Control of tissue homeostasis by the extracellular matrix: Synthetic heparan sulfate as a promising therapeutic for periodontal health and bone regeneration.

Proteoglycans are core proteins associated with carbohydrate/sugar moieties that are highly variable in disaccharide composition, which dictates their function. These carbohydrates are named glycosaminoglycans, and they can be attached to proteoglycans or found free in tissues or on cell surfaces. Glycosaminoglycans such as hyaluronan, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparin/heparan sulfate have multiple functions including involvement in inflammation, immunity and connective tissue structure, and integrity. Heparan sulfate is a highly sulfated polysaccharide that is abundant in the periodontium including alveolar bone. Recent evidence supports the contention that heparan sulfate is an important player in modulating interactions between damage associated molecular patterns and inflammatory receptors expressed by various cell types. The structure of heparan sulfate is reported to dictate its function, thus, the utilization of a homogenous and structurally defined heparan sulfate polysaccharide for modulation of cell function offers therapeutic potential. Recently, a chemoenzymatic approach was developed to allow production of many structurally defined heparan sulfate carbohydrates. These oligosaccharides have been studied in various pathological inflammatory conditions to better understand their function and their potential application in promoting tissue homeostasis. We have observed that specific size and sulfation patterns can modulate inflammation and promote tissue maintenance including an anabolic effect in alveolar bone. Thus, new evidence provides a strong impetus to explore heparan sulfate as a potential novel therapeutic agent to treat periodontitis, support alveolar bone maintenance, and promote bone formation.

Systemic Dietary Hesperidin Modulation of Osteoclastogenesis, Bone Homeostasis and Periodontal Disease in Mice.

This study aimed to evaluate the effects of hesperidin (HE) on in vitro osteoclastogenesis and dietary supplementation on mouse periodontal disease and femoral bone phenotype. RAW 264.7 cells were stimulated with RANKL in the presence or absence of HE (1, 100 or 500 µM) for 5 days, and evaluated by TRAP, TUNEL and Western Blot (WB) analyses. In vivo, C57BL/6 mice were given HE via oral gavage (125, 250 and 500 mg/kg) for 4 weeks. A sterile silk ligature was placed between the first and second right maxillary molars for 10 days and microcomputed tomography (µCT), histopathological and immunohistochemical evaluation were performed. Femoral bones subjected or not to dietary HE (500 mg/kg) for 6 and 12 weeks were evaluated using µCT. In vitro, HE 500 µM reduced formation of RANKL-stimulated TRAP-positive(+) multinucleated cells (500 µM) as well as c-Fos and NFATc1 protein expression (p < 0.05), markers of osteoclasts. In vivo, dietary HE 500 mg/kg increased the alveolar bone resorption in ligated teeth (p < 0.05) and resulted in a significant increase in TRAP+ cells (p < 0.05). Gingival inflammatory infiltrate was greater in the HE 500 mg/kg group even in the absence of ligature. In femurs, HE 500 mg/kg protected trabecular and cortical bone mass at 6 weeks of treatment. In conclusion, HE impaired in vitro osteoclastogenesis, but on the contrary, oral administration of a high concentration of dietary HE increased osteoclast numbers and promoted inflammation-induced alveolar bone loss. However, HE at 500 mg/kg can promote a bone-sparing effect on skeletal bone under physiological conditions.

Bleeding assessment in female patients with the Hermansky-Pudlak syndrome-A case series.

