Correction: Gallbladder polyps: Correlation of size and clinicopathologic characteristics based on updated definitions.

[This corrects the article DOI: 10.1371/journal.pone.0237979.].

Integrating Augmented Reality in Spine Surgery: Redefining Precision with New Technologies.

INTRODUCTION: The integration of augmented reality (AR) in spine surgery marks a significant advancement, enhancing surgical precision and patient outcomes. AR provides immersive, three-dimensional visualizations of anatomical structures, facilitating meticulous planning and execution of spine surgeries. This technology not only improves spatial understanding and real-time navigation during procedures but also aims to reduce surgical invasiveness and operative times. Despite its potential, challenges such as model accuracy, user interface design, and the learning curve for new technology must be addressed. AR's application extends beyond the operating room, offering valuable tools for medical education and improving patient communication and satisfaction. MATERIAL AND METHODS: A literature review was conducted by searching PubMed and Scopus databases using keywords related to augmented reality in spine surgery, covering publications from January 2020 to January 2024. RESULTS: In total, 319 articles were identified through the initial search of the databases. After screening titles and abstracts, 11 articles in total were included in the qualitative synthesis. CONCLUSION: Augmented reality (AR) is becoming a transformative force in spine surgery, enhancing precision, education, and outcomes despite hurdles like technical limitations and integration challenges. AR's immersive visualizations and educational innovations, coupled with its potential synergy with AI and machine learning, indicate a bright future for surgical care. Despite the existing obstacles, AR's impact on improving surgical accuracy and safety marks a significant leap forward in patient treatment and care.

TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern.

A fusion between tubulin polymerization-promoting protein (TPPP), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (BRD9), TPPP-BRD9 fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the TPPP-BRD9 fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors' database. Among the 16 TPPP-BRD9 fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p < 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a "syringoid" appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, TPPP-BRD9 fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the TPPP-BRD9 fusion-positive pattern of GBC.

LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder Cancer Cells.

Long non-coding RNAs (lncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including cancer. Long intergenic non-protein-coding RNA 662 (LINC00662) has been reported to be involved in different cancers, including colorectal, prostate, and breast cancer. However, its role in gallbladder cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial-mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC.

Adenomyomas of the Gallbladder: An Analysis of Frequency, Clinicopathologic Associations, and Relationship to Carcinoma of a Malformative Lesion.

CONTEXT.­: The nature and associations of gallbladder (GB) "adenomyoma" (AM) remain controversial. Some studies have attributed up to 26% of GB carcinoma to AMs. OBJECTIVE.­: To examine the true frequency, clinicopathologic characteristics, and neoplastic changes in GB AM. DESIGN.­: Cholecystectomy cohorts analyzed were 1953 consecutive cases, prospectively with specific attention to AM; 2347 consecutive archival cases; 203 totally embedded GBs; 207 GBs with carcinoma; and archival search of institutions for all cases diagnosed as AM. RESULTS.­: Frequency of AM was 9.3% (19 of 203) in totally submitted cases but 3.3% (77 of 2347) in routinely sampled archival tissue. A total of 283 AMs were identified, with a female to male ratio = 1.9 (177:94) and mean size = 1.3 cm (range, 0.3-5.9). Most (96%, 203 of 210) were fundic, with formed nodular trabeculated submucosal thickening, and were difficult to appreciate from the mucosal surface. Four of 257 were multifocal (1.6%), and 3 of 257 (1.2%) were extensive ("adenomyomatosis"). Dilated glands (up to 14 mm), often radially converging to a point in the mucosa, were typical. Muscle was often minimal, confined to the upper segment. Nine of 225 (4%) revealed features of a duplication. No specific associations with inflammation, cholesterolosis, intestinal metaplasia, or thickening of the uninvolved GB wall were identified. Neoplastic change arising in AM was seen in 9.9% (28 of 283). Sixteen of 283 (5.6%) had mural intracholecystic neoplasm; 7 of 283 (2.5%) had flat-type high-grade dysplasia/carcinoma in situ. Thirteen of 283 cases had both AM and invasive carcinoma (4.6%), but in only 5 of 283 (1.8%), carcinoma arose from AM (invasion was confined to AM, and dysplasia was predominantly in AM). CONCLUSIONS.­: AMs have all the features of a malformative developmental lesion, and may not show a significant muscle component (ie, the name "adeno-myoma" is partly a misnomer). While most are innocuous, some pathologies may arise in AMs, including intracholecystic neoplasms, flat-type high-grade dysplasia or carcinoma in situ, and invasive carcinoma (1.8%, 5 of 283). It is recommended that gross examination of GBs include serial slicing of the fundus for AM detection and total submission if one is found.

