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Background and Objectives : Primary prostatic stromal sarcoma is an exceptionally rare urological malignancy, constituting less than 0.1% of all prostatic cancers. It poses a significant clinical challenge due to its aggressive behavior and poor prognosis. Materials and Methods : We report the case of a 34-year-old male who presented with nonspecific lower urinary tract symptoms, including dysuria and increased urinary frequency. The initial diagnostic workup, including digital rectal examination and Magnetic Resonance Imaging (MRI), revealed a lobulated lesion within the prostate. A transurethral resection (TUR) was performed for diagnostic purposes, and histopathological examination revealed a "malignant mesenchymal tumor". The patient underwent a laparoscopic radical prostatectomy. The pathology report confirmed the diagnosis of prostatic stromal sarcoma. The postoperative follow-up, including systemic CT and MRI, showed no evidence of recurrence or metastasis thus far. Results : Multidisciplinary management is essential for optimizing treatment outcomes in all urologic malignancies; however, it becomes particularly challenging and crucial in rare cases such as primary prostatic stromal sarcoma. In our case, the patient benefited from a coordinated approach involving urology, pathology, and oncology, underscoring the importance of collaborative care for rare and aggressive tumors like this. This case highlights the importance of early detection, complete surgical excision, and consideration of adjuvant therapies, given the aggressive nature of the disease. The role of novel therapeutic strategies, including immunotherapy and targeted therapies, is also discussed in the context of metastatic sarcomas. Conclusions : This case underscores the critical need for a comprehensive, multidisciplinary approach to managing primary prostatic stromal sarcoma. Ongoing research on innovative therapies offers hope for improved outcomes in metastatic stages. more...

Purpose: To determine the accuracy of magnetic resonance imaging-proton density fat fraction (MRI-PDFF) measurements for detecting liver fat content in potential living liver donors and to compare these results using liver biopsy findings., Methods: A total of 139 living liver donors (men/women: 83/56) who underwent MRI between January 2017 and September 2021 were included in this analysis retrospectively. The PDFFs were measured using both MR spectroscopy (MRS) and chemical shift-based MRI (CS-MRI) for each donor in a blinded manner., Results: Significant positive correlations were found between liver biopsy and MRS-PDFF and CS-MRI PDFF in terms of hepatic steatosis detection [r = 0.701, 95% confidence interval (CI): 0.604–0.798, r = 0.654, 95% CI: 0.544–0.765, P < 0.001, respectively). A weak level correlation was observed between liver biopsy, MRI methods, and vibration-controlled transient elastography attenuation parameters in 42 available donors. Based on receiver operating characteristic (ROC) analysis, MRS-PDFF and CS-MRI PDFF significantly distinguished >5% of histopathologically detected hepatic steatosis with an area under the ROC curve (AUC) of 0.837 ± 0.036 ( P < 0.001, 95% CI: 0.766–0.907) and 0.810 ± 0.036 ( P < 0.001, 95% CI: 0.739–0.881), respectively. The negative predictive values (NPVs) of MRS-PDFF and CS-MRI PDFF were 88.3% and 81.3%, respectively. In terms of distinguishing between clinically significant hepatic steatosis (≥10% on histopathology), the AUC of MRS-PDFF and CS-MRI were 0.871 ± 0.034 ( P < 0.001 95% CI: 0.804–0.937) and 0.855 ± 0.036 ( P < 0.001, 95% CI: 0.784–0.925), respectively. The NPVs of MRS-PDFF and CS-MRI were 99% and 92%, respectively., Conclusion: The methods of MRS-PDFF and CS-MRI PDFF provide a non-invasive and accurate approach for assessing hepatic steatosis in potential living liver donor candidates. These MRI PDFF techniques present a promising clinical advantage in the preoperative evaluation of living liver donors by eliminating the requirement for invasive procedures like liver biopsy., Competing Interests: Conflict of interest disclosure: The authors declared no conflicts of interest. more...

Background and Study Aims: We aimed to investigate the effect of removing milk and dairy products from diets on functional dyspepsia (FD) symptoms, as the aetiology remains unclear and new management approaches are needed., Patients and Methods: This cross-sectional cohort study included 120 patients, with a mean age of 42.5 ± 12.3, of whom 77 (64.2 %) were female, with FD diagnosed by the Rome IV criteria. Patients were divided equally into two groups: those who eliminated milk and dairy products from their diet under the advice of a dietician without medical treatment and those who did not. The severity of symptoms was assessed using the gastrointestinal symptom rating scale (GSRS) at the beginning and end of a one-month period., Results: The restricted and unrestricted diet groups showed no significant differences in age, body mass index, symptom frequency and duration, weight changes, FD subtype, and gastroscopy results (p > 0.05). The diet group had more female patients (p = 0.01) and higher GSRS scores at the beginning (p = 0.01) but similar scores at the end of the study (p = 0.99). After one month, both groups had improved GSRS scores (p = 0.01), but the diet group had a more significant decrease in total symptom scores (p = 0.01) and in 7 of the 15 subsets (p < 0.05)., Conclusion: Of the 120 FD patients who followed up for one month, 60 who removed milk products had a more significant reduction in GSRS symptom score and 7 of the 15 symptom subset scores than 60 patients receiving an unrestricted diet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.) more...

Purpose: Height age (HA) and bone age (BA) delay is well known in the patients with short stature. Therefore assessing pituitary hypoplasia based on chronological age (CA) might cause overdiagnosis of pituitary hypoplasia. We aimed to investigate the diagnostic and prognostic value of the PH and PV based on CA, HA, or BA in the patients with GHD., Methods: Fifty-seven patients with severe and 40 patients with partial GHD and 39 patients with ISS assigned to the study. For defining the most accurate diagnosis of pituitary hypoplasia, PH and PV were evaluated based on CA, BA and HA. The relationship of each method with clinical features was examined., Results: The mean PV was significantly larger in patients with ISS compared to the GH-deficient patients. PV was more correlated with clinical features including height SDS, stimulated GH concentration, IGF-1 and IGFBP-3 SDS, height velocity before and after rGH therapy. We found BA-based PV could discriminate GHD from ISS (Sensitivity: 17%, specificity: 98%, positive predictive value: 94%, negative predictive value: 39%), compared to the other methods based on PH or PV respect to CA and HA. 3% of patients with ISS, 17% of patients with GHD had pituitary hypoplasia based on PV-BA., Conclusion: PV based on BA, has the most accurate diagnostic value for defining pituitary hypoplasia. But it should be kept in mind that there might be still misdiagnosed patients by this method. PV is also a significant predictor for the rGH response., (© 2024. The Author(s).) more...

