scholarly journals Postmortem Study of Organ-Specific Toxicity in Glioblastoma Patients Treated with a Combination of Temozolomide, Irinotecan and Bevacizumab

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.

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii124-ii125
Author(s):  
Jay-Jiguang Zhu ◽  
Guangrong Lu ◽  
Mayank Rao ◽  
Ping Zhu ◽  
Nadine Linendoll ◽  
...  

Abstract Combined chemotherapy with temozolomide (TMZ), bevacizumab (BEV) and irinotecan (IRI) [TBI] has been used in patients with recurrent or progressive high-grade gliomas. Patients tolerated the regimen well with increased frequency of reversible clinical myelosuppression (CM), hypertension and proteinuria. However, organ-specific toxicities have never been evaluated by post-mortem examination. From 2009 to 2019, post-mortem examinations were performed in seventy-six decedents, including gliomas (N=68, 44/M and 24/F, median age: 59, ranging 23–80 years old) and brain metastases (N=8, 5/M and 3/F, ranging 39–75 years old). Twenty-four glioma subjects were treated with 1–25 cycles TBI (median 5.5) at glioma recurrence. All subjects’ clinical information, treatment histories and adverse events were collected. Five (7.7%, 5/65) glioma decedents (excluding three glioma patients who never received TMZ) permanently discontinued TMZ due to severe CM during concurrent chemoradiation therapy. There is no significantly elevated severity of CM from TBI when compared to standard of care therapies, nor when comparing extended TMZ treatment to the standard 12 cycles of TMZ. However, exposure to IRI significantly increased the CM occurrence (p< 0.05). Among glioma decedents, the most common cause of death was tumor progression (63.2 %, N=43), followed by aspiration pneumonia (48.5%, N=33). No deaths were attributed to acute toxicity from TBI. An electromicroscopic (EM) examination was performed in addition to routine autopsy procedures to investigate the cause of hypertension and proteinuria frequently developing in patients received BEV therapy. Ultrastructural evidence of thrombotic microangiopathy was observed in the kidneys among BEV users; however, it is difficult to conclude such changes were related to BEV due to rapid autolytic changes and artifacts. CONCLUSION: IRI, not the extended use of TMZ, significantly increased the frequency of reversible CM in recurrent glioma patients. There are no unexpected adverse events or organ-specific toxicities detected among glioma decedents who received the TBI regimen.


2012 ◽  
Vol 21 (4) ◽  
pp. 126-134 ◽  
Author(s):  
Celia Stewart

The most common causes of death in individuals with Huntington's disease (HD) are aspiration pneumonia and choking on food. The goal of this systematic review is to describe the scope of dysphagia symptoms and current treatments for individuals with HD. This review includes studies that met the following criteria: original research, presentation of swallowing symptoms and/or treatment, and availability in print and in English. Nine research studies and two review articles met the inclusion criteria. No random control or nonrandom studies were found. Dysphagia symptoms were reported in all phases of the swallow.


1970 ◽  
Vol 40 (1) ◽  
pp. 18-21 ◽  
Author(s):  
MN Hossain ◽  
Z Rahman ◽  
S Akhter

A cross sectional study was carried out at the department of Forensic Medicine in Dhaka Medical College during the period of January 2008 to December 2009. Data were collected from 3rd copy of the post mortem reports which were preserved in the department of Forensic Medicine with the verbal consent of the doctors who performed autopsy report. During this period total 5114 autopsies were conducted. Out of this 970 cases (19%) were suicidal in nature. It was noticed that all suicidal deaths occurred from 10 years to all age group respectively, but top amongst age group of suicidal deaths occurred in between 21 to 30 years of people. Suicidal deaths are more common in female than male. Suicidal deaths due to hanging is highest, next common causes of death due to organophosphorus compund poisoning. Suicidal deaths by hanging is more in female than male but in poisoning cases male are more lvictimised than female. Objectives of our study are to see the occurrence and methods of suicidal death. DOI: http://dx.doi.org/10.3329/bmj.v40i1.9957 BMJ 2011; 40(1): 18-21


GYNECOLOGY ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 39-41
Author(s):  
Zalina K. Batyrova ◽  
Zaira K. Kumykova ◽  
Elena V. Uvarova ◽  
Vladimir D. Chuprynin ◽  
Natalya A. Buralkina ◽  
...  

