Management of a Giant Renal Artery Aneurysm in a Patient with Severe Hemophilia A

Patient: Male, 54-year-old Final Diagnosis: Giant right renal artery aneurysm Symptoms: Bilateral leg edema Medication: — Clinical Procedure: — Specialty: Hematology • Radiology • Urology OBJECTIVE: Rare coexistence of disease or pathology BACKGROUND: Classical hemophilia, or hemophilia A, is an X-linked recessive genetic disorder characterized by deficiency in clotting factor VIII. Renal artery aneurysms (RAAs) are also rare and are defined as a focal dilatation of the renal artery that exceeds 1.5 cm in diameter. These 2 rare conditions – giant RAA and hemophilia A – were simultaneously observed in our patient. This report presents a male patient with hemophilia A with a 10-cm aneurysm of the right renal artery, which was treated with transarterial coil embolization and factor VIII infusion. The giant RAA was an incidental finding and was suspected after the abdominal ultrasound (US). CASE REPORT: We present the case of a 10-cm right RAA in a 54-year-old man with hemophilia A. The patient had a congenital severe coagulation factor VIII deficiency (hemophilia A). He presented at a routine hematologist visit with an atypical symptom of severe symmetrical leg edema. Laboratory tests showed increased levels of creatinine and proteinuria. Investigations proceeded with computed tomography (CT) and digital subtraction angiography (DSA). Endovascular coiling of the aneurysm was performed with perioperative recombinant coagulation factor VIII substitution, and the recovery was uneventful. At 6-year follow-up there are no signs of proteinuria, and kidney function was stable. CONCLUSIONS: We present a case of renal artery aneurysm effectively treated by endovascular embolization, showing the importance of managing patients with hemophilia A according to a guidelines-based multidisciplinary approach and ensuring the lowest possible risk of peri- and intraoperative complications by using minimally-invasive treatments

CD63 and Dna Mismatch Repair Protein Expression in Prostate Cancer

Publisher Copyright: © 2020 Kristofs Folkmanis et al., published by Sciendo.Protein expression levels in immunohistochemistry and molecular biomarkers have been reported for their ability to predict recurrence, progression, development of metastases, and patient survival. The molecular features in low- and high-grade prostate cancer can differ and influence treatment decision and prognosis. The objective of the current study was to compare the expression of exosomal biomarkers CD63 and mismatch repair proteins (MSH2, MSH6, MLH1, and PMS2) by immunohistochemistry (IHC) in tissue of patients with prostate cancer and benign hyperplasia. Altogether, 62 patients with prostate acinar adenocarcinoma and 20 patients with prostate benign hyperplasia were enrolled in this retrospective study. CD63, MSH2, MSH6, MLH1, and PMS2 expression was analysed by immunohistochemistry. The obtained results showed that CD63 expression was significantly higher in patients with Grade III-V prostate cancer compared to Grade I-II, respectively; 2.23 (1-3) vs 0.92 (0-2) score, p = 0.001. In addition, a significant positive correlation between CD63 expression and grade groups was revealed (Rho = +0.54; p < 0.0001). Furthermore, progression-free survival was significantly higher in patients with low CD63 expression, compared to high CD63 expression (p = 0.0007). MMR expression was absent in 14 patients (four patients with Grade I-II cancer and 10 patients with Grade III-cancer). MMR was present in all cases of benign prostate hyperplasia (mild to moderate staining). The conclusion was that high grade prostate cancer (Grade groups III-V) was characterised by increased CD63 expression, which correlated with progression-free survival.publishersversionPeer reviewe

HLA Class II-DRB,-DQA and-DQB genotypes in peripheral blood shows shifts during the course of sepsis

