Evaluation of Bone Turnover Markers Such as Osteoprotegerin, Sclerostin and Dickkopf-1 in Subclinical Hyperthyroidism.

In this study, it was aimed to assess effects of subclinical hyperthyroidism (SH) on bone metabolism using osteoprotegerin (OPG), sclerostin, Dickkopf-1 (DKK1) and biochemical parameters. This cross-sectional prospective study included 40 patients with SH and 40 euthyroid controls. Serum OPG, sclerostin, DKK-1, type-1 procollagen, C-terminal polypeptide (CTx) and 24-hours urine N-terminal telopeptide (NTx) were measures using ELISA kit. Bone mineral density measurements were performed using dual energy X-ray absorptiometry (DEXA). Risk for 10-years hip and major fracture was estimated by Turkish version of FRAX. No significant difference was detected in age, gender, body mass index, smoking and menopause rates between SH and control groups. The risk for 10-years hip fracture and major osteoporotic fracture were estimated as 4.45% and 0.55% in SH group, respectively. The OPG levels were significantly lower in patients with SH than controls (P = 0.017). No significant difference was detected in other bone formation and degradation parameters. No significant correlation was detected between OPG level and risk for major osteoporotic fracture (P > 0.05); however, a negative correlation was detected between OPG level and risk for hip fracture (rho = 0.233; P = 0.038). Serum OPG is markedly affected in patients with SH. In addition, OPG seemed to be associated with osteoporotic fracture risk. Available data show that SH is significantly associated with risk for fracture; thus, it is important to assess risk for fracture in patients with SH.

Does the Distance of the Tumor from the Surgical Margin Affect Biochemical Recurrence in Patients with Pathological Organ-Confined Prostate Cancer?

OBJECTIVE: To investigate the effect of the distance between tumor and surgical margin on biochemical recurrence in patients with organ-confined prostate cancer. MATERIAL AND METHOD: The data of 208 patients, who underwent radical prostatectomy between 2012-2018, were retrospectively analyzed. The surgical margin status of 147 pathologically organ-confined patients was categorized as positive, close ( < 1mm) and negative. Surgical margin status and parameters affecting biochemical recurrence were examined. Furthermore, multivariate analysis was done to determine the parameters associated with biochemical recurrence. RESULTS: Biochemical recurrence was detected in 21 (14.2%) of 147 patients. 38 (27.9%) men had negative surgical margins, 68 (46.2%) had close surgical margins and 41 (25.9%) had positive surgical margins. Tumor volume and ISUP grade were found to be statistically significant for positive surgical margin and close surgical margin patients compared to negative surgical margin patients. Close surgical margin was not statistically associated with biochemical recurrence. Preoperative high PSA (p < 0.001) and positive surgical margin (p=0.021) were independent risk factors for biochemical recurrence. CONCLUSION: According to our results, it is not necessary to include the presence of a close surgical margin in the pathology reports in patients with pathological organ-confined tumors and negative surgical margins.

Emerging B-Cell Therapies in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease of unknown etiology, whose hallmark is the production of autoantibodies. B cells are promising targets for novel SLE therapies. In 2011, belimumab (Benlysta®), a fully humanized monoclonal antibody inhibiting B-cell activation and proliferation, was the first medication in 50 years to be approved by the US Food and Drug Administration to treat adult SLE. This review discusses the current experience with B-cell-targeted therapies, including those targeting B-cell-surface antigens (rituximab, ocrelizumab, ofatumumab, obinutuzumab, obexelimab, epratuzumab, daratumumab), B-cell survival factors (belimumab, tabalumab, atacicept, blisibimod), or B-cell intracellular functions (ibrutinib, fenebrutinib, proteasome inhibitors), for the management of SLE. It focuses on ongoing clinical trials and real-world post-marketing use, where available, including their safety profiles, and concludes with our recommendations for B-cell-centric approaches to the management of SLE.

Small vessel vasculitis secondary to Mycobacterium chelonae.

Mycobacterial infection can be seriously debilitating and challenging to diagnose. The infection can mimic vasculitis associated with positive anti-neutrophilic cytoplasmic autoantibodies (ANCA). This clinical scenario is exemplified with a well-studied case of a 63-year-old Caucasian man with uncontrolled diabetes and ulcerative colitis on immunosuppressive agents. The patient was hospitalized for 3 months with worsening painful hand ulcerations. Primary vasculitis was first suspected, but the patient was later diagnosed with vasculitis secondary to Mycobacterium chelonae infection. Report includes discussion on sequence of testing which led to the diagnosis. After proper diagnosis and change to proper antibiotics, the patient's vasculitis improved over time. It is our hope that this report further raises awareness of mycobacterial infection as a mimicker of vasculitis. We also provide a review of relevant literature on non-tuberculosis mycobacterial (NTM) infection including a review of 22 articles and 12 cases found in the literature. The salient features of the literature review include that 10 of the 12 cases were patients who had risk factors of immunosuppression due to medications, and all patients were infected by mycobacterium causing skin vasculitis. After given the proper directed antibiotic treatment, 11 of the 12 patients had a reported improved outcome.