Background. Adnexal torsion (AT) takes fifth place among all emergency gynecological conditions. Suspicion of AT requires immediate diagnosis and urgent surgical treatment. The most common causes of AT are various volumetric formations, such as functional or dermoid ovarian cysts, contributing to an increase in its volume and/or anomalies in the development of the ligamentous apparatus. Timely diagnosis and detorsion contributes to the full restoration of impaired venous outflow and lymphatic drainage of the ovarian tissue, preventing the development of severe ischemia and necrosis. Over the past few decades, a surgical organ-preserving approach in managing patients with AT has been the gold standard of care. Materials and methods. The article describes the results of a retrospective study of cases of AT in children and adolescents treated at the Department of Pediatric and adolescent gynecology Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology with an assessment of the clinical and anamnestic features of this cohort of patients and the choice of therapeutic tactics. Conclusion. A multidisciplinary approach is critical to optimizing the delivery of care in cases of AT, including minimally invasive detorsion and preserving the functionality of the ovary as a treatment standard that should be used in the management of children and adolescents.


Blood ◽  
2016 ◽  
Vol 128 (8) ◽  
pp. 1043-1049 ◽  
Author(s):  
Ronald Chang ◽  
Jessica C. Cardenas ◽  
Charles E. Wade ◽  
John B. Holcomb

Abstract Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratory-based evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be “normal” after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge.


2021 ◽  
Vol 48 (2) ◽  
pp. 66-73
Author(s):  
Oladele S. Olatunya ◽  
Adefunke O. Babatola ◽  
Adewuyi T. Adeniyi ◽  
Adebukola B. Ajite ◽  
Isaac O. Oluwayemi ◽  
...  

Background: ‘Brought- in-dead’ (BID) refers to the demise of an individual before presentation to a health facility. This study assessed the pattern of paediatric BID cases seen at a tertiary health facility in southwest Nigeria. Method: A cross-sectional, descriptive study was done at the Children Emergency Ward (CEW) of the hospital between January 2014 and December 2018. The patterns of BID cases and presumed causes of death were determined using a standardized checklist adapted from the WHO verbal autopsy instrument. Results: Ninety-eight BID cases were seen during the study, constituting 2.5% of total patients seen during the period. The median (IQR) age of cases was 24.0 (8.75 – 63.0) months and 72.4% were under-fives. Most had symptoms related to the haematologic (36.7%), respiratory (24.5%) or digestive (20.4%) systems. Severe anaemia 31(31.6%), gastroenteritis 19 (19.4) and aspiration 17 (17.3%) were the most common causes of death. The median (IQR) duration of illness before presentation was 3.0 (1.0 – 7.0) days but most presented from 4 – 7 days of illness. A significant relationship was found between the duration of illness and whether or not pre-hospital treatment was received (p < 0.0001). Unprescribed drugs purchased over the counter were the most commonly used treatment in 79.1% of cases (p < 0.0001). Conclusion: This study has highlighted the prevalence and pattern of paediatric BID in a tertiary health facility in southwest Nigeria and the factors that were associated with it. More efforts need to be geared towards community sensitization and pediatric health care to prevent factors drivingits menace.


