- Email: [email protected]
Severity of histological damage in celiac disease and correlation with serum antitransglutaminase antibody levels
e298
Abstracts / Digestive and Liver Disease 45 (2013) e263–e311
model antigen sampling in the intestine, DC were co-cultured with colonic Caco-2 cells in a transwell system. In this set-up, formation of transepithelial protrusions by DC was less efficient in var DC compared to wt. In accordance, antigen uptake and processing by DC derived from var patients was decreased significantly in the in vitro model of antigen sampling through the intestinal barrier. Conclusion: DCs of pediatric CD patients showed a marked impairment of bacterial uptake and antigen processing, as well as a decreased maturation. Moreover autophagy is involved in the proper interactions between DC and intestinal epithelium. Our results indicate that an autophagy defect is associated with an impairment of intestinal innate immunity in pediatric CD.
had multiple episodes of catheter-related sepsis. Two patients required admission for dehydratation and metabolic acidosis secondary to an intercurrent GI infection. Currently median weight’s centile is 28.7 and height’s centile is 27.2 (range 3–75). Conclusions: The rate of complications such as infections and allergic reactions in our case series is reduced compare to what published in literature. However we observed an high rate of surgical complications (intestinal obstruction) requiring new interventions. The mean time of PN weaning was 13.5 months with the vast majority of patients weaned using an hydrolyzed formula. The current growth status is satisfactory in most of the patients.
PO43 PO42 SHORT BOWEL DISEASE IN INFANTS: STATE OF ART IN OUR CENTER
SEVERITY OF HISTOLOGICAL DAMAGE IN CELIAC DISEASE AND CORRELATION WITH SERUM ANTITRANSGLUTAMINASE ANTIBODY LEVELS
L. Tonelli 1 , S. Gatti 1 , R. Annibali 1 , M. Rossi 1 , V. Albano 1 , G. Cobellis 2 , C. Catassi 1
L. Tonelli, S. Gatti, R. Annibali, M. Rossi, V. Albano, C. Catassi
1
Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy
Department of Pediatrics, Università Politectinica delle Marche, Ancona, Italy 2 Department of Pediatric Surgery, Università Politectinica delle Marche, Ancona, Italy Introduction: Short bowel syndrome (SBS) is clinically defined by malabsorption, diarrhea and malnutrition related to functional or anatomical loss of small bowel (>50%). In children the main causes are necrotizing enterocolitis (NEC) and intestinal atresia (IA). The incidence is about 24.5/100,000 newborns. Patients often require parenteral nutrition (PN) to allow a long term proper nutrition. A large proportion receive Home Parenteral Nutrition (HPN) with variable and not always successful weaning from PN. There’s no consensus on the optimal feeding formula for infants affected by SBS during the weaning from PN, usually an hydrolyzed formula (HF) or an aminoacid based formula (AAF) are required. Complications such as infections, mechanical catheteral insertion, and intestinal occlusion may occur. A long term growth and nutritional follow up of these patients is mandatory. Case series: We present 7 cases of patients affected by SBS who were referred to the our center in the last 3 years. The study population include 5 males and 2 females with a current mean age of 3 years. Main clinical characteristics are reported in the Table 1. Five of them (71%) had NEC in their first days of life, while in the remaining (29%) congenital intestinal atresia was diagnosed. The median residual bowel length was 67.2 cm and 4 of them had ileocecal valve resected. All the patients had an ileostomy and subsequent re-anastomosis, after a variable period of time ranging from 2 to 25 months. All of them required PN with a mean duration of 13.5 months, 5 were discharged on HPN. Five patients (71%) were weaned from PN using a HF and the remaining 2 with an AAF. In terms of complications 5 patients required further surgery and intestinal resection for a secondary intestinal occlusion. One patient
