Carotid Near-Occlusion: Surgical or Conservative Management? Retrospective Multicenter Study.

BACKGROUND: Carotid near-occlusion (CNO) represents an anatomical-functional condition characterized by severe (more than 90%) internal carotid artery stenosis which can lead to a distal lumen diameter greater or less than 2 mm. CNO can be divided into a less severe subgroup (without lumen full collapse: diameter >2 mm) and a more severe subgroup (with lumen full collapse: diameter <2 mm). The decision for revascularization is still highly debated in Literature. The aim of the present multicenter retrospective study is to analyze the incidence of perioperative (30 days) and follow-up complications in 2 groups of patients with or without distal internal carotid lumen full collapse. METHODS: Between January 2011 and March 2023, in 5 Vascular Surgery Units, 67 patients (49 male, 73% and 18 females, 27%) with CNO underwent carotid endarterectomy: 28 (41.7%) with lumen diameter <2 mm and 39 (58.3%) with diameter >2 mm. 19 patients were symptomatic and 48 asymptomatic. The outcomes considered for comparative analysis were: perioperative neurological and cardiac complications, carotid restenosis or occlusion at follow-up. Both groups were homogeneous in terms of risk factors, morphological features and pharmacological treatments. RESULTS: In the group with lumen <2 mm, 3 perioperative major events (10.7%) occurred (1 ischemic stroke, 1 hemorrhagic stroke, 1 myocardial infarction) and 2 (7.1%) at follow-up (average 11 ± 14.5 months; 1 asymptomatic carotid occlusion, 1 hemodynamic restenosis treated with stenting). No event was recorded in the group with lumen >2 mm. CONCLUSIONS: According to our results CNO patients show different complication risk according to the presence or not of distal lumen collapse. The later seems to play a significant role in perioperative and follow-up complication rate. These results therefore support a surgical treatment only in patients with CNO without lumen full collapse.

Gastric Th17 Cells Specific for H+/K+-ATPase and Serum IL-17 Signature in Gastric Autoimmunity.

Human gastric autoimmunity [autoimmune gastritis (AIG)] is characterized by inflammation of the gastric mucosa and parietal cell loss. The gastric parietal cell proton pump H+/K+-adenosine triphosphatase (H+/K+-ATPase) is the major autoantigen in AIG. Our work aimed to investigate the gastric H+/K+-ATPase-specific T helper 17 (Th17) responses in AIG and serum interleukin (IL)-17 cytokine subfamily in AIG patients, in healthy subjects [healthy controls (HCs)], and in patients with iron deficiency anemia (IDA) without AIG. We analyzed the activation of gastric lamina propria mononuclear cells (LPMCs) by H+/K+-ATPase and the IL-17A and IL-17F cytokine production in eight patients with AIG and four HCs. Furthermore, we compared serum levels of IL-17A, IL-17F, IL-21, IL-17E, IL-22, and IL-23 in 43 AIG patients, in 47 HCs, and in 20 IDA patients without AIG. Gastric LPMCs from all AIG patients, but not those from HCs, were activated by H+/K+-ATPase and were able to proliferate and produce high levels of IL-17A and IL-17F. AIG patients have significantly higher serum IL-17A, IL-17F, IL-21, and IL-17E (393.3 ± 410.02 pg/ml, 394.0 ± 378.03 pg/ml, 300.46 ± 303.45 pg/ml, 34.92 ± 32.56 pg/ml, respectively) than those in HCs (222.99 ± 361.24 pg/ml, 217.49 ± 312.1 pg/ml, 147.43 ± 259.17 pg/ml, 8.69 ± 8.98 pg/ml, respectively) and those in IDA patients without AIG (58.06 ± 107.49 pg/ml, 74.26 ± 178.50 pg/ml, 96.86 ± 177.46 pg/ml, 10.64 ± 17.70 pg/ml, respectively). Altogether, our results indicate that IL-17A and IL-17F are produced in vivo in the stomach of AIG patients following activation with H+/K+-ATPase and that serum IL-17A, IL-17F, IL-21, and IL-17E levels are significantly elevated in AIG patients but not in patients without AIG. These data suggest a Th17 signature in AIG and that IL-17A, IL-17F, IL-21, and IL-17E may represent a relevant tool for AIG management.