INTRODUCTION: The Hermansky-Pudlak syndrome (HPS) is an autosomal recessive rare disorder characterized by oculocutaneous albinism, bleeding diathesis, chronic granulomatous colitis and/or pulmonary fibrosis. HPS is the most common single-gene disorder in Puerto Rico with a prevalence of 1:1,800 in the Northwest of the island. Risk of menorrhagia and post-partum hemorrhage (PPH) in cases of women with HPS have been described in the medical literature, but data regarding comprehensive description of bleeding diathesis remains lacking. For this reason, we aim to identify bleeding events using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT), a standardized quantitative tool that translates the range of severity of bleeding symptoms into a cumulative bleeding score (BS). OBJECTIVE: To use the ISTH-BAT in HPS in order to describe bleeding symptoms and allow for comparison with other inherited bleeding disorders. METHODS: Puerto Rican females and adult participants with HPS based on genetic linkage were enrolled. The ISTH-BAT was administered and results were identified using descriptive statistical analysis. RESULTS: Questionnaire answers of twelve women with HPS-1 and HPS-3 were evaluated. Participants' mean BS was HPS-1 (11.4) and HPS-3 (8.0) Participants with HPS-1 and HPS-3 reported abnormal bleeding events that presented during dental extractions, menorrhagia, surgical interventions, gastrointestinal, oral cavity and post-partum. Patients with history of pulmonary fibrosis (PF) showed a higher mean bleeding score than those who had no history of PF. CONCLUSIONS: Female patients with HPS type 1 and 3 experienced abnormal bleeding events according to the ISTH-BAT bleeding score. Bleeding medications were inconsistently used and varied independently from healthcare professionals. The benefits of this study were to understand the history of bleeding complications in patients with HPS type 1 and 3 using an international validated system. The results of this study will help design strategies to improve the care we provide to this population.

The Zika Virus: An Association to Guillain-Barré Syndrome in the United States - A Case Report.

Case of a 37 year-old Puerto Rican male with no past medical history who was admitted to the hospital after developing paresthesia in the upper and lower extremities with associated skin rash, weakness, and dysautonomia. After rigorous analysis of the clinical patterns, neurologic manifestations, laboratory workups, CSF analysis, and nerve conduction studies we conclude the existence of a strong relationship between the Zika virus and the Guillain-Barré syndrome. The patient recovered promptly and his response to treatment was excellent.

Diagnostic performance of fecal immunochemical test and sigmoidoscopy for advanced right-sided colorectal neoplasms.

BACKGROUND: Colorectal cancer screening effect on right-sided colorectal neoplasia is limited. We compared fecal immunochemical test and simulated sigmoidoscopy diagnostic accuracy for advanced right-sided neoplasia detection. METHODS: We analyzed 1,292 individuals with complete screening colonoscopy with a fecal immunochemical test determination before colonoscopy. Sigmoidoscopy and "hybrid strategy" (sigmoidoscopy or fecal hemoglobin concentration ≥ 20 µg hemoglobin/g) diagnostic yield were simulated according to UK Flexible Sigmoidoscopy, Screening for COlon REctum (SCORE), and Norwegian Colorectal Cancer Prevention (NORCCAP) trials criteria to complete colonic examination. We compared sensitivity and specificity of both strategies and of "hybrid strategy" for advanced right-sided neoplasia with McNemar test. RESULTS: An advanced right-sided neoplasia was detected in 47 (3.6 %) subjects. A fecal hemoglobin concentration ≥ 20 µg hemoglobin/g was determined in 6.6 % of the subjects and 10.1, 12.7, and 23.5 % met UK, SCORE, and NORCCAP criteria, respectively. Fecal immunochemical test was statistically more specific than sigmoidoscopy strategies (93.8 %, UK 90.3 %, SCORE 87.7 %, NORCCAP 77.8 %; p < 0.001). In contrast, fecal immunochemical test sensitivity for advanced right-sided neoplasia (17 %) was not statistically different than UK (21.3 %; p = 0.7) or SCORE (23.4 %; p = 0.5), although it was inferior than NORCCAP strategy (42.5 %; p < 0.001). Adding fecal immunochemical test to sigmoidoscopy increased number of positives (8.5-25.7 %), sensitivity (10-30 %), and significantly reduced advanced right-sided neoplasia specificity (p < 0.001). CONCLUSIONS: Fecal immunochemical test and sigmoidoscopy diagnostic yield for advanced right-sided neoplasia are low. Fecal immunochemical test is more specific than sigmoidoscopy but less sensitive than sigmoidoscopy according to NORCCAP criteria.

Fecal immunochemical test accuracy in familial risk colorectal cancer screening.

