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

Triggering 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

Post-mortem diagnosis of intravascular large B-cell lymphoma

Intravascular large B-cell lymphoma (IVLBCL) is a rare (<1%), typically aggressive extranodal variant of mature non-Hodgkin B-cell lymphoma. IVLBCL is characterized by malignant lymphoid cells lodged within blood vessels, particularly capillary channels. Herein, we present a case of a 50-year-old man with a history of myeloradiculitis (∼1 year) and paraparesis requiring hospitalization. During the course of his hospital stay, computed tomography (CT), magnetic resonance imaging, CT-positron emission tomography, and biopsy failed to establish a diagnosis. The patient died 2 months later from bilateral pneumonia. Postmortem examination was undertaken to determine the cause of death. Histologic sections of the patient’s brain, heart, lung, and liver showed aggregates of highly atypical cells bearing enlarged, pleomorphic, and hyperchromatic nuclei. Strong intravascular positivity for CD45 and CD20 markers indicated the cells were of B-cell origin, supporting a diagnosis of IVLBCL

Role of post mortem CT (PMCT) in high energy traumatic deaths

Background. Post Mortem Computed Tomography (PMCT) is being increasingly implemented in forensic field and could be an adjuvant to classic autopsies. In this study we evaluated the feasibility of complementation of conventional autopsy in trauma victims with PMCT. Materials and methods. A total of 21 subjects, who had sustained various types of blunt high-energy trauma, were selected from the casuistry of the Section of Legal Medicine at University of Pisa: before autopsy, a PMCT examination (Toshiba Aquilion 16 CT scanner) was performed, and after the acquisition of the raw images, MPR and VR reconstructions were performed with dedicated software. Results. PMCT is more sensitive than conventional autopsy in detecting skeletal injuries, whilst autopsy constitutes the method of choice for the detection of thoracic and abdominal visceral injuries. Conclusion. PMCT should be considered a useful tool in addition to conventional autopsy in evaluating trauma victims: it detects further bone fractures in body parts difficult to investigate during autopsy (i.e. posterior regions), facilitating the pathologist in the reconstruction of events and in determining the cause of death

Autopsy findings in COVID-19-related deaths. A literature review

Although many clinical reports have been published, little is known about the pathological post-mortem findings from people who have died of the novel coronavirus disease. The need for postmortem information is urgent to improve patient management of mild and severe illness, and treatment strategies. The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. A systematic literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from database inception to June 2020 was performed. We found 28 scientific papers; the total amount of cases is 341. The major histological feature in the lung is diffuse alveolar damage with hyaline membrane formation, alongside microthrombi in small pulmonary vessels. It appears that there is a high incidence of deep vein thrombosis and pulmonary embolism among COVID-19 decedents, suggesting endothelial involvement, but more studies are needed. A uniform COVID-19 post-mortem diagnostic protocol has not yet been developed. In a time in which international collaboration is essential, standardized diagnostic criteria are fundamental requirements

Neutropenic enterocolitis and sepsis: Towards the definition of a pathologic profile

Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: Rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. Case report: A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. Literature Review: To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. Conclusions: Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic “neutropenic enterocolitis and sepsis” appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile

A perspective on management of limb fractures in obese children: is It time for dedicated guidelines?

Limb fractures are the most common injuries in pediatric orthopedics. Early and late complications are often not preventable, even when providing the best treatment; furthermore, these injuries are largely implicated in medico-legal claims. The development of evidence-based guidelines is one of the main goals of medical research. Approved guidelines for diagnosis, treatment, and follow up are fundamental to obtain the best results in medical practice. Guidelines in pediatric traumatology have been developed, even though specific conditions, like obesity, could influence their drafting. The cast and fixation systems usually applied in pediatric fractures provide a growth plate sparing, a satisfying reduction, and good stress resistance, mostly because of a lower bodyweight compared to adults. Several studies suggest that obesity influences the bone quality, the management, and the outcomes in cases of fracture. High body weight increases the risk of trauma, modifies fracture characteristics, and increases the risk of incomplete reduction. Fractures in obese children have a higher rate of complications, regardless of conservative or surgical treatment. In obese children, surgical treatment is often used more frequently than with non-obese children. Such considerations are valid both for lower and upper limb fractures. The aim of this paper is to discuss recent scientific literature and provide a perspective on the benefits of a dedicated approach in the management of obese children. Guideline updates could improve healthcare quality in a pediatric setting, and also reduce medico-legal implications

