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962 Clinical Utility of Measuring Infliximab and Human Anti-Chimeric Antibody Levels in Patients with Inflammatory Bowel Disease Waqqas Afif, Edward V. Loftus, William A. Faubion, Karen A. Hanson, William J. Sandborn Background: Treatment with infliximab (IFX) can result in immunogenicity through the formation of human anti-chimeric antibodies (HACAs). These antibodies are associated with a decreased duration of response, whereas therapeutic levels of IFX are associated with durable clinical response. We evaluated the clinical utility of measuring serum IFX and HACA levels. Methods: We retrospectively reviewed charts of patients with inflammatory bowel disease who had IFX drug and HACA levels measured over a three-year period from 2005-2008. The clinical utility of these tests was assessed by determining whether the result affected clinical management. The management and subsequent clinical response to therapeutic changes based on test results was evaluated. Fisher's exact test and log-rank test for discontinuation were used for statistical analysis. Results: One hundred and fifty-five patients underwent IFX level and HACA status testing. The median time to initial testing after IFX initiation was 50 weeks (IQR: 22.7-120). The main indications for testing were: loss of response to IFX (50.3%), partial response after initiation of IFX (22.6%) and possible autoimmune/delayed hypersensitivity reaction (14.8%). HACAs were identified in 35 patients (22.6%) and therapeutic IFX levels were found in 51 (32.9%). Of 177 total tests assessed, the results impacted treatment decisions in 73.4% (95% CI: 66-80%). In those with positive HACAs, change to another anti-TNF was associated with a complete or partial response in 91.6% of patients whereas increasing the dose had a response of 16.7% (p<0.004). In those with sub-therapeutic levels, increasing the dose was associated with complete or partial clinical response in 86.2% of patients while changing to another anti-TNF resulted in a response of 40% (p<0.048). Patients with clinical symptoms and therapeutic IFX levels were: continued at the same dose 70.8% of the time (95% CI: 49-87%) and had no evidence of active inflammation by endoscopic/radiographic assessment 61.9 % of the time (95% CI, 38-82%). In patients with therapeutic IFX levels who continued the same dose and those with non-therapeutic levels who were dose-escalated, the median time to discontinuation of IFX after the test date was similar at 51 weeks (IQR: 45-92). Conclusions: Measurement of IFX level and HACA status impacts management and is clinically useful. Increasing the IFX dose in patients who have HACAs is ineffective, whereas in patients with non-therapeutic IFX levels, this strategy may be more effective than changing to another anti-TNF agent. Changing treatment based on clinical symptoms alone may lead to inappropriate manage- ment. 963 Results from a Prospective Study Combining Infliximab, Surgery, and Methotrexate in Severe Fistulising Ano-Perineal Crohn's Disease Pauline Roumeguere, Dominique Bouchard, Francois Pigot, Frederic Juguet, Alain Castinel, Elise Chanteloup, Delphine Gaye, Maylis Capdepont, Frank Zerbib, David Laharie Introduction: Infliximab (IFX) is effective in treating fistulising Crohn's disease (CD). How- ever, clinical recurrence may happen because of persistence of fistula tracks as observed with MR-imaging. Initial IFX induction associated with an optimal surgical procedure, then followed by a maintenance therapy should be evaluated regarding anatomic healing and prolonged clinical response. The aim of this open prospective study was to evaluate the short- and long-term efficacy of a combined schedule comprising short course of IFX, associated with local optimal surgery, followed by long-term methotrexate (MTX) in patients with severe fistulising ano-perineal CD. Patients and methods: From January 2006 to Nov- ember 2007, all consecutive patients with severe fistulising ano-perineal CD were prospect- ively included after primary abscess drainage. At inclusion, patients received MTX (25mg/ week IM during all the study) and 3 IFX infusions (5mg/kg at weeks 0, 2, and 6). During second surgical step performed at week 4, all setons were removed and an optimal surgical procedure (including fistula laying out, fibrin glue injection, flap …) was done. IFX was then stopped and MTX continued as maintenance therapy. Clinical response