Purpose: We aimed to compare recurrence-free survival (RFS) and progression-free survival (PFS) of the patients with pure high-grade (HG) vs mixed-grade (MG) nonmuscle-invasive bladder cancer who received adequate bacillus Calmette-Guérin therapy., Materials and Methods: We conducted a retrospective cohort analysis using data from an institutional database. The study included patients diagnosed with HG nonmuscle-invasive bladder cancer at the initial transurethral resection specimen between 2010 and 2020. The initial transurethral resection specimens of all patients were reevaluated by a dedicated uropathologist. The percentage of low-grade tumor areas accompanying HG areas was determined for each case. Time-to-event analysis was performed using the Kaplan-Meier method. RFS and PFS rates were compared between groups., Results: Of the 203 patients enrolled in the study, 69 (34%) had MG tumors. Recurrence was observed in 41 out of 134 patients (30.6%) in the HG group and in 19 out of 69 patients (27.5%) in the MG group. The 36-month RFS rates were 69% (CI: 62-77) and 72% (CI: 62-83) for the HG-urothelial carcinoma (UC) and MG-UC groups, respectively. The RFS rates were similar between groups (log-rank, P = .58). Progression was observed in 22 out of 134 patients (16.4%) in the HG group and in 4 out of 69 patients (5.8%) in the MG group. The 36-month PFS rates were 84% (CI: 77-90) and 94% (CI: 89-100) for the HG-UC and MG-UC groups, respectively. The pure HG-UC group had a worse PFS than the MG-UC group (log-rank, P = .042). Multivariate analysis demonstrated that age and tumor grade were significant risk factors for the development of progression., Conclusions: The indication of MG-UC category separately from pure HG carcinomas in the pathology report seems to be an important issue that can guide patient management. In this way, both more accurate risk classification and more accurate patient counseling can be performed. More importantly, the treatment plan can be made more accurately. For more precise conclusions, our results should be supported by prospective studies with larger sample size. more...

Objectives: The aims of the present study were to investigate a combination of magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE) or MRE and fibrosis score 4 (FIB-4) in the detection of significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Methods: Between November 5, 2021, and March 4, 2022, a total of 119 consecutive patients with MASLD were included. Liver stiffness was measured using liver biopsy, MRE, VCTE, and FIB-4. Data were collected from outpatient visit charts. Significant fibrosis was defined as ≥ stage 2 fibrosis., Results: All 119 MASLD patients were Caucasian, and their median age was 55 years. MRE, VCTE, and FIB-4 demonstrated significant accuracy in the detection of significant fibrosis with an area under the ROC curve (AUC) of 0.848 ± 0.036 (p < 0.001), 0.632 ± 0.052 (p = 0.012), and 0.664 ± 0.051 (p = 0.001), respectively. However, the diagnostic performance of MRE was superior compared to that of VCTE (AUC difference: 0.216 ± 0.053, p < 0.001) and FIB-4 (AUC difference: 0.184 ± 0.058, p = 0.001). With logistic regression analysis, it was determined that when compared to MRE alone, a combination of MRE and TE (p = 0.880) or MRE and FIB-4 (p = 0.455) were not superior for detecting significant fibrosis., Conclusions: MRE alone is an accurate and non-invasive method for the identification of MASLD patients with significant fibrosis., Clinical Relevance Statement: Magnetic resonance elastography alone accurately detects significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease., Key Points: • In routine clinical practice, several non-invasive biochemical-based biomarkers and imaging methods are widely used to assess liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. • Magnetic resonance elastography (MRE) is more accurate than vibration-controlled transient elastography (VCTE) or fibrosis score 4 (FIB-4) for assessing liver fibrosis and identifying significant fibrosis in patients with metabolic dysfunction-associated steatotic liver disease. • The combination of MRE and VCTE or MRE and FIB-4 was not superior to MRE alone., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.) more...

Childhood-onset type 1 diabetes mellitus (DM) is a common chronic metabolic disease associated with life-threatening complications. Diabetic ketoacidosis (DKA) is an acute complication of type 1 DM that has significant mortality mostly due to cerebral edema. Other putative complications of DKA include hypokalemia, hypophosphatemia, hypoglycemia, intracerebral and peripheral venous thrombosis, rhabdomyolysis, acute pancreatitis, and acute kidney injury (AKI) (Murdoch IA et al., Acta Paediatr 1993; 82:498-500)., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.) more...

Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the major causes of liver disease worldwide. Although various molecular mechanisms are effective in the initiation and progression, the exact pathway is not completely clarified. Recent findings suggest a role of the endocannabinoid system in the pathology of NAFLD. Inulin has been shown to be beneficial for NAFLD. With the first study, we investigated the effects of inulin supplementation on NAFLD via the endocannabinoid system in Wistar rats fed high-fat diet., Methods: Male Wistar rats were fed with control, control plus inulin, high-fat, and high-fat plus inulin diets for 12 wk. Inulin was added to diets in 15% weight/weight. Biochemical parameters, insulin, and adiponectin levels were determined. Steatosis, lobular inflammation, and total NAFLD activity scores (NAS) were determined by histopathological analysis and by magnetic resonance imaging. Anandamide and 2-arachidonylglycerol levels were measured by the liquid chromatography-tandem mass spectrometry method. Gene expression levels were determined by the quantitative polymerase chain reaction method., Results: Our results showed that the NAS of the high-fat diet was 4.16 ± 0.30, which was significantly higher than that of the other groups. Inulin decreased Homeostasis model assessment measuring insulin resistance (HOMA-IR), serum triacylglycerol, total cholesterol, and Aspartate aminotransferaselevels. Inulin also significantly decreased Cannabinoid receptor-1 and Patatin-like phospholipase-3 gene expressions in the liver. The 2-arachidonylglycerol levels in the liver were lower in the inulin-added groups. These effects of inulin were associated with NAS., Conclusions: Inulin prevented the development of NAFLD, possibly by affecting the expression of genes involved in the pathogenesis of NAFLD in the liver via endocannabinoids. The results of this study show that inulin may be a promising molecule in the treatment/prevention of NAFLD., (Copyright © 2022 Elsevier Inc. All rights reserved.) more...

