Pernicious Anemia Research Articles

Gastric Cancer Risk Factors ina Veteran Population.

Risk factors for gastric cancer in the United States are not well understood, especially in populations with a low proportion of immigrants. We conducted a matched case-control study in a Veteran Affairs Medical Center to identify risk factors for gastric cancer. Gastric cancer patients and age- and sex-matched controls were identified in a 1:4 ratio from January 1, 1997 to October 31, 2018. Demographic, medical, endoscopic, and histologic data were extracted. We performed conditional logistic regression to estimate odds ratios and 95% CIs for associations between potential risk factors and gastric cancer. Most gastric cancer cases were diagnosed on initial endoscopy (71.4%). Of these, the most common presenting stage was stage IV (40.8%). Risk factors for gastric cancer included Black and Asian race and never or current (compared to former) drinkers, although Helicobacter pylori eradication and pernicious anemia were associated with decreased risk. The high proportion of late-stage gastric cancer diagnoses highlights the need for improved risk stratification as well as screening and surveillance protocols in the U.S. population. Racial disparities among veterans in an equal-access system necessitate further investigation into the etiology of these disparities.

Early diagnosis of autoimmune gastritis

Early diagnosis of autoimmune gastritis (AIG) is quite difficult in a physician’s daily practice. Since the disease is asymptomatic for a long time, it is often diagnosed already with severe atrophy with the loss of a large number of gastric glands and potentially significant pernicious anemia, and sometimes with the onset of cancer. Morphological and endoscopic changes do not occur immediately and are not specific in patients with AIG. In this case, non-invasive diagnostics play a key role. The diagnostics of AIG are often done in patients with vitamin B12 and iron deficiency. However, the development of these deficiencies can take a long time. The non-invasive technique with the determination of such biomarkers as pepsinogen I, II (PGI, PG II), their ratio, gastrin-17, as well as Helicobacter pylori (H. pylori) infection, including a cytotoxic (CagA +) strain, is used to exclude preclinical stages of AIG. The titer determination of anti-parietal cell antibodies and the anti-intrinsic factor antibodies allows identifying the immune nature of gastritis. But recent studies show that these markers can be negative in some patients. This article actualizes the problem of early diagnosis of AIG and demonstrates the importance of practical application of currently existing non-invasive methods for the diagnosis of stomach diseases.

Association of vitiligo with multiple cutaneous and extra-cutaneous autoimmune diseases: a nationwide cross-sectional study.

Previous studies found conflicting results about associations of vitiligo with different autoimmune diseases. To evaluate associations of vitiligo with multiple autoimmune diseases. A cross-sectional study representativeof 612,084,148 US patients from theNationwide Emergency Department Sample(NEDS) 2015-2019was performed. Vitiligo and autoimmune diseases were identified using International Classification of Diseases-10 codes. The most frequent autoimmune disorders in patients with vitiligo were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, Addison's disease, and systemic sclerosis (SSc). Vitiligo was associated with any autoimmune disorder (adjusted odds ratio [95% confidence interval] 1.45 [1.32-1.58]). Cutaneous disorders with largest effect-sizes were alopecia areata (186.22 [115.31-300.72]) and SSc (32.13 [25.28-40.82]). Non-cutaneous comorbidities with largest effect-sizes were primary sclerosing cholangitis (43.12 [18.98-97.99]), pernicious anemia (41.26 [31.66-53.78]), Addison's disease (33.85 [26.68-42.9]), and autoimmune thyroiditis (31.65 [26.34-38.02]). Vitiligo is associated with multiple cutaneous and non-cutaneous autoimmune diseases, especially in females and older age.

Changes in hepatic blood flow in patients with comorbidity of chronic obstructive pulmonary disease and vitamin B12 deficiency anemia

Changes in hepatic blood flow in patients with comorbidity of chronic obstructive pulmonary disease and vitamin B12 deficiency anemia

Essential thrombocythemia masked by vitamin B 12 deficiency megaloblastic anemia: A case report

The association of megaloblastic vitamin B12 deficiency anemia and essential thrombocythemia is very rarely described in the literature. We reported a case of a 65-year-old patient with an isolated chronic anemic syndrome secondary to megaloblastic vitamin B12 deficiency anemia treated with vitamin B12 therapy by injection. The evolution was marked three months after treatment by the an ischemic cerebrovascular accident and thrombocytosis. Additional investigations confirmed essential thrombocythemia. The patient was put under hydroxyuria and an anticoagulant treatment with a good evolution.