was defined by a reduction in 50% or more of draining fistulas at two or more consecutive study visits. The primary end-point was clinical response at week 14. Secondary end-points were: i) time to loss of response for responders at week 14; ii) Perineal Disease Activity Index -PDAI- , and van Assche MR-imaging score at weeks 0, 14 and 50; iii) safety. Results: Thirty-four CD patients (26W; mean age 38.5 years) were included. All had complex fistula, including 9 recto-vaginal, and 10 ano-rectal stenosis. At week 14, 85% had clinical response, and it was complete in 73.5%. Median time to loss of response was 69 weeks. Median PDAI decreased from 11 to 3, and 0 (p<0.001), and median van Assche score decreased from 15 to 9, and 6 (p0.001) at weeks 0, 14, and 50 respectively. Adverse events occurred in 62% of cases, with 15% severe infections. Conclusion: Treatment combining initial IFX induction, and two steps sphincter-sparing surgical procedure was very effective in achieving short- term response in severe fistulising ano-perineal CD. MTX as a maintenance therapy may provide long-term remission. MTX should be compared to IFX in maintenance therapy after an optimised induction treatment. 964 Multiple Salivary Biomarkers for Pancreatic Cancer Detection James J. Farrell, Lei Zhang, M. Sugimoto, A. Hirayama, T. Soga, H. Zhou, David Elashoff, K. Gao, B. Paster, M. Tomita, David T. Wong Background: Early detection of pancreatic cancer carries the best hope for improved survival in this disease. Saliva offers great advantages for the non-invasive surveillance of human health and detection of disease. This study explored the translational value of three discovery platforms (microbial, transcriptomic and metabolomic) to identify discriminatory salivary biomarkers for pancreatic cancer detection. Methods: Three salivary biomarker discovery technologies were used to profile transcriptome and metabolome in saliva supernatant and microbiota in saliva pellet from an initial exploratory cohort including patients with pancreatic A-147 AGA Abstracts cancer, and chronic pancreatitis, and healthy controls. The Affymetrix U133 Plus 2.0 array was used to discover altered gene expression which were validated by RT-PCR. Differentially present salivary metabolites were investigated using capillary electrophoresis with mass spectrometry. The Human Oral Microbe Identification Microarray was used to investigate altered microbial content in saliva pellet. Candidate biomarkers discovered from these studies were then subjected to an independent clinical validation using a separate cohort of 30 early pancreatic cancer (PC), 30 chronic pancreatitis (CP) and 30 healthy matched-control (H) saliva samples. Results: Three discriminatory panels of salivary biomarkers were discovered and validated from the microbial, transcriptomic and metabolomic studies. The level of six microbial biomarkers, eleven mRNA biomarkers and eight metabolites was found to be significantly different between PC, CP and healthy controls (P<0.05). The combination of four biomarkers (mRNA biomarker MBD3L2, GLTSCR2; microbial biomarker Prevotella nigrescens, Neisseria elongata) yielded an ROC-plot AUC value of 0.94 (95% CI, 0.837 to 0.984; P < 0.001) with sensitivity (89.3%) and specificity (89.3%) in distinguishing PC from healthy control. Additionally, these biomarkers could also distinguish PC from CP (ROC-plot AUC, 0.90) Conclusion: We have discovered and validated six microbial, eleven mRNA and eight metabolite biomarkers for pancreatic cancer detection in saliva. Combination of multiple (4) salivary biomarkers can detect pancreatic cancer with strong discrimination. This is the first report demonstrating the value of multiple salivary biomarkers for the detection of pancreatic cancer. 965 Comparative Yield of Endosonography and Magnetic Resonance Imaging in Individuals At High-Risk for Pancreatic Cancer Femme Harinck, Irma Kluijt, Jan-Werner Poley, Annemieke Cats, Cora M. Aalfs, Dirk J. Gouma, Chung Y. Nio, Paul Fockens, Marco Bruno Introduction: Individuals at high-risk for pancreatic cancer (PC) are mutation carriers of PC prone hereditary syndromes and first-degree relatives of patients with PC from familial PC kindreds. Two non-invasive pre-cursor lesions are known: pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). A surveillance program may improve the prognosis of individuals at risk by detecting asymptomatic early cancers or, more preferably, precursor