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease

Effects of the pesticide lindane on granulosa cell ultrastructure

The excessive exposure to pesticides in the Aral Sea area was correlated to the increased reproductive pathologies in those regions. One of the principal chemical employed was the gamma-hexachlorocycloexane herbicide Lindane (L), a persistent organochlorine that may induces alterations in granulosa cell (GCs) survival. However, a comprehensive experimental study on the L-induced dose-effect morphological alterations, has not yet addressed. Therefore, we studied by means of transmission and scanning electron microscopy, the morphological changes of mouse GCs, matured in vitro with increasing concentrations of L. GCs showed several dose-dependent changes, in respect to controls. In particular, we observed significant reduction of GC microvilli and decrease of cytoplasmic processes between adjacent GCs. In addition, peripheral aggregation of chromatin under the nuclear membrane, extensive plasma membrane blebbing, abundant GC remnants and cellular debris were also present. Mitochondria, endoplasmic reticula and Golgi apparatuses did not show significant changes. In conclusion, our results showed a dose-dependent toxicity of L on GCs, associated to morphological signs of apoptosis. Alterations of GCs may be associated to impaired oocyte competence and sterility

Real-world utilization and outcomes of systemic therapy among patients with advanced or recurrent endometrial cancer in the United States

OBJECTIVE: Evaluate systemic therapy utilization patterns and outcomes by line of therapy among patients with advanced/recurrent endometrial cancer (EC) treated in the United States. METHODS: This retrospective observational study used the Optum Clinformatics Extended Data Mart Date of Death database (1 January 2004-31 December 2019) and included de-identified data from adult patients with advanced/recurrent EC who were treated with first-line (1L) platinum-based chemotherapy and initiated second-line (2L) anti-neoplastic therapy. The index date was the date of 1L therapy initiation. The number and sequence of treatments received and the proportion of patients who received each type of treatment for each line of therapy were evaluated. To account for new drug approvals, patients first treated in 2018 or 2019 were also assessed separately. RESULTS: Among the 1317 patients who met all eligibility criteria, 520 (39.5%) and 235 (17.8%) patients received 3 or 4+ lines of treatment, respectively, during a median total follow-up time of 25.2 months (range, 2.5-173.3 months) following the index date. Chemotherapy, including platinum- and non-platinum-based regimens, was the most common treatment across all lines of therapy: 2L, 80.0%; 3L, 66.2%; 4L+, 80.4%. Overall, 2.5%, 2.3%, and 8.9% of 2L, 3L, and 4L + patients, respectively, received anti-program death 1 (anti-PD-1) immunotherapies. In patients first treated in 2018 and 2019 ( CONCLUSIONS: Among patients with advanced/recurrent EC treated with 1L platinum-based therapy in clinical practice, chemotherapy was the most common treatment choice across all lines of therapy. Immunotherapy use was low overall but increased in patients who started treatment in 2018 or 2019. Overall, median TTNT decreased as lines of therapy increased

Vitamin D status of inmates. The experience of penitentiaries prisons in the province of Salerno in Southern Italy

Introduction: Prisoners are at risk of developing vitamin D deficiency due to their lacking exposure to sunlight. So far, there are no published studies evaluating blood levels of vitamin D in relation to the health status of inmates and the quality of the Italian prison system. Aim: To investigate vitamin D status and its determinants in a cohort of prisoners. Subject and methods: One hundred and seventy-two (172) pri-son inmates (males, n=159, age 47± 11.3 years; females, n=13, age 43.91±12.18 years) of three penitentiaries in the province of Salerno. Vitamin D deficiency, insufficiency and sufficiency were respectively defined as a 25(OH)D level <20 ng/mL; from 20 to 30 ng/mL, >30 ng/mL. Results: In our group, Vitamin D deficiency occurs in 77.32% of the prisoners with 32.55% of the cases having severe insufficiency. Prisoners with higher BMI show lower circulating vitamin D levels (p<0.001). No significant relationship was found with the duration of detention (Pearson R: 0.01). Conclusion: In this cohort of inmates the vitamin D status is determined by BMI, but not by the duration of the detention