Background: Colorectal cancer is one of the primary causes of cancer-related deaths and 5-fluorouracil (5-FU) therapy remains the cornerstone of treatment in these patients. Resistance to 5-FU represents a major obstacle; therefore, finding new predictive and prognostic markers is crucial for improvement of patient outcomes. Recently a new type of programmed cell death was discovered—necroptosis, which depends on receptor interacting protein 3 (RIPK3). Preclinical data showed that necroptotic cell death is an important effector mechanism of 5-FU-mediated anticancer activity. Purpose: To investigate the predictive and prognostic performance of RIPK3 expression in primary tumors. Methods: Colon cancer patients (n=74) with metastatic stage were included in this retrospective study and all were treated with first-line 5-FU based chemotherapy. Immunohistochemical staining was performed. Results: The progression free survival for the low expression group of RIPK3 was 5.6 months (95% CI, 4.4-6.8) vs 8.4 months (95% CI, 6.4-10.3) of the group with high expression (p=0.02). Moreover, patients with high expression of RIPK3 were associated with lower risk of disease progression HR 0.61 (95% CI, 0.38-0.97; p=0.044). Patients with high expression levels of RIPK3 also had significantly longer mean overall survival (OS) of 29.3 months (95% CI, 20.8-37.8) as compared with those with low expression: 18.5 months (95% CI, 15.06-21.9) (p= 0.036). In addition, univariate analysis showed that high level of RIPK3 expression was associated with a longer OS HR 0.59 (95% CI, 0.35-0.98; p=0.044). Conclusions: This study suggests that expression of RIPK3 in primary tumors of metastatic colon cancer patients should be further investigated for its potential as a promising predictive and prognostic marker.
Introduction The novel coronavirus variant - severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes clinically (novel coronavirus disease 2019 or COVID-19) have placed medical science into a frenzy due to the significant morbidity and mortality, as well as the myriad of clinical complications developing as a direct result of infection. The most notable and one of the most severe changes in COVID-19 develops in the lungs. Materials and methods All cases of real-time polymerase chain reaction (rtPCR)-proved COVID-19 subjected to autopsy were withdrawn from the central histopathology archive of a single tertiary medical institution - St. Marina University Hospital - Varna, Varna, Bulgaria. Pulmonary gross and histopathology changes observed on light microscopy with hematoxylin and eosin as well with other histochemical and immunohistochemical stains were compared with the time from patient-reported symptom onset to expiration, to compare the extent and type of changes based on disease duration. Results A total of 27 autopsy cases fit the established criteria. All cases clinically manifested with severe COVID-19. From the selected 27 cases, n=14 were male and n=13 were female. The mean age in the cohort was 67.44 years (range 18-91 years), with the mean age for males being 68.29 (range 38-80 years) and the mean age for females being 66.54 (range 18-91 years). Gross changes in patients who expired in the first 10 days after disease onset showed a significantly increased mean weight - 1050g, compared to a relatively lower weight in patients expiring more than 10 days after symptom onset - 940g. Histopathology changes were identified as intermittent (developing independent from symptom onset and persisting) - diffuse alveolar damage with hyaline membranes - acute respiratory distress syndrome, endothelitis with vascular degeneration and fibrin thrombi; early (developing within the first week, but persisting) - type II pneumocyte hyperplasia, alveolar cell multinucleation and scant interstitial mononuclear inflammation; intermediate (developing within the late first and second weeks) - Clara cell hyperplasia and late (developing after the second week of symptom onset) - respiratory tract and alveolar squamous cell metaplasia and fibrosis. Conclusion COVID-19-associated pulmonary pathology, both gross and histopathology, show a time-related dynamic with persistent early and a myriad of later developing dynamic changes in patients with severe disease. These changes underline both the severity of the condition, as well as the mechanisms and the probability of long-lasting severe complications in patients with post-COVID syndrome.
The Eurasian smoke tree (Cotinus coggygria) is used by the Balkan folk medicine for its antiseptic and antimicrobial properties as well as for treatment of gingival and throat inflammations. Although C. coggygria has been applied mainly externally because of the large gallotannins content, there are few reports for internal use of its leaves against gastric ulcer, diarrhoea, nephritis, anthrax, asthma, cardiac and urinal diseases and even diabetes mellitus. The aim of this study is to examine the toxicity of C. coggygria leaves aqueous infusion in experimental animals. Male Wistar rats were treated by stomach gavage with different concentrations of herb infusion (1, 2 and 4%) or distilled water at doses of 10 ml/kg b.w. After 30 days of treatment, the animals were sacrificed and the blood and organs were collected for biochemical and histopathological analyses. Results showed that treatment with aqueous infusion from C. coggygria did not cause subchronic toxicity on liver and kidney. Histological investigation did not detect pathological deviations in the organs of treated groups compared with control. No significant changes were observed in the serum levels of hepatic enzymes, urea, creatinine, triacylglycerols and totalThe financial support from the Medical Science Fund of the Medical University of Varna is greatly acknowledged. 749 thyols. The subchronic administration of C. coggygria infusion is non-toxic in the applied concentrations and therefore it can be used to study healing effects as reported by the Balkan traditional medicine.
Adrenal oncocytoma is an extremely rare neoplasm, which is mostly non-functional. Only five cases of childhood adrenal oncocytoma have been described so far, all of which were hormonally active. Currently, guidelines for management and follow-up are not available. We report a 9-year-old girl with benign adrenal oncocytoma, presenting with severe short-term virilization. After diagnostic work-up the patient underwent laparoscopic unilateral adrenalectomy. For the first 2 weeks following surgery she suffered marked mood swings, irritability and fatigue. There were no other clinical and/or laboratory abnormalities except the rapid drop-down of androgen levels to normal values. Follow-up showed no signs of recurrence and in the absence of signs of adrenal insufficiency, we speculate that, the rapid drop of androgen levels after removal of the tumor might be the reason for the deteriorated psychoemotional condition of our patient.
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