Severe Retroperitoneal Hemorrhage in a COVID-19 Patient on a Therapeutic Dose of Low Molecular Weight Heparin: A Case Report.

Extensive drug treatment for coronavirus disease 2019 (COVID-19) includes low molecular weight heparin (LMWH). At therapeutic doses of LMWH, there is an increased risk of bleeding complications. Spontaneous, non-traumatic bleeding into the retroperitoneum is a life-threatening condition that can progress very rapidly. We describe a complication of COVID-19 bronchopneumonia treatment in which a patient developed a shock condition caused by non-traumatic bleeding into the retroperitoneum and abdominal wall due to LMWH overdose. The patient was operated on under difficult conditions - in biosafety level 3 (BSL-3). This case is exceptionally fascinating and informative. Nowadays, it is essential to point out possible complications associated with the treatment of COVID-19. Based on this report, we emphasize the need for careful LMWH dosing and quick and accurate diagnosis. Surgeons should maintain a higher index of suspicion for spontaneous bleeding in non-specific abdominal pain patients with COVID-19 or patients receiving therapeutic doses of LMWH.

Extraabdominal Rupture of an Inflammatory Abdominal Aortic Aneurysm in a Patient With Aortodecubital Fistula: A Case Report.

Aortodecubital fistula is a pathologic communication between aorta and a decubitus ulcer. It is very rarely encountered vascular condition in abdominal aortic aneurysms (AAA), with difficult diagnostics and high mortality. Patients often present with systemic and local infection and are at risk for hemorrhage. We present a paraplegic patient with fistulous communication between an inflamed abdominal aortic aneurysm and a sacral decubitus ulcer, leading to intermittent bleeding episodes and finally to exsanguination. While extremely rare, this case emphasizes the need for early, accurate diagnosis and salvage intervention when possible.

Mediastinal Pancreatic Pseudocyst with Hemoptysis - A Thoracic Complication of Pancreatitis.

Mediastinal pancreatic pseudocysts are rarely encountered complications of pancreatic diseases. Pseudocysts most often expand into surrounding structures, just rarely into the mediastinum. Usually, they present with abdominal pain, and the symptoms correlate with the location of the pseudocysts. We describe a case of a pancreatic pseudocyst that penetrated the thoracic cavity through the diaphragm and set up a communication with the bronchial tree developing an episode of massive hemoptysis. This case is of particular interest because just a few similar cases were published before. Based on this report, we emphasize the need for early accurate diagnosis; surgeons should maintain a higher index of suspicion for mediastinal pancreatic pseudocyst in patients with chronic pancreatitis.

Expression of miR-34a-5p is up-regulated in human colorectal cancer and correlates with survival and clock gene PER2 expression.

Colorectal cancer represents a leading cause of cancer death. MicroRNAs (miRNAs) are small non-coding RNA molecules that have been extensively studied in tumours, since changes in their levels can reveal patient prognosis. Cancer progression is also influenced by the circadian system whose functioning is based on the rhythmic expression of clock genes. Therefore, we performed macroarray screening of tumour and adjacent tissues in patients undergoing surgery for colorectal carcinoma. We identified 17 miRNAs showing expression that was more than 100 times higher in tumour tissue compared to adjacent tissue. From in silico analysis, miR-34a-5p was selected as showing a computer-predicted interaction with PER2. Real-time PCR revealed a negative correlation between expression of PER2 mRNA and miR-34a in patients with more advanced cancer stage. Expression of miR-34a was up-regulated in cancer tissue compared to adjacent tissue. High miR-34a expression was associated with better survival of patients. miR-34a showed lower expression levels in male patients with lymph node involvement, and a trend towards decreased expression in male patients with distant metastases. Male patients, but not female patients, with high expression of miR-34a and who were free of distant metastases and/or lymph node involvement showed better survival. Therefore, we proposed that expression of miR-34a was regulated in a sex-dependent manner and could be considered a marker of prognosis in earlier cancer stages in male patients.

Sex-dependent correlation between survival and expression of genes related to the circadian oscillator in patients with colorectal cancer.

