Inflammatory rheumatic diseases (IRD) and autoimmune liver diseases (AILD) share many similarities regarding epidemiology, genetics, immunology and therapeutic regimens, so it is not surprising that ...approximately 20% of patients with AILD are diagnosed with an IRD as well. Clinical features and biochemical hallmarks of IRD and AILD often intertwine and cross diagnostic criteria. Therefore, the real distinction of underlying disorders in a patient with these comorbidities may be challenging. The present report is the first report of simultaneously developed juvenile dermatomyositis (JDM) and autoimmune sclerosing cholangitis (ASC) with both entities fulfilling the latest guidelines for a definite diagnosis. Both of these diagnoses are difficult to definitely establish since ASC has a similar serologic profile as autoimmune hepatitis and liver histological analysis is frequently non-specific, whereas clinically amyopathic JDM diagnosis depends mostly on classical dermatological symptoms, while the rest of the diagnostic criteria, including the necessity for skin or muscle biopsy and the presence of myositis specific antibodies, are still not uniformed. In spite of these challenges, our patient clearly met European League Against Rheumatism/American College of Rheumatology classification criteria for CAJDM and The European Society for Pediatric Gastroenterology, Hepatology and Nutrition diagnostic criteria for ASC. Since elevated serum transaminases, the presence of serum antinuclear antibodies and hypergammaglobulinemia could be explained as a part of both JDM and ASC, the underlying pathophysiology remains debatable. Intriguingly, JDM and ASC share genetic predisposition including human leukocyte antigen allele DRB1*0301 and tumor necrosis factor α 308A allele. Furthermore, both humoral and cellular components of the adaptive immune system contribute to the pathogenesis of JDM and ASC. Moreover, recent findings indicate that the loss of the CD28 expression on T-cells plays a significant role in their pathogenesis along with the Th17 immune pathway. Despite these common features that suggest shared autoimmunity, AILD and autoimmune myositis are traditionally studied and managed independently. The lack of therapies that target the underlying cause results in a high rate of adverse events due to unspecific immunosuppressive therapy. Shared autoimmunity is an ideal area to develop new, targeted immunotherapy that would hopefully be beneficial for more than one disease.
Anal carcinoma is a rare tumor in the general population accounting for 1%-2% of all malignancies. Most anal cancers are squamous cell carcinomas. Human papillomavirus and immunosuppression are the ...main risk factors for developing anal squamous cell carcinoma. Therefore, the incidence rate of anal squamous cell carcinoma is significantly higher in renal transplant recipients than in the general population. We present a patient who developed anal cancer nine years after renal transplantation. Since there was a significant diagnostic delay in our patient, we would like to emphasize the importance of regular screening for anal cancer in renal transplant recipients.
An oxidative degradation product of the polyunsaturated fatty acids, 4-hydroxynonenal (4-HNE), is of particular interest in cancer research due to its concentration-dependent pleiotropic activities ...affecting cellular antioxidants, metabolism, and growth control. Although an increase in oxidative stress and lipid peroxidation was already associated with prostate cancer progression a few decades ago, the knowledge of the involvement of 4-HNE in prostate cancer tumorigenesis is limited. This study investigated the appearance of 4-HNE-protein adducts in prostate cancer tissue by immunohistochemistry using a genuine 4-HNE monoclonal antibody. Plasma samples of the same patients and samples of the healthy controls were also analyzed for the presence of 4-HNE-protein adducts, followed by metabolic profiling using LC-ESI-QTOF-MS and GC-EI-Q-MS. Finally, the analysis of the metabolic pathways affected by 4-HNE was performed. The obtained results revealed the absence of 4-HNE-protein adducts in prostate carcinoma tissue but increased 4-HNE-protein levels in the plasma of these patients. Metabolomics revealed a positive association of different long-chain and medium-chain fatty acids with the presence of prostate cancer. Furthermore, while linoleic acid positively correlated with the levels of 4-HNE-protein adducts in the blood of healthy men, no correlation was obtained for cancer patients indicating altered lipid metabolism in this case. The metabolic pathway of unsaturated fatty acids biosynthesis emerged as significantly affected by 4-HNE. Overall, this is the first study linking 4-HNE adduction to plasma proteins with specific alterations in the plasma metabolome of prostate cancer patients. This study revealed that increased 4-HNE plasma protein adducts could modulate the unsaturated fatty acids biosynthesis pathway. It is yet to be determined if this is a direct result of 4-HNE or whether they are produced by the same underlying mechanisms. Further mechanistic studies are needed to grasp the biological significance of the observed changes in prostate cancer tumorigenesis.