lesions. Endosonography (EUS) has been shown to be a potentially valuable tool. Data for MRI are lacking. We present preliminary results of a comparative study between baseline EUS and MRI screening investigations in individuals entering a yearly surveillance program. Methods: Asymptomatic high-risk individuals prospectively underwent EUS and MRI. Both investigations were carried out and scored according to predefined criteria. Investigators were blinded to the results of the alternative imaging modality. Results: Thirty-three individuals underwent both EUS and MRI. In 25 (76%) cases no focal lesions were detected by either technique. In eight individuals (24%) focal lesions were detected, one with a mass lesion (11mm) and seven with cystic lesions. Focal lesions were detected by both techniques in four individuals (12%), by MRI only in two (6%) and by EUS only in two (6%). Of the four individuals in whom both MRI and EUS detected lesions, lesions were comparable in size, number and location in two cases. In the other two cases, the number varied from 5 reported by EUS to 11 by MRI. Cysts that were missed by EUS ranged from 2-4mm and were predominantly located in the tail (4/6). In two individuals in whom only MRI suggested a focal lesion, these were classified as simple cysts, one located in the head (3mm) and one in the tail (4mm). The mass lesion was only detected by EUS and proven to be an adenocarcinoma. A small cyst (3mm) in the corpus was also only detected by EUS. Communication between cysts and the pancreatic duct (PD) was more often reported by EUS than MRI (4 vs 1). Conclusion: Based on these preliminary results, EUS and MRI seem complementary techniques to detect (pre)malignant lesions in individuals at high-risk for developing pancreatic cancer. MRI detected more cystic lesions, but EUS detected communication between cyst and PD more often. The latter is valuable information since it differentiates a simple cyst from a side-branch IPMN. EUS detected one adenocarcin- oma in these 33 patients, which was missed by MRI. 966 Prevalence of Pancreatic Cysts in Individuals Undergoing Preventive Medical Examination By Magnetic Resonance Imaging (MRI) Koen de Jong, Chung Y. Nio, John Hermans, Marcel G. Dijkgraaf, Dirk J. Gouma, Casper H. van Eijck, Eddy van Heel, Gunter Klaβ, Paul Fockens, Marco Bruno Introduction: The true prevalence of pancreatic cysts (PCs) in the general population is unknown. Asymptomatic PCs are diagnosed with increasing frequency due to a more wide spread use of diagnostic advanced cross-sectional imaging and the increased frequency at which individuals undergo preventive medical examinations. PC(s) may be identified as a coincidental finding with subsequent clinical management dilemmas. We investigated the prevalence of PCs in individuals undergoing screenings MRI performed at their own initiative and cost. Aims & Methods: This study includes 3000 consecutive persons who underwent an abdominal MRI (non-secretin) as part of a preventive medical examination (Prescan, Rheine, Germany) between 3-2007 and 9-2008. All individuals had completed an application form with questions about medical history and presence of abdominal complaints. MRI reports and application forms were retrospectively reviewed. Primary endpoint was PC prevalence. Secondary endpoints were: age-, gender distribution, PC characteristics, presence of liver- or kidney cysts, presence of abdominal complaints, and previous pancreatic disease. Results: Until the end of 11-2008, 1761 persons (M=1119) with a mean age of 51 years (SD, 11.0; range, 21-86) have been investigated. PCs were reported in 38 persons, representing a prevalence of 2.2 per 100 persons (95% CI, 1.6-3.0). Mean age of individuals with PC(s) was 60 years (SD, 9.6). No difference in prevalence by sex was found (p=0.960). PC sizes ranged from 2 to 54mm (median, 9mm; 30mm, n=2, 5.3%) and were solitary in 82% of cases. 8% of PCs were multilocular. 36.8% of PCs were located in the tail. Communication with pancreatic duct was reported in 10%. PC presence correlated with increasing age, no PCs were identified <40 years, and prevalence of PCs from 70-80 years was 8.1% (95% CI, 3.5-17.5). No other pancreatic MRI abnormalities were reported in any of the 1761 persons. Liver or kidney cyst(s) were present in 39% and 47% of cases with PCs as opposed to 25% and 35% in those without PCs (p=0.042; p=0.122). 5.3% of individuals with PC(s) had AGA Abstracts

