A Lymph Node Ratio Model for Prognosis of Patients with Pancreatic Neuroendocrine Tumors.

The objective of this study was to determine the prognostic value of lymph node (LN) involvement and the LN ratio (LNR) and their effect on recurrence rates and survival in patients with pancreatic neuroendocrine tumors (PNETs) undergoing surgery. This single-center retrospective study reviewed the medical records of 95 consecutive patients diagnosed with PNETs who underwent surgery at our medical center between 1997 and 2017. The retrieved information included patient demographics, pathology reports, treatments, and oncological outcomes. Results: 95 consecutive potentially suitable patients were identified. The 78 patients with PNETs who underwent surgery and for whom there was adequate data were included in the analysis. Their mean ± standard deviation age at diagnosis was 57.4 ± 13.4 years (range 20-82), and there were 50 males (64%) and 28 females (36%). 23 patients (30%) had LN metastases (N1). The 2.5- and 5-year disease-free survival (DFS) rates for the entire cohort were 79.5% and 71.8%, respectively, and their 2- and 5-year overall survival (OS) rates were 85.9% and 82.1%, respectively. The optimal value of the LNR was 0.1603, which correlated with the outcome (2-year OS p = 0.002 HR = 13.4 and 5-year DFS p = 0.016 HR = 7.2, respectively, and 5-year OS and 5-year DFS p = 0.004 HR = 9 and p = 0.001 HR = 10.6, respectively). However, the multivariate analysis failed to show that the LNR was an independent prognostic factor in PNETs. Patients with PNETs grade and stage are known key prognostic factors influencing OS and DFS. According to our results, LNR failed to be an independent prognostic factor.

Does inflammatory bowel disease coexist with systemic lupus erythematosus?

BACKGROUND: The data regarding the association between inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE) is mostly composed of case reports and case series indicating an infrequent association. OBJECTIVES: To investigate the association between IBD and SLE. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. RESULTS: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The prevalence of UC was significantly higher in patients with SLE than in controls in a univariate analysis (0.4% and 0.2%, respectively; p<0.017). However, in a multivariate logistic regression model SLE was not associated with UC (OR 1.67, 95% CI 0.99-2.815, p<0.052). The prevalence of CD was higher in patients with SLE than in controls in a univariate analysis (0.7% and 0.3%, respectively; p<0.001). A multivariate logistic regression model confirmed this finding and corroborated that SLE was associated with comorbid CD (OR 2.23, 95% CI 1.46-3.4, p<0.001). CONCLUSIONS: Patients with SLE have a greater prevalence of CD than matched controls. The distinction of IBD from SLE gastrointestinal involvement can be challenging as clinical manifestations, laboratory tests, and radiographic findings may appear similar between the two diseases. Therefore, physicians treating patients with rather IBD or SLE should consider this potential association.

All disease begins in the gut: Celiac disease co-existence with SLE.

BACKGROUND: Case reports and case series have indicated a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE), but additional population-based studies are required. The true prevalence of CD in SLE patients is still unknown, but is indeed an important factor when considering the clinical implications, notably the necessity of screening strategies in SLE patients. Our objective was to investigate the association between CD and SLE using a community-based approach in a real-life population database. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of CD in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. RESULTS: The study included 5018 patients with SLE and 25,090 age- and sex-matched controls. The prevalence of CD was significantly higher in patients with SLE than in controls in univariate analysis (0.8% and 0.2%, respectively, p<0.001). Also, SLE was associated with CD (OR 3.92, 95% CI 2.55-6.03, p<0.001) in a multivariate logistic regression model. CONCLUSIONS: Patients with SLE had a greater prevalence of CD than matched controls in a large case-control study. A complex combination of genetic, immunological and novel environmental factors may explain this positive association. Physicians should keep in mind that CD can be a tricky diagnosis in SLE patients, yet a treatable condition, probably more common in this population than we used to think.

The effect of Intravenous Immunoglobulin (IVIG) on \textit{ex vivo} activation of human leukocytes.