Publisher Copyright: © 2019 Linda BÄra et al. published by Sciendo. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.Undeniably, sepsis is still a profoundly damaging and life-threatening condition for many individuals. With multiple changes in sepsis patients it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. The aim of this study was to investigate genetically determined predisposition to developed sepsis by analysis of distribution of human leukocyte antigen (HLA) class II genes. Samples from patients with sepsis were collected at Pauls Stradiņš Clinical University Hospital, Latvia, in an intensive care unit between October 2016 and May 2017. The study group included 62 patients with sepsis, who were genotyped for HLA-DR; DQ using real time polymerase chain reaction-sequence specific primer (RT PCR-SSP). As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. The summarised results showed that the frequency of alleles DRB1∗04:01 (OR = 5.54; 95% CI = 1.88-16.29); DRB1∗07:01 (OR = 19.03; 95% CI = 2/37-152.82); DQA1∗05:01 (OR = 14.17; 95% CI = 5.67-35.4); and DQB1∗02:01 (OR = 50.00; 95% CI = 2.90-861.81) were significantly increased in patients with sepsis compared to the control group patients. The frequency of DRB1∗16:01 (OR = 0.17, 95% CI = 0.04-0.59); DRB1∗17:01 (OR = 0.04; 95% CI = 0.00-0.69); DQA1∗01:01 (OR = 0.04; 95% CI = 0.00-0.31); DQA1∗01:02 (OR = 0.03; 95% CI = 0.00-0.23); DQB1∗02:02 (OR = 0.12; 95% CI = 0.03-0.42) alleles was lower in sepsis patients than in control subjects. The most frequent HLA-DRB1/DQA1/DQB1 haplotypes that was significantly increased in patients with sepsis were: DRB1∗01:01/DQA1∗05:01/DQB1∗03:01 (OR = 12.6; 95% CI = 1.51-105.0; p < 0.003). Sepsis patients with pneumonia and alleles and DRB1 04:01; 07:01, DQB1 02:01 had the highest mortality rate. Undoubtedly, our preliminary data showed that development of sepsis can be associated with alleles and haplotypes of HLA class II genes. For more precise conclusion the research should be continued to include a larger patient group.Peer reviewe

Effects of urinary extracellular vesicles from prostate cancer patients on the transcriptomes of cancer-associated and normal fibroblasts

Funding Information: This work was funded by the Latvian Council of Science, Project No. lzp-2018/0269. Publisher Copyright: © 2022, The Author(s).Background: Increasing evidence suggests that cancer-derived extracellular vesicles (EVs) alter the phenotype and functions of fibroblasts and trigger the reprogramming of normal fibroblasts into cancer-associated fibroblasts (CAFs). Here, we for the first time studied the effects of urinary EVs from PC patients and healthy males on the transcriptional landscape of prostate CAFs and normal foreskin fibroblasts. Methods: Patient-derived prostate fibroblast primary cultures PCF-54 and PCF-55 were established from two specimens of PC tissues. EVs were isolated from urine samples of 3 patients with PC and 2 healthy males and used for the treatment of prostate fibroblast primary cultures and normal foreskin fibroblasts. The EV-treated fibroblasts were subjected to RNA sequencing analysis. Results: RNA sequencing analysis showed that the fibroblast cultures differed significantly in their response to urinary EVs. The transcriptional response of foreskin fibroblasts to the urinary EVs isolated from PC patients and healthy controls was very similar and mostly related to the normal functions of fibroblasts. On the contrary, PCF-54 cells responded very differently - EVs from PC patients elicited transcriptional changes related to the regulation of the cell division and chromosome segregation, whereas EVs from healthy males affected mitochondrial respiration. In PCF-55 cells, EVs from both, PC-patients and controls induced the expression of a number of chemokines such as CCL2, CCL13, CXCL1, CXCL8, whereas pathways related to regulation of apoptotic signaling and production of cell adhesion molecules were triggered specifically by EVs from PC patients. Conclusion: This study demonstrates that urinary EVs from PC patients and healthy controls elicit distinct transcriptional responses in prostate CAFs and supports the idea that EVs contribute to the generation of functional heterogeneity of CAFs. Moreover, this study suggests that the changes in the gene expression pattern in EV recipient cells might serve as a novel type of functional cancer biomarkers.publishersversionPeer reviewe

