Postmortem studies [Neurosurgery Wiki]

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====== Postmortem studies ======

[[Postmortem]] studies are a type of neurobiological research, which provides information to researchers and individuals who will have to make medical decisions in the future.
Postmortem researchers conduct a longitudinal study of the brain of an individual, who has some sort of phenomenological condition (i.e. cannot speak, trouble moving left side of body, Alzheimer's, etc.) that is examined after death. Researchers look at certain lesions in the brain that could have an influence on cognitive or motor functions.
These irregularities, damage, or other cerebral anomalies observed in the brain are attributed to an individual's pathophysiology and their environmental surroundings. Postmortem studies provide a unique opportunity for researchers to study different brain attributes that would be unable to be studied on a living person.
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Systemic [[chemotherapy]] including monotherapy with [[temozolomide]] (TMZ) or [[bevacizumab]] (BEV); two-drug combinations, such as [[irinotecan]] (IRI) and BEV, TMZ and BEV and a three-drug combination with TMZ, IRI and BEV (TIB) have been used in treating patients with progressive [[high-grade glioma]]s including [[glioblastoma]] (GBM). Most patients tolerated these regimens well with known side effects of [[hypertension]], [[proteinuria]], and reversible clinical [[myelosuppression]] (CM). However, organ- or system- specific toxicities from [[chemotherapy]] agents have never been examined by postmortem study. 

Postmortem tissues (from all major systems and organs) were prospectively collected and examined by standard institution autopsy and neuropathological procedures from 76 subjects, including gliomas (N = 68, 44/M, and 24/F) and brain metastases (N = 8, 5/M, and 3/F) between 2009 and 2019. Standard hematoxylin and eosin (H&E) were performed on all major organs including brain specimens. Electronic microscopic (EM) study was carried out on 14 selected subject's kidney samples per standard EM protocol. Medical records were reviewed with adverse events (AEs) analyzed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. A swimmer plot was utilized to visualize the timelines of patient history by treatment group. The binary logistic regression models were performed to explore any associations between treatment strategies and incident myelosuppression.

Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at tumor recurrence. Exposure to IRI significantly increased the frequency of CM (p = 0.05). No unexpected adverse events clinically, or permanent end-organ damage during postmortem examination was identified in glioma subjects who had received standard or prolonged duration of BEV, TMZ or TIB regimen-based chemotherapies except rare events of bone marrow suppression. The most common causes of death (COD) were tumor progression (63.2%, N = 43) followed by aspiration pneumonia (48.5%, N = 33) in glioma subjects. No COD was attributed to acute toxicity from TIB. The study also demonstrated that postmortem kidney specimen is unsuitable for studying renal ultrastructural pathological changes due to autolysis.

There is no organ or system toxicity by postmortem examinations among glioma subjects who received BEV, TMZ or TIB regimen-based chemotherapies regardless of durations except for occasional bone marrow suppression and reversible myelosuppression clinically. IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. COD most commonly resulted from glioma [[tumor progression]] with infiltration to [[brain stem]] and [[aspiration pneumonia]]
((Lu G, Zhu P, Rao M, Linendoll N, Buja LM, Bhattacharjee MB, Brown RE, Ballester LY, Tian X, Pilichowska M, Wu JK, Hergenroeder GW, Glass WF, Chen L, Zhang R, Pillai AK, Hunter RL, Zhu JJ. Postmortem study of organ-specific toxicity in glioblastoma patients treated with a combination of temozolomide, irinotecan and bevacizumab. J Neurooncol. 2022 Oct 6. doi: 10.1007/s11060-022-04144-y. Epub ahead of print. PMID: 36203027.)).