The aim of this study was to compare the number of newly diagnosed, histopathologically confirmed cases of urothelial carcinoma before and during the COVID-19 pandemic at the Zagreb University ...Hospital Center. We retroactively collected and analyzed 300 histopathologically confirmed urothelial carcinoma between January 1, 2019, and December 31, 2020, at the Department of Pathology and Cytology, Zagreb University Hospital Center. Our results showed that during the COVID-19 pandemic, there was a statistically significant decrease (p=0.001; χ2-test) in the number of newly diagnosed, histopathologically confirmed cases of urothelial carcinoma at the Zagreb University Hospital Center. There was a decrease in the absolute number of newly diagnosed urothelial carcinoma by 25.8% in the observed time of the pandemic (March 19, 2020 to December 31, 2020) as compared to the same period of the previous year (March 19, 2019 to December 31, 2019). Our study is the first study of this type based on the number of newly diagnosed urothelial carcinoma in Croatia. Observing the early period of the pandemic, our results provide important foundation for future monitoring and long-term consequences of the pandemic on the morbidity and mortality of urothelial carcinoma.The aim of this study was to compare the number of newly diagnosed, histopathologically confirmed cases of urothelial carcinoma before and during the COVID-19 pandemic at the Zagreb University Hospital Center. We retroactively collected and analyzed 300 histopathologically confirmed urothelial carcinoma between January 1, 2019, and December 31, 2020, at the Department of Pathology and Cytology, Zagreb University Hospital Center. Our results showed that during the COVID-19 pandemic, there was a statistically significant decrease (p=0.001; χ2-test) in the number of newly diagnosed, histopathologically confirmed cases of urothelial carcinoma at the Zagreb University Hospital Center. There was a decrease in the absolute number of newly diagnosed urothelial carcinoma by 25.8% in the observed time of the pandemic (March 19, 2020 to December 31, 2020) as compared to the same period of the previous year (March 19, 2019 to December 31, 2019). Our study is the first study of this type based on the number of newly diagnosed urothelial carcinoma in Croatia. Observing the early period of the pandemic, our results provide important foundation for future monitoring and long-term consequences of the pandemic on the morbidity and mortality of urothelial carcinoma.
The aim of this study was to compare the number of biopsy and surgical procedures on prostate, as well as the number of newly diagnosed, histologically confirmed cases of prostate cancer during the ...COVID-19 pandemic at Zagreb University Hospital Center (UHC). We retrospectively collected and processed a total of 1344 histopathologic findings of the prostate at the Zagreb UHC. Our results show that during the COVID-19 pandemic, there was a statistically significant decrease in the absolute number of biopsy and surgical procedures on prostate at Zagreb UHC, and so was the number of newly diagnosed, histologically confirmed cases of prostate cancer. During the observed time of the pandemic (March 19, 2020 to December 31, 2020), there was a 37.5% decrease in the absolute number of newly diagnosed prostate cancer cases compared to the same period of the previous year (March 19, 2019 to December 31, 2019). To our knowledge, this is the first study of this kind that is based on the number of prostate cancer diagnoses in Croatia. By observing the early period of the pandemic, our results provide important guidelines for monitoring and understanding the long-term consequences of the pandemic on the prostate cancer morbidity and mortality.The aim of this study was to compare the number of biopsy and surgical procedures on prostate, as well as the number of newly diagnosed, histologically confirmed cases of prostate cancer during the COVID-19 pandemic at Zagreb University Hospital Center (UHC). We retrospectively collected and processed a total of 1344 histopathologic findings of the prostate at the Zagreb UHC. Our results show that during the COVID-19 pandemic, there was a statistically significant decrease in the absolute number of biopsy and surgical procedures on prostate at Zagreb UHC, and so was the number of newly diagnosed, histologically confirmed cases of prostate cancer. During the observed time of the pandemic (March 19, 2020 to December 31, 2020), there was a 37.5% decrease in the absolute number of newly diagnosed prostate cancer cases compared to the same period of the previous year (March 19, 2019 to December 31, 2019). To our knowledge, this is the first study of this kind that is based on the number of prostate cancer diagnoses in Croatia. By observing the early period of the pandemic, our results provide important guidelines for monitoring and understanding the long-term consequences of the pandemic on the prostate cancer morbidity and mortality.