Background and Aims: The aim of the present study was to determine incident cases of extrahepatic malignancy in patients with nonalcoholic fatty liver disease (NAFLD) and to identify whether the factors are associated with cancer development., Methods: Between 15 January 2001 and 14 March 2021, a total of 1365 patients had been diagnosed with NAFLD were enrolled in the study., Results: The median follow-up period was 59.5 months. The mean age was 50.9 ± 10.9 years. The female gender was predominant (57%). During the follow-up period, 62 extrahepatic malignancies and 11 hepatocellular carcinomas were identified. Of all extrahepatic malignancies, 51 were solid organ malignancies and 11 were hematological malignancies. Female breast cancer was the most frequent (25.8%), followed by thyroid cancer (19.4%), lymphoma (12.9%), and lung cancer (9.7%). In univariate and multivariable analyses, after adjusting for age and sex, the presence of diabetes and high initial baseline gamma glutamyl transpeptidase (GGT) levels were significantly associated with the development of extrahepatic malignancies [hazard ratio (HR) = 1.82, 95% confidence interval (CI): 1.04-3.20, P = 0.036] and HR = 1.96, 95% CI: 1.14-3.38, P = 0.015, respectively). In 424 biopsy-proven NAFLD patients, the development of extrahepatic cancer was significantly associated with the severity of hepatic fibrosis (HR = 3.31, 95% CI: 1.36-8.07; P = 0.008)., Conclusion: Extrahepatic malignancies are frequently seen in patients with NAFLD. Diabetes mellitus, high baseline GGT levels, and significant hepatic fibrosis are associated with the development of extrahepatic cancer in patients with NAFLD., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.) more...

Competing Interests: The authors have no conflict of interest to declare.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Subepithelial polyclonal immunoglobulin deposits and >70% M-type phospholipase A2 receptor antibody positivity are typical findings in idiopathic MN. A 58-year-old female patient was admitted with clinical presentation of nephrotic syndrome. Autoimmune diseases, infections, and malignancies were ruled out after clinical and laboratory evaluations. Diagnostic work-up revealed serum PLA2R antibody negativity and diffuse thickening of glomerular capillary wall on biopsy, while glomerular capillary wall IgG, C3, and Lambda monotypic light chain deposition and PLA2R1 positivity were detected by immunofluorescence and immunohistochemical examination, respectively. Following prednisolone treatment, creatinine and proteinuria were markedly regressed. The MN cases with a light chain deposits are rare and experience regarding their treatment are insufficient., (© 2021 S. Karger AG, Basel.) more...

Background and Study Aims: The role of cytomegalovirus (CMV) infection for disease reactivation in ulcerative colitis (UC) patients remains controversial and diagnostic tests are yet to be standardized. We aimed to define the clinical relevance of CMV detection by mucosal polymerase chain reaction (PCR) in UC patients by comparing the clinical course of UC in CMV-treated and CMV-untreated groups in tissue CMV-PCR positive cases., Patients and Methods: In this retrospective study, 141 patients diagnosed with moderate-to-severe UC admitted to our clinic with disease flare, colonic tissue CMV PCR was assessed., Results: The median age of the study population was 39 years, and 99 (70.2%) patients were male. Eighty-eight (62.4%) patients were CMV-PCR (+) and 53 (37.6%) were CMV PCR (-). The CMV-PCR (+) and CMV PCR (-) groups showed no significant difference concerning age, sex, disease duration, site of involvement and disease activity and administered treatments. The median tissue CMV-PCR was 41,098 IU/mL (IQR:2,344.25-136,192). Thirty-four of 88 CMV-PCR (+) patients received antiviral therapy. The tissue CMV-PCR level of patients who received antiviral therapy was 124,381 IU/mL (IQR: 19,309-412,335), and it was 6,292 IU/mL (IQR: 997-71,154) in patients who did not receive antiviral therapy; (p < 0.001). Sixteen (47.1%) of 34 patients who received antiviral therapy achieved remission. Two of the non-responders underwent colectomy (one because of dysplasia and one who did not respond subsequent biologic agent either). Remaing 16 achieved remission by escalating the immunsuppresive/biologic agent therapy., Conclusion: CMV infection is responsible for only a minority of cases of UC flares and all are steroid-resistant cases. Most of the patients non-responsive to antiviral treatment respond to increased anti-inflammatory treatment. Hesitancy in the decision of escalating immunsuppresive treatment rather than CMV disease may be responsible for worsening disease course and increased colectomy rate in a significant number of the patients who are tissue CMV-PCR (+)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.) more...

Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare.

Autoimmune pancreatitis (AIP) type 1 is an IgG4-related disease (IgG4-RD), characterized by inflammatory pseudotumors and histologically by dense lymphoplasmacytic infiltrates rich in IgG4 positive plasma cells, storiform fibrosis, and obliterative phlebitis. Although quite rare, IgG4-RD was found to be associated with medium or small vessel vasculitides. A new overlap syndrome between IgG4-RD and ANCA-associated vasculitis (AAV) has recently been described in the adult population. Here we present a 16-year-old adolescent girl admitted with abdominal pain, episcleritis, palpable purpura, salivary gland enlargement, and bloody diarrhea. Laboratory investigations revealed findings of glomerulonephritis. Abdominal imaging surprisingly revealed a focal mass in the pancreatic tail, while the c-ANCA level was found to be quite high as well as serum IgG4 level. Biopsy of the pancreatic mass showed lymphoplasmacytic IgG4 positive cells infiltrating the pancreas with storiform fibrosis compatible with IgG4-related AIP. The renal biopsy that was done simultaneously showed necrotizing granulomatous vasculitis indicating AAV. Renal biopsy showed IgG4 positive plasma cells very rarely by immunohistochemical examination, which does not indicate any significance for IgG4-RD. Our diagnosis was IgG4-related AIP and AAV overlap syndrome, which has not been reported in the pediatric populations yet. IgG4-RD should be investigated in patients with ANCA-associated vasculitis who shows atypical organ involvement. We searched the Pubmed/Medline and Google Scholar databases to identify clinical findings, treatment, and outcome of the patients with IgG4-related AIP and AAV., (© 2021. International League of Associations for Rheumatology (ILAR).) more...