INTRODUCTION: Intravenous immunoglobulin (IVIG) has been widely used to treat various conditions, including inflammatory and autoimmune diseases. IVIG has been shown to have a direct influence on neutrophils, eosinophils and lymphocytes. However, many aspects IVIG's effect on neutrophils activation still remain unknown. OBJECTIVE: To evaluate the effect of IVIG on PMA-induced activation of neutrophils, with and without priming with TNF-α, in a series of in vitro experiments performed on whole blood. RESULTS: Our data coincided with well-known literature indicating that the effect of phorbol 12-myristate 13-acetate (PMA) on human leukocytes includes activation of neutrophils, monocytes and eosinophils, increase of chemiluminescence (CL) and induction of netosis, resulting in assembly of traps. In presence of IVIG (10 mg/mL), CL was reduced by 25% in response to PMA compared to PMA-induced leukocyte activation without IVIG. Decreasing IVIG concentration to 1 mg/mL and below did not inhibit PMA-induced activation of CL.PMA-induced activation after TNF-α priming resulted in approximately 50% increase of amplitude of CL response to PMA. Moreover, maximum CL was reached by minute 5, which was more rapid than in the absence of TNF-α-priming (in this case maximum CL was reached by minute 15).The IVIG concentrations did not affect morphological changes of leukocytes after sequential addition of TNF-α and PMA. IVIG had no effect on leukocyte content and on PMA-induced CL of primed leukocytes.Addition of IVIG under TNF-α priming significantly increased the number of traps in the smears in response to PMA activation. Of note, such an increase in the number of traps was depended on the IVIG concentration in plasma. CONCLUSION: In conclusion, we suggest that IVIG is able to reduce the degradation of traps under priming with TNF-α. Moreover, IVIG might switch the activation of primed leukocytes to netosis.

Prevalence of Classic and Non-Classic Antiphospholipid Antibodies in Multiple Sclerosis.

BACKGROUND: The association between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) has been suggested previously, but prior studies provided contradicting findings. OBJECTIVES: To characterize the expression profile of eight classic and non-classic aPL in patients diagnosed with MS. METHODS: Using the BioPlex 2200 immunoassay, we measured the levels of serum immunoglobulin (Ig)M and IgG isotypes of three classic aPL and five non-classic aPL in 98 subjects with MS and 237 healthy controls. RESULTS: Three non-classic aPL were significantly more prevalent among MS patients in comparison to the control group. These antibodies included IgM and IgG against phosphatidylserine-ß2GPI (PS-B2), IgG prothrombin complex (PT-PT) and IgM prothrombin (PT). The positive results according to Bonferroni correction are PS-B2 IgG and PT-PT IgG. The remaining aPL profiles did not differ significantly between the two groups. CONCLUSIONS: An association between certain non-classic aPL and MS has been established. The specific role of these autoantibodies in the pathogenesis of the condition remains uncertain.

The effects of maternal vitamin D on neonatal growth parameters.

UNLABELLED: Vitamin D facilitates calcium absorption and bone building. Presence of vitamin D is highly important in pregnant women due to its effect on the development of the fetal skeleton. The study population comprised 208 low-risk pregnant women of a heterogeneous population. Maternal and fetal serum concentrations of vitamin D were measured using the Liaison 25(OH)D Assay (DiaSorin, Italy). CONCLUSION: Maternal vitamin D serum concentrations correlate with neonatal vitamin D serum concentrations but do not affect neonatal weight and/or head circumference. WHAT IS KNOWN? • Vitamin D is known to be also involved in immunomodulation and cellular proliferation and differentiation. • Vitamin D is highly important in pregnant women for its effect on fetal musculoskeletal and neurological development. WHAT IS NEW? • No association was detected between maternal or neonatal vitamin D concentration with neonatal growth parameters or obstetrical complications, and no association was found between maternal vitamin D serum concentrations and maternal obstetrical complication rate. • A strong correlation was demonstrated between maternal and neonatal serum vitamin D concentrations.

A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients.

Recent research in systemic lupus erythematosus (SLE) yielded new antigens and antibodies in SLE patients. We describe the various autoantibodies that can be detected in patients with SLE. A literature review, using the terms "autoantibody" and "systemic lupus erythematosus", was conducted to search for articles on autoantibodies in SLE, their target antigens, association with disease activity and other clinical manifestations. One hundred and eighty autoantibodies were so far described in SLE patients. These include autoantibodies that target nuclear antigens, cytoplasmic antigens, cell membrane antigens, phospholipid-associated antigens, blood cells, endothelial cells, and nervous system antigens, plasma proteins, matrix proteins, and miscellaneous antigens. The target of an autoantibody, the autoantigen properties, autoantibody frequencies in SLE, as well as clinical associations, and correlation with disease activity are described for all 180 autoantibodies. SLE is so far the autoimmune disease with the largest number of detectable autoantibodies. Their production could be antigen-driven, the result of a polyclonal B cell activation, impaired apoptotic pathways, or the outcome of an idiotypic network dysregulation.

Cardiovascular and metabolic risk factors in inherited autoinflammation.

