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Τρίτη 22 Νοεμβρίου 2022

Asparaginase‐related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System (FAERS) data and literature review

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Asparaginase-related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System (FAERS) data and literature review

This study investigated the association between asparaginase and diabetic ketoacidosis from the perspective of adverse reaction signal detection and literature review. The reporting odd ratio (ROR) of diabetic ketoacidosis (DKA) caused by l-asparaginase was statistically significant, but there was not a statistical association for DKA caused by pegaspargase. Combined with the results of literature review, we speculated that the asparaginase dosage form may affect the occurrence of DKA.


Abstract

What is Known and Objective

Diabetic ketoacidosis (DKA) may occur during asparaginase use. However, limited by the study population, the association between asparaginase and DKA has not been elucidated. The purpose of this study was to determine the potential association between asparaginase and DKA and analyse related clinical characteristics and possible risk factor.

Methods

Disproportionality analysis with the reporting odd ratio (ROR) was used to detect the adverse reaction signals of asparaginase-associated DKA in Food and Drug Administration Adverse Event Reporting System (FAERS). A literature review was conducted to further analyse clinical characteristics, possible risk factor and something noteworthy in asparaginase-associated DKA.

Results and Discussion

A total of 12 reports of DKA associated with l-asparaginase (l-asp) and 6 reports associated with pegaspargase (PEG-asp) were extracted in FAERS, more than 50% of the cases were classified as serious adverse events. DKA was a positive signal of l-asp (ROR = 2.397, 95% CI 1.360–4.226), while not closely related to the use of PEG-asp (ROR = 1.602, 95% CI 0.719–3.570). Searched in PubMed, Embase and Web of Science, a total of eight patients were collected. The patients were mainly adolescent patients, aged between 11 and 25 years old with a median age of 16 years. Drug dosage form distribution is unbalanced, 7 patients received l-asp and only 1 received PEG-asp.

What is New and Conclusions

The ROR of KDA caused by l-asp was statistically significant, but there was not a statistical association for DKA caused by PEG-asp. Asparaginase dosage form may affect the occurrence of DKA, but further research is needed.

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Relapse after non‐metastatic rhabdomyosarcoma: The impact of routine surveillance imaging on early detection and post‐relapse survival

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Patients with rhabdomyosarcoma (RMS) whose disease relapses have little chance of being cured, so front-line treatments are usually followed up with surveillance imaging in an effort to detect any recurrences as early as possible, and thereby improve post-relapse outcomes. The real benefit of such routine surveillance imaging in RMS remains to be demonstrated, however. This retrospective, single-center study examines how well surveillance imaging identifies recurrent tumors and its impact on post-relapse survival.

Methods

The analysis concerned 79 patients <21 years old treated between 1985 and 2020 whose initially localized RMS relapsed. Clinical findings, treatment modalities, and survival were analyzed, comparing patients whose relapse was first suspected from symptoms they developed (clinical symptoms group) with those whose relapse was identified by radiological surveillance (routine imaging group).

Results

Tumor relapses came to light because of clinical symptoms in 42 cases, and on routine imaging in 37. The time to relapse was much the same in the two groups. The median overall survival (OS) and 5-year OS rate were, respectively, 10 months and 12.6% in the clinical symptoms group, and 11 months and 27.5% in the routine imaging group (p-value .327). Among patients with favorable prognostic scores, survival was better for those in the routine imaging group (5-year OS 75.0% vs. 33.0%, p-value .047).

Conclusion

It remains doubtful whether surveillance imaging has any real impact on RMS relapse detection and patients' post-relapse survival. Further studies are needed to establish the most appropriate follow-up recommendations, taking the potentially negative effects of regular radiological exams into account.

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The fate of interneurons, GABAA receptor sub‐types and perineuronal nets in Alzheimer's disease

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Alzheimer's disease (AD) is the most common neurological disease, which is associated with gradual memory loss and correlated with synaptic hyperactivity and abnormal oscillatory rhythmic brain activity that precedes phenotypic alterations and is partly responsible for the spread of the disease pathology. Synaptic hyperactivity is thought to be because of alteration in the homeostasis of phasic and tonic synaptic inhibition, which is orchestrated by the GABAA inhibitory system, encompassing subclasses of interneurons and GABAA receptors, which play a vital role in cognitive functions, including learning and memory. Furthermore, the extracellular matrix, the perineuronal nets (PNNs) which often go unnoticed in considerations of AD pathology, encapsulate the inhibitory cells and neurites in critical brain regions and have recently come under the light for their crucial role in synaptic stabilisation and excitatory-inhibitory balance and when disrupted, serve as a potential trigger for AD-associated synaptic imbalance. Therefore, in this review, we summarise the current understanding of the selective vulnerability of distinct interneuron subtypes, their synaptic and extrasynaptic GABAAR subtypes as well as the changes in PNNs in AD, detailing their contribution to the mechanisms of disease development. We aim to highlight how seemingly unique malfunction in each component of the interneuronal GABA inhibitory system can be tied together to result in critical circuit dysfunction, leading to the irreversible symptomatic damage observed in AD.

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FACE-Q satisfaction following upper third facial gender-affirming surgery using custom bone-section guides

alexandrossfakianakis shared this article with you from Inoreader
Postoperative satisfaction after facial gender-affirming surgery (FGAS) has not yet been assessed using a validated questionnaire. There is currently no postoperative satisfaction questionnaire specific to transgender patients concerning facial surgery. The contributions of three-dimensional planning in fronto-orbital surgery in trans women and the use of bone cutting guides for facial feminization surgery have been demonstrated. The primary objective of this study was to evaluate postoperative satisfaction with the upper third of the face in trans women using a validated questionnaire – FACE-Q – after fronto-orbital surgery using custom-made bone cutting guides. (Source: International Journal of Oral and Maxillofacial Surgery)
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