postmortem studies
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2022 ◽  
Author(s):  
Guangrong Lu ◽  
Mayank Rao ◽  
Ping Zhu ◽  
Nadine Linendoll ◽  
Maximilian L. Buja ◽  
...  

Abstract Purpose Systemic 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 gliomas including glioblastoma. Most patients tolerated these regimens well with well-established sides effects of hypertension, proteinuria, and reversible clinical myelosuppression (CM). However, organ-specific toxicities have never been examined by postmortem studies. Methods Postmortem tissues (from all major organs) were prospectively collected and examined by standard institution autopsy and brain cutting procedures from 76 decedents, 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 and brain samples harvested. Electronic microscopic (EM) study was carried on selected subjects kidney samples per standard EM protocol. Results Twenty-four glioma subjects were treated with TIB [median: 5.5 (range: 1-25) cycles] at glioma recurrence. Exposure to IRI significantly increased the frequency of CM (p=0.05). No unexpected adverse events were detected clinically or permenant end-organ damage by postmortem examination among subjects who received TIB compared to subjects who received standard of care (SOC) therapies. Among glioma decedents, the most common causes of death (COD) were tumor progression (63.2%, N=43), followed by aspiration pneumonia (48.5%, N=33). 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. Conclusion IRI, but not the extended use of TMZ, significantly increased CM in recurrent glioma patients. There is no permanent organ-specific toxicity among glioma decedents who received prolonged BEV, TMZ or TIB regimen based chemotherapies except expected occasional myelosuppresson. COD are most commonly resulted from glioma tumor progression and aspiration pneumonia.


Author(s):  
Francesca Sanguedolce ◽  
Magda Zanelli ◽  
Elisabetta Froio ◽  
Alessandra Bisagni ◽  
Maurizio Zizzo ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Arsénia J. Massinga ◽  
Marcelino Garrine ◽  
Augusto Messa ◽  
Nélio A. Nobela ◽  
Nadia Boisen ◽  
...  

Abstract Background Klebsiella spp. are important pathogens associated with bacteremia among admitted children and is among the leading cause of death in children < 5 years in postmortem studies, supporting a larger role than previously considered in childhood mortality. Herein, we compared the antimicrobial susceptibility, mechanisms of resistance, and the virulence profile of Klebsiella spp. from admitted and postmortem children. Methods Antimicrobial susceptibility and virulence factors of Klebsiella spp. recovered from blood samples collected upon admission to the hospital (n = 88) and postmortem blood (n = 23) from children < 5 years were assessed by disk diffusion and multiplex PCR. Results Klebsiella isolates from postmortem blood were likely to be ceftriaxone resistant (69.6%, 16/23 vs. 48.9%, 43/88, p = 0.045) or extended-spectrum β-lactamase (ESBL) producers (60.9%, 14/23 vs. 25%, 22/88, p = 0.001) compared to those from admitted children. blaCTX-M-15 was the most frequent ESBL gene: 65.3%, 9/14 in postmortem isolates and 22.7% (5/22) from admitted children. We found higher frequency of genes associated with hypermucoviscosity phenotype and invasin in postmortem isolates than those from admitted children: rmpA (30.4%; 7/23 vs. 9.1%, 8/88, p = 0.011), wzi-K1 (34.7%; 8/23 vs. 8%; 7/88, p = 0.002) and traT (60.8%; 14/23 vs. 10.2%; 9/88, p < 0.0001), respectively. Additionally, serine protease auto-transporters of Enterobacteriaceae were detected from 1.8% (pic) to 12.6% (pet) among all isolates. Klebsiella case fatality rate was 30.7% (23/75). Conclusion Multidrug resistant Klebsiella spp. harboring genes associated with hypermucoviscosity phenotype has emerged in Mozambique causing invasive fatal disease in children; highlighting the urgent need for prompt diagnosis, appropriate treatment and effective preventive measures for infection control.


Author(s):  
Jia-Yi Li ◽  
Wen Li

Neural transplantation is a potential therapeutic method for Parkinson’s disease (PD). Fetal dopaminergic (DA) neurons have been important transplantation cell sources in the history of replacement therapy for PD. Several decades of preclinical animal experiments and clinical trials using fetal DA neuron transplantation in PD therapy have shown not only promising results but also problems. In order to reveal possible factors influencing the clinical outcomes, we reviewed fetal DA neuron transplantation therapies from 1970s to present, with a special focus on postmortem studies. Firstly, we gave a general description of the clinical outcomes and neuroanatomy of grafted cases; secondly, we summarized the main available postmortem studies, including the cell survival, reinnervation, and pathology development. In the end, we further discussed the link between function and structure of the grafts, seeking for the possible factors contributing to a functional graft. With our review, we hope to provide references for future transplantation trials from a histological point of view.