Background: Celiac disease (CD) is a autoimmune disorder triggered by gluten ingestion. According to the new European guidelines, biopsy can be avoided in children with typical symptoms, high titre antibodies and HLA-DQ2/DQ8 genotypes. Objectives: To evaluate the correlation between serological data, histological changes and clinical findings in children with CD. To analyze the temporal trend of upper endoscopy performed for diagnosis of CD in children referred to our centre and to compare features of children diagnosed with and without biopsy. Patients and methods: Data from 125 children with CD were retrospectively reviewed. During the study period (Jan 2011–Jun 2013) the new diagnostic criteria for diagnosis of CD were applied. Clinical presentation, levels of serum IgA-anti-transglutaminase (tTG), IgG-deamidated-gliadin-peptides (DGP) and antiendomisialantibodies (EMA), histological findings (Marsh classification) and HLA DQ2-DQ8 were collected. Correlations between levels of antibodies, Marsh grade and clinical presentation (atypical, typical, silent) were identified. Moreover clinical, serological and histological findings were compared between 2 groups (children with a biopsy-proven diagnosis and without biopsy). The temporal trend of biopsy/diagnosis ratio was analyzed. Results: One hundred twenty-five patients (mean age 7.32 years ± 4.26, F/M: 2.47) were diagnosed with CD. The majority (47.2%) presented with typical symptoms, 28.8% had atypical presentation and 24% were asymptomatic. Diagnosis of CD was confirmed in 116 (92.8%). HLA DQ2-cis was found to be the most prevalent haplotype (31%). Seventy-five (60%) underwent biopsy and the remaining 50 (40%) did not require histological
Table 1
Patient (male: M; female: F)
Gestat. age
Underlying disease
GL(M) AA(M) RC(M) LG(M) VL(F) MS(F) OA(M)
Preterm (33w) Preterm (32w) Preterm (34w) Term Term Preterm (34w) Preterm (34w)
NEC NEC NEC NEC IA NEC IA
Residual bowel (cm) 120 60 70 47.5 40 65 68
Residual ileo-cecal valve
Timing of stoma closure (months)
PN total duration (months)
Current age and growth status (centiles)
Yes No Yes Yes No No Yes
2 2 4 10 8 5 25
4 3 6 36 24 Currently on PN 3
3 yrs w 50◦ ; h 3◦ 12 mo w 75◦ ; h 50◦ 5 yrs w 10◦ ; h 25◦ 4 yrs w 10◦ ; h 10◦ 5 yrs w 50◦ ; h 75◦ 18 mo w 3◦ ; h 3◦ 6 mo w 3◦ ; h 25◦
Abstracts / Digestive and Liver Disease 45 (2013) e263–e311
confirmation. Of those that underwent endoscopy 66 had major intestinal changes (Marsh 2–3). The remaining 9 patients (Marsh 0–1) were considered as having potential-CD. Increasing Marsh score was positively correlated with mean values of tTG (p = 0.040) and DGP (p = 0.057), but no correlation was found either with EMA (semi-quantitative parameter) or clinical presentation. Patients requiring biopsy were found to be 4-years older (p = 0.001) and to have lower values of tTG (p = 0.05) and DGP (p = 0.001) compared to those in which biopsy has been avoided. A trend toward an increasing proportion of patients requiring endoscopy and histological confirmation has been observed, despite a reduction in the number of total diagnosis. Conclusions: This data confirm that increased levels of tTG and DGP antibodies in CD are correlated with increasing severity of the histological lesions. This finding further support the validity of the new guidelines. We recently observed an increase in the relative number of upper endoscopies performed for confirmation of CD in our centre. This data could simply reflect a recent change in clinical presentation, with a trend toward more atypical and complex cases referred to our service, therefore a longer period of observation is needed.