Viral nephropathy is a term defines glomerular, tubular and/or vascular injury in kidney caused by viruses itself or virus-induced immune mechanisms. It is difficult to prove causality between the renal disease and the viral infection, however, renal biopsy findings can help in this regard. Several viruses such as hepatitis B and C, Human immun deficiciency virus (HIV), Hantavirus, Cytomegalovirus (CMV), an recently Coronavirus are shown to affect the kidney. Treatment of viral nephropathies are unique regarding the diagnosis which can be made only with renal biopsy in most of the situations. We present two patients presented with acute kidney injury and thrombocytopenia caused by different viruses (Hantavirus and HIV) that affect multiple areas in kidney that revealed with kidney biopsy. Supportive treatment in the patient with Hantavirus nephropathy and HIV treatment along with eculizumab and supportive treatment in the patient with HIVAN were successfully implemented. more...

Background: The risk of malignancy in resected gastrointestinal stromal tumors (GISTs) depends on tumor size, location, and mitotic index. Reportedly, the Ki67 index has a prognostic value in resected GISTs. We aimed to analyze the accuracy of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) samples with reference to Ki67 index, using surgical specimens as the gold standard., Methods: Fifty-five patients who underwent EUS-FNA followed by surgical resection for gastric GISTs were retrospectively analyzed. Patients' age and sex; tumors' size and location; mitotic index, cell type, cellularity, pleomorphism, presence of ulceration, hemorrhage, necrosis, mucosal or serosal invasion, growth pattern, and Ki67 index based on pathology were investigated., Results: Location in fundus, ulceration, hemorrhage, mucosal invasion, and Ki67 index in surgical specimens were significant in predicting high-risk groups (p < 0.05) on univariate analysis. Frequency of bleeding (p = 0.034) and the Ki67 index (p = 0.018) were the only independent significant factors in multivariate analysis. The optimal cutoff level of Ki67 was 5%, with 88.2% sensitivity and 52.8% specificity (p = 0.021). The mean Ki67 index was lower in EUS-FNA samples than in surgical specimens (2% [1-15] versus 10% [1-70], p = 0.001). The rank correlation coefficient value of Ki67 was 0.199 (p = 0.362) between EUS-FNA and surgical samples and showed no reliability for EUS-FNA samples., Conclusion: The Ki67 index in resected specimens correlated with high-risk GISTs, although it had no additive value to the current criteria. The Ki67 index in EUS-guided FNA samples is not a reliable marker of proliferation in GISTs., (© 2020 S. Karger AG, Basel.) more...

Aim: Traditional serrated adenomas are the rarest member of the serrated polyps, that have endoscopic and morphologic similarities with conventional adenomas, tubulovillous adenomas, in particular. We aimed to compare the histopathologic and immunohistochemical features of TSAs showing overt dysplasia with conventional TVAs in a compartmental manner using digitalized images., Patients and Methods: For 25 TSAs and 25 TVAs, extent of the morphologic features including cytoplasmic eosinophilia, mid-zonal nuclei, ECFs, slit-like serration, brush border, gastric foveolar-like epithelium and goblet cells were evaluated. Immunohistochemistry was perfomed using primary antibodies including CK7, CK20, MUC2, MUC5AC, MUC6, B-catenin, Ki67, p53, p16, MLH1, MSH2, MSH6 and PMS2., Results: Eosinophilic cells, mid-zonal nuclei, slit-like serration and ECF were significantly more extensive in TSAs compared to TVAs (p<0,001) while gastric epithelium was also more extensive in TSA cohort with a lower significance (p<0,01). Cut-offs for these features yielding the highest sensitivity and specificity in discriminating TSAs from TVAs were determined ; mid-zonal nucleus resulted as the best discriminating histopathologic feature (100%, 92%) followed by eosinophilia (88%, 92%),and slit-like serration (84%, 92%) with highest sensitivity and specificities, respectively. Compartmental immunohistochemical evaluation revealed that CK20 and CK7 were mainly expressed in ECF while MUC5AC together with CK7 were found in epithelial compartment more frequently in TSAs compared to TVAs. P16 was more common in TSAs in all compartments whereas Ki67 and p53 were restricted to dysplastic compartments in both polyp groups., Conclusions: The present study demonstrated that mid-zonal nuclei, eosinophilic cells and slit-like serration followed by ECF proved to be the most discriminatory features for TSAs.The correct diagnosis of TSAs will allow to develop appropriate treatment and follow up modalities which seem to be crucial as their progression rate may be different from TVAs., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.) more...

Hypertension is an important risk factor for cardiovascular diseases. Besides cardiovascular system, it could cause damage to liver. It has been shown that endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of hypertension. ERS inhibitor tauroursodeoxycholic-acid (TUDCA) has favorable effects on various pathologies including cardiovascular, metabolic and hepatic diseases. In this study, the hepatoprotective effect and mechanism of TUDCA were investigated in the deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Male Wistar rats were used and divided into four groups: Control, DOCA, TUDCA and DOCA + TUDCA. Hypertension was induced by DOCA-salt administration for twelve weeks after the unilateral nephrectomy. TUDCA was given for the last 4 weeks. Systolic blood pressure was measured by using tail-cuff method. At the end of the treatment, liver was isolated and weighed. The expressions of various proteins and histopathological evaluation were examined in the liver. TUDCA markedly decreased systolic blood pressure in the hypertensive animals. Hypertension caused increase in the expressions of glucose-regulated protein-78 (GRP78), matrix metalloproteinase-2 (MMP-2) and phospho-inhibitor κB-α (p-IκB-α) and the decrease in the expression of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase2 (SERCA2) and phospho-extracellular signal-regulated kinase (p-ERK) in the liver. Alterations in these protein expressions were not detected in the TUDCA-treated hypertensive group. Also, hepatic balloon degeneration, inflammation and fibrosis were observed in the hypertensive group. TUDCA improved inflammation and fibrosis in the hypertensive liver. Our findings indicate that the detrimental effect of DOCA-salt-induced hypertension on the liver was defended by the inhibition of ERS. Hepatic ERS and its treatment should be taken into consideration for therapeutic approaches to hypertension. more...