Consumption of the whole-grain rye bread and progression of prostate cancer

Funding Information: This study was supported by the project framework of the European Regional Development Fund (ERAF) No. 2010/0273/2DP/2.1.1.0/10/APIA/VIAA/083 „Assessment of Local Origin Cereal Species’ Potential and Development of Varieties for Specific Dietary Foods Production”. Copyright: Copyright 2013 Elsevier B.V., All rights reserved.Whole-grain rye intake has been suggested to have anti-cancer effect, including changes in serum hormones and reduced prostate specific antigen (PSA) in animals and humans. In this study, we investigated the effect of high intake of whole-grain rye bread on prostate cancer progression as assessed by PSA concentration in men diagnosed with prostate cancer. Fifteen men with prostate cancer who did not receive prior therapy were randomised and given a daily supplement of 250 g refined wheat bread for two weeks and, afterwards, 250 g whole-grain rye bread for six weeks. Blood samples were taken from fasting men at baseline and after two and six weeks to measure the PSA and sex hormones. The dietary intake was: energy intake 3452 kcal; protein intake 166 g, carbohydrate intake 334 g, fat 149 g, saturated fat intake 52 g, and fibre intake 40 g. Plasma total PSA, free PSE, testosterone concentrations and free androgen index tended to be higher after refined white bread treatment and lower after whole-grain rye treatment. However, none of the differences were statistically significant. There were no significant changes in sex hormone binding globulin, luteinising hormone, and follicle stimulating hormone. In this intervention trial, whole-grain rye consumption did not result in significant changes in PSA and sex hormones, which may be related to high fat intake. Further prospective trials are indicated to evaluate the potential of whole-grain rye bread, taking into account other factors.publishersversionPeer reviewe

Body height affects the strength of immune response in young men, but not young women

Body height and other body attributes of humans may be associated with a diverse range of social outcomes such as attractiveness to potential mates. Despite evidence that each parameter plays a role in mate choice, we have little understanding of the relative role of each, and relationships between indices of physical appearance and general health. In this study we tested relationships between immune function and body height of young men and women. In men, we report a non-linear relationship between antibody response to a hepatitis-B vaccine and body height, with a positive relationship up to a height of 185 cm, but an inverse relationship in taller men. We did not find any significant relationship between body height and immune function in women. Our results demonstrate the potential of vaccination research to reveal costly traits that govern evolution of mate choice in humans and the importance of trade-offs among these traits

The obesity paradox predicts the second wave of COVID-19 to be severe in western countries

Funding Information: This work was funded by the Latvian Council of Science grants lzp-2018/1-0393 (I.A.K.), lzp-2018/2-0057 (T.K.), and lzp-2020/2-0271 (T.K.). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.While COVID-19 infection and mortality rates are soaring in Western countries, Southeast Asian countries have successfully avoided the second wave of the SARS-CoV-2 pandemic despite high population density. We provide a biochemical hypothesis for the connection between low COVID-19 incidence, mortality rates, and high visceral adiposity in Southeast Asian populations. The SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a gateway into the human body. Although the highest expression levels of ACE2 are found in people’s visceral adipose tissue in Southeast Asia, this does not necessarily make them vulnerable to COVID-19. Hypothetically, high levels of visceral adiposity cause systemic inflammation, thus decreasing the ACE2 amount on the surface of both visceral adipocytes and alveolar epithelial type 2 cells in the lungs. Extra weight gained during the pandemic is expected to increase visceral adipose tissue in Southeast Asians, further decreasing the ACE2 pool. In contrast, weight gain can increase local inflammation in fat depots in Western people, leading to worse COVID-related outcomes. Because of the biological mechanisms associated with fat accumulation, inflammation, and their differential expression in Southeast Asian and Western populations, the second wave of the pandemic may be more severe in Western countries, while Southeast Asians may benefit from their higher visceral fat depots.publishersversionPeer reviewe

Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles

Introduction: Prostate cancer (PCa), one of the most prevalent malignancies affecting men worldwide, presents significant challenges in terms of early detection, risk stratification, and active surveillance. In recent years, liquid biopsies have emerged as a promising non-invasive approach to complement or even replace traditional tissue biopsies. Extracellular vesicles (EVs), nanosized membranous structures released by various cells into body fluids, have gained substantial attention as a source of cancer biomarkers due to their ability to encapsulate and transport a wide range of biological molecules, including RNA. In this study, we aimed to validate 15 potential RNA biomarkers, identified in a previous EV RNA sequencing study, using droplet digital PCR. Methods: The candidate biomarkers were tested in plasma and urinary EVs collected before and after radical prostatectomy from 30 PCa patients and their diagnostic potential was evaluated in a test cohort consisting of 20 benign prostate hyperplasia (BPH) and 20 PCa patients’ plasma and urinary EVs. Next, the results were validated in an independent cohort of plasma EVs from 31 PCa and 31 BPH patients. Results: We found that the levels of NKX3-1 (p = 0.0008) in plasma EVs, and tRF-Phe-GAA-3b (p &lt; 0.0001) tRF-Lys-CTT-5c (p &lt; 0.0327), piR-28004 (p = 0.0081) and miR-375-3p (p &lt; 0.0001) in urinary EVs significantly decreased after radical prostatectomy suggesting that the main tissue source of these RNAs is prostate and/or PCa. Two mRNA biomarkers—GLO1 and NKX3-1 showed promising diagnostic potential in distinguishing between PCa and BPH with AUC of 0.68 and 0.82, respectively, in the test cohort and AUC of 0.73 and 0.65, respectively, in the validation cohort, when tested in plasma EVs. Combining these markers in a biomarker model yielded AUC of 0.85 and 0.71 in the test and validation cohorts, respectively. Although the PSA levels in the blood could not distinguish PCa from BPH in our cohort, adding PSA to the mRNA biomarker model increased AUC from 0.71 to 0.76. Conclusion: This study identified two novel EV-enclosed RNA biomarkers–NKX3-1 and GLO1–for the detection of PCa, and highlights the complementary nature of GLO1, NKX3-1 and PSA as combined biomarkers in liquid biopsies of PCa.</p

