Immunohistochemical Expression of Placental Vitamin D Receptors in Pregnancies Complicated by Early and Late-Onset Preeclampsia.

The aim of our study was to determine whether the immunohistochemical expression of placental vitamin D receptors is altered in pregnancies complicated by preeclampsia. Vitamin D receptor expression was immunohistochemically analysed in the placentas of three groups: a control group, and early- and late-onset preeclampsia groups. Total immunohistochemical intensity staining of placentas showed that the control group had a median vitamin D receptor (VDR) expression significantly higher than the placentas of mothers with early- and late-onset preeclampsia. There was no difference among the three groups in a semiquantitative analysis of VDR staining of the stroma only. Vitamin D receptors showed lower median expression in preeclampsia-affected pregnancies, especially early-onset preeclampsia. Therefore, Vitamin D receptor expression may be an important marker for normal placentation and preeclampsia onset.

Vitamin D and Diabetic Retinopathy.

Diabetic retinopathy (DR) is the most common eye disease complication of diabetes, and hypovitaminosis D is mentioned as one of the risk factors. Vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are the best-known forms of vitamin D. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D, with the sun being one of its main sources. Vitamin D is synthesized in the skin by exposure to sunlight without protective factors, but care must be taken to avoid the development of sunburn. It not only plays an important role in maintaining healthy bones and immune system but has also been highlighted in numerous studies to have an influence on various diseases, including diabetic retinopathy. A large number of people suffer from vitamin D hypovitaminosis worldwide, and diagnosis is made by measuring the concentration of 25-hydroxyvitamin D (25(OH)D) in serum. Its deficiency can cause numerous diseases and, as such, supplementation is necessary. Clinical studies have proven the effectiveness of vitamin D supplementation in the treatment of diabetic retinopathy, but with a doctor's recommendation and supervision due to possible negative side effects.

Expression of E26 transformation specific-1 (ETS-1) in tumour-infiltrating lymphocytes (TILs) is adverse prognostic factor in invasive breast cancer.

AIM OF THE STUDY: The microenvironment depicts the relationship between tumour cells and immune response, and every insight into stromal lymphocytes could contribute to explain their role and activity. E26 transformation specific-1 (ETS-1) is a transcription factor that is active in cell proliferation. We analysed its immunohistochemical expression in tumour infiltrating lymphocytes (TILs) in invasive breast cancer and correlated its immunohistochemical score (IHS) to traditional predictive and prognostic factors and survival. MATERIALS AND METHODS: The sample contains data of 121 patients with invasive breast cancer, not otherwise specified (NOS) who underwent mammectomy and lymphadenectomy in 2002 at the Clinical Hospital Centre Zagreb, Croatia. Paraffin blocks of the tumour tissue were collected from the pathological archive. Three representative areas of every patient were chosen and multiple tissue samples were made. Immunohistochemical staining with rabbit anti-ETS-1 (Novocastra, UK) and the ABC method was performed on a DAKO Autostainer. The expression of ETS-1 in stromal TILs was analysed on an Olympus 41 microscope. The IHS score was calculated and correlated with clinical and pathological parameters, as well as disease-free survival (DFS) and overall survival (OS). RESULTS: In almost all patients (95%), some expression of ETS-1 in TILs was found. A moderate/high score of ETS-1 correlated with larger tumour size and higher histological grade, high proliferation index and low progesterone receptors (PgR). The patients with moderate/high ETS-1 expression in TILs had shorter DFS than patients with weak/negative ETS-1 expression. CONCLUSION: In invasive breast cancer NOS, expression of ETS-1 in TILs is an adverse prognostic factor.

Accidental death from a fall from height at workplace turned out to be a COVID-19 death.