Objectives: Endoplasmic reticulum stress (ERS) has been shown to play a crucial role in the pathogenesis of hypertension. However, the role and mechanisms of ERS on hypertension-induced cardiac functional and morphological changes remain unclear. In this study, the effect of ERS inhibition with tauroursodeoxycholic acid (TUDCA) on hypertension-induced cardiac remodelling was examined., Methods: Hypertension was induced by deoxycorticosterone-acetate (DOCA) and salt administration in uni-nephrectomized rats for 12 weeks. TUDCA was administered for the last four weeks. Rhythmic activity and contractions of the right atrium and left papillary muscle (LPM) were recorded. In the left ventricle, the expression of various proteins was examined and histopathological evaluation was performed., Key Findings: Hypertension-induced increments in systolic blood pressure and ventricular contractions were reversed by TUDCA. In the hypertensive heart, while expressions of glucose-regulated protein-78 (GRP78), phospho-dsRNA-activated protein kinase-like ER kinase (p-PERK), sarcoplasmic reticulum Ca-ATPase-2 (SERCA2), matrix metalloproteinase-2 (MMP-2) and nuclear NF-κB p65 increased; Bcl-2 (B-cell lymphoma-2) expression decreased and the altered levels of all these markers were restored by TUDCA. In the microscopic examination, TUDCA treatment attenuated hypertension-stimulated cardiac inflammation and fibrosis., Conclusions: These results suggest that ERS inhibition may ameliorate cardiac contractility through improving ERS-associated calcium mishandling, apoptosis, inflammation and fibrosis, thereby offering therapeutic potential in hypertension-induced cardiac dysfunction., (© 2019 Royal Pharmaceutical Society.) more...

In this study, the effect of liver X receptor (LXR) activation on hypertension-induced cardiac structural and functional alterations was investigated. Hypertension was induced by deoxycorticosterone acetate (DOCA)-salt administration in uninephrectomized rats for 6 weeks. LXR agonist GW3965 (3-{3-[(2-chloro-3-trifluoromethyl-benzyl)-(2,2-diphenyl-ethyl)-amino]-propoxy}-phenyl)-acetic acid was given for the past week. Rhythmic activity and contractions of the isolated heart tissues were recorded. Biochemical parameters were assessed in ventricular tissue and plasma samples. Cardiac expressions of various proteins were examined, and histopathological evaluation was performed in the left ventricle and liver. GW3965 reduced systolic blood pressure and enhanced noradrenaline-stimulated papillary muscle contraction induced by DOCA-salt + uninephrectomy. Plasma and tissue total antioxidant capacity (TAC) increased and tissue 4-hydroxynonenal (4-HNE) levels decreased in the DOCA-salt group. GW3965 elevated plasma and tissue TAC levels in both of groups. Glucose-regulated protein-78 (GRP78), phospho-dsRNA-activated-protein kinase-like ER kinase (p-PERK), matrix metalloproteinase-2 (MMP-2), and nuclear factor-κB p65 (NF-κB p65) expression was augmented, and inhibitor-κB-α (IκB-α) expression was reduced in hypertensive hearts. The altered levels of all these markers were reversed by GW3965. Also, GW3965 ameliorated DOCA-salt + uninephrectomy-induced cardiac and hepatic inflammation and fibrosis. However, GW3965 unchanged the plasma lipid levels and hepatic balloon degeneration score. These results demonstrated that LXR activation may improve hypertension-induced cardiac changes without undesired effects. more...

Autoinflammatory diseases (AIDs) are a recently described group of conditions caused by mutations in multiple genes that code for proteins of the innate immune system. Cryopyrin-associated periodic syndromes (CAPS) are autoinflammatory diseases comprising three clinically overlapping disorders: familial cold urticarial syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). CAPS have been associated with gain-of-function variations in NLRP3 (NOD-like receptor family, pyrin containing domain-3). However, a new class of autoinflammatory disease resembling FCAS or MWS has been described in patients with NLRP12 mutations. Here, we report a 6-year-old boy diagnosed with AID who developed an unexpected C3 glomerulopathy during attacks and carried a novel variation in NLRP12. Following treatment with IL (interleukin) 1 targeting agents, all symptoms and inflammation resolved. This is the first case in the literature affected by both autoinflammatory disease and C3 glomerulopathy. more...

In AA amyloidosis, while kidney biopsy is widely considered for diagnosis by clinicians, there is no evidence that the detailed investigation of renal histopathology can be utilized for the prognosis and clinical outcomes. In this study, we aimed to obtain whether histopathologic findings in kidney biopsy of AA amyloidosis might have prognostic and clinical value. This is a retrospective cohort study that included 38 patients who were diagnosed with AA amyloidosis by kidney biopsy between 2005 and 2013.The kidney biopsy specimens of patients were evaluated and graded for several characteristics of histopathological lesions and their relationship with renal outcomes. Segmental amyloid deposition in the kidney biopsy was seen in 29%, global amyloid deposition in 71, diffuse involvement of glomeruli in 84.2%, focal involvement in 7%, glomerular enlargement in 53%, tubular atrophy in 75% and interstitial fibrosis in 78% of patients. Histopathologically, glomerular enlargement, interstitial fibrosis, tubular atrophy, interstitial inflammation and global amyloid deposition were significantly associated with lower estimated glomerular filtration rate (eGFR) (p = .02, p < .001, p = .001, p = .009, p = .002, respectively) in univariate analysis. In multivariate analysis, tubular atrophy was the only predictor of eGFR (p = .019 B = -20.573). In the follow-up at an average of 27 months, 18 patients developed end-stage renal disease (ESRD). Among them, global amyloid deposition was the only risk factor for the development of ESRD (p = .01, OR = 18.750, %95 CI= 2.021-173.942). This is the first study showing that the histopathological findings in kidney biopsy of AA amyloidosis might have a prognostic and clinical value for renal outcomes. more...