Early treatment of subacute combined degeneration of the spinal cord in pernicious anemia will improve the outcome

Vitamin B12 deficiency is probably more common than what is reported in the literature. B12 is an essential vitamin, and its deficiency can lead to neuropsychiatric manifestations such as peripheral neuropathy, myelopathy, cerebellar ataxia, dementia, delirium, even psychosis and mood disorders. We report a case of 45 year old polish male presented with symptoms and signs suggestive of SCD of the spinal cord, due to severe vitamin B12 deficiency as a result of pernicious anemia. Cervical spine MRI showed enhancement in the bilateral posterior columns of the cervical spinal cord with a classic inverted V appearance. Metabolic workup revealed severe vitamin B12 deficiency, complete blood analysis indicated megaloblastic anemia. Intramuscular injection of cobalamin was started on a timely manner with complete resolution of symptoms.

Update in Molecular Aspects and Diagnosis of Autoimmune Gastritis.

Recent studies have advanced our understanding of the pathophysiology of autoimmune gastritis, particularly its molecular aspects. The most noteworthy recent advancement lies in the identification of several candidate genes implicated in the pathogenesis of pernicious anemia through genome-wide association studies. These genes include PTPN22, PNPT1, HLA-DQB1, and IL2RA. Recent studies have also directed attention towards other genes such as ATP4A, ATP4B, AIRE, SLC26A7, SLC26A9, and BACH2 polymorphism. In-depth investigations have been conducted on lymphocytes and cytokines, including T helper 17 cells, interleukin (IL)-17A, IL-17E, IL-17F, IL-21, IL-19, tumor necrosis factor-α, IL-15, transforming growth factor-β1, IL-13, and diminished levels of IL-27. Animal studies have explored the involvement of roseolovirus and H. pylori in relation to the onset of the disease and the process of carcinogenesis, respectively. Recent studies have comprehensively examined the involvement of autoantibodies, serum pepsinogen, and esophagogastroduodenoscopy in the diagnosis of autoimmune gastritis. The current focus lies on individuals demonstrating atypical presentations of the disease, including those diagnosed in childhood, those yielding negative results for autoantibodies, and those lacking the typical endoscopic characteristics of mucosal atrophy. Here, we discuss the recent developments in this field, focusing on genetic predisposition, epigenetic modifications, lymphocytes, cytokines, oxidative stress, infectious agents, proteins, microRNAs, autoantibodies, serum pepsinogen, gastrin, esophagogastroduodenoscopy and microscopic findings, and the risk of gastric neoplasm.

Features of regional blood flow in young people with vitamin B<sub>12</sub> deficiency anemia

Aim. To investigate specific features of regional blood flow in the liver of young people with vitamin B12 deficiency anemia (VBDA).Materials and methods. A total of 64 patients diagnosed with VBDA with the median age of 38 years and 95% confidence interval [26; 49] were examined. Hemodynamic parameters of the liver and central circulation were assessed using pulsedwave Doppler ultrasound with color and power imaging. Statistical data was processed by Statistica 25.0.Results. At the onset of VBDA, the revealed hemodynamic disorders are primarily associated with a 13.8% decrease in the ratio of the linear velocity of the portal flow and the diameter of the portal vein, which leads to liver blood stagnation. A long medical history of VBDA is associated with the venous collector of hepatic hemodynamics and a decrease in the volume values (16.8%) against the background of increased peripheral vascular tone of hepatic vessels (23.5%). A correlation between the indicators of regional blood flow in the liver and the type of central hemodynamics was revealed, being most pronounced in severe VBDA and the hypokinetic hemodynamics type.Conclusion. Assessment of the regional blood flow of the liver was found to be an effective method for diagnosing the state of target organs in VBDA and for verifying the predictors of VBDA severity.