Advances towards the use of gastrointestinal tumor patient-derived organoids as a therapeutic decision-making tool.

In December 2022 the US Food and Drug Administration (FDA) removed the requirement that drugs in development must undergo animal testing before clinical evaluation, a declaration that now demands the establishment and verification of ex vivo preclinical models that closely represent tumor complexity and that can predict therapeutic response. Fortunately, the emergence of patient-derived organoid (PDOs) culture has enabled the ex vivo mimicking of the pathophysiology of human tumors with the reassembly of tissue-specific features. These features include histopathological variability, molecular expression profiles, genetic and cellular heterogeneity of parental tissue, and furthermore growing evidence suggests the ability to predict patient therapeutic response. Concentrating on the highly lethal and heterogeneous gastrointestinal (GI) tumors, herein we present the state-of-the-art and the current methodology of PDOs. We highlight the potential additions, improvements and testing required to allow the ex vivo of study the tumor microenvironment, as well as offering commentary on the predictive value of clinical response to treatments such as chemotherapy and immunotherapy.

Targeting hypoxia-inducible factor-1 alpha suppresses Helicobacter pylori-induced gastric injury via attenuation of both cag-mediated microbial virulence and proinflammatory host responses.

Helicobacter pylori-induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1α) is a key transcriptional regulator of immunity and carcinogenesis. To examine the role of this mediator within the context of H. pylori-induced injury, we first demonstrated that HIF-1α levels were significantly increased in parallel with the severity of gastric lesions in humans. In interventional studies targeting HIF-1α, H. pylori-infected mice were treated ± dimethyloxalylglycine (DMOG), a prolyl hydroxylase inhibitor that stabilizes HIF-1α. H. pylori significantly increased proinflammatory chemokines/cytokines and inflammation in vehicle-treated mice; however, this was significantly attenuated in DMOG-treated mice. DMOG treatment also significantly decreased function of the H. pylori type IV secretion system (T4SS) in vivo and significantly reduced T4SS-mediated NF-κB activation and IL-8 induction in vitro. These results suggest that prolyl hydroxylase inhibition protects against H. pylori-mediated pathologic responses, and is mediated, in part, via attenuation of H. pylori cag-mediated virulence and suppression of host proinflammatory responses.

ThyroidPrint®: clinical utility for indeterminate thyroid cytology.

Molecular testing contributes to improving the diagnosis of indeterminate thyroid nodules (ITNs). ThyroidPrint® is a ten-gene classifier aimed to rule out malignancy in ITN. Post-validation studies are necessary to determine the real-world clinical benefit of ThyroidPrint® in patients with ITN. A single-center, prospective, noninterventional clinical utility study was performed, analyzing the impact of ThyroidPrint® in the physicians' clinical decisions for ITN. Demographics, nodule characteristics, benign call rates (BCRs), and surgical outcomes were measured. Histopathological data were collected from surgical biopsies of resected nodules. Of 1272 fine-needle aspirations, 109 (8.6%) were Bethesda III and 135 (10.6%) were Bethesda IV. Molecular testing was performed in 155 of 244 ITN (63.5%), of which 104 were classified as benign (BCR of 67.1%). After a median follow-up of 15 months, 103 of 104 (99.0%) patients with a benign ThyroidPrint® remained under surveillance and one patient underwent surgery which was a follicular adenoma. Surgery was performed in all 51 patients with a suspicious for malignancy as per ThyroidPrint® result and in 56 patients who did not undergo testing, with a rate of malignancy of 70.6% and 32.1%, respectively. A higher BCR was observed in follicular lesion of undetermined significance (87%) compared to atypia of undetermined significance (58%) (P < 0.05). False-positive cases included four benign follicular nodules and six follicular and four oncocytic adenomas. Our results show that, physicians chose active surveillance instead of diagnostic surgery in all patients with a benign ThyroidPrint® result, reducing the need for diagnostic surgery in 67% of patients with preoperative diagnosis of ITN.

Implementation of the updated Sydney system biopsy protocol improves the diagnostic yield of gastric preneoplastic conditions: Results from a real-world study.