A non-invasive combined strategy to improve the appropriateness of upper gastrointestinal endoscopy.

Background and aim Increasing the appropriateness of upper gastrointestinal endoscopy (UGIE) improves the quality of care while containing costs. The aim of this study was to improve the appropriateness of UGIE through a process involving evaluation of prescriptions and the use of a non-invasive alternative. Materials and methods A senior endoscopist evaluated the appropriateness of all outpatient referrals for UGIE and established the proper timing. Referrals were either accepted and programmed, canceled, or substituted by a non-invasive evaluation of gastric function, determining serum levels of gastrin-17 (G17), Pepsinogen I (PGI) and II (PGII), and antibodies against Helicobacter pylori. Results A total of 5102 requests for UGIE examinations were evaluated; 540 (10.4%) were inappropriate and had been prescribed for: gastroesophageal reflux disease (n=307), surveillance with erroneous timing (n=113), dyspepsia (n=66), other indications (n=20), and absence of written indication (n=34). Gastric function was evaluated in 282/540 patients; findings included normal values in 94 patients without proton-pump inhibitor therapy (PPI) and in 48 on PPI, active H pylori infection in 56, previous H pylori infection in 30, GERD in n=50, and atrophic gastritis in n=4. UGIE was performed in the latter 4 cases.  Within 2 years (range 1-22 months) of the initial refusal, 105/504 patients underwent UGIE, with normal endoscopic findings in 71/105 (67.5%), and with no cases of cancer. Conclusions This strategy, based on a strict control of prescriptions, is effective to increase the appropriateness while containing public health costs. The use of gastric function testing improves patient selection for UGIE endoscopy.

Low Levels of Gastrin 17 are Related with Endoscopic Findings of Esophagitis and Typical Symptoms of GERD.

BACKGROUND AND AIMS: In clinical practice, most patients with symptoms suggestive of gastroesophageal reflux disease (GERD) undergo esophago-gastro-duodenoscopy (EGD), despite its low sensitivity in detecting reflux stigmata. Gastrin 17 (G-17) has been proposed to be related with GERD, due to the negative feedback between acid secretion and this hormone. We assessed the clinical usefulness of fasting G-17 serum determination for a non-invasive diagnosis of GERD in patients with typical symptoms. METHODS: We consecutively enrolled patients complaining of typical GERD symptoms in two different settings: a single referral center and a primary care setting. Control groups consisted of dyspeptic patients. All subjects underwent assessment of serum levels of G-17 and EGD. RESULTS: At the academic hospital, 100 GERD patients (n=89 with erosive esophagitis and 11 with Barrett's esophagus) had statistically significant low levels of G-17 as compared with 184 dyspeptic patients (1.7±1.2 pg/L vs 8.9±5.7 pg/L p<0.0001). Similarly, in the primary care setting, 163 GERD patients had statistically significant low levels of G-17 as compared with 132 dyspeptic patients (0.5±0.2 pg/L vs. 4.0±2.6 pg/L, p<0.0001). Moreover, in the primary care setting, no statistically significant differences were found for G-17 levels between patients with erosive and non-erosive reflux pattern (0.4±0.2 vs 0.7±0.3; p=0.08). In primary care, the accuracy of G-17 less than 1 pg/L to diagnose non-invasively GERD was 94.3%. CONCLUSIONS: Low levels of G-17 were detected in patients with erosive esophagitis and Barrett's esophagus in a referral center and in patients with typical GERD symptoms in a sample of patients from a primary care setting.

Influence of earthquakes on the occurrence of aortic aneurysm ruptures.