2020 ◽  
Vol 1 (1) ◽  
pp. 1-4
Author(s):  
Lia Artika Sari ◽  
Enny Susilawati

ABSTRAK Latar Belakang: Kanker merupakan salah satu penyebab kematian yang paling utama di dunia, sekitar 40 wanita tiap harinya terdiagnosa kanker leher rahim. Kanker leher rahim disebabkan oleh virus HPV, infeksi HPV sendiri sering kali tidak menimbulkan gejala. Desa Suka Maju merupakan salah satu desa yang terdapat di Kabupaten Muaro Jambi dan mempunyai jumlah wanita usia subur berjumlah 820 orang, namun hanya 17,11% wanita usia subur yang baru memanfaatkan pelayanan IVA.Metode: Dengan memberikan penyuluhan kepada wanita usia subur dengan (WUS) sebanyak 40 orang, dan diberikan pre dan post test untuk mengevaluasi pengetahuan wanita usia subur mengenai pemeriksaan IVA Hasil: terjadi kenaikan pengetahuan wanita usia subur di Desa Sukamaju sebesar 87,5%.Kesimpulan: Penyuluhan dapat meningkatkan pengetahuan wanita usia subur terhadap pentingnya pemeriksaan IVA. ABSTRACT Background: Cancer is one of the most common causes of death in the world. About 40 women are diagnosed with cervical cancer every day. Cervical cancer is caused by the HPV virus, HPV infection itself often causes no symptoms. Suka Maju Village is one of the villages in Muaro Jambi Regency that has 820 women of childbearing age, but only 17.11% of women of childbearing age have just used IVA services.Methods: employed in community service was to provide counseling to women of reproductive age with (WUS) as 40 women, and then given pre and posttests to evaluate the knowledge of women of childbearing age After being given counseling on IVA examinations. In brief,Result: There was an increase in the knowledge of women of childbearing age in Sukamaju Village by 87.5 %. Conclusion: Health education can increasedthe knowledge of women of childbearing age on the importance of IVA Chencking


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250708
Author(s):  
Sasha Peiris ◽  
Hector Mesa ◽  
Agnes Aysola ◽  
Juan Manivel ◽  
Joao Toledo ◽  
...  

Background Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs. Methods and findings A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings. Conclusions The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.


2019 ◽  
Vol 1 (2) ◽  
pp. 33-38

Introduction: Cancer is one of the most common causes of death among females. In our research, cancer data were collected in Wasit Governorate for patients who were referred to Al-Zahra Educational Hospital for the period From February 2010 to February 2019. The results showed that breast cancer is the most common type of cancer in Wasit governorate and by percentage (35.4%) with 341 out of 966 cases of cancer. Methods: Data were collected from data base between the year (2010 to 2019), with the highest rate of cases in 2013, which isaround 139 cases , of these cases around 71 were breast cancer (51.07% recurrence). Surprisingly the lowest cases were recorded in a year after (2014) with total cancer cases of 65 from them 21 cases of breast cancer only. Results: About the relationship between breast cancer and gender, breast cancer recorded 95.60% of the cases in females, while percentage of men cases only 4.39%. Conclusion: The higher percentage of the cases were around 40- 49 years old , 92 cases (27%) , 80 cases (23.5%) were in the age group (50-59 years) and 65cases (19%) were in the age group (30-39 years) and 51 cases (15%) were in the age group (60-69 years) ). The lowest percentage of breast cancer was in the 10-19 age group, with only two cases (0.5%).


Author(s):  
Parveen. A ◽  
Devika. R

Cardiovascular diseases, like coronary heart disease or artery disorders (arteriosclerosis, including artery solidification), heart failure (myocardial infarction), arrhythmias, congestive heart condition, stroke, elevated vital signs (hypertension), rheumatic heart disorder, and other circulatory system dysfunctions are the most common causes of death worldwide. Cardiovascular disorders are treated with stenting, coronary bypass surgery grafting, anticoagulants, antiplatelet agents, and other pharmacological and surgical procedures; however, these have limitations due to their adverse effects. Fibrinolytic agents degrade fibrin through enzymatic and biochemical processes. There are various enzymes that are currently used as a treatment for CVDs, like Streptokinase, Nattokinase, Staphylokinase, Urokinase, etc. These enzymes are derived from various sources like bacteria, fungi, algae, marine organisms, plants, snakes, and other organisms. This review deals with the fibrinolytic enzymes, their mechanisms, sources, and their therapeutic potential.


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