Postmortem Diagnosis Of Sepsis Research Articles

Multiorgan immunohistochemical endothelial expression of E-selectin in a forensic case of sepsis

Sepsis is one of the major threats for the survival and prognosis of patients in intensive care units. In cases where detailed clinical data and monitoring is available, the diagnosis of sepsis is reliable. But when clinical data are incomplete or missing and sepsis is only suspected based on the autopsy results, the picture is often equivocal. This report describes the gross pathological findings obtained from the autopsy of a 48-year-old woman with Crohn’s disease after surgical intervention. Macroscopically, we found intestinal perforation and signs of peritonitis. Histologically, the pulmonary/bronchial arteries were lined with E-selectin (CD 62E)-positive endothelial cells, which are an established postmortem histological marker of sepsis. We extended our investigations to the cerebral cortex and subcortical medullary layer. The endothelium of the cortical vessels and those in the cerebral medullary layer were likewise immunopositive for E-selectin. Furthermore, numerous TMEM119-positive, highly ramified microglial cell profiles were found in the grey and white matter. Microglial cells were lining the vascular profiles. In addition, TMEM119-positive microglial profiles were abundant in the cerebrospinal fluid (CSF). Multiorgan E-selectin positivity of the vascular endothelia provides further evidence for the postmortem diagnosis of sepsis.

Fatal Pediatric Streptococcal Infection: A Clinico-Pathological Study.

Purpose and ContextStreptococcal Infection (SI) is an important cause of pediatric death in children, yet limited reports exist on autopsy findings in fatal SI cases.MethodCase records (1997–2019) of SI with no pre-existing risk factors were reviewed and selected. Their clinical and pathological findings in the autopsy reports were analyzed.ResultsIn our cohort of 38 cases based on bacterial culture results, SI was most commonly caused by Streptococcus pneumoniae (SPn; 45%) and Streptococcus pyogenes (SPy; 37%). 92% of decedents had some prodromal symptoms prior to terminal presentation. The clinical course was often rapid, with 89% found unresponsive, suddenly collapsing, or dying within 24 hours of hospital admission. 64% of deaths were attributed to sepsis, more frequently diagnosed in the SPy group than in the SPn group (71% vs 48%). Pneumonia was found in both SPn and SPy groups, whereas meningitis was exclusively associated with SPn.ConclusionOur study shows fatal SI is most commonly caused by either SPn or SPy, both of which are frequently associated with prodromal symptoms, rapid terminal clinical course, and evidence of sepsis. Postmortem diagnosis of sepsis is challenging and should be correlated with clinical features, bacterial culture results, and autopsy findings.

Post-mortem diagnosis of sepsis: when it's too late.

Post-mortem diagnosis of sepsis is often very difficult to make, especially in the elderly affected by multiple comorbidities. However, clinical evaluation following histology, immunohistochemistry, microbiological tests, immunoassays and proteomics can improve reliability of this post-mortem diagnosis.

Post-Mortem Investigations for the Diagnosis of Sepsis: A Review of Literature

To date, sepsis is still one of the most important causes of death due to the difficulties concerning the achievement of a correct diagnosis. As well as in a clinical context, also in a medico-legal setting the diagnosis of sepsis can reveal challenging due to the unspecificity of the signs detected during autopsies, especially when no ante-mortem clinical data, laboratory, and cultural results are available. Thus, a systematic review of literature was performed to provide an overview of the main available and updated forensic tools for the post-mortem diagnosis of sepsis. Moreover, the aim of this review was to evaluate whether a marker or a combination of markers exist, specific enough to allow a correct and definite post-mortem diagnosis. The review was conducted searching in PubMed and Scopus databases, and using variable combinations of the keywords “post mortem sepsis diagnosis”, “macroscopic signs”, “morphology”, “histology”, “immunohistochemical markers”, “biochemical markers”, and “forensic microbiology”. The article selection was carried out following specific inclusion and exclusion criteria. A total of 44 works was identified, providing data on morphological aspects of the organs examined, histological findings, immunohistochemical and biochemical markers, and cultural assays. The review findings suggested that the post-mortem diagnosis of sepsis can be achieved by a combination of data obtained from macroscopic and microscopic analysis and microbial investigations, associated with the increased levels of at least two of three biochemical and/or immunohistochemical markers evaluated simultaneously on blood samples.

Biochemical markers and microbiology in post-mortem diagnosis of sepsis: a systematic review

Biochemical markers and microbiology in post-mortem diagnosis of sepsis: a systematic review

Searching for highly sensitive and specific biomarkers for sepsis: State-of-the-art in post-mortem diagnosis of sepsis through immunohistochemical analysis.