Background/aims: Diabetic kidney disease (DKD) is one of the most frequent microvascular complications of diabetes and is the leading cause of end-stage kidney disease worldwide. In patients with diabetes, non-diabetic kidney disease (NDKD) can also occur. NDKD can be either alone or superimposed with the DKD. In this study, we aimed to investigate the utility of kidney biopsy in patients with type 2 diabetes mellitus (T2DM) and the predictability of diagnosing DKD versus NDKD from clinical and laboratory data. We also evaluated the prevalence and etiology of NDKD in patients with T2DM., Methods: We retrospectively reviewed type 2 diabetic patients who had kidney biopsy in the last 10 years for diagnosing possible NDKD in our center. In all patients kidney biopsies were performed because of atypical clinical features and biopsy samples were examined by light and immunofluorescence microscopy. Clinical parameters, laboratory workup and office blood pressures were recorded for each patient at the time of biopsy., Results: Eight patients were excluded due to missing data. A total of 48 patients (female/male: 26/22 and mean age: 59±8 years) were included in the study. According to the biopsy findings, 24 (50%) patients had NDKD alone, 20 (41.7%) had DKD alone and 4 (8.3%) had coexisting DKD and NDKD. The most common NDKD diagnoses were membranous nephropathy (29.2%), tubulointerstitial nephritis (20.8%) and IgA nephropathy (12.5%). There were no significant differences in three groups with respect to the duration of diabetes, proteinuria, hematuria and glycated hemoglobin A1c levels. Diabetic retinopathy (DR) was the most significant finding, which was associated with DKD. Positive and negative predictive values of DR for DKD were 88 and 81%, respectively., Conclusion: This study demonstrated a high prevalence of NDKD in patients with T2DM. The absence of DR strongly predicted NDKD. Clinical decision alone can lead to wrong diagnosis and delay in appropriate therapy. Clinicians should consider the kidney biopsy more liberally when there is uncertainty on the exact etiology of the kidney disease. However, prospective multicenter studies are needed to clarify the prognosis and outcomes of patients with diabetics., (© 2017 The Author(s). Published by S. Karger AG, Basel.) more...

Henoch-Schonlein purpura (HSP) is the most common vasculitis in children. Vasculitic processes can involve the lung. Although diffuse alveolar hemorrhage may be seen as one of the manifestation of HSP, it is not a frequent presentation. Here we reported the case of a 10-year-old girl with HSP nephritis who developed pulmonary hemorrhage. The patient was treated successfully with intravenous methylprednisolone. A review of the literature revealed that young age may be a good prognostic sign and that immunosuppressive drugs and supportive management are essential in the treatment., (Sociedad Argentina de Pediatría.) more...

Simple predictors are needed for the screening of nonalcoholic fatty liver disease (NAFLD) in obese children. We aimed to assess the role of anthropometric parameters in the prediction of NAFLD. Three hundred and thirty two obese children (152 male, 180 female) aged 4.6-17.0 years were included in this study. Weight, height, waist (WC), and hip circumference were measured. Body mass index (BMI), waist-hip-ratio (WHR), and waist-height-ratio (WHtR) were calculated. Obesity was defined as BMI for age and sex ≥ 95th percentile. NAFLD was diagnosed using ultrasonography (US). NAFLD was present in 60.8% of obese children. Fatty liver prevalence differed significantly by gender and puberty (55.0% of girls vs 67.7% of boys, and 28.7% in prepubertal vs 71.3% in pubertal children; p < 0.05). Significantly higher BMI, BMI standard deviation score (SDS), WC, and WHtR were found in obese children with NAFLD compared to obese children without NAFLD (p < 0.05). Only WHtR was found to be an independent predictor for NAFLD in a logistic regression analysis (p < 0.001, B:1.096, 95% CI 1.047-1.148). Fatty liver is common among obese children, particularly in obese boys. WHtR is a simple and easy index for predicting of NAFLD in obese children and can be used for mass screening in public health. more...

Introduction: The aim of this study was to assess whether epidermal growth factor receptor (EGFR) overexpression was a significant prognostic factor in clear cell renal cell carcinoma (CRCC) and whether its prognostic significance was affected by immunohistochemical expression patterns., Materials and Methods: Immunohistochemistry was performed on 100 cases of CRCC using an antibody against EGFR. Tumors were grouped by nuclear grade (NG) as low-NG (NG1, 2) or high NG (NG3, 4), and by pathological stage as localized (pT1, 2), or locally invasive (pT3, 4). Clinical disease was grouped by clinical stage as early stage (stage I, II), or late stage (stage III, IV). Evaluation of the EGFR overexpression was based on cytoplasmic (EGFR Cyt), and membranous (EGFR Mem) staining., Results: EGFR Cyt correlated with high NG (P = 0.001), lymphovascular invasion (P = 0.028), regional lymph node involvement (P = 0.027), metastasis (P = 0.001), late stage (P = 0.003), cancer-specific death (P = 0.036), and was a predictor for disease-specific survival (P = 0.012) whereas EGFR Mem correlated with only local invasion (P = 0.021) and perirenal invasion (P = 0.009) and did not show any correlation with cancer-specific death or disease specific survival., Conclusion: Our findings suggest that EGFR overexpression is an important prognostic factor in CRCC, and its prognostic value differs significantly with respect to the location of EGFR immunostaining. This prognostic difference may give direction on the management and treatment of CRCC patients. more...