Pyoderma gangrenosum associated with limited cutaneous systemic sclerosis: a rare case with literature review.

Pyoderma gangrenosum (PG) is a skin disease characterized by painful ulcers that, when not appropriately treated, can lead to permanent disfigurement. Pyoderma gangrenosum has been observed in a multitude of autoimmune disorders such as rheumatoid arthritis, inflammatory bowel disease (IBD), and sarcoidosis (Feld et al. J Rheumatol. 39(1):197, 2012; Herrero et al. J Rheumatol. 36:7:1557-1558, 2009). It is rarely associated with autoimmune disorders such as systemic sclerosis. We report a case of a patient with known limited cutaneous systemic sclerosis who developed an ulcerated lesion on the 2nd digit of the left hand. The lesion was initially thought to be cellulitis and the patient underwent superficial wound debridement. Postoperatively, the patient's lesions worsened. The patient was treated with intravenous (IV) methylprednisolone and 0.05% topical clobetasol due to high suspicion for PG with complete resolution of ulcerated lesions and minimal scarring.

Angiostrongyliasis infection masquerading as granulomatosis with polyangiitis: a case-based review.

Pulmonary angiitis is a small vessel vasculitis commonly reported in granulomatosis with polyangiitis (GPA) but is rarely attributed to angiostrongyliasis. We report a case of a patient with well-controlled rheumatoid arthritis, who was treated for GPA based on lung biopsy results with glucocorticoids (GC). Upon re-review of the initial pathology, along with peripheral eosinophilia and history of recent travel, the patient was eventually diagnosed with angiostrongylus-like nematode infection. GCs were subsequently discontinued and instead, the patient was treated with anthelmintics with complete resolution of symptoms. Commonly associated with eosinophilic meningitis or abdominal angiostrongyliasis in humans, clinical pulmonary manifestations of this parasite species are rare. With parasitic infiltration of the pulmonary vessels mimicking clinical GPA, diagnosis and treatment can be difficult in these patients. We discuss the third-reported case and first-reported survivor of Angiostrongylus-induced pulmonary angiitis followed by a focused review of the literature.

Rare Plasmacytoid Urothelial Carcinoma of the Bladder: Two Case Reports.

Plasmacytoid urothelial carcinoma is a rare and aggressive form of urothelial carcinoma characterized with delayed presentation and poor prognosis. Very few cases of this carcinoma have been reported in the literature. Here, we report and discuss two cases of bladder plasmacytoid urothelial carcinoma of a 57-year-old male presented with renal colic, and a 33-year-old female presented with macroscopic hematuria. Pathologic examinations of the transurethral biopsies revealed urothelial carcinoma with plasmacytoid appearance. Subsequently, immunohistochemicalevaluation showed positive expression of epithelial markers and CD138. Additionally, losing of the membranous expression of E-cadherin verified the diagnosis of plasmacytoid urothelial carcinoma.

Arterial Inflammation Detected With 18 F-Fluorodeoxyglucose-Positron Emission Tomography in Rheumatoid Arthritis.

OBJECTIVE: In addition to traditional risk factors, excess cardiovascular disease (CVD) in rheumatoid arthritis (RA) is attributed to enhanced vascular and/or systemic inflammation. In several small studies using 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (18 F-FDG-PET/CT) to directly assess vascular inflammation, FDG uptake was higher in RA patients than in controls. Using a substantially larger sample of RA patients, we sought to identify RA disease characteristics independently associated with vascular FDG uptake. METHODS: RA patients underwent cardiac FDG-PET/CT, with aortic inflammation assessed by quantification of FDG uptake in the ascending aorta, calculated as the mean and maximum (max) standardized uptake value (SUV) of the entire ascending aorta and of its most diseased segment (SUV MDS). Univariate and multivariable regression models were constructed to model the associations of patient characteristics with aortic FDG uptake. RESULTS: Ninety-one RA patients were scanned. In multivariable models, in addition to the independent associations of hypertension and body mass index with increased aortic FDG uptake, the prevalence of rheumatoid nodules correlated with the SUV mean and SUV MDS mean measures, while anti-cyclic citrullinated peptide (anti-CCP) antibodies correlated inversely with these measures and with the SUV max and SUV MDS max (P < 0.05). A significant association of RA disease activity with aortic FDG uptake was observed but was restricted to anti-CCP seropositivity. CONCLUSION: Traditional CV risk factors and RA disease characteristics (rheumatoid nodules and the Disease Activity Score in 28 joints using the C-reactive protein level in anti-CCP antibody-positive individuals) were independently associated with ascending aortic FDG uptake in RA patients without clinical CVD.