There is little information on fecal immunochemical test (FIT) in familial risk colorectal cancer (CRC) screening. Our study assesses FIT accuracy, number needed to scope (NNS) and cost to detect a CRC and an advanced neoplasia (AN) in this setting. We performed a multicentric, prospective, double-blind study of diagnostic tests on individuals with first-degree relatives (FDRs) with CRC submitted to screening colonoscopy. Two stool samples were collected and fecal hemoglobin in the first sample (FIT1) and the highest in both samples (FITmax) were determined. Areas under the curve (AUC) for CRC and AN as well as the best FIT1 and FITmax cutoff value for CRC were determined. At this threshold, NNS and the cost per lesion detected were calculated. A total of 595 individuals were included (one FDR > 60 years, 413; two FDR or one ≤ 60 years, 182). AN and CRC were found in 64 (10.8%) and six (1%) patients, respectively. For CRC diagnosis, FIT1 AUC was 0.96 [95% confidence interval (CI): 0.95-0.98] and FITmax AUC was 0.95 (95% CI: 0.93-0.97). For AN diagnosis, FIT1 and FITmax AUC were 0.74 (95% CI: 0.66-0.82). The best cutoff point for CRC was 115. At this threshold, the NNS to detect a CRC was 5.67 and 7.67, and the cost per CRC was 1,064€ and 1591.33€ on FIT1 and FITmax strategies, respectively. FIT shows high accuracy to detect CRC in familial CRC screening. Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.

Mitigation of BMP-induced inflammation in craniofacial bone regeneration and improvement of bone parameters by dietary hesperidin.

Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n = 10/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 µg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 4 weeks prior to surgeries until euthanasia at day 7 or 14 post-surgery. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested at day 14 were subjected to microcomputed tomography and histology. HE + BMP2-treated rats had a statistically significant decrease in expression of inflammatory genes compared to BMP2 alone. The high-dose BMP2 alone caused cystic-like regeneration with incomplete defect closure. HE + BMP2 showed virtually complete bone fusion. Collagen fibril birefringence pattern (red color) under polarized light indicated high organization in BMP2-induced newly formed bone (NFB) in HE-supplemented group (p < 0.05). Clear changes in osteocyte lacunae as well as a statistically significant increase in osteoclasts were found around NFB in HE-treated rats. A significant increase in trabecular volume and thickness, and trabecular and cortical density was found in femurs of HE-supplemented rats (p < 0.05). Our findings show, for the first time, that dietary HE has a remarkable modulatory role in the function of locally delivered high-dose BMP2 in bone regeneration possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function and collagen maturation in regenerated and native bone. In conclusion, HE had a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration.

Subtype of SCLC Is an Intrinsic and Persistent Feature Through Systemic Treatment.

Introduction: SCLC is an aggressive malignancy with poor outcome. Most patients have disease recurrence despite treatments with multiple modalities. Subtyping of SCLC has been proposed recently, and novel agents targeting specific subtypes are actively being investigated. In this study, we evaluated the plasticity of subtypes in paired pre- and post-treatment samples. The aim was to understand possible subtype evolution after chemotherapy resistance that could lead to alternate targeted therapy strategies. Methods: A total of 68 samples from 32 patients with sufficient paired specimens were identified from 1998 to 2022. ASCL1, NEUROD1, and POU2F3 immunohistochemistry studies were performed on all cases, and subtyping by predominant expression was determined. Subtype comparison in each patient was performed, and expression analysis was performed on the basis of subtypes. Results: Of 32 cases, 28 (88%) had the same subtype in pre- and first post-treatment specimens. Protein expression level of subtype-specific transcription factor remained stable after chemotherapy. Two of five (40%) NEUROD1-predominant SCLC switched to ASCL1-predominant phenotype after treatment. One case had a pitfall of scoring ASCL1 on specimen with marked crushing artifacts. One case revealed the challenge of proper subtyping for samples with borderline POU2F3 expression. Conclusions: Subtype of SCLC generally remains the same after acquiring chemotherapy resistance. Plasticity was observed with rare cases switching from NEUROD1-predominant to ASC1-predominant SCLC. Resubtyping is unnecessary for the consideration of novel subtype-specific targeted agents, except cases with NEUROD1-predominant subtype.