BACKGROUND: The updated Sydney system biopsy protocol (USSBP) standardizes the sampling of gastric biopsies for the detection of preneoplastic conditions (e.g., gastric intestinal metaplasia [GIM]), but the real-world diagnostic yield is not well-described. AIM: To determine whether regular application of USSBP is associated with higher detection of chronic atrophic gastritis (CAG), GIM and autoimmune gastritis (AIG). METHODS: We performed a real-world retrospective study at an academic urban tertiary hospital in Chile. We manually reviewed medical records from consecutive patients undergoing esophagogastroduodenoscopy (EGD) from January to December 2017. Seven endoscopists who performed EGDs were categorized into two groups (USSBP 'regular' and USSBP 'infrequent') based on USSBP adherence, using minimum 20% adherence as the prespecified threshold. Multivariable logistic regression models were used to estimate the odds ratios (aOR) and 95% confidence intervals (CI) for the association between endoscopist groups and the likelihood of diagnosing CAG, GIM or AIG. RESULTS: 1206 patients were included in the study (mean age: 58.5; 65.3% female). The USSBP regular group demonstrated a higher likelihood of detecting CAG (20% vs. 5.3%; aOR 4.03, 95%CI: 2.69-6.03), GIM (12.2% vs. 3.4%; aOR 3.91, 95%CI: 2.39-6.42) and AIG (2.9% vs. 0.8%; aOR 6.52, 95%CI: 1.87-22.74) compared to infrequent group. Detection of advanced-stage CAG (Operative Link for Gastritis Assessment stage III/IV) was significantly higher in the USSBP regular vs. infrequent group (aOR 5.84, 95%CI: 2.23-15.31). CONCLUSIONS: Routine adherence to USSBP increases the detection rates of preneoplastic conditions, including CAG, GIM and AIG. Standardized implementation of USSBP should be considered in high gastric cancer risk populations.

Eosinophilic Cholecystitis and Eosinophils in Gallbladder Injuries: A Clinicopathological Analysis of 1050 Cholecystectomies.

"Eosinophilic cholecystitis" has been an elusive concept. Around 1050 consecutive cholecystectomies with chronic (CC, n = 895), subacute (SAC, n = 100), and acute cholecystitis (AC, n = 55) were reviewed for eosinophilic infiltration. Eosinophilic hot spots (>40 eosinophils/HPF) were seen in 63% of SAC and 35% of AC (vs. 6% of CC, p < 0.001). Eosinophils were mostly encountered in areas of wall thickening, revealing edema with early collagenization and young tissue-culture-type fibroblasts. However, in ten chronic cholecystitis patients (<1%), prominent eosinophilia with eosinophil-rich foci (>100 eosinophils/HPF) was noted. These ten cases, classified as "eosinophilic cholecystitis", were analyzed further: The patients were relatively young (mean age = 43 years), with a 9:1 female:male ratio. None had blood eosinophilia/eosinophilia syndromes. Although one had ulcerative colitis, others did not have any autoimmune diseases. The mean gallbladder wall thickness was 3.5 mm (vs. 4.2 mm in ordinary CC). In conclusion, eosinophils are a part of especially subacute injuries in the gallbladder. They are typically condensed in the areas of healing and appear to signify a distinctive state of injury in which there are erosions leading to slow/sustained exposure of the mural tissues to the bile contents that induce chemical injury/recruit eosinophils. Eosinophilic cholecystitis is a very uncommon occurrence and appears to be an exaggerated response in allergic patients who are prone to recruit eosinophils in reaction to injury.

Epigenetic reprogramming of cell cycle genes by ACK1 promotes breast cancer resistance to CDK4/6 inhibitor.

Hormone receptor-positive, HER2-negative advanced breast cancers exhibit high sensitivity to CDK4/6 inhibitors such as palbociclib. However, most patients inevitably develop resistance, thus identification of new actionable therapeutic targets to overcome the recurrent disease is an urgent need. Immunohistochemical studies of tissue microarray revealed increased activation of non-receptor tyrosine kinase, ACK1 (also known as TNK2) in most of the breast cancer subtypes, independent of their hormone receptor status. Chromatin immunoprecipitation studies demonstrated that the nuclear target of activated ACK1, pY88-H4 epigenetic marks, were deposited at cell cycle genes, CCNB1, CCNB2 and CDC20, which in turn initiated their efficient transcription. Pharmacological inhibition of ACK1 using its inhibitor, (R)-9b dampened CCNB1, CCNB2 and CDC20 expression, caused G2/M arrest, culminating in regression of palbociclib-resistant breast tumor growth. Further, (R)-9b suppressed expression of CXCR4 receptor, which resulted in significant impairment of metastasis of breast cancer cells to lung. Overall, our pre-clinical data identifies activated ACK1 as an oncogene that epigenetically controls the cell cycle genes governing the G2/M transition in breast cancer cells. ACK1 inhibitor, (R)-9b could be a novel therapeutic option for the breast cancer patients that have developed resistance to CDK4/6 inhibitors.

