Discrepancies between clinical and pathological findings seen at renal biopsy in rheumatological diseases.

OBJECTIVE: Renal biopsy contributes to the diagnosis, follow-up, and treatment of many rheumatic conditions. This study assessed the diagnostic role and safety of renal biopsies in a tertiary rheumatology clinic. METHODS: Renal biopsies performed between June 2020 and December 2022 were screened, and demographic, clinical, histopathological, and safety data were collected from patient records. RESULTS: In this study, 33 males and 38 females were included. Except for 1 patient who received acetylsalicylic acid, antiaggregant, and/or anticoagulant drugs were stopped before the biopsy. Complications included a decrease of hemoglobin in 8 patients (11.3%) and microscopic hematuria in 40 patients (56.3%). Control ultrasonography was performed in 16 patients (22.5%), and a self-limiting hematoma was found in 4 of them (5.6%) without additional complications. While less than 10 glomeruli were obtained in 9 patients (9.9%), diagnosis success was 94.4%. Histopathological data were consistent with one of the pre-biopsy diagnoses in 54 of 67 cases (80.6%) but showed discrepancies in 19.4% (n=13) of patients. A repeat biopsy was performed in 7 patients for re-staging or insufficient biopsy. CONCLUSIONS: Renal biopsy significantly contributes to rheumatology practice, especially in patients with complex clinical and laboratory findings or in whom different treatments can be given according to the presence, severity, and type of renal involvement. Although the possibility of obtaining insufficient tissue and the need for re-staging and repeat biopsy in the follow-up might be expected, complication risk does not seem to be a big concern. Renal biopsy often evidenced discrepancies between pre-biopsy diagnosis and histopathological findings.

Molecular communication between Apelin-13, Apelin-36, Elabela, and nitric oxide in gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a type of diabetes that affects from 3.8% to 6.9% of pregnancies worldwide, causing significant mortality and unfavorable obstetric outcomes, such as delivery trauma and macrosomia risk. The fundamental processes of this metabolic disorder that first appeared during pregnancy are still unknown. Tissue hormones, particularly adipokines, have aided in understanding the pathophysiology of numerous disorders in recent years. This study aims to determine if Apelin-13 (APLN-13), Apelin-36 (APLN-36), Elabela (ELA), and nitric oxide (NO) molecules have all a part in the pathophysiology of GDM. PATIENTS AND METHODS: The study included 30 pregnant control women and 30 pregnant women who had been diagnosed with GDM in the second trimester and whose body mass index and age were compatible with each other. Blood samples were collected from 60 participants during the second trimester (30 control pregnant women and 30 GDM pregnant women) and postpartum (17 controls vs. 14 GDM). In these blood samples, the amounts of APLN-13, APLN-36, ELA, and NO were studied using the ELISA method. In addition, the participants' glucose, lipid profiles, and other parameters were obtained from the hospital record files. At postpartum, 29 pregnant women (13 control and 16 pregnant women with GDM) dropped out of the study without explanation. RESULTS: In the second trimester and postpartum plasma of mothers with GDM, APLN-13, APLN-36, NO, and ELA molecules were found to be significantly higher (< 0.05), compared to those of the control mothers, while APLN-13, APLN-36, NO values were significantly lower (0.05). While APLN-13, APLN-36, NO amounts in mothers with GDM were positively correlated with glucose amounts, they were negatively correlated with ELA amounts. Similarly, the triglyceride amounts in mothers with GDM were positively correlated with APLN-13, APLN-36 and NO, while they were negatively correlated with the ELA amounts. Due to gestational diabetes, APLN-13, APLN-36, NO, glucose, and triglyceride increased, and ELA decreased. CONCLUSIONS: It is predicted that the glucose increase in GDM is because Apelins reduce glucose transport to erythrocytes by inhibiting the sodium-dependent glucose transporter (SGLT) and that the increase in triglyceride and NO may be associated with high glucose levels in GDM. As a result, we believe that the above-mentioned chemicals may cause GDM Pathology by triggering one another.

Disulfiram, as a candidate NF-κB and proteasome inhibitor, prevents endometriotic implant growing in a rat model of endometriosis.

OBJECTIVE: Disulfiram (DSF) exerts its therapeutic effects through oxidative, proteasome, and nuclear factor kappa beta (NF-κB) pathways. The study was planned to test the impact of DSF on growing of endometriotic implants in rats with experimentally induced endometriosis. PATIENTS AND METHODS: Thirty rats were labeled as the control (n = 8), sham (n = 6), GnRH-agonist (n = 8) and the DSF (n = 8) groups. The rats in the group 3 exposed to single dose leuprolide acetate. The rats in group 4 were treated with DSF for 21 days. The serum activity of oxidant and antioxidant markers, total oxidant status (TOS), total antioxidant status (TAS), interleukin-1ß, and tumor necrosis factor-α (TNF-α) were determined. Implants were processed for NF-κB, PCNA, and CD34 immunostaining. RESULTS: The serum concentration of malondialdehyde in the DSF group was significantly higher than those in other groups. The concentration of TAS, TNF-α, and interleukin-1ß in the DSF group considerably decreased compared to control group. Following treatment with DSF while the percentage of Grade 1 and 2 implants increased the percentage of Grade 3 and 4 implants decreased. The implants disappeared totally in two cases in the DSF group and one case in the GnRH-agonist group. The mean H-Scores of implant NF-κB and PCNA in DSF treated animals were found to significantly lower than those of the control group. CONCLUSIONS: By decreasing NF-κB expression, angiogenesis, and cell proliferation DSF prevents the growth of endometriotic implants.

Familial Mediterranean fever gene (MEFV) mutations and disease severity in systemic lupus erythematosus (SLE): implications for the role of the E148Q MEFV allele in inflammation.

OBJECTIVE: Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients. MATERIAL AND METHOD: The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis. RESULTS: None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis (p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04-16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69-197.13). CONCLUSIONS: Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature. In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.

Ankylosing spondylitis and a diagnostic dilemma: coccydynia.

OBJECTIVES: Coccydynia is defined as pain in or around the tail bone area. The most common cause of coccydynia is either a trauma such as a fall directly on to the coccyx or repetitive minor trauma. The etiology remains obscure in up to 30% of patients. The literature on the contribution of rheumatic diseases to coccydynia is scarce. Our objective was to investigate the prevalence of coccydynia in ankylosing spondylitis (AS) patients. METHODS: One hundred and seven consecutive patients with AS were evaluated for coccydynia were enrolled between January and November 2012 for a cross-sectional analysis. Seventy-four consecutive patients were followed for mechanical back pain as controls and the AS patients were interviewed for the presence of coccydynia. The data collected was evaluated on SPSS® version 11.5 and Microsoft Excel® Programmes. RESULTS: Prevalence of coccydynia in AS (38.3%) was significantly higher than the control group (p<0.0001) in both female and male AS patients (female AS vs. control=40.9% vs. 18.4%, p=0.015 and male AS vs. control=36.5% vs. 8.0%, p=0.005). Both genders were affected equally in the AS group whereas coccydynia was slightly more frequent in female patients in the control group. CONCLUSIONS: Coccydynia is a previously neglected symptom of AS and it is almost three times more common in AS than in non-specific chronic low back pain. Our observation may implicate that inflammatory diseases have a role in the etiology of coccydynia, especially in those without a history of recent or past trauma and coccydynia may be a factor associated with the severity of AS as well.