Clinicopathological characteristics of autoimmune gastritis: A single-center retrospective study

Background and AimAutoimmune gastritis (AIG) is a prominent risk factor for pernicious anemia (PA) and gastric neoplasia. This study aimed to investigate the clinicopathological characteristics of AIG patients in China, with a focus on those who had positive anti-intrinsic factor antibodies (AIFA). MethodsA total of 103 AIG patients who were diagnosed between January 2018 and August 2022 were reviewed in a large academic tertiary teaching hospital. Patients were divided into two groups based on the presence or absence of AIFA, and their serologic and histopathological characteristics were analyzed. ResultsThe mean age of the 103 AIG patients was 54.16±11.92 years (range 23–79), with 69 (66.99%) being women. AIFA were present in 28.16% of patients. Patients with AIFA-positive had a higher risk of PA than those with AIFA-negative, as demonstrated by a larger mean corpuscular volume (MCV), lower hemoglobin level, and lower vitamin B-12 level (P<0.05). There were no statistically significant differences in gastric histopathology, gastrin level, and pepsinogen level when patients were divided into AIFA-positive and AIFA-negative group. Of the 103 cases, 34 (33.01%) were concomitant with other autoimmune diseases, with autoimmune thyroid diseases being the most common (25.24%, 26/103). Thyroid peroxidase antibody, which accounted for 45.45% (25/55), was the most prevalent thyroid antibody, followed by anti-thyroglobulin antibody (34.55%, 19/55), thyroid stimulating antibody (12.73%, 7/55), and thyrotropin receptor antibody (3.64%, 2/55). ConclusionThis study highlights the increased risk of severe anemia in AIFA-positive AIG patients, particularly for PA. Clinicians should consider the presence of AIFA as a warning sign for PA and prioritize early diagnosis and appropriate treatment to prevent serious complications.

B12 deficiency

Vitamin B12 (cobalamin) deficiency is an important cause of macrocytic anaemia. It often presents insidiously, with some patients developing neurological and psychiatric sequalae. Pernicious anaemia is the most common cause of B12 deficiency in the Western world. However, with rising numbers of strict vegans, an ageing population and patients undergoing bariatric surgery, clinicians need to be aware of other causes and likely patient groups who may present with features of B12 deficiency.

The effect of vitamin B12 on DNA adduction by styrene oxide, a genotoxic xenobiotic

Vitamin B12 (cyano- or hydroxo-cobalamin) acts, via its coenzymes, methyl- and adenosyl-cobalamin, as a partner for enzymatic reactions in humans catalysed by methionine synthase and methylmalonyl-CoA mutase. As well as its association with pernicious anaemia, human B12 deficiency may also be a risk factor for neurological illnesses, heart disease and cancer. In the present work the effect of vitamin B12 (hydroxocobalamin) on the formation of DNA adducts by the epoxide phenyloxirane (styrene oxide), a genotoxic metabolite of phenylethene (styrene), has been studied using an in vitro model system. Styrene was converted to its major metabolite styrene oxide as a mixture of enantiomers using a microsomal fraction from the livers of Sprague-Dawley rats with concomitant inhibition of epoxide hydrolase. However, microsomal oxidation of styrene in the presence of vitamin B12 gave diastereoisomeric 2-hydroxy-2-phenylcobalamins. The quantitative formation of styrene oxide-DNA adducts was investigated using 2-deoxyguanosine or calf thymus DNA in the presence or absence of vitamin B12. Microsomal incubations containing either deoxyguanosine or DNA in the absence of vitamin B12 gave 2-amino-7-(2-hydroxy-1-phenylethyl)-1,7-dihydro-6H-purin-6-one [N7-(2-hydroxy-1-phenylethyl)-guanine], and 2-amino-7-(2-hydroxy-2-phenylethyl)-1,7-dihydro-6H-purin-6-one [N7-(2-hydroxy-2-phenylethyl)guanine] as the principal adducts. With deoxyguanosine the level of formation of guanine adducts was ca. 150 adducts/106 unmodified nucleoside. With DNA the adduct level was 36 pmol/mg DNA (ca. 1 adduct/0.83 × 105 nucleotides). Styrene oxide adducts from deoxyguanosine or DNA were not detected in microsomal incubations of styrene in the presence of vitamin B12. These results suggest that vitamin B12 could protect DNA against genotoxicity due to styrene oxide and other xenobiotic metabolites. However, this potential defence mechanism requires that the 2-hydroxyalkylcobalamins derived from epoxides are not ‘anti-vitamins’ and ideally liberate, and therefore, recycle vitamin B12. Otherwise, depletion of vitamin B12 leading to human deficiency could increase the risk of carcinogenesis initiated by genotoxic epoxides.