The autoptical observations commonly ascribed to sepsis deal with unspecific general and local signs of inflammation or ischemia, such as myocardial inflammation, pulmonary edema and infiltration, cerebral swallowing, and tubular necrosis in the kidney. In the two last decades, some studies have been carried out to implement immunohistochemical markers for post-mortem diagnosis. All of these target molecules are specifically up-regulated or down-regulated during systemic inflammatory responses, especially for infective causes. Among these, we found some antigens expressed on leukocyte surfaces (very late antigen-4 (VLA-4), cluster differentiation-15 (CD15)), enzyme contained in neutrophils granules (lysozyme (LZ), lactoferrin (LF)), endothelial markers and junctions (E-selectin, vascular endothelial cadherin (VE-cadherin)), and soluble factors (vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNFα), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (s-TREM-1)). All of these showed potential reliability in differentiating sepsis cases from controls. Further studies are needed to provide a concrete validation for a combination of markers on specific organ samples in order to reach a post-mortem diagnosis of sepsis also in the absence of clinical records.

An immunohistochemical study of the diagnostic value of TREM-1 as marker for fatal sepsis cases

ABSTRACTTriggering receptor expressed on myeloid cells-1 (TREM-1) is produced and up-regulated by exposure of myeloid cells to lipopolysaccharides or other components of either bacterial or fungal origin, which causes it to be strongly expressed on phagocytes that accumulate in inflamed areas. Because TREM-1 participates in septic shock and in amplifying the inflammatory response to bacterial and fungal infections, we believe it could be an immunohistochemical marker for postmortem diagnosis of sepsis. We tested the anti-TREM-1 antibody in 28 cases of death by septic shock and divided them into two groups. The diagnosis was made according to the criteria of the Surviving Sepsis Campaign. In all cases, blood cultures were positive. The first group was comprised subjects that presented high ante-mortem serum procalcitonin and the soluble form of TREM-1 (s-TREM-1) values. The second group comprised subjects in which s-TREM-1 was not measured ante-mortem. We used samples of brain, heart, lung, liver and kidney for each case to test the anti-TREM-1 antibody. A semiquantitative evaluation of the immunohistochemical findings was made. In lung samples, we found immunostaining in the cells of the monocyte line in 24 of 28 cases, which suggests that TREM-1 is produced principally by cells of the monocyte line. In liver tissue, we found low TREM-staining in the hepatocyte cytoplasm, duct epithelium, the portal-biliary space and blood vessel. In kidney tissue samples, we found the TREM-1 antibody immunostaining in glomeruli and renal tubules. We also found TREM-1 staining in the lumen of blood vessels. Immunohistochemical staining using the anti-TREM-1 antibody can be useful for postmortem diagnosis of sepsis.

Postmortem diagnosis of sepsis: A preliminary immunohistochemical study with an anti-procalcitonin antibody.

Postmortem diagnosis of sepsis: A preliminary immunohistochemical study with an anti-procalcitonin antibody.

Usefulness of pericardial and pleural fluids for the postmortem diagnosis of sepsis

The purpose of this study was to evaluate the postmortem distributions of procalcitonin (PCT), C-reactive protein (CRP), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and soluble interleukin-2 receptor (sIL-2R) levels in postmortem serum from femoral blood, pericardial fluid and pleural fluid in a series of sepsis-related fatalities (12 subjects) and control cases (20 subjects) that underwent medico-legal investigations. Our aim was to assess the diagnostic potential of the results obtained from pericardial and pleural fluid analysis in identifying sepsis-related deaths. All sepsis-related cases had a documented, clinical diagnosis that was established in vivo during hospitalization. Pneumonia was the main infectious focus identified during autopsy and histology. Pseudomonas aeruginosa, Klebsiella pnemoniae and Escherichia coli were the most commonly identified bacteria in blood and lung tissue cultures. The preliminary results corroborate the usefulness of PCT, CRP, sTREM-1 and sIL-2R determination in postmortem serum for the identification of sepsis-related deaths. Moreover, the data suggest that, as far as PCT, CRP, sTREM-1 and sIL-2R measurements are concerned, pericardial and pleural fluids can be considered suitable alternatives to postmortem serum should femoral blood prove unavailable at autopsy.

Endocan measurement for the postmortem diagnosis of sepsis

The vascular endothelium has been shown to play a pivotal role in the pathophysiology of sepsis through the expression of surface proteins and secretion of soluble mediators. Endocan (endothelial cell-specific molecule-1), a 50-kDa dermatan sulfate proteoglycan, is expressed by endothelial cells in lung and kidney and can be detected at low levels in the serum of healthy subjects. Increased concentrations were described in patients with sepsis, severe sepsis and septic shock compared to healthy individuals, with serum concentrations related to the severity of illness. In the present study, we investigated endocan, procalcitonin and C-reactive protein in postmortem serum from femoral blood in a series of sepsis-related fatalities and control individuals who underwent medicolegal investigations. Endocan was also measured in pericardial fluid. Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases with documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various noninfectious causes of death. Postmortem serum endocan concentrations were significantly higher in the sepsis group, with values ranging from 0.519 ng/ml to 6.756 ng/ml. In the control group, endocan levels were undetectable in eleven out of sixteen cases. The results of the data analysis revealed similar endocan concentrations in the pericardial fluid of both studied groups. Endocan can be considered a suitable biological parameter for the detection of sepsis-related deaths in forensic pathology routine.