Recent evidence supports the important role of the circadian system in cancer progression in humans. The aim of the present study is to evaluate clock (cry1, cry2 and per2) and clock-controlled (vascular endothelial growth factor-a, early growth response protein 1 and estrogen receptor ß) gene expression in colorectal cancer and adjacent tissue and identify a possible link between survival of patients and expression of above mentioned genes. The study includes 64 patients of both sexes with previously diagnosed colorectal cancer. RNA was extracted from the tumor tissue and adjacent parts of the resected colon, and real-time PCR was used for detection of clock gene expression. Expression of cry2 and per2 was significantly downregulated in tumor tissue compared to adjacent tissues. After splitting of the cohort according to sex, we detected downregulated levels of cry2 and per2 in male patients, but not in females. Splitting of male and female sub-cohorts according to presence of metastases revealed significant donwregulation of cry2 expression in female patients without distant metastasis. Better survival rate was associated with low expression of cry2 in female patients. Moreover, we observed an increase in cry1 expression in female patients with distant metastases in tumor compared to adjacent tissue. Accordingly, women with high expression of cry1 in tumor tissue displayed worse survival, which was not observed in men. Taken together, expression of clock and clock-controlled genes in tumors of males and females clustered according to presence of distant metastases correlated with survival analysis. Studied clock-controlled genes also showed sex-dependent changes. Low expression of vegf-a in tumor correlated with better survival in men but not in women. High expression of estrogen receptor ß mRNA was related to better survival in women but not in men. Low expression of vegf-a, egr1 and estrogen receptor ß was associated with worse survival in women compared to men. Our data indicate sex-dependent associations between clock and clock-controlled gene expression in cancer tissue and patient's survival prognosis.

Expression of cell cycle regulatory factors hus1, gadd45a, rb1, cdkn2a and mre11a correlates with expression of clock gene per2 in human colorectal carcinoma tissue.

Deregulated expression of clock gene per2 has previously been associated with progression of cancer. The aim of the present study was to identify genes related to per2 expression and involved in cell cycle control. Patients surgically treated for colorectal carcinoma with up-regulated and down-regulated per2 expression in cancer versus adjacent tissue were studied. Total RNA from cancer tissue of these patients was used to specify genes associated with altered per2 expression using the Human Cell Cycle RT(2) profiler PCR array system. We identified seven genes positively correlated (hus1, gadd45α, rb1, cdkn2a, cdk5rp1, mre11a, sumo1) and two genes negatively correlated (cdc20, birc5) with per2 expression. Expression of these seven genes was subsequently measured by real time PCR in all patients of the cohort. Patients were divided into three groups according to TNM classification. We observed an increase in gene expression in cancer tissue compared to adjacent tissue in the first group of patients in all genes measured. Expression of genes positively associated with per2 gene expression was dependent on tumor staging and changes were observed preferentially in cancer tissue. For genes negatively associated with per2 expression we also detected changes in expression dependent on tumor staging. Expression of cdc20 and birc5 was increasing in the proximal tissue and decreasing in the cancer tissue. These results implicate functional involvement of per2 in the process of carcinogenesis via newly uncovered genes. The relevancy of gene expression for determination of diagnosis and prognosis should be considered in relation to tumor staging.

Deregulated expression of the per2 gene in human colorectal carcinoma.

The circadian system is involved in the control of cell proliferation and apoptosis. The aim of this study was to analyze expression of the human per2 gene in patients who underwent surgery for colorectal carcinoma. The study included 25 patients of both genders. Patients were exposed to light from 6:00 a.m. until 9:00 p.m. according to standard hospital practice. Tissue samples were taken from the tumor as well as from the proximal and distal areas of the resected colon at the time of surgery. Surgery was performed during the morning hours. Expression of per2 mRNA was measured by real-time PCR. There was a significant negative correlation between per2 gene expression and tumor staging. Expression of per2 mRNA did not correlate with whether the tumor was localized in the colon or rectum. In comparison with ectomized tissue without malignancy from patients with colorectal carcinoma, our data demonstrate per2 mRNA deregulation in tumor tissue, and suggest a way in which the circadian system can influence tumorigenesis.