Mitigation of BMP-induced Inflammation in Craniofacial Bone Regeneration and Improvement of Bone Parameters by Dietary Hesperidin.

Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n=10/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 µg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 4 weeks prior to surgeries until euthanasia at day 7 or 14. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested at day 14 were subjected to microcomputed tomography and histology. HE+BMP2-treated rats had a statistically significant decrease in expression of inflammatory genes compared to BMP2 alone. The high-dose BMP2 caused cystic-like regeneration with incomplete defect closure. HE+BMP2 showed virtually complete bone fusion. Red collagen fibrils were significantly higher in BMP2-induced newly formed bone (NFB) in HE-supplemented group (p<0.05) indicating high organization. Clear changes in osteocyte lacunae as well as a statistically significant increase in osteoclasts were found around NFB in HE rats. A significant increase in trabecular volume and thickness, and trabecular and cortical density was found in femurs of HE-supplemented rats (p<0.05). Our findings show, for the first time, that dietary HE has a remarkable modulatory role in locally delivered high-dose BMP2-induced bone possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function and collagen maturation in regenerated and native bone. In conclusion, HE has a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration.

Challenges in the Use of Targeted Therapies in Non-Small Cell Lung Cancer.

Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there has been a significant change in the management of patients with oncogene-addicted advanced-stage NSCLC. Increasing amounts of identifiable oncogene drivers have led to the development of molecularly targeted drugs. Undoubtedly, the future of thoracic oncology is shifting toward increased molecular testing and the use of targeted therapies. For the most part, these novel drugs have proven to be safe and effective. As with all great innovations, targeted therapies pose unique challenges. Drug toxicities, resistance, access, and costs are some of the expected obstacles that will need to be addressed. This review highlights some of the major challenges in the use of targeted therapies in NSCLC and provides guidance for the future strategies.

Dosimetric predictors of pneumonitis in locally advanced non-small cell lung cancer patients treated with chemoradiation followed by durvalumab.

OBJECTIVES: The incidence and predictors of pneumonitis for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) in the era of consolidation durvalumab have yet to be fully elucidated. In this large single institution analysis, we report the incidence of and factors associated with grade 2 + pneumonitis in NSCLC patients treated with the PACIFIC regimen. MATERIALS AND METHODS: We identified all patients treated at our institution with definitive CRT followed by durvalumab from 2018 to 2021. Clinical documentation and imaging studies were reviewed to determine grade 2 + pneumonitis events, which required the following: 1) pulmonary symptoms warranting prolonged steroid taper, oxygen dependence, and/or hospital admission and 2) radiographic findings consistent with pneumonitis. RESULTS: One-hundred ninety patients were included. The majority received 60 Gray (Gy) in 30 fractions with concurrent carboplatin and paclitaxel. Median number of durvalumab cycles received was 12 (IQR: 4-22). At a median follow-up of 14.8 months, 50 (26.3%) patients experienced grade 2 + pneumonitis with a 1-year cumulative incidence of 27.8% (95% CI: 21.9-35.4). Seventeen (8.9%) patients experienced grade 3 + pneumonitis and 4 grade 5 (2.1%). Dosimetric predictors of pneumonitis included ipsilateral and total lung volume receiving 5 Gy or greater (V5Gy), V10Gy, V20Gy, V40Gy, and mean dose and contralateral V40Gy. Heart V5Gy, V10Gy, and mean dose were also significant variables. Overall survival estimates at 1 and 3 years were 87.4% (95% CI: 82.4-92.8) and 60.3% (95% CI: 47.9-74.4), respectively. CONCLUSION: We report a risk of pneumonitis higher than that seen on RTOG 0617 and comparable to the PACIFIC study. Multiple lung and heart dosimetric factors were predictive of pneumonitis.

Stability and remineralization of proteoglycan-infused dentin substrate.