962 Clinical Utility of Measuring Infliximab and Human Anti-Chimeric Antibody Levels in Patients with Inflammatory Bowel Disease

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962

Clinical Utility of Measuring Infliximab and Human Anti-Chimeric AntibodyLevels in Patients with Inflammatory Bowel DiseaseWaqqas Afif, Edward V. Loftus, William A. Faubion, Karen A. Hanson, William J.Sandborn

Background: Treatment with infliximab (IFX) can result in immunogenicity through theformation of human anti-chimeric antibodies (HACAs). These antibodies are associated witha decreased duration of response, whereas therapeutic levels of IFX are associated withdurable clinical response. We evaluated the clinical utility of measuring serum IFX andHACA levels. Methods: We retrospectively reviewed charts of patients with inflammatorybowel disease who had IFX drug and HACA levels measured over a three-year period from2005-2008. The clinical utility of these tests was assessed by determining whether theresult affected clinical management. The management and subsequent clinical response totherapeutic changes based on test results was evaluated. Fisher's exact test and log-rank testfor discontinuation were used for statistical analysis. Results: One hundred and fifty-fivepatients underwent IFX level and HACA status testing. The median time to initial testingafter IFX initiation was 50 weeks (IQR: 22.7-120). The main indications for testing were:loss of response to IFX (50.3%), partial response after initiation of IFX (22.6%) and possibleautoimmune/delayed hypersensitivity reaction (14.8%). HACAs were identified in 35 patients(22.6%) and therapeutic IFX levels were found in 51 (32.9%). Of 177 total tests assessed,the results impacted treatment decisions in 73.4% (95% CI: 66-80%). In those with positiveHACAs, change to another anti-TNF was associated with a complete or partial response in91.6% of patients whereas increasing the dose had a response of 16.7% (p<0.004). In thosewith sub-therapeutic levels, increasing the dose was associated with complete or partialclinical response in 86.2% of patients while changing to another anti-TNF resulted in aresponse of 40% (p<0.048). Patients with clinical symptoms and therapeutic IFX levelswere: continued at the same dose 70.8% of the time (95% CI: 49-87%) and had no evidenceof active inflammation by endoscopic/radiographic assessment 61.9 % of the time (95% CI,38-82%). In patients with therapeutic IFX levels who continued the same dose and thosewith non-therapeutic levels who were dose-escalated, the median time to discontinuationof IFX after the test date was similar at 51 weeks (IQR: 45-92). Conclusions: Measurementof IFX level and HACA status impacts management and is clinically useful. Increasing theIFX dose in patients who have HACAs is ineffective, whereas in patients with non-therapeuticIFX levels, this strategy may be more effective than changing to another anti-TNF agent.Changing treatment based on clinical symptoms alone may lead to inappropriate manage-ment.

963

Results from a Prospective Study Combining Infliximab, Surgery, andMethotrexate in Severe Fistulising Ano-Perineal Crohn's DiseasePauline Roumeguere, Dominique Bouchard, Francois Pigot, Frederic Juguet, AlainCastinel, Elise Chanteloup, Delphine Gaye, Maylis Capdepont, Frank Zerbib, DavidLaharie

Introduction: Infliximab (IFX) is effective in treating fistulising Crohn's disease (CD). How-ever, clinical recurrence may happen because of persistence of fistula tracks as observedwith MR-imaging. Initial IFX induction associated with an optimal surgical procedure, thenfollowed by a maintenance therapy should be evaluated regarding anatomic healing andprolonged clinical response. The aim of this open prospective study was to evaluate theshort- and long-term efficacy of a combined schedule comprising short course of IFX,associated with local optimal surgery, followed by long-term methotrexate (MTX) in patientswith severe fistulising ano-perineal CD. Patients and methods: From January 2006 to Nov-ember 2007, all consecutive patients with severe fistulising ano-perineal CD were prospect-ively included after primary abscess drainage. At inclusion, patients received MTX (25mg/week IM during all the study) and 3 IFX infusions (5mg/kg at weeks 0, 2, and 6). Duringsecond surgical step performed at week 4, all setons were removed and an optimal surgicalprocedure (including fistula laying out, fibrin glue injection, flap …) was done. IFX wasthen stopped and MTX continued as maintenance therapy. Clinical response was definedby a reduction in 50% or more of draining fistulas at two or more consecutive study visits.The primary end-point was clinical response at week 14. Secondary end-points were: i)time to loss of response for responders at week 14; ii) Perineal Disease Activity Index -PDAI-, and van Assche MR-imaging score at weeks 0, 14 and 50; iii) safety. Results: Thirty-fourCD patients (26W; mean age 38.5 years) were included. All had complex fistula, including9 recto-vaginal, and 10 ano-rectal stenosis. At week 14, 85% had clinical response, and itwas complete in 73.5%. Median time to loss of response was 69 weeks. Median PDAIdecreased from 11 to 3, and 0 (p<0.001), and median van Assche score decreased from 15to 9, and 6 (p≤0.001) at weeks 0, 14, and 50 respectively. Adverse events occurred in 62%of cases, with 15% severe infections. Conclusion: Treatment combining initial IFX induction,and two steps sphincter-sparing surgical procedure was very effective in achieving short-term response in severe fistulising ano-perineal CD. MTX as a maintenance therapy mayprovide long-term remission. MTX should be compared to IFX in maintenance therapy afteran optimised induction treatment.