Diagnostic value of lipopolysaccharide-binding protein and procalcitonin for sepsis diagnosis in forensic pathology

The aims of this study were twofold. The first was to investigate the diagnostic performance of two biochemical markers, procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP), considering each individually and then combined, for the postmortem diagnosis of sepsis. We also tested the usefulness of pericardial fluid for postmortem LBP determination. Two study groups were formed, a sepsis-related fatalities group of 12 cases and a control group of 30 cases. Postmortem native CT scans, autopsy, histology, neuropathology, and toxicology as well as other postmortem biochemical investigations were performed in all cases. Microbiological investigations were also carried out in the septic group. Postmortem serum PCT and LBP levels differed between the two groups. Both biomarkers, individually considered, allowed septic states to be diagnosed, whereas increases in both postmortem serum PCT and LBP levels were only observed in cases of sepsis. Similarly, normal PCT and LBP values in postmortem serum were identified only in non-septic cases. Pericardial fluid LBP levels do not correlate with the presence of underlying septic states. No relationship was observed between postmortem serum and pericardial fluid LBP levels in either septic or non-septic groups, or between pericardial fluid PCT and LBP levels.

Procalcitonin and C-reactive protein in pericardial fluid for postmortem diagnosis of sepsis

The aim of this study was to investigate the presence and concentrations of procalcitonin and C-reactive protein in pericardial fluid and compare these levels to those found in the postmortem serum obtained from the femoral blood. Two groups were formed, a sepsis-related fatalities group and a control group. Postmortem native CT scans, autopsies, histology, neuropathology and toxicology as well as other postmortem biochemistry investigations were performed in all cases. Pericardial fluid procalcitonin levels were significantly different between the cases of sepsis-related fatalities and those of the control group. Postmortem serum procalcitonin levels below the detection limit were also reflected in undetectable pericardial fluid levels. Similarly, a large increase in postmortem serum procalcitonin levels was reflected in a large increase of procalcitonin pericardial fluid levels. Based on these findings, pericardial fluid could be an alternative to postmortem serum for the determination of procalcitonin levels in cases where postmortem serum is not available and measurements of procalcitonin are required to circumstantiate the pathogenesis of death.

Evaluation of C-reactive protein, procalcitonin, tumor necrosis factor alpha, interleukin-6, and interleukin-8 as diagnostic parameters in sepsis-related fatalities

The aims of this study were to investigate the usefulness of serum C-reactive protein, procalcitonin, tumor necrosis factor alpha, interleukin-6, and interleukin-8 as postmortem markers of sepsis and to compare C-reactive protein and procalcitonin values in serum, vitreous humor, and cerebrospinal fluid in a series of sepsis cases and control subjects, in order to determine whether these measurements may be employed for the postmortem diagnosis of sepsis. Two study groups were formed, a sepsis group (eight subjects coming from the intensive care unit of two university hospitals, with a clinical diagnosis of sepsis in vivo) and control group (ten autopsy cases admitted to two university medicolegal centers, deceased from natural and unnatural causes, without elements to presume an underlying sepsis as the cause of death). Serum C-reactive protein and procalcitonin concentrations were significantly different between sepsis cases and control cases, whereas serum tumor necrosis factor alpha, interleukin-6, and interleukin-8 values were not significantly different between the two groups, suggesting that measurement of interleukin-6, interleukin-8, and tumor necrosis factor alpha is non-optimal for postmortem discrimination of cases with sepsis. In the sepsis group, vitreous procalcitonin was detectable in seven out of eight cases. In the control group, vitreous procalcitonin was clearly detectable only in one case, which also showed an increase of all markers in serum and for which the cause of death was myocardial infarction associated with multi-organic failure. According to the results of this study, the determination of vitreous procalcitonin may be an alternative to the serum procalcitonin for the postmortem diagnosis of sepsis.