Long Non-Coding RNAs (lncRNAs) as Regulators of the PI3K/AKT/mTOR Pathway in Gastric Carcinoma.

Gastric cancer (GC) represents ~10% of the global cancer-related deaths, increasingly affecting the younger population in active stages of life. The high mortality of GC is due to late diagnosis, the presence of metastasis and drug resistance development. Additionally, current clinical markers do not guide the patient management adequately, thereby new and more reliable biomarkers and therapeutic targets are still needed for this disease. RNA-seq technology has allowed the discovery of new types of RNA transcripts including long non-coding RNAs (lncRNAs), which are able to regulate the gene/protein expression of many signaling pathways (e.g., the PI3K/AKT/mTOR pathway) in cancer cells by diverse molecular mechanisms. In addition, these lncRNAs might also be proposed as promising diagnostic or prognostic biomarkers or as potential therapeutic targets in GC. This review describes important topics about some lncRNAs that have been described as regulators of the PI3K/AKT/mTOR signaling pathway, and hence, their potential oncogenic role in the development of this malignancy.

Glioblastoma Microenvironment and Invasiveness: New Insights and Therapeutic Targets.

Glioblastoma (GBM) is the most common and malignant primary brain cancer in adults. Without treatment the mean patient survival is approximately 6 months, which can be extended to 15 months with the use of multimodal therapies. The low effectiveness of GBM therapies is mainly due to the tumor infiltration into the healthy brain tissue, which depends on GBM cells' interaction with the tumor microenvironment (TME). The interaction of GBM cells with the TME involves cellular components such as stem-like cells, glia, endothelial cells, and non-cellular components such as the extracellular matrix, enhanced hypoxia, and soluble factors such as adenosine, which promote GBM's invasiveness. However, here we highlight the role of 3D patient-derived glioblastoma organoids cultures as a new platform for study of the modeling of TME and invasiveness. In this review, the mechanisms involved in GBM-microenvironment interaction are described and discussed, proposing potential prognosis biomarkers and new therapeutic targets.

Reappraisal of T1b gallbladder cancer (GBC): clinicopathologic analysis of 473 in situ and invasive GBCs and critical review of the literature highlights its rarity, and that it has a very good prognosis.

There are highly conflicting data on relative frequency (2-32%), prognosis, and management of pT1b-gallbladder carcinoma (GBC), with 5-year survival ranging from > 90% in East/Chile where cholecystectomy is regarded as curative, versus < 50% in the West, with radical operations post-cholecystectomy being recommended by guidelines. A total of 473 in situ and invasive extensively sampled GBCs from the USA (n = 225) and Chile (n = 248) were re-evaluated histopathologically per Western invasiveness criteria. 349 had invasive carcinoma, and only 24 were pT1. Seven cases previously staged as pT1b were re-classified as pT2. There were 19 cases (5% of all invasive GBCs) qualified as pT1b and most pT1b carcinomas were minute (< 1mm). One patient with extensive pTis at margins (but pT1b focus away from the margins) died of GBC at 27 months, two died of other causes, and the remainder were alive without disease (median follow-up 69.9 months; 5-year disease-specific survival, 92%). In conclusion, careful pathologic analysis of well-sampled cases reveals that only 5% of invasive GBCs are pT1b, with a 5-year disease-specific survival of > 90%, similar to findings in the East. This supports the inclusion of pT1b in the "early GBC" category, as is typically done in high-incidence regions. Pathologic mis-staging of pT2 as pT1 is not uncommon. Cases should not be classified as pT1b unless extensive, preferably total, sampling of the gallbladder to rule out a subtle pT2 is performed. Critical appraisal of the literature reveals that the Western guidelines are based on either SEER or mis-interpretation of stage IB cases as "pT1b." Although the prognosis of pT1b-GBC is very good, additional surgery (radical cholecystectomy) may be indicated, and long-term surveillance of the biliary tract is warranted.