Th17 cytokines and factors modulating their activity in patients with pernicious anemia

The effects of specific cytokines produced by T cell subsets (such as Th1, Th2, and newly discovered Th17, Treg, Tfh, or Th22) are diverse, depending on interactions with other cytokines, distinct signaling pathways, phase of the disease, or etiological factor. The immunity equilibrium of the immune cells, such as the Th1/Th2, the Th17/Treg, and the Th17/Th1 balance is necessary for the maintenance of the immune homeostasis. If the balance of the T cells subsets is damaged, the autoimmune response becomes enhanced which leads to autoimmune diseases. Indeed, both the Th1/Th2 and the Th17/Treg dichotomies are involved in the pathomechanism of autoimmune diseases. The aim of the study was to determine the cytokines of Th17 lymphocytes as well as the factors modulating their activity in patients with pernicious anemia. The magnetic bead-based immunoassays used (Bio-Plex) allow simultaneous detection of multiple immune mediators from one serum sample. In our study, we showed that patients suffering from pernicious anemia develop the Th1/Th2 imbalance with a quantitative advantage of cytokines participating in Th1-related immune response, the Th17/Treg imbalance with a quantitative advantage of cytokines participating in Treg-related response, as well as the Th17/Th1 imbalance with a quantitative predominance of cytokines participating in Th1-related immune response. Our study results indicate that T lymphocytes and their specific cytokines play an role in the course of pernicious anemia. The observed changes may indicate the immune response to pernicious anemia or be an element of the pernicious anemia pathomechanism.

Adrenocortical corticosteroids and megaloblastic anemia responsible ischemic stroke: A case report

Stroke disease can result from traditional cardiovascular risk factors and by cancer, especially adrenocortical corticosteroids by hypercoagulability and megaloblastic anemia would be possibly though hyperhomocysteinemia. We report the case of a patient aged 65 years, without significant pathological , diagnosed with a left adrenocortical retained in front of a mass at the level of the left adrenal compartment, irregular shape, fairly well limited, isodense to spontaneous contrast (33UH), enhanced by the PDC in a heterogeneous way delimiting areas of necrosis measuring 9cm, with an absolute Wash out of 25% and relative to 11%. Associated with an attack of the general condition evolving rapidly gradually is a weight loss of 16 kilogram over 2 months. With the biological Assessment a cortisol cycle broken with cortisolemia from midnight to 12, braking at 1.7 and CLU at 4 times normal. The patient presented during hospitalization megaloblastic anemia and thrombocytopenia with vitamin B12 deficiency confirmed by myelogram and anti-intrinsic positive antibody treated with courses of hydroxocobalamin in intramuscular, after 4 days the patient presented upon waking left hemiplegia, left facial paralysis with dysarthria on Cerebral CT scan showed ischemic stroke of the right middle cerebral artery. The patient was put on anticoagulant therapy. The evolution was marked in a context of improvement of anemia and thrombocytopenia and the resumption of motor skills of the left hemibody. The patient is put out before the criterion of non-operability to predict a tumor excision after a good medical preparation for surgery. There is a relationship between Biermer anemia and neoplastic pathologies in stroke disease.