Objective: We aimed to compare insulin sensitivity indices, fasting vs glucose stimulated, in children and adolescents with non-alcoholic fatty liver disease., Patients and Methods: Two hundred-eleven obese children with median age of 11.24 ± 2.65 years were evaluated. After initial clinical and anthropometric examination, B-mode ultrasonography (USG) was performed and all subjects underwent Oral Glucose Tolerance Test (OGTT). Quantitative insulin sensitivity check index (QUICKI), homeostatic model assessment for insulin resistance (Homa-IR), the insulinogenic index (IGI), the Matsuda index, and the oral glucose insulin sensitivity (OGIS) model were used to determine peripheral insulin sensitivity., Results: 59.24% (68 boys, 57 girls) of obese children had NALFD. The prevalence of FLD in obese adolescents was significantly higher than in prepubertal children (65.8% vs. 51.5%). Fasting glucose, insulin, Homa-IR, QUICKI, and OGIS and Matsuda were significantly different between subjects with and without NALFD. Insulin and glucose indices were not found to be significantly different in the prepubertal group, whereas Homa-IR, QUICKI, Matsuda, and OGIS were significantly different in the pubertal group. Age, waist circumference, and OUICKI were found to be risk factors associated with the presence of NALFD in the logistic-regression analysis., Conclusions: Age, waist circumference, and OUICKI were found to be risk factors associated with NALFD. As the value of QUICKI decreases, the probability of having steatosis increases. Although OGTT results gave the information about the glucose tolerance of a subject, indices derived from OGTT were not found to be superior to the traditional surrogates such as Homa-IR or QUICKI. more...

Objectives: To examine the prognostic significance of Gelsolin, NF-κB, and p53 in clear cell renal cell carcinoma (CRCC), which has an unpredictable behavior and tendency for recurrence and metastasis., Materials and Methods: Immunohistochemistry was performed on 100 consecutive cases of CRCC using antibodies against Gelsolin, NF-κB, and p53. Tumors were grouped by nuclear grade (NG) as low NG (NG1, 2) or high NG (NG3, 4), and by pathological stage as localized (pT1, 2) or locally invasive (pT3, 4). Clinical stage was grouped as early stage (stage I, II) or late stage (stage III, IV). Evaluation was based on cytoplasmic (NF-κB(Cyt)) and nuclear (NF-κB(Nuc)) expression for NF-κB, nuclear expression for p53, membranous and cytoplasmic expression for Gelsolin., Results: Gelsolin expression correlated with high NG (p = 0.001), metastasis (p = 0.003), late stage (p = 0.008), and cancer death (p = 0.001). NF-κB(Cyt) expression correlated with high NG (p = 0.002), perirenal invasion (p = 0.010), local invasion (p = 0.020), and late stage (p= 0.003). NF-κB(Nuc) expression failed to predict the prognosis of CRCC. p53 expression correlated with high NG (p = 0.045), lymphovascular invasion (p = 0.05), metastasis (p = 0.001), late stage (p = 0.028), and cancer death (p = 0.034). However, only Gelsolin was found to correlate with disease-specific survival, (p = 0.006), and neither NF-κB nor p53 showed such relation., Conclusion: Expressions of Gelsolin, NF-κB(Cyt), and p53 associated with aggressive behavior of CRCC, while Gelsolin expression specifically indicated poor disease-specific survival. The results of the present study served to determine biomarkers for predicting high-risk patients with CRCC, expected to show aggressive phenotype., (Copyright © 2015 Elsevier GmbH. All rights reserved.) more...

Background: Hereditary vitamin D-resistant rickets (HVDRR) is a rare genetic disorder caused by mutations in the vitamin D receptor (VDR) gene, which result in end-organ resistance to 1,25-(OH)2D3. PATIENTs with HVDRR are mostly treated using i.v. calcium therapy with a central catheter. However, central catheter-related complications have been reported., Patient: The patient was a 3-year-old boy presenting with waddling gait and alopecia. He had hypocalcemia [8 mg/dl (2 mmol/l)], hyperparathyroidism (1,232 ng/l), and elevated 1,25-(OH)2D3 levels (>250 pmol/l). DNA sequence analyses of the VDR gene showed a homozygous C-T transition at codon 152, resulting in a non-sense mutation in exon 5., Interventions and Outcomes: The patient was initially treated with calcitriol (80 ng/kg/day) and high-dose oral calcium (150 mg/kg/day) for one year. At the end of the first year, intermittent (5 days per month) i.v. calcium therapy without a central catheter was initiated because of insufficient clinical and radiological improvement. After 2 years of intermittent i.v. calcium therapy, there was a clear improvement based on clinical progress and on X-ray and biochemical findings. No peripheral complications were reported either., Conclusion: HVDRR with a non-sense mutation in the ligand-binding domain and alopecia was successfully treated with intermittent i.v. calcium without a central catheter., (© 2015 S. Karger AG, Basel.) more...

The role of the renal biopsy in lupus nephritis is to provide the diagnosis and to define the parameters of prognostic and therapeutic significance for an effective clinicopathological correlation. Various classification schemas initiated by World Health Organization in 1974 have been proposed until the most recent update by International Society of Nephrology/Renal Pathology Society in 2004. In this paper, we reviewed the new classification system with the associated literature to highlight the benefits and the weak points that emerged so far. The great advantage of the classification emerged to provide a uniform reporting for lupus nephritis all over the world. It has provided more reproducible results from different centers. However, the studies indicated that the presence of glomerular necrotizing lesion was no longer significant to determine the classes of lupus nephritis leading to loss of pathogenetic diversity of the classes. Another weakness of the classification that also emerged in time was the lack of discussions related to the prognostic significance of tubulointerstitial involvement which was not included in the classification. Therefore, the pathogenetic diversity of the classification still needs to be clarified by additional studies, and it needs to be improved by the inclusion of the tubulointerstitial lesions related to prognosis. more...