CONTEXT: The natural progression of metabolic abnormalities among patients with inherited autoinflammation is unclear. OBJECTIVE: The objective of the study was to assess the cardiometabolic risk of participants with familial Mediterranean fever (FMF). DESIGN AND SETTING: This study included nationwide cross-sectional and longitudinal cohorts. PARTICIPANTS: The prevalence of components of the metabolic syndrome at age 17 years was assessed from the medical database of the Israeli Defense Force from 1973 through 1997. Included were 745 males with FMF, 902 healthy male siblings, and a control group of 787,714 participants. A prospective follow-up study traced the incidence of components of the metabolic syndrome to age 45 years among 57 FMF and 1568 control army personnel participants. INTERVENTIONS: Body mass index (BMI) and blood pressure (BP) were measured at age 17 years (cross-sectional); lifestyle, anthropometric, and biochemical data were periodically recorded from age 25 years. MAIN OUTCOME MEASURES: Abnormal BMI or BP (age 17 y) and Adult Treatment Panel III criteria of the metabolic syndrome were measured. RESULTS: In multivariable regression analysis adjusted for known confounders of obesity, FMF participants had an odds ratio of 0.65 for the occurrence of overweight [95% confidence interval (CI) 0.44-0.96, P = .03] and 0.66 (95% CI 0.48-0.92, P = .012) for hypertension-range BP; their siblings tended to obesity (odds ratio 1.48; 95% CI 1.04-2.11, P = .008). In the follow-up arm, a multivariable analysis adjusted for age, birth year, BMI, education, socioeconomic status, ethnicity, and physical activity yielded hazard ratios of 0.32 (95% CI 0.10-0.82, P = .002) for incident obesity, 0.49 (95% CI 0.25-0.95, P = .037) for incident triglycerides 150 mg/dL or greater, 0.56 (95% CI 0.31-0.98, P = .048) for low-density lipoprotein cholesterol 130 mg/dL or greater, and 2.14 (1.368-3.359, P = .001) for high-density lipoprotein cholesterol less than 40 mg/dL for FMF participants compared with controls. Incident elevated BP was lower among FMF participants (hazard ratio 0.49; 95% CI 0.23-1.00, P = .05), whereas dysglycemia incidence was comparable. CONCLUSIONS: FMF is associated with lower rates of most components of the metabolic syndrome compared with normal subjects, unlike other inflammatory conditions.

Gastrointestinal-associated autoantibodies in different autoimmune diseases.

BACKGROUND: Gastrointestinal (GI)-related autoantibodies (Abs) are rarely evaluated in autoimmune diseases (AID) other than inflammatory bowel disease, autoimmune hepatitis and celiac disease. Our aim was to determine the prevalence of these antibodies in a wide spectrum of AID. METHODS: We examined 923 serum samples representing 18 AID and compared them with 338 samples from healthy subjects. We used the BioPlex 2200-immunoassay (Bio-Rad, USA) to test samples for the presence of IgA and IgG directed at gliadin (AGA), tissue-transglutaminase (tTG), and Saccharomyces cerevisiae (ASCA). RESULTS: Prevalence of IgA AGA was significantly higher in antiphospholipid syndrome (APS) (7.1 %, P=0.012) and in pemphigus vulgaris (25%, P =0.008) patients, as compared with healthy controls. Presence of IgG-AGA was more common among Crohn's disease (20.5%, P = 0.023) and rheumatoid arthritis (6.5%, P=0.027) patients. IgG anti tTG were frequently observed in APS (6.1%, P=0.012), in giant cell arteritis (11.5%, P=0.013) and in ulcerative colitis (11.1%, P=0.018) patients, and as expected, higher prevalence of ASCA (IgA 19.3% and IgG 27.7%) was found in Crohn's disease. IgG ASCA were also found in systemic lupus erythematosus (SLE) (4.5%, P=0.01), in Graves' disease (5.7%, P=0.018), in cryoglobulinemia (7.1%, P=0.006), and in patients with vasculitides (6.5%, P=0.002). In contrast, lower prevalence of IgG type AGA was found in SLE (P=0.034), cryoglobulinemia (P=0.019) and vasculitides (P=0.013) patients. CONCLUSIONS: Our findings suggest an association between GI-related- Abs and a wide spectrum of AID. The clinical implication of these findings is yet to be determined.

Gluten sensitivity in multiple sclerosis: experimental myth or clinical truth?

Patients with neurological disease of unknown etiology sometimes present with antigliadin and antitissue transglutaminase antibodies. The association between these antibodies and multiple sclerosis has been previously suggested. The purpose of this study was to determine the prevalence of these antibodies in multiple sclerosis patients. We determined the level of serum immunoglobulin A and immunoglobulin G antigliadin and antitissue transglutaminase antibodies in 98 patients with multiple sclerosis. We found a highly significant increase in titers of immunoglobulin G antibodies against gliadin and tissue transglutaminase in the multiple sclerosis patients. Seven patients had a positive IgG AGA, whereas only 2 controls presented positive titers (P = 0.03). Four patients had positive IgG anti-tTG while all the controls tested negative (P = 0.02). However, immunoglobulin A antibodies against gliadin and tissue transglutaminase were not statistically higher in the multiple sclerosis group in comparison to the control group. Our findings support the associations between antibodies against gliadin and tissue transglutaminase to multiple sclerosis. The specific role of these antibodies in the pathogenesis of multiple sclerosis remains uncertain and requires additional research. A gluten free diet should be considered in specific cases of patients who present with gluten antibodies.