Immunohistochemical detection of CCR2 and CX3CR1 in sepsis-induced lung injury

Sepsis is a systemic inflammatory disease with high mortality. In the present study, we immunohistochemically examined CCR2 and CX3CR1 expression in sepsis-induced lung injury, and discussed its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48 h. Immunohistochemically, mononuclear cells recruited into the lungs expressed CCR2 and CX3CR1 in both sepsis and non-septic groups. In double-color immunofluorescence analysis, CCR2- or CX3CR1-positive cells could be identified as CD68-positive macrophages. Moreover, most of CD68-positive macrophages expressed both CCR2 and CX3CR1. Morphometrically, the average of CCR2- and CX3CR1-positive macrophages was significantly increased in sepsis group, compared with control group (sepsis vs. control: 41.6 ± 1.3% vs. 8.0 ± 0.4% in CCR2; 36.2 ± 1.3% vs. 9.2 ± 0.4% in CX3CR1). These observations implied that CCR2- or CX3CR1-positive macrophages were recruited into the lungs under several pathological conditions. In particular, their recruitment might be more evident in sepsis. Moreover, from the forensic aspects, immunohistochemical detection of CCR2 and CX3CR1 expression in the lungs can be considered as valuable diagnostic tools for the postmortem diagnosis of sepsis.

Postmortem diagnosis of sepsis

Human sepsis is a spectrum of pathophysiological changes in the host system resulting from a generalized activation and systemic expression of the host's inflammatory pathways in response to infection. Since autopsy findings and routine histology in cases of suspected fatal sepsis are most often unspecific and unconvincing, a number of studies has recently dealt with different methods and markers to better define criteria for the postmortem diagnosis of sepsis. Research carried out on specimens obtained postmortem from sepsis-associated fatalities is an important tool to improve our understanding of inflammatory organ changes and the associated underlying pathophysiological mechanisms. One pitfall the investigator has to be aware of is how to select appropriate case material that constitutes the basis for the setting-up of reference values that derive from such studies. Since no scientific studies have investigated the value of cardiac blood samples in the present context, autopsy blood samples for the determination of biochemical sepsis markers have to derive from the femoral vein. In both sepsis cases as well as controls, the time of death has to be well defined.

Immunohistochemical expression of tumor necrosis factor-α in sepsis-induced lung injury.

Sepsis is asevere, systemic inflammatory disease caused by various kinds of microbes. In the present study, we immunohistochemically examined tumor necrosis factor (TNF)-α expression in sepsis-induced lung injury, and discuss its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48 hours. Immunohistochemical analysis using anti-human TNF-α rabbit polyclonal antibodies was carried out. In sepsis and control groups, immunoreactivity for TNF-α was strongly detected in round-shaped mononuclear cells. The intensity of the immunohistochemical staining reaction was homogeneous in all lobes of the lungs examined. Furthermore, a double-color immunofluorescence analysis revealed that macrophages were a main cellular source of TNF-α in the lungs. To semiquantitatively evaluate the expression of TNF-α in the lungs, the ratios of the number of TNF-α-positive macrophages to total number of macrophages were calculated. Morphometrically, in lungs of the sepsis group, the ratio of TNF-α-positive macrophages was significantly higher, compared with the control group. TNF-α expression in the lungs can become a clue for the postmortem diagnosis of pulmonary inflammation, especially, TNF-α-positive ratios of 20% of more might suggest sepsis as the cause of death.

Serial monitoring of interleukin-1beta, soluble interleukin-2 receptor and lipopolysaccharide binding protein levels after death A comparative evaluation of potential postmortem markers of sepsis.

We prospectively monitored the postmortem course of interleukin-1beta (IL-1beta), soluble interleukin-2 receptor (sIL-2R) and lipopolysaccharide binding protein (LBP) in septic and non-septic fatalities to evaluate their potential as biochemical postmortem markers of sepsis. Serum concentrations were determined by chemiluminescent immunometric assays. In both the sepsis group and the control group a postmortem increase of IL-1beta levels with the progression of time after death was observed, in both groups mainly starting from the reference concentration of healthy individuals (5 pg/ml) and with no significant differences at later time points postmortem. SIL-2R (reference limit 1,000 U/ml) was highly elevated in all individuals included in the sepsis group at all time points postmortem with statistically significant differences between the sepsis and control groups (p<0.01). An excessive postmortem decrease of sIL-2R serum levels associated with progression of time after death was observed in all cases included in the sepsis group in contrast to just 1 out of 16 control cases. LBP (reference limit <10 g/ml) was elevated in all sepsis cases whereas in the control group LBP levels were below 10 microg/ml in 88%. The postmortem time course of LBP serum concentrations showed a continuous increase in both the sepsis and control groups. We conclude that sIL-2R and LBP seem to represent appropriate diagnostic tools for the postmortem diagnosis of sepsis in forensic autopsy practice. sIL-2R serum levels above 1,000 U/ml and LBP serum levels above 10 microg/ml in peripheral venous blood obtained in the early postmortem interval can be regarded as diagnostic hints for an underlying septic condition in a deceased person.