2021 ◽  
pp. 1-4
Author(s):  
Anders Björklund

In two recent postmortem studies, Jeffrey Kordower and colleagues report new findings that open up for an interesting discussion on the status of GDNF/NRTN signaling in patients with Parkinson’s disease (PD), adding an interesting perspective on the, admittedly very limited, signs of restorative effects previously seen in GDNF/NRTN-treated patients. Their new findings show that the level of the GDNF signaling receptor Ret is overall reduced by about 65% relative to non-PD controls, and most severely, up to 80%, in nigral neurons containing α-synuclein inclusions, accompanied by impaired signaling downstream of the Ret receptor. Notably, however, the vast majority of the remaining nigral neurons retained a low level of Ret expression, and hence a threshold level of signaling. Further observations made in two patients who had received AAV-NRTN gene therapy 8–10 years earlier suggest the intriguing possibility that NRTN is able to restore Ret expression and upregulate its own signaling pathway. This “wind-up” mechanism, which is likely to depend on an interaction with dopaminergic transcription factor Nurr1, has therapeutic potential and should encourage renewed efforts to turn GDNF/NRTN therapy into success, once the recurring problem of under-dosing is resolved.


Author(s):  
Elena S. Romanova ◽  
Valery V. Vasilyev ◽  
Galina Startseva ◽  
Vadim Karev ◽  
Margarita G. Rybakova ◽  
...  

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 412
Author(s):  
Natalia Rakislova ◽  
Lorena Marimon ◽  
Mamudo R. Ismail ◽  
Carla Carrilho ◽  
Fabiola Fernandes ◽  
...  

Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, b) compare the performance of MIA versus complete autopsy, and c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the main cause of death, being responsible for the different stages of diffuse alveolar damage. No COVID-19 infection was detected in the personnel performing the MIAs or complete autopsies. In conclusion, MIA might be a feasible, adequate and safe alternative for cause of death investigation in COVID-19 cases.


2021 ◽  
Vol 12 ◽  
Author(s):  
Elan D. Louis

The past 10 years has seen a remarkable advance in our understanding of the disease traditionally referred to as “essential tremor” (ET). First, the clinical phenotype of ET has been expanded from that of a bland, unidimensional, and monosymptomatic entity to one with a host of heterogeneous features. These features include a broader and more nuanced collection of tremors, non-tremor motor features (e.g., gait abnormalities) and a range of non-motor features, including cognitive, psychiatric, sleep, and other abnormalities. The natural history of these features, as well as their relationships with one another and with disease duration and severity, are better appreciated than they were previously. Studies of disease etiology have identified a number of candidate genes as well as explored several environmental determinants of disease. In addition, the decade has seen the beginnings and expansion of rigorous postmortem studies that have identified and described the postmortem changes in the brains of patients with ET. This emerging science has given rise to a new notion that the disease, in many cases, is one of cerebellar system degeneration. Across all of these studies (clinical, etiological, and pathophysiological) is the observation that there is heterogeneity across patients and that “essential tremor” is likely not a single disease but, rather, a family of diseases. The time has come to use the more appropriate terminology, “the essential tremors,” to fully describe and encapsulate what is now apparent. In this paper, the author will review the clinical, etiological, and pathophysiological findings, referred to above, and make the argument that the terminology should evolve to reflect advances in science and that “the essential tremors” is a more scientifically appropriate term.


Author(s):  
Cornelius J Clancy ◽  
Ilan S Schwartz ◽  
Brittany Kula ◽  
M Hong Nguyen

Abstract Background Limited clinical data suggest ~16% prevalence of bacterial superinfections among critically ill patients with coronavirus disease 2019 (COVID-19). Methods We reviewed postmortem studies of patients with COVID-19 published in English through 26 September 2020 for histopathologic findings consistent with bacterial lung infections. Results Worldwide, 621 patients from 75 studies were included. The quality of data was uneven, likely because identifying superinfections was not a major objective in 96% (72/75) of studies. Histopathology consistent with potential lung superinfection was reported in 32% (200/621) of patients (22-96 years old; 66% men). Types of infections were pneumonia (95%), abscesses or empyema (3.5%), and septic emboli (1.5%). Seventy-three percent of pneumonias were focal rather than diffuse. Predominant histopathologic findings were intra-alveolar neutrophilic infiltrations that were distinct from those typical of COVID-19-associated diffuse alveolar damage. In studies with available data, 79% of patients received antimicrobial treatment; most common agents were beta-lactam/beta-lactamase inhibitors (48%), macrolides (16%), cephalosoprins (12%), and carbapenems (6%). Superinfections were proven by direct visualization or recovery of bacteria in 25.5% (51/200) of potential cases, and 8% of all patients in postmortem studies. In rank order, pathogens included Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae. Lung superinfections were causes of death in 16% of potential cases, and 3% of all patients with COVID-19. Conclusions Potential bacterial lung superinfections were evident at postmortem examination in 32% of persons who died with COVID-19 (proven, 8%; possible, 24%), but they were uncommonly the cause of death.


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