964

Multiple Salivary Biomarkers for Pancreatic Cancer DetectionJames J. Farrell, Lei Zhang, M. Sugimoto, A. Hirayama, T. Soga, H. Zhou, David Elashoff,K. Gao, B. Paster, M. Tomita, David T. Wong

Background: Early detection of pancreatic cancer carries the best hope for improved survivalin this disease. Saliva offers great advantages for the non-invasive surveillance of humanhealth and detection of disease. This study explored the translational value of three discoveryplatforms (microbial, transcriptomic and metabolomic) to identify discriminatory salivarybiomarkers for pancreatic cancer detection. Methods: Three salivary biomarker discoverytechnologies were used to profile transcriptome and metabolome in saliva supernatant andmicrobiota in saliva pellet from an initial exploratory cohort including patients with pancreatic

A-147 AGA Abstracts

cancer, and chronic pancreatitis, and healthy controls. The Affymetrix U133 Plus 2.0 arraywas used to discover altered gene expression which were validated by RT-PCR. Differentiallypresent salivary metabolites were investigated using capillary electrophoresis with massspectrometry. The Human Oral Microbe Identification Microarray was used to investigatealtered microbial content in saliva pellet. Candidate biomarkers discovered from these studieswere then subjected to an independent clinical validation using a separate cohort of 30 earlypancreatic cancer (PC), 30 chronic pancreatitis (CP) and 30 healthy matched-control (H)saliva samples. Results: Three discriminatory panels of salivary biomarkers were discoveredand validated from the microbial, transcriptomic and metabolomic studies. The level of sixmicrobial biomarkers, eleven mRNA biomarkers and eight metabolites was found to besignificantly different between PC, CP and healthy controls (P<0.05). The combination offour biomarkers (mRNA biomarker MBD3L2, GLTSCR2; microbial biomarker Prevotellanigrescens, Neisseria elongata) yielded an ROC-plot AUC value of 0.94 (95% CI, 0.837 to0.984; P < 0.001) with sensitivity (89.3%) and specificity (89.3%) in distinguishing PCfrom healthy control. Additionally, these biomarkers could also distinguish PC from CP(ROC-plot AUC, 0.90) Conclusion: We have discovered and validated six microbial, elevenmRNA and eight metabolite biomarkers for pancreatic cancer detection in saliva. Combinationof multiple (4) salivary biomarkers can detect pancreatic cancer with strong discrimination.This is the first report demonstrating the value of multiple salivary biomarkers for thedetection of pancreatic cancer.

965

Comparative Yield of Endosonography and Magnetic Resonance Imaging inIndividuals At High-Risk for Pancreatic CancerFemme Harinck, Irma Kluijt, Jan-Werner Poley, Annemieke Cats, Cora M. Aalfs, Dirk J.Gouma, Chung Y. Nio, Paul Fockens, Marco Bruno