OBJECTIVE: This study tested the effects of small leucine-rich proteoglycan (SLRP) proteins on phosphoric acid (PA)-treated dentin bonding overtime and the role of such SLRPs in the remineralization potential of demineralized dentin collagen. METHODS: Coronal dentin sections of human molars were used. SLRPs were either decorin (DCN) or biglycan (BGN) in core or proteoglycan form (with glycosaminoglycans, GAGs). Groups were: No treatment (control), DCN core, DCN + GAGs, BGN core, BGN + GAGs. Samples were etched with PA for 15 s and prior to application of Adper Single Bond Plus and composite buildup an aliquot of the specific SLRPs was applied over dentin. Twenty-four hours or 6 months after the bonding procedure, samples were tested for microtensile bond strength (MTBS). Debonded beams were analyzed by scanning electron microscopy (SEM). For remineralization studies, dentin blocks were fully demineralized, infused with the SLRPs, placed in artificial saliva for 2 weeks, and evaluated by transmission electron microscopy (TEM). RESULTS: MTBS test presented a mean of 51.4 ± 9.1 MPa in control with no statistically significant difference to DCN core (47.6 ± 8.3) and BGN core (48.3 ± 6.5). The full proteoglycan groups DCN + GAGs (27.4 ± 4.5) and BGN + GAGs (36.4 ± 13.6) showed decreased MTBS compared to control (p < 0.001). At 6 months, control or core-treated samples did not have a statistically significant difference in MTBS. However, SLRPs with GAGs showed statistically significant improvement of bonding (62.5 ± 6.0 for DCN and 52.8 ± 8.1 for BGN, p < 0.001) compared to their baseline values. SEM showed that GAGs seem to favor water retention but overtime help remineralization. TEM of demineralized dentin indicated a larger collagen fibril diameter pattern of samples treated with core proteins compared to control and a smaller diameter with DCN + GAGs in water with evidence of mineralization with DCN + GAGS, BGN core and BGN + GAGs. SIGNIFICANCE: In conclusion, core proteins seem not to affect dentin adhesion significantly but the presence of GAGs can be detrimental to immediate bonding. However, after ageing of samples, full proteoglycans, particularly DCN, can significantly improve bonding overtime while promoting remineralization which can prove to be clinically beneficial.

Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there has been a significant change in the management of patients with oncogene-addicted advanced-stage NSCLC. Increasing amounts of identifiable oncogene drivers have led to the development of molecularly targeted drugs. Undoubtedly, the future of thoracic oncology is shifting toward increased molecular testing and the use of targeted therapies. For the most part, these novel drugs have proven to be safe and effective. As with all great innovations, targeted therapies pose unique challenges. Drug toxicities, resistance, access, and costs are some of the expected obstacles that will need to be addressed. This review highlights some of the major challenges in the use of targeted therapies in NSCLC and provides guidance for the future strategies.

Fecal immunochemical test accuracy in average-risk colorectal cancer screening.

AIM: To assess the fecal immunochemical test (FIT) accuracy for colorectal cancer (CRC) and advanced neoplasia (AN) detection in CRC screening. METHODS: We performed a multicentric, prospective, double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy. Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample (FIT1) and the highest level of both samples (FITmax) using the OC-sensor™. Areas under the curve (AUC) for CRC and AN were calculated. The best FIT1 and FITmax cut-off values for CRC were determined. At this threshold, number needed to scope (NNS) to detect a CRC and an AN and the cost per lesion detected were calculated. RESULTS: About 779 individuals were included. An AN was found in 97 (12.5%) individuals: a CRC in 5 (0.6%) and an advanced adenoma (≥ 10 mm, villous histology or high grade dysplasia) in 92 (11.9%) subjects. For CRC diagnosis, FIT1 AUC was 0.96 (95%CI: 0.95-0.98) and FITmax AUC was 0.95 (95%CI: 0.93-0.97). For AN, FIT1 and FITmax AUC were similar (0.72, 95%CI: 0.66-0.78 vs 0.73, 95%CI: 0.68-0.79, respectively, P = 0.34). Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28% and 42% and specificity between 91% and 97%. At the best cut-off point for CRC detection (115 ng/mL), the NNS to detect a CRC were 10.2 and 15.8; and the cost per CRC was 1814€ and 2985€ on FIT1 and FITmax strategies respectively. At this threshold the sensitivity, NNS and cost per AN detected were 30%, 1.76, and 306€, in FIT1 strategy, and 36%, 2.26€ and 426€, in FITmax strategy, respectively. CONCLUSION: Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.