Association of Elevations of Specific T Cell and Monocyte Subpopulations in Rheumatoid Arthritis With Subclinical Coronary Artery Atherosclerosis.

OBJECTIVE: Coronary artery disease (CAD) is the leading cause of excess deaths in rheumatoid arthritis (RA). However, identification of features denoting patients with a risk of developing CAD is lacking. The composition of circulating peripheral blood mononuclear cell (PBMC) subsets in RA patients differs markedly from that in healthy controls with regard to the extent of T cell activation, with clonal expansion and differentiation to effector memory status, and presence of inflammatory monocytes. In this study, we sought to evaluate whether elevations in these PBMC subpopulations in RA patients could denote those with an increased risk of subclinical CAD, as determined by the presence of coronary artery calcification (CAC). METHODS: The study cohort comprised 72 patients with RA who underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and the presence of CAC. RESULTS: Among the 72 patients with RA, 33% had CAC and exhibited significant increases in the levels of circulating CD4 T cell subsets denoting activation and differentiation to the effector memory phenotypes. Analogous increases in the levels of CD8 T cell subsets, as well as in the CD14(high)CD16+ intermediate monocyte subset, were also present in these patients, as compared to those without CAC. The increases in the CD4 and CD8 T cell subsets were highly intercorrelated, whereas the increases in CD14(high)CD16+ monocytes were independent of elevations in the CD4 T cell subsets. After adjustments for relevant confounders, the levels of CD4+CD56+CD57+ T cells and CD14(high)CD16+ monocytes remained associated with the presence of CAC. CONCLUSION: These findings indicate that PBMC subsets are markers for the presence of CAC and suggest that mechanisms of atherogenesis in RA may operate in part through the elevations in these subsets, raising further questions about the mechanisms underlying the presence of such alterations in cell composition in patients with RA and the potential for shared etiologic pathways between RA and cardiovascular disease.

Inflammation, adiposity, and atherogenic dyslipidemia in rheumatoid arthritis: is there a paradoxical relationship?

Dyslipidemia is highly prevalent in rheumatoid arthritis (RA) and appears to be present very early in the RA disease process, in some studies even before a diagnosis of clinical RA has been made. The association between lipid measures and the risk of cardiovascular disease (CVD) in RA appears to be paradoxical, whereby lower levels of total cholesterol (TC), low-density lipoprotein (LDL-C), and atherogenic ratios are associated with higher CVD risk. This may be due to the lipid-lowering effects of RA-related systemic inflammation. Therefore, standard CVD risk calculators have been shown to underperform in RA. Data also suggest that lipoprotein particle sizes and the apolipoprotein cargo of lipoproteins skew toward atherogenic dyslipidemia in RA and may contribute to the initiation and progression of atherosclerosis. Inflammatory burden in RA may also alter the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol (HDL-C). Adipose tissue is quantitatively increased in RA patients compared with matched non-RA controls and may be more inflamed and metabolically dysfunctional compared with an otherwise similar non-RA patient. In vitro, animal, and a handful of non-RA human, studies suggest that inflamed, metabolically dysfunctional adipose tissue contributes directly to lower HDL-C levels. In turn, lower HDL-C that has been altered functionally by inflammation may lead to expanded adipose mass and further adipose dysfunction and inflammation. In the last part of this review, we speculate how the RA disease state may recapitulate these processes.

Transient leukemia-associated pericardial tamponade in a neonate with Down syndrome.

Approximately 10% of neonates with Down syndrome may develop a form of megakaryoblastic leukemia that usually disappear spontaneously during the first months of the life. Although it seems to have a benign course, it may also be lethal and severe in some cases, especially in the form of hydrops and/or cardiopulmonary failure. Herein, we report a male infant with Down syndrome who was admitted with respiratory distress due to severe pericardial effusion leading to pericardial tamponade in the first 2 weeks of life. Pericardiosentesis and pericardial tube replacement in combination with steroid therapy was performed. He responded well to these therapies and his leukemia resolved on the fourth month of life. This case suggests that severe pericardial effusion and pericardial tamponade may be life-threatening complications of transient leukemia of Down syndrome and also it may be managed successfully with appropriate treatments.