The prognostic value of the type and extent of extracapillary proliferation (ECP) in pauci-immune necrotizing crescentic glomerulonephitis (PIGN) was evaluated in this study. In 141 PIGN cases, all glomeruli with ECP were grouped according to type (cellular, fibrocellular and fibrous) and extent of the lesions in Bowman's space; (segmental, semicircumferential and circumferential, which might be termed full moon-FM). Cases with cellular and fibrous lesions involving ≥ 50% of glomeruli with ECP were classified as cellular and fibrous groups, respectively, while the remaining cases were classified as fibrocellular. Cases with segmental and circumferential (FM glomerulus) lesions involving ≥ 50% of glomeruli with ECP were classified as ECPI and ECPIII (FM) groups, respectively, while the rest were classified as ECPII. All the cases were classified according to Berden et al. Significant results were only nearly obtained for the FM group, including the need for dialysis. The Cox regression model revealed a 2.6-fold risk for FM cases regarding dialysis requirement. We propose that the percentage of FM glomeruli should be noted in the pathology report, and cases with more than 50% of FM glomeruli (FM group) should be identified in the group with increased risk of dialysis requirement. Our series also suggests that classification according to Berden et al. is of clinical relevance., (Copyright © 2012 Elsevier GmbH. All rights reserved.) more...

Background: PAX2 is a member of paired box gene family and expressed during development of urogenital system. This study aimed to evaluate PAX2 expression pattern in hyperplastic and malignant endometrial tissues in comparison to non-pathological endometrial changes and to investigate the presence of any correlation between the PAX2 expression and tumor behavior., Methods: The study was performed on the archival material of 121 endometrial tissues including complex hyperplasia (n = 18), complex atypical hyperplasia (n = 20), and endometrioid type adenocarcinoma (n = 47) as study groups, and proliferative endometrium (n = 21) and atrophic endometrium (n = 16) as control groups. One representative block for each case was selected for immunohistochemical evaluation. Sections with 4μm thickness were cut from the blocks and incubated with PAX2 rabbit anti-human polyclonal antibody., Results: PAX2 nuclear staining was detected in all of the endometrial tissues. The mean percentages of PAX2 staining cells were 80.8, 96.7, 88.6, 92.7, and 99.2% with proliferative endometrium, atrophic endometrium, complex hyperplasia, complex atypical hyperplasia, and adenocarcinoma, respectively (Kruskal-Wallis; P < 0.001). The frequency of PAX2 staining increased as the pathology progressed in the manner of complex hyperplasia → complex atypical hyperplasia → adenocarcinoma. In cancer cases, there was no correlation between PAX2 expression levels and the stage, histological grade, myometrial invasion, and lymph node status., Conclusions: PAX2 is expressed in hyperplastic and malignant endometrium as well as proliferative and atrophic endometrium. As the neoplastic lesion progresses from a premalignant state to endometrial cancer, PAX2 expression increases. These findings suggest that PAX2 may contribute to the development of endometrial cancer. more...

Mixed cryoglobulinemia is commonly related to chronic HCV infection, and renal complications occur frequently. Typical renal involvement presents with diffuse proliferative glomerular pathology, similar to membranoproliferative glomerulonephritis, with necrotizing arteritis of medium-sized vessels, referred to as cryoglobulinemic glomerulonephritis. However, the histological appearance may vary according to the clinical presentation and treatment applied. Not only membranoproliferative glomerulonephritis but also certain types of systemic vasculitis (Systemic Lupus Erythematosus, Polyarteritis Nodosa), thrombotic microangiopathy, and Waldenstrom's Macroglobulinemia may exhibit similar histopathological findings in the biopsy with cryoglobulinemic glomerulonephritis. For an optimal differential diagnosis, clinicopathological correlation and serological findings should accompany the pathological findings. We present a case of cryoglobulinemic glomerulonephritis, and discuss the differential diagnosis in detail., (Copyright © 2012 Elsevier GmbH. All rights reserved.) more...

Aim: Gastric aspiration is still applied in many centres during delivery room management of the newborn without any supporting evidence. We aimed to determine whether gastric aspiration affects vital signs, oxygenation, nutrition and short-term prognosis of the newborn., Method: A total of 310 eligible healthy term newborns, identified from a total of 1300 live births, were randomly allocated to receive either gastric aspiration or standard care. During the first 20min, SpO(2), heart rate, cyanosis and retraction scores were recorded once in a min; and blood pressure, respiration rate and neuroadaptive capacity were recorded once in every 5min. Information about nutrition and vomiting behaviours of the babies were taken from the mothers of the neonates on the postnatal 1st day at bedside and by a telephone call on the 7th day., Results: No difference was determined between the groups in terms of 1st to 5thmin Apgar scores, attainment duration of SpO(2) to 85%, 92% and 95%, mean heart rate and respiration rate. Retraction frequency and mean systolic blood pressure of the 5th-min values were found to be significantly higher in the gastric aspiration group. There was no difference between the groups regarding breastfeeding starting time and vomiting frequency., Conclusion: No positive effect of gastric aspiration in delivery room management of the newborn was observed. Conversely, the negative effects of gastric aspiration in neonates were observed with respect to physiological parameters. Our data suggest that gastric aspiration is not useful and may even be harmful in delivery room management of the healthy term newborns., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.) more...

Objective: The aim of this study was to present a case of hepar lobatum resulting from metastatic rectal carcinoma., Clinical Presentation and Intervention: A 50-year-old man presented with a 2-year history of bleeding per anum, tenesmus, malaise and weakness. Initially, the patient received neoadjuvant chemoradiotherapy followed by abdominoperineal resection of the rectum. Abdominal computed tomography showed lobar enlargement and lobulated contour, mainly in the left lobe of the liver, but no primary or metastatic lesions were detected. Laparotomy revealed an irregularly lobulated hepatic deformity. Liver biopsy showed a necrotic tumor growth from adenocarcinoma of the rectum in subcapsular localizationof the liver., Conclusion: This case showed a patient with hepar lobatum carcinomatosum caused by metastatic rectal carcinoma. The report further highlights the need for clinicians and surgeons to keep in mind the possibility of hepar lobatum carcinomatosum while caring for rectal carcinoma patients, especially when the lobulated contour of the liver is detected at preoperative imaging studies or when the coarsely lobated liver is encountered during surgery for carcinoma of the rectum., (Copyright © 2010 S. Karger AG, Basel.) more...