Environmental and Lifestyle Risk Factors in the Carcinogenesis of Gallbladder Cancer.

Gallbladder cancer (GBC) is an aggressive neoplasm that in an early stage is generally asymptomatic and, in most cases, is diagnosed in advanced stages with a very low life expectancy because there is no curative treatment. Therefore, understanding the early carcinogenic mechanisms of this pathology is crucial to proposing preventive strategies for this cancer. The main risk factor is the presence of gallstones, which are associated with some environmental factors such as a sedentary lifestyle and a high-fat diet. Other risk factors such as autoimmune disorders and bacterial, parasitic and fungal infections have also been described. All these factors can generate a long-term inflammatory state characterized by the persistent activation of the immune system, the frequent release of pro-inflammatory cytokines, and the constant production of reactive oxygen species that result in a chronic damage/repair cycle, subsequently inducing the loss of the normal architecture of the gallbladder mucosa that leads to the development of GBC. This review addresses how the different risk factors could promote a chronic inflammatory state essential to the development of gallbladder carcinogenesis, which will make it possible to define some strategies such as anti-inflammatory drugs or public health proposals in the prevention of GBC.

Gallbladder reporting and data system (GB-RADS) for risk stratification of gallbladder wall thickening on ultrasonography: an international expert consensus.

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0-5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management.

Consenso chileno de diagnóstico y manejo de neoplasias quísticas pancreáticas. Club de páncreas Chile-SCHGE / Chilean consensus on diagnosis and management of pancreatic cystic neoplasms

Pancreatic cystic neoplasms (PCN) are frequently detected on abdominal images performed for non-pancreatic indications. Their prevalence in asymptomatic population ranges from 2.7 to 24.8%, and increases with age. There are several types of pancreatic cysts. Some may contain cancer or have malignant potential, such as mucinous cystic neoplasms, including mucinous cystadenoma (MCN) and intraductal papillary mucinous neoplasms (IPMN). In contrast, others are benign, such as serous cystadenoma (SCA). However, even those cysts with malignant potential rarely progress to cancer. Currently, the only treatment for pancreatic cysts is surgery, which is associated with high morbidity and occasional mortality. The Board of the Chilean Pancreas Club of the Chilean Gastroenterology Society developed the first Chilean multidisciplinary consensus for diagnosis, management, and surveillance of PCN. Thirty experts were invited and answered 21 statements with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree. A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. The consensus was approved by the Board of Directors of the Chilean Pancreas Club for publication.

Mucocutaneous Manifestations in Autoimmune Gastritis: A Prospective Case-Control Study.

INTRODUCTION: Autoimmune gastritis (AIG) is associated with nutritional deficiencies, autoimmune diseases, and gastric malignancies. The aims of the study were to test the hypothesis that mucocutaneous (MC) manifestations occur more often in patients with vs without AIG and to delineate patterns of MC manifestations in AIG. METHODS: A single-center, prospective 2:1 case-control study was conducted. Cases were patients with the diagnosis of AIG based on consistent serologic and histologic findings. Controls had a normal gastric biopsy. MC manifestations were independently evaluated by 3 experienced dermatologists. We conducted a multivariable logistic regression model adjusted for age, sex, Helicobacter pylori, tobacco use, and alcohol consumption to estimate the association between AIG (vs no AIG) and MC manifestations (adjusted odds ratio; 95% confidence interval). RESULTS: We prospectively enrolled 60 cases and 30 controls (mean age 53.5 ± 15.8 vs 53.4 ± 14.5 years; 75% vs 73.3% women). The pooled prevalence of MC immune-mediated diseases was higher in patients with vs without AIG (66.7% vs 23.3%; adjusted odds ratio 12.01 [95% confidence interval: 3.51-41.13]). In patients with AIG, seropositive vs seronegative anti-intrinsic factor antibodies more often had concomitant immunological diseases with MC manifestations (100% vs 58.5%; P = 0.016). The most common MC immune-mediated diseases in AIG were Sjögren syndrome (n = 5, 8.3%), alopecia areata (n = 5, 8.3%), and vitiligo (n = 4, 6.7%). Nutritional deficiency-related MC findings, mainly xerosis, lingual, and nail disorders, were also more common in AIG. DISCUSSION: This is the first comparative study specifically designed to evaluate MC manifestations in AIG. We demonstrated that AIG is more frequently associated with both immune- and nutritional deficiency-related MC manifestations, which might have both diagnostic and therapeutic clinical implications.