(015) Vulvar Lichen Sclerosus is Associated with New Diagnoses of Mood Disorders

Abstract Introduction Vulvar lichen sclerosus (VLS) often presents with chronic pruritus. While VLS is associated with feelings of isolation, risk of mood disorders among females with VLS has yet to be quantified on a large scale. Objective Our objective was to assess the association of VLS with development of depressive episode, anxiety disorder, major depressive disorder (MDD), and prescription of antidepressants and benzodiazepines, and to evaluate the impact of VLS treatment. Methods A US claims database network (TriNetX Diamond Network) was queried from 2009 to 2022. Cohorts included women aged ≥18 with lichen sclerosus (LS) (ICD-10: L90.0) without prior diagnosis of MDD (F33), depressive episode (F32), or anxiety disorder (F40-F48) or previously prescribed antidepressants (VA: CN600) or benzodiazepines (CN302). We compared a control cohort of women with LS sparing the vulva with women with LS affecting the vulva (N90.4). We conducted a sub-analysis by age (18-40, 41-55, and &amp;gt;55 years). We compared women aged ≥18 with VLS who received treatment (topical steroids (DE200), vaginal estrogen (GU500), prednisone (8640), hydroxyzine (5553), amitriptyline (704), gabapentin (25480), or tacrolimus (42316)) with women aged ≥18 with VLS who did not receive treatment within 6 months of VLS diagnosis. Finally, we compared women receiving only topical VLS treatment (topical steroids, vaginal estrogen, and tacrolimus) with those receiving no treatment. Outcomes of interest were depressive episodes, anxiety disorder, MDD or prescription of antidepressants or benzodiazepines within 6 months of VLS diagnosis. Propensity score matching was performed for age, ethnicity, race, type 1 diabetes (E10), vitiligo (L80), autoimmune thyroiditis (E06.3), alopecia areata (L63), pernicious anemia (D51.0), overweight and obesity (E66), type 2 diabetes (E11), hyperlipidemia (E78), essential hypertension (I10), and alcohol abuse (F10.10). Results 124,237 patients had LS sparing the vulva and 16,676 had VLS. VLS was associated with increased risk of depressive episode (risk ratio (RR) [95% Confidence Interval] 1.62 [1.32-1.99]), anxiety disorder (RR 1.82 [1.50-2.22]), and MDD (RR 2.61 [1.69-4.03]) (Table 1) compared to LS sparing the vulva. Women with VLS were also more likely to receive antidepressants (RR 1.91 [1.60-2.29]) and benzodiazepines (RR 1.70 [1.44-2.01]). Among menopausal women, VLS was associated with increased risk of anxiety disorder (RR 2.00 [1.10-3.63]) (Table 2). Among postmenopausal women, VLS was associated with increased risk of depressive episode (RR 1.73 [1.38-2.17]), MDD (RR 2.60 [1.64-4.12]), anxiety disorder (RR 1.58 [1.29-1.94]), antidepressants (RR 1.55 [1.30-1.86]), and benzodiazepines (RR 1.48 [1.24-1.76]). Among women with VLS, VLS treatment was associated with decreased risk of depressive episode (RR 0.68 [0.47-0.98]) and increased risk of antidepressants (RR 2.00 [1.54-2.59]) and benzodiazepines (RR 1.70 [1.31-2.20]) compared to women without VLS treatment (Table 3). Stratifying by treatment type, women treated solely with topicals had numerically, but not significantly, lower risk of developing depressive episode (RR 0.73 [0.48-1.11]) compared to women without VLS treatment. Conclusions We demonstrate that women with VLS, compared to those with LS sparing the vulva, have an increased risk of antidepressant and benzodiazepine prescriptions and development of depressive episode, anxiety disorder, or MDD. Patients with VLS should be screened for these conditions, and VLS treatment should be considered. Disclosure No

(190) Prescription Patterns in Women with Vulvar Lichen Sclerosus With and Without a Diagnosis of Sexual Dysfunction - A Claims Database Cohort Analysis