BACKGROUND: Catastrophic events have been correlated to increased incidence of cardio-vascular events, but no correlation between RAA and seismic activities have ever been investigated. METHODS: Hospital admissions related to RAA between January 2014 and December 2016 were retrospectively assessed in nine vascular centers of central Italy and correlated with date-matched seismic events. Correlation between RAA presentation and seismic event was first evaluated by Linear Regression analysis. Incidence of RAA events, mortality rate, and type of intervention were analyzed during seismic days (SD) and compared to outcomes during non-seismic days (nSD). RESULTS: A total of 376 patients were admitted with a diagnosis of RAA, and a total of 783 seismic events were reviewed. Twenty patients died before intervention (untreated). Open surgery was performed in 72.8%, endovascular treatment in 27.2%. General mortality at 30 days was 26.6% (30.5% for open surgery; 21.6% for endovascular treatment; P=0.24). Linear regression analysis between RAA and seismic periods revealed a significant correlation (slope=0.11±0.04, equation: y = 0.1143 x + 3.034, P=0.02). Incidence of RAA was 0.34 event per day during the entire period, 0.32 during nSD and 0.44 during SD (P=0.006). During seismic days, patients with RAA were older (80.5 years during SD vs. 77 years during nSD, P=0.12), were in poorer general condition at admission and remained untreated more frequently (8% SD vs. 4.7% nSD, P=0.3), and had a higher mortality rate at 30 days (46.2% SD vs. 27.2% nSD, P=0.012). CONCLUSIONS: During seismic days, the incidence of RAA is higher in comparison to non-seismic days. Patients with rupture during seismic days have a higher risk of death.

Autoimmunity and Gastric Cancer.

Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms.

The ANA-reflex test as a model for improving clinical appropriateness in autoimmune diagnostics.

Reflex tests are widely used in clinical laboratories, for example, to diagnose thyroid disorders or in the follow-up of prostate cancer. Reflex tests for antinuclear antibodies (ANA) have recently gained attention as a way to improve appropriateness in the immunological diagnosis of autoimmune rheumatic diseases and avoid waste of resources. However, the ANA-reflex test is not as simple as other consolidated reflex tests (the TSH-reflex tests or the PSA-reflex tests) because of the intrinsic complexity of the ANA test performed by the indirect immunofluorescence method on cellular substrates. The wide heterogeneity of the ANA patterns, which need correct interpretation, and the subsequent choice of the most appropriate confirmatory test (ANA subserology), which depend on the pattern feature and on clinical information, hinder any informatics automation, and require the pathologist's intervention. In this review, the Study Group on Autoimmune Diseases of the Italian Society of Clinical Pathology and Laboratory Medicine provides some indications on the configuration of the ANA-reflex test, using two different approaches depending on whether clinical information is available or not. We further give some suggestions on how to report results of the ANA-reflex test.

Diagnosis and classification of pernicious anemia.

Pernicious anemia (PA) is a complex disorder consisting of hematological, gastric and immunological alterations. Diagnosis of PA relies on histologically proven atrophic body gastritis, peripheral blood examination showing megaloblastic anemia with hypersegmented neutrophils, cobalamin deficiency and antibodies to intrinsic factor and to gastric parietal cells. Anti-parietal cell antibodies are found in 90% of patients with PA, but have low specificity and are seen in atrophic gastritis without megaloblastic anemia as well as in various autoimmune disorders. Anti-intrinsic factor antibodies are less sensitive, being found in only 60% of patients with PA, but are considered highly specific for PA. The incidence of PA increases with age and is rare in persons younger than 30 years of age. The highest prevalence is seen in Northern Europeans, especially those in the United Kingdom and Scandinavia, although PA has been reported in virtually every ethnic group. Because of the complexity of the diagnosis, PA prevalence is probably underestimated and no reliable data are available on the risk of gastric cancer as the end-stage evolution of atrophic gastritis in these patients.

Clinical usefulness of the serological gastric biopsy for the diagnosis of chronic autoimmune gastritis.

AIM: To assess the predictive value for chronic autoimmune gastritis (AIG) of the combined assay of anti-parietal-cell antibodies (PCA), anti-intrinsic-factor antibodies (IFA), anti-Helicobacter pylori (Hp) antibodies, and measurement of blood gastrin. METHODS: We studied 181 consecutive patients with anemia, due to iron deficiency resistant to oral replacement therapy or to vitamin B12 deficiency. RESULTS: 83 patients (45.8%) tested positive for PCA and underwent gastroscopy with multiple gastric biopsies. On the basis of the histological diagnosis, PCA-positive patients were divided into 4 groups: (1) 30 patients with chronic atrophic gastritis; they had high concentrations of PCA and gastrin and no detectable IFA; (2) 14 subjects with metaplastic gastric atrophy; they had high PCA, IFA, and gastrin; (3) 18 patients with nonspecific lymphocytic inflammation with increased PCA, normal gastrin levels, and absence of IFA; (4) 21 patients with multifocal atrophic gastritis with "borderline" PCA, normal gastrin, absence of IFA and presence of anti-Hp in 100% of the cases. CONCLUSIONS: The assay of four serological markers proved particularly effective in the diagnostic classification of gastritis and highly correlated with the histological profile. As such, this laboratory diagnostic profile may be considered an authentic "serological biopsy."