Abstract Background Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have ...undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. Case presentations Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. Conclusions MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.
Background: Acute hepatitis-associated aplastic anemia (AHAAA) is a rare clinical syndrome characterized by the development of aplastic anemia 2–3 months following an episode of acute hepatitis. ...Several immunosuppressive agents, but not mycophenolate mofetil (MMF), and bone marrow transplantation are the standard treatment options for AHAAA. Case Report: In this report, we present a case of a young boy with AHAAA manifesting as acute liver failure. The etiology was type 1 autoimmune hepatitis responsive to the second-line therapeutic combination of steroids and MMF. The liver has fully recovered, but bone marrow failure ensued. After 4 months, Clinical and laboratory improvement occurred without the need for bone marrow transplantation. An important aspect of this case is the full recovery of aplastic anemia without calcineurin inhibitors, anti-thymocyte globulin utilization, or bone marrow transplantation. Conclusion: Our case history supports MMF as a potentially crucial adjunctive therapy for patients with AHAAA who poorly respond to standard procedures.
Seminoma (SE) is the most frequent type of testicular tumour, affecting predominantly young men. Early detection and diagnosis of SE could significantly improve life quality and reproductive health ...after diagnosis and treatment. Copy number variation (CNV) has already been associated with various cancers as well as SE. In this study, we selected four genes (
,
,
, and
) for CNV analysis in genomic DNA (gDNA), which are located on chromosomes susceptible to gains, and whose aberrant expression was already detected in SE. Furthermore, CNV was analysed in cell-free DNA (cfDNA) from seminal plasma. Analysis was performed by droplet digital polymerase chain reaction (ddPCR) on gDNA from SE and nonmalignant testicular tissue. Seminal plasma cfDNA from SE patients before and after surgery was analysed, as well as from healthy volunteers. The CNV hotspot in gDNA from SE tissue was detected for the first time in all analysed genes, and for two genes,
and
it was reflected in cfDNA from seminal plasma. Although clinical value is yet to be determined, presented data emphasize a potential use of CNV as a potential SE biomarker from a liquid biopsy.
Lupus nephritis (LN) is one of the most severe features of systemic lupus erythematosus (SLE). Data on LN is scarce in the Croatian population. We analysed the characteristics of LN patients ...diagnosed at our tertiary referral centre. In this retrospective study, we analysed the following features of patients with biopsy-proven LN diagnosed between 2011 and 2020: demographics, renal laboratory parameters, renal histopathology, and treatment. A total of 38 patients were included (30 females; mean age 39+ or -15 years).The most common indication for kidney biopsy was proteinuria (89%). The proportion of LN classes was: class I (2.6%), II (5.3%), III (18.4%), IV (42.1%), V (13.2%), III+V (10.5%), IV+V (5.3%).The median time from SLE diagnosis to histologic confirmation of LN was 1.0 year. All patients were treated with methylprednisolone (MP), 68% received MP pulses. Induction treatment included intravenous (IV) cyclophosphamide (CYC) (71%) (15 patients treated per Euro-Lupus and 9 per the National Institutes of Health regimen), oral CYC (3%), or mycophenolate mofetil (11%). 79% of patients received antimalarials. While there is heterogeneity between different populations, our patient profile was similar to that from other European studies. Further follow-up of this group is necessary to assess outcomes in our population. Key words: systemic lupus erythematosus, lupus nephritis, treatment, population characteristics
•Secondary autoimmune diseases have frequently been associated with alemtuzumab in the treatment of RRMS.•We present a person with MS who developed thyroiditis and systemic erythematous lupus (SLE) ...after treatment of RRMS with alemtuzumab.•SLE has not been previously associated with alemtuzumab administration
Alemtuzumab is a humanized monoclonal antibody targeting CD52 protein that has shown great efficacy in the treatment of relapsing remitting multiple sclerosis and is associated with prolonged remission of the disease. Although it is highly effective, alemtuzumab can lead to serious adverse advents among which the most common are secondary autoimmune diseases. We present a patient who was treated with alemtuzumab for relapsing remitting multiple sclerosis. Her disease remained stable in a follow-up period of over ten years. However, during the follow-up period she developed thyroiditis one year, as well as systemic erythematous lupus seven years after the last alemtuzumab infusion, a disease not previously associated with alemtuzumab administration.
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