Clinicopathological Significance of Exosomal Proteins CD9 and CD63 and DNA Mismatch Repair Proteins in Prostate Adenocarcinoma and Benign Hyperplasia

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Introduction. Recently, it has been shown that exosomal biomarkers and DNA mismatch repair proteins (MMR) could play an important role in cancer risk stratification and prognosis assessment. The gold standard for prostate carcinoma (PCa) diagnosis is biopsy and histopathological examination. Thus, the complex evaluation of exosomal and MMR proteins could be beneficial for prostate cancer risk stratification and diagnostics. The aim of the current study was to evaluate and compare the expression of exosomal proteins CD9 and CD63 and MMR proteins in the tissue of patients with prostate benign hyperplasia (BPH) and PCa. Methods. The study was retrospective. Altogether, 92 patients with PCa and 20 patients with BPH (control group) were enrolled in the study. Exosomal and MMR protein expression was analyzed by immunohistochemistry (IHC). The follow-up for each PCa patient in our study lasted till disease progression and/or a maximum of 5 years. Results. Low-grade PCa was observed in 56 patients and high-grade PCa in 36 patients. CD63 expression was significantly higher in patients with high-grade PCa compared to those with low-grade PCa. CD9 expression was significantly downregulated in PCa patients compared to the control group. MMR protein expression deficiency was observed in 10 PCa patients. MMR proteins were maintained in all cases of BPH. The study found a negative correlation between MMR protein loss and PCa ISUP grade groups. Progression-free survival (PFS) in patients with MMR deficiency was significantly shorter than in patients with maintained MMR expression. Conclusions. CD9 protein expression was downregulated in PCa, compared to BPH, while CD63 protein expression was upregulated in high-grade PCa but downregulated in low-grade PCa. CD63 protein upregulation, CD9 downregulation, and loss of MMR protein characterized the shorter PFS of high-grade PCa patients. CD9, CD63, and MMR could be the routine immunohistochemical biomarkers for the diagnosis and risk stratification of PCa.publishersversionPeer reviewe

The Obesity Paradox Predicts the Second Wave of COVID-19 to Be Severe in Western Countries

While COVID-19 infection and mortality rates are soaring in Western countries, Southeast Asian countries have successfully avoided the second wave of the SARS-CoV-2 pandemic despite high population density. We provide a biochemical hypothesis for the connection between low COVID-19 incidence, mortality rates, and high visceral adiposity in Southeast Asian populations. The SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a gateway into the human body. Although the highest expression levels of ACE2 are found in people's visceral adipose tissue in Southeast Asia, this does not necessarily make them vulnerable to COVID-19. Hypothetically, high levels of visceral adiposity cause systemic inflammation, thus decreasing the ACE2 amount on the surface of both visceral adipocytes and alveolar epithelial type 2 cells in the lungs. Extra weight gained during the pandemic is expected to increase visceral adipose tissue in Southeast Asians, further decreasing the ACE2 pool. In contrast, weight gain can increase local inflammation in fat depots in Western people, leading to worse COVID-related outcomes. Because of the biological mechanisms associated with fat accumulation, inflammation, and their differential expression in Southeast Asian and Western populations, the second wave of the pandemic may be more severe in Western countries, while Southeast Asians may benefit from their higher visceral fat depots