Abstract Introduction Vulvar lichen sclerosus (VLS) often presents with intense pruritus and recurrent painful lesions, negatively impacting quality of life and, potentially, the ability to engage in sexual penetration. VLS treatment ranges from topical steroids to systemic antipruritic agents. No studies have yet characterized how concurrent sexual dysfunction impacts VLS treatment. Objective The objective of our study is to assess prescribing patterns in women with VLS with sexual dysfunction compared to women without a diagnosis of sexual dysfunction. Methods A US claims database network (TriNetX Research Network) was queried from 2009 to 2022. We compared women aged ≥18 with VLS (ICD-10: N90.4) and sexual dysfunction (R37 or F52) with women aged ≥18 with VLS but no diagnosis of sexual dysfunction. Outcomes of interest were prescription of opioids (N02A), topical steroids (DE200), vaginal estrogen (GU500), prednisone (8640) or intramuscular (IM) triamcinolone (10759), benzodiazepines (CN302), antifungals (D01) or oral fluconazole (4450), or antipruritic agents including hydroxyzine (5553), amitriptyline (704), gabapentin (25480), or citalopram (2556) within 6 months of the initial diagnosis of VLS. Propensity-matching between the cohorts age, ethnicity, race, type 1 diabetes (E10), vitiligo (L80), autoimmune thyroiditis (E06.3), alopecia areata (L63), pernicious anemia (D51.0), overweight and obesity (E66), type 2 diabetes (E11), hyperlipidemia (E78), essential hypertension (I10), and alcohol abuse (F10.10) was conducted. Results We identified 32,241 women with VLS that did not have concurrent sexual dysfunction (average age 59.5) and 416 women with VLS that had concurrent sexual dysfunction (average age 58.9). After propensity-score matching, the average age of women in each cohort was between 58 and 59 years old (Table 1). Women diagnosed with concurrent sexual dysfunction (n=416) were significantly more likely to receive vaginal estrogen prescriptions (Risk Ratio (RR) 2.00, 95% Confidence Interval (CI) 1.47-2.73), benzodiazepines (RR 1.39, 95% CI 1.00-1.942), and topical anti-inflammatory agents (RR 1.26, 95% CI 1.08-1.47) compared to an equivalent number of propensity-score matched women without a diagnosis of concurrent sexual dysfunction (Table 2). Prescription rates for systemic VLS treatments including oral prednisone or intramuscular triamcinolone (RR 1.06, 95% CI 0.56-1.98), opioids (RR 0.96, 95% CI 0.66-1.40), antifungals (RR 1.35, 95% CI 0.97-1.89), antipruritic agents hydroxyzine, amitriptyline, gabapentin, or citalopram (RR 1.35, 95% CI 0.94-1.93) did not significantly differ between women with or without concurrent sexual dysfunction. Conclusions Our results demonstrate that VLS treatment patterns differ with concurrent sexual dysfunction, with vaginal estrogen, benzodiazepines, and topical anti-inflammatory agents prescribed at higher rates to those with concurrent sexual dysfunction. Rates of prescriptions of opioids, antifungals, oral prednisone, intramuscular triamcinolone, hydroxyzine, amitriptyline, gabapentin, and citalopram were similar between the groups. Given the pruritic vulvar lesions associated with VLS, the low percentage (1.29%) of women with VLS and concurrent sexual dysfunction highlights a potential pattern of underdiagnosis; further study is required to investigate the relationship between VLS and sexual dysfunction. Disclosure No

A Case of Autoimmune Metaplastic Atrophic Gastritis with Concurrent Pernicious Anemia and Coombs-Negative Hemolysis

Pernicious anemia is an autoimmune disease characterized by atrophic gastritis and vitamin B12 deficiency. Concurrent hemolytic anemia has been described, however its prevalence and mechanism are not well understood. Herein, we present the case of a 40-year-old female who presented with abdominal pain, fatigue, and a 50-lb weight loss over four months. She was found to have macrocytic anemia, leukopenia, moderate neutropenia, and severe vitamin B12 deficiency. Further laboratory testing (indirect hyperbilirubinemia, low haptoglobin, increased lactate dehydrogenase, low reticulocyte index) implied the presence of intravascular hemolysis with a poor bone marrow response. Peripheral blood smear showed hypersegmented neutrophils consistent with megaloblastic anemia and schistocytes suggestive of hemolysis. Notably, the direct Coombs test was negative.The patient’s serum was positive for anti-intrinsic factor and anti-parietal cell antibodies. Esophagogastroduodenoscopy revealed H. Pylori-negative, metaplastic atrophic gastritis with no evidence of malignancy. Thus, a diagnosis of pernicious anemia was confirmed in addition to hemolytic anemia. She was treated with intramuscular cyanocobalamin, resulting in improvement of symptoms, cytopenias, and hemolytic markers. Hemolysis is a rare complication of vitamin B12 deficiency, and multifactorial anemia must always be considered.