Introduction: Individuals at high-risk for pancreatic cancer (PC) are mutation carriers of PCprone hereditary syndromes and first-degree relatives of patients with PC from familial PCkindreds. Two non-invasive pre-cursor lesions are known: pancreatic intraepithelial neoplasia(PanIN) and intraductal papillary mucinous neoplasia (IPMN). A surveillance program mayimprove the prognosis of individuals at risk by detecting asymptomatic early cancers or,more preferably, precursor lesions. Endosonography (EUS) has been shown to be a potentiallyvaluable tool. Data for MRI are lacking. We present preliminary results of a comparativestudy between baseline EUS and MRI screening investigations in individuals entering a yearlysurveillance program. Methods: Asymptomatic high-risk individuals prospectively underwentEUS and MRI. Both investigations were carried out and scored according to predefinedcriteria. Investigators were blinded to the results of the alternative imaging modality. Results:Thirty-three individuals underwent both EUS and MRI. In 25 (76%) cases no focal lesionswere detected by either technique. In eight individuals (24%) focal lesions were detected,one with a mass lesion (11mm) and seven with cystic lesions. Focal lesions were detectedby both techniques in four individuals (12%), by MRI only in two (6%) and by EUS onlyin two (6%). Of the four individuals in whom both MRI and EUS detected lesions, lesionswere comparable in size, number and location in two cases. In the other two cases, thenumber varied from 5 reported by EUS to 11 by MRI. Cysts that were missed by EUSranged from 2-4mm and were predominantly located in the tail (4/6). In two individualsin whom only MRI suggested a focal lesion, these were classified as simple cysts, one locatedin the head (3mm) and one in the tail (4mm). The mass lesion was only detected by EUSand proven to be an adenocarcinoma. A small cyst (3mm) in the corpus was also onlydetected by EUS. Communication between cysts and the pancreatic duct (PD) was moreoften reported by EUS than MRI (4 vs 1). Conclusion: Based on these preliminary results,EUS and MRI seem complementary techniques to detect (pre)malignant lesions in individualsat high-risk for developing pancreatic cancer. MRI detected more cystic lesions, but EUSdetected communication between cyst and PD more often. The latter is valuable informationsince it differentiates a simple cyst from a side-branch IPMN. EUS detected one adenocarcin-oma in these 33 patients, which was missed by MRI.

966

Prevalence of Pancreatic Cysts in Individuals Undergoing Preventive MedicalExamination By Magnetic Resonance Imaging (MRI)Koen de Jong, Chung Y. Nio, John Hermans, Marcel G. Dijkgraaf, Dirk J. Gouma, CasperH. van Eijck, Eddy van Heel, Gunter Klaβ, Paul Fockens, Marco Bruno

Introduction: The true prevalence of pancreatic cysts (PCs) in the general population isunknown. Asymptomatic PCs are diagnosed with increasing frequency due to a more widespread use of diagnostic advanced cross-sectional imaging and the increased frequency atwhich individuals undergo preventive medical examinations. PC(s) may be identified as acoincidental finding with subsequent clinical management dilemmas. We investigated theprevalence of PCs in individuals undergoing screenings MRI performed at their own initiativeand cost. Aims & Methods: This study includes 3000 consecutive persons who underwentan abdominal MRI (non-secretin) as part of a preventive medical examination (Prescan,Rheine, Germany) between 3-2007 and 9-2008. All individuals had completed an applicationform with questions about medical history and presence of abdominal complaints. MRIreports and application forms were retrospectively reviewed. Primary endpoint was PCprevalence. Secondary endpoints were: age-, gender distribution, PC characteristics, presenceof liver- or kidney cysts, presence of abdominal complaints, and previous pancreatic disease.Results: Until the end of 11-2008, 1761 persons (M=1119) with a mean age of 51 years (SD,11.0; range, 21-86) have been investigated. PCs were reported in 38 persons, representing aprevalence of 2.2 per 100 persons (95% CI, 1.6-3.0). Mean age of individuals with PC(s)was 60 years (SD, 9.6). No difference in prevalence by sex was found (p=0.960). PC sizesranged from 2 to 54mm (median, 9mm; ≥30mm, n=2, 5.3%) and were solitary in 82% ofcases. 8% of PCs were multilocular. 36.8% of PCs were located in the tail. Communicationwith pancreatic duct was reported in 10%. PC presence correlated with increasing age, noPCs were identified <40 years, and prevalence of PCs from 70-80 years was 8.1% (95% CI,3.5-17.5). No other pancreatic MRI abnormalities were reported in any of the 1761 persons.Liver or kidney cyst(s) were present in 39% and 47% of cases with PCs as opposed to 25%and 35% in those without PCs (p=0.042; p=0.122). 5.3% of individuals with PC(s) had

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