Characteristics of adenomas detected by fecal immunochemical test in colorectal cancer screening.

BACKGROUND: Fecal immunochemical test (FIT) diagnostic accuracy for colorectal adenoma detection in colorectal cancer screening is limited. METHODS: We analyzed 474 asymptomatic subjects with adenomas detected on colonoscopy in two blinded diagnostic tests studies designed to assess FIT diagnostic accuracy. We determined the characteristics of adenomas (number, size, histology, morphology, and location) and the risk of metachronous lesions (according to European guidelines). Finally, we performed a logistic regression to identify those variables independently associated with a positive result. RESULTS: Advanced adenomas were found in 145 patients (75.6% distal and 24.3% only proximal to splenic flexure). Patients were classified as low (59.5%), intermediate (30.2%), and high risk (10.3%) according to European guidelines. At a 100-ng/mL threshold, FIT was positive in 61 patients (12.8%). Patients with advanced adenomas [odds ratio (OR), 8.8; 95% confidence interval (CI), 4.76-16.25], distal advanced adenomas (OR, 6.7; 95% CI, 1.9-8.8), high risk (OR, 20.1; 95% CI, 8.8-45.8), or intermediate risk lesions (OR, 6; 95% CI, 2.9-12.4) had more probabilities to have a positive test. The characteristics of adenomas independently associated were number of adenomas (OR, 1.22; 95% CI, 1.04-1.42), distal flat adenomas (OR, 0.44; 95% CI, 0.21-0.96), pedunculated adenomas (OR, 2.28; 95% CI, 1.48-3.5), and maximum size of distal adenomas (mm; OR, 1.24; 95% CI, 1.16-1.32). CONCLUSIONS: European guidelines classification and adenoma location correlates with the likelihood of a positive FIT result. IMPACT: This information allows us to understand the FIT impact in colorectal cancer prevention. Likewise, it should be taken into account in the development of new colorectal adenomas biomarkers.

Diagnostic accuracy of fecal immunochemical test in average- and familial-risk colorectal cancer screening.

BACKGROUND: There is little information about the fecal immunochemical test (FIT) in familial-risk colorectal cancer (CRC) screening. OBJECTIVES: The objective of this article is to investigate whether FIT diagnostic accuracy for advanced neoplasia (AN) differs between average and familial-risk (first-degree relative) patients. METHODS: A total of 1317 consecutive participants (595 familial) who collected one stool sample before performing a colonoscopy as a CRC screening test were included. FIT diagnostic accuracy for AN was evaluated with Chi-square test at a 20 µg hemoglobin/g of feces cut-off value. Finally, we determined which variables were independently related to AN. RESULTS: An AN was found in 151 (11.5%) patients. The overall accuracy was not statistically different between both cohorts for AN (88.4%, 91.7%; p = 0.051). At the cut-off stablished, differences in FIT sensitivity (31.1%, 40.6%; p = 0.2) or specificity (96.5%, 97.3%; p = 0.1) were not statistically significant. Finally, independent variables such as sex (male) (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.4-3.1), age (50-65, >65 years) (OR 2.1, 95% CI 1.1-4.3; OR 2.7, 95% CI 1.2-6.1), previous colonoscopy (OR 0.4, 95% CI 0.2-0.9) and FIT ≥20 µg/g feces (OR 17.7, 95% CI 10.8-29.1) were associated with AN diagnosis. CONCLUSIONS: FIT accuracy for AN detection is equivalent in average and familial-risk CRC screening cohorts.