Autoantibodies to parietal cells as predictors of atrophic body gastritis: a five-year prospective study in patients with autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITD) can be associated with autoimmune gastritis (AIG), but the frequency of this association is poorly characterized. We performed a prospective study to: a) characterize the frequency of parietal cell (PCA) and intrinsic factor (IFA) autoantibodies in AITD patients; b) evaluate the development of histologically- and functionally-proven AIG after five years and to assess the predictive role of PCA for AIG at baseline; and c) analyze the trend of PCA levels in the course of the disease. We studied 208 consecutive adult patients affected by AITD (166 Hashimoto's thyroiditis, 42 Graves' disease). PCA, IFA and plasma gastrin levels were measured with ELISA methods at baseline and after 5years. At baseline, 51/208 (24.5%) AITD patients were positive for PCA and 10/208 (4.8%) for IFA. 25 out of 54 PCA/IFA-positive AITD patients (all without gastric or haematologic symptoms) agreed to participate in the follow-up study. After 5years, 6 (24%) of these 25 patients showed a histologically proven AIG, with lymphocytic infiltration and/or atrophy of body gastric mucosa. The trend analysis of PCA concentration showed that autoantibody levels rise progressively over time, reach a peak level and then fall, according to the progressive destruction of gastric mucosa and to the disappearance of the target autoantigen (proton pump). The presence of PCA predicts the development of autoimmune gastritis in AITD patients. Antibody levels measured with a sensitive quantitative immunometric method are useful for early diagnosis and early treatment of the disease.

Antibodies to the lens and cornea in anti-DFS70-positive subjects.

Autoantibodies against DFS70 (dense fine speckles 70) antigen have recently been identified among antinuclear antibodies (ANA) in patients with various inflammatory diseases and in patients with different types of cancer. These antibodies are recognized using indirect immunofluorescence (IIF) on HEp-2 cells, by a fine speckled nuclear staining in interphase HEp-2 cells and a positive reaction in the chromosome region of mitotic cells. Given that the DFS70 protein is also known as the lens epithelium-derived growth factor, this study was performed with two objectives: (a) to assess the prevalence of these antibodies in patients sent for ANA testing and in 334 patients with different types of neoplasia and (b) to determine whether the lens tissue was a suitable substrate for the detection of antibodies specific to lens proteins. During routine workup for ANA detection by the IIF method, we found 172 DFS70-positive sera among 21,516 consecutive samples (prevalence, 0.8%). In the group of patients with neoplastic disease, 6 of 334 (1.8%) were anti-DFS70-positive. DFS70-positive sera were then assayed by the IIF method on cryostatic sections of mouse eye at a dilution of 1:40 with an anti-human IgG conjugate. Among the 172 DFS70-positive samples detected by the ANA screening, 32 (19%) were strongly reactive against the reticular fibers of the lens; 8 (5%) were positive only to the corneal epithelium (nuclear negative); 5 (3%) were positive both for the cornea and the lens fibers; 13 (7%) stained only the nuclei of lens and cornea cells, and 4 (2%) were positive against the ciliary muscle. Among the patients with neoplastic diseases, only one with lung cancer reacted weakly with the reticular fibers of the lens. Sera from 20 healthy blood donors were negative. In this preliminary study, we have shown that the prevalence of anti-DFS70 antibodies is much lower than previously reported, both in patients screened for ANA and in patients with cancer. We have also seen that some DFS70-positive sera have antibodies that recognize antigens of the lens. Further studies are needed to investigate the fine specificity and the possible significance of these new autoantibodies.