Coronavirus 2019 disease (COVID-19) has rapidly evolved into a pandemic during the first months of 2020. The general extent of organ involvement, as well as microscopic changes in the organs of the diseased remains insufficiently documented so far. Herein we are reporting the case of a Caucasian male who apparently died in a workplace allegedly by a fall from height and was found to be SARS-CoV-2 positive just prior to the autopsy. The circumstances of his death required a medicolegal investigation. Gross autopsy findings included minor external injuries and focal subarachnoid hemorrhage together with ribs and sternum fractures resulting from resuscitation attempt. In addition, visceral congestion was noticed, especially visible in lungs. Traumatic findings suitable to explain sudden death were absent. However, lungs histopathology analysis revealed diffuse alveolar damage with massive capillary congestion. Pathology in other organs included myocardial fibrosis, left ventricular hypertrophy, severe generalized atherosclerosis, glomerulosclerosis, focal liver necrosis, liver microabscesses and intrahepatal cholestasis. Lab test confirmed the presence of SARS-CoV-2 in nasopharygeal swab taken postmortem. Only afterwards, the investigation brought out that he was suffering complaints consistent with respiratory infection in the days before death. Based on all findings, the death was ruled as natural, caused by COVID-19. Learnings from this case urge medical staff in the autopsy suite to consider the presence of SARS-CoV-2 in sudden deaths during the pandemic, to enable adequate personal protection gear is worn and to ensure the proper cause of death is determined where misleading circumstances exist.

IL-12 concentrations in the aqueous humor and serum of diabetic retinopathy patients.

BACKGROUND: Previous studies suggest that inflammation plays an important part in the pathogenesis of diabetes. Cytokines may have a role in both positive and negative control of immunological reactions. Among many cytokines, interleukin 12 (IL-12) is known to be a strong pro-inflammatory cytokine. METHODS: A total of 76 participants were enrolled in this study and classified into four groups: 23 diabetic patients with non-treated retinopathy, 17 diabetic patients with treated retinopathy, 12 diabetic patients without retinopathy, and 24 healthy control patients. Serum and aqueous humor samples were taken for the analysis of IL-12 concentration. RESULTS: The aqueous humor IL-12 concentration was significantly elevated in the patients with non-treated diabetic retinopathy (χ(2)(3, n = 76) = 27.137; p < 0.001). No significant differences in IL-12 serum concentrations between the groups were found (F = 0.405, p = 0.750). Correlation analysis of IL-12 concentrations in the serum and aqueous humor showed a linear association between the two variables only in non-diabetic patients (p = 0.003). CONCLUSIONS: This is the first study to show a significantly higher concentration of pro-inflammatory cytokine IL-12 in the aqueous humor of non-treated diabetic retinopathy patients in comparison with diabetic patients treated for retinopathy, without retinopathy, or with healthy individuals. Because the serum levels of IL-12 did not differ considerably between the studied groups, it is plausible that this is due to its local production and secretion.

Prognostic value of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase N/CD13 in breast cancer patients.

The aim of this study was to analyse the expression of matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase APN/CD13 in breast carcinoma samples, and their possible prognostic value in breast cancer patients. The expression of MMP-2, MMP-9 and APN/CD13 in tumor cells was analysed in 138 breast carcinomas by immunohistochemical staining of tumor cells using the semiquantitative method for the detection of cytoplasmic and membrane reaction in tumor cells as well as stromal cells positivity. MMP-2 was positive in tumor cells of 52.9% patients and in stromal cells of 74.6% patients, while MMP-9 positive tumor and stromal cells were found in 84.8 and 63.8% patients, respectively. Tumor cell APN/CD13 expression was found in 36.2% patients. Stromal cell MMP-2 expression correlated significantly with tumor size and neoangiogenesis. A positive correlation was also observed between tumor cell MMP-9 expression and hormone receptor status. Stromal cell coexpression of MMP-2/MMP-9 correlated significantly with tumor size. APN/CD13 expression in tumor cells significantly correlated with tumor type and neoangiogenesis. Overall survival was significantly shorter in patients with MMP-2, MMP-2/MMP-9 positive tumor cells, and tended to be shorter in patients with APN/CD13 positive tumor cells. Coexpression of MMP-2/MMP-9 in tumor cells was an independent risk factor for patient survival (OD = 13.9). Our results suggest that MMP-2, MMP-9, APN/CD13 expression and MMP-2/MMP-9 coexpression in combination with other standard prognostic factors can serve as a poor prognostic factor in the evaluation of breast cancer prognosis.