsUniversité de MontréalUniversity of TorontoQueen's University
Fundersnot available
KeywordsMedicineShiga toxinEscherichia coliUremic toxinsMicrobiologyToxinHemolytic anemiaHaemolytic-uraemic syndromeHemodialysisImmunologyInternal medicineBiochemistry

Abstract

fetched live from OpenAlex

INTRODUCTION AND AIMS: Hemolytic uremic syndrome (HUS) has two forms: Shiga toxin-producing Escherichia coli HUS (STEC-HUS) and atypical HUS (aHUS). The underlying common pathophysiology is thrombotic microangiopathy (TMA), triggering endothelial damage. Complement activation has been reported in both diseases. In STEC-HUS, Shiga toxin upregulates P-selectin activating the alternate complement pathway. In aHUS, genetic mutations produce dysregulated alternate complement pathway activation. Traditionally, STEC-HUS treatment is supportive. In aHUS, eculizumab, a monoclonal antibody to C5, blocks formation of C5b-9, the membrane attack complex. Selected case reports have shown improvements in STEC-HUS patients treated with eculizumab. Herein, we describe a case of a 17 year old female with STEC-HUS treated with eculizumab. METHODS: Retrospective case study. RESULTS: The patient presented with bloody diarrhea, gross hematuria, thrombocytopenia hemolytic anemia, acute kidney injury (with macro-proteinuria) requiring dialysis. She was empirically treated with plasmapheresis. Stool PCR was positive for STEC, confirming STEC-HUS. ADAMTS-13 activity was normal and serum C5b-9 levels were elevated. She did not improve with plasmapheresis, therefore eculizumab was started. Within 48 hours, she developed visual loss, hemiparesis and seizures in the context of severe hypertension. MRI head showed posterior reversible encephalopathy syndrome. Continued eculizumab therapy resulted in complete resolution of TMA and normalization of kidney function. Subsequent testing of this patient's serum for complement activation by quantifying C5b-9 deposition on endothelial cells demonstrated elevated C5b-9 deposition at initiation of eculizumab, which normalized with eculizumab treatment. CONCLUSIONS: Few cases of STEC-HUS have been treated with eculizumab. This case is unusual given its severity of complement activation resulting from STEC-HUS. This raises the possibility of an underlying genetic predisposition to aHUS in this patient, but also suggests that eculizumab therapy might be beneficial in severe STEC-HUS.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.506
Threshold uncertainty score0.736

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.010
GPT teacher head0.246
Teacher spread0.236 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2017
Admission routes1
Has abstractyes

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