Incidence and Predictors of Gastric Neoplastic Lesions in Corpus-Restricted Atrophic Gastritis: A Single-Center Cohort Study.

Corpus-restricted atrophic gastritis is a chronic inflammatory disorder leading to possible development of type 1 neuroendocrine tumors (T1gNET), intraepithelial neoplasia (IEN), and gastric cancer (GC). We aimed to assess occurrence and predictors of gastric neoplastic lesions in patients with corpus-restricted atrophic gastritis at long-term follow-up. A prospective single-center cohort of patients with corpus-restricted atrophic gastritis adhering to endoscopic-histological surveillance was considered. Follow-up gastroscopies were scheduled according to the management of epithelial precancerous conditions and lesions of the stomach guidelines. In case of new/worsening of known symptoms, gastroscopy was anticipated. Cox regression analyses and Kaplan-Meier survival curves were obtained. Two hundred seventy-five patients with corpus-restricted atrophic gastritis (72.0% female, median age 61 [23-84] years) were included. At a median follow-up of 5 (1-17) years, the annual incidence rate person-year was 0.5%, 0.6%, 2.8%, and 3.9% for GC/high-grade IEN, low-grade IEN, T1gNET, and all gastric neoplastic lesions, respectively. All patients showed at baseline operative link for gastritis assessment (OLGA)-2, except 2 low-grade (LG) IEN patients and 1 T1gNET patient with OLGA-1. Age older than 60 years (hazard ratio [HR] 4.7), intestinal metaplasia without pseudopyloric metaplasia (HR 4.3), and pernicious anemia (HR 4.3) were associated with higher risk for GC/HG-IEN or LG-IEN development and shorter mean survival time for progression (13.4, 13.2, and 11.1, respectively, vs 14.7 years, P = 0.01). Pernicious anemia was an independent risk factor for T1gNET (HR 2.2) and associated with a shorter mean survival time for progression (11.7 vs 13.6 years, P = 0.04) as well as severe corpus atrophy (12.8 vs 13.6 years, P = 0.03). Patients with corpus-restricted atrophic gastritis are at increased risk for GC and T1gNET despite low-risk OLGA scores, and those aged older than 60 years with corpus intestinal metaplasia or pernicious anemia seem to display a high-risk scenario.

Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK

A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. Research Foundation Flanders.

Status of Vitamin B12, Zinc, Copper, Selenium, Manganese, Molybdenum and Cobalt in Severe Acute Malnutrition.

To define the vitamin B12 levels and other micronutrients status in severe acute malnutrition (SAM) children. This was a prospective hospital based cross-sectional study. Children with severe acute malnutrition as per WHO criteria. (i) Pernicious anemia (ii) Autoimmune gastritis (iii) SAM children on exclusive vitamin B12 supplementation. All enrolled children underwent a detailed clinical history, general physical examination with more emphasis on clinical features of vitamin B12 and other micronutrients deficiencies. Three ml of venous blood was collected to estimate vitamin B12 and other micronutrients. Primary outcome was percentage of deficiency of serum vitamin B12, zinc, copper, selenium, manganese, molybdenum and cobalt in SAM children. Fifty children were included in the study. The mean age of children was 15.60±12.90 mo with male to female ratio 0.85:1. The common clinical presentation in order of frequency were upper respiratory infection (URI) symptoms 35 (70%), hepatomegaly 24 (48%), Hyperpigmentation17 (34%), angular cheilitis 14 (28%), tremors 11 (22%), edema 07 (14%), and hypotonia 05 (10%). Anemia was found in 44 (88%) children. Prevalence of vitamin B12 deficiency was 34%. Other micronutrient deficiencies observed were cobalt 24 (100%), copper 05 (12%), zinc 04 (9.5%), and molybdenum 03 (12.5%). No statistical significance was found between clinical symptoms and levels of vitamin B12 with different age and sex. Prevalence of low vitamin B12 and cobalt were more common than other micronutrients.

A case of synchronous association of stomach neuroendocrine tumor and pernicious anemia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)