PO44 AUTOIMMUNE ENTEROPATHY IN A 13 YEARS OLD CELIAC GIRL SUCCESSFULLY TREATED WITH INFLIXIMAB C.M. Trovato 1 , S. Leoni 1 , D. Iorfida 1 , I. Celletti 1 , S. Gatti 1 , P. Di Matteo 1 , G. Di Nardo 1 , A. Marchegiano 3 , F. Valitutti 1 , S. Cucchiara 1 , M. Barbato 2 1
Pediatric Sapienza University, Gastroenterology and Liver Unit, Rome, Italy 2 Sapienza University, Gastroenterology and Liver Unit, Rome, Italy 3 Clinic Sciences Department of Sapienza University, Gastroenterology Unit, Rome, Italy Autoimmune enteropathy is a rare cause of small bowel villous atrophy, characterized by malabsorption, unresponsiveness to dietary restriction, circulating autoantibodies to enterocytes and an overall predisposition to autoimmunity. Albeit mainly regarded as a disease of early childhood, several adult-onset autoimmune enteropathy cases have been identified. This report describes for the first time the life-threatening clinical presentation and the management of overlapping autoimmune enteropathy in a compliant-to-diet young celiac girl. A 13 years old celiac girl was admitted to our unit because of vomiting, weight loss, diarrhea, neurological disturbances such as head tremors, vertical nystagmus and lower limb hyperesthesia. She was on parenteral nutrition. After celiac disease diagnosis at 2 years old, according to espghan criteria, she had always been compliant on a strict gluten-free diet and her medical history was unremarkable. Blood tests showed hypoproteinemia (Albumin = 30 g/L) and hypokalemia (K = 3 mmol/L), the latter requiring strict daily correction. Total IgA count was within the normal range. Serologic testing for anti-tranglutaminase and anti-endomysial antibodies were both negative. To further investigate hypoproteinemia and malabsorption, anterograde enteroscopy was then performed under general anesthesia. Stomach biopsies revealed autoimmune atrophic fundic gastritis. Biopsies along the small bowel showed microerosions, atrophic mucosa, apoptotic bodies and crypt abscesses; the intraepithelial lymphocyte count was normal, whilst plasma cells and lymphocytes were markedly increased
e299
in the lamina propria. While she was still under general anesthesia, colonoscopy was also performed: large bowel biopsies highlighted microerosions and crypt abscesses, with an overall lymphocyte increase in both the epithelium and in the lamina propria. Direct immunofluorescence for serum anti-enterocyte antibody testing turned out to be positive. The diagnosis of autoimmune enteropathy was established on histological findings and on the presence of anti-enterocyte antibodies. She was treated with Azathioprine (75 mg per day), Methylprednisolone (60 mg per day) and group B vitamins, which brought clinical improvement with remission of neurological symptoms, vomiting and diarrhea. Afterwards, the girl was partially fed orally while continuing on parenteral nutrition. When Methylprednisolone was gradually reduced, watery diarrhea reappeared. Infliximab (5 mg/kg) was then commenced. After the second infusion, two weeks later, the girl tremendously improved, with remission of diarrhea, switch to exclusive oral nutrition and slight weight gain (0.470 kg). After six months on Infliximab (infusions at 0, 2, 6, 14, 22 weeks), the girl continued to gain weight and did not report any complaints; anti-enterocyte antibodies were negative, and a follow-up upper GI endoscopy revealed on histology a completely healed villous architecture.
PO45 A PROSPECTIVE, COMPARATIVE, RANDOMIZED, CONTROLLED STUDY ON THE EFFICACY OF THE TREATMENT WITH MAGNESIUM (MG-) ALGINATE IN INFANTS WITH GASTROESOPHAGEAL REFLUX D. Ummarino, E. Sciorio, F. Crocetto, E. Miele, A. Staiano Department of Pediatrics, University “Federico II”, Naples, Italy Aim: Gastroesophageal reflux (GER) is a frequent condition during the first year of life, that can be treated with lifestyle changes and reassurance. However, some children show distressing symptoms, which may require treatments that can improve the quality of life. The aim of our study was to evaluate the efficacy of Mgalginate in the treatment of GER in infant compared with rice starch thickened formula or with reassurance. Methods: This prospective, comparative, randomized, controlled trial was conducted in patients younger than 1 year, affected by suggestive symptoms of gastroesophageal reflux. All patients underwent a validate questionnaire for assessment of clinical score (I-GERQ). The patients were randomized for 8 weeks into 3 groups according to the treatment (Group A: Mg-alginate; Group B: tickened formula feeding; Group C: reassurance, that consist in lifestyle changes and reassurance on the goodness of the condition). A clinical evaluation and score of symptoms was practiced after one month (T1) and after two months (T2) of treatment. Results: We enrolled 35 patients (mean age 5.56 ± 2.34). Fourteen children were treated with Mg-alginate (Group A), 10 with thickened formula (Group B) and 11 were only reassured (Group C). The mean values of the results of the questionnaire I-GERQ at T0 were similar in the three groups. At the end of the study (T2) in Group A 12 patients (85.7%) out of 14 showed a resolution of the symptoms, while the patients healed in Group B and in Group C were 6/10 (60%) and 6/11 (54.5%), respectively (ORG-TF : 4; ORG-R : 5; p < 0.05). Moreover, patients treated with alginate showed a lower clinical score in T2 compared with the other groups (Group A: 2.36; Group B: 5.67; Group C: 7.18).
Abstracts / Digestive and Liver Disease 45 (2013) e263–e311
model antigen sampling in the intestine, DC were co-cultured with colonic Caco-2 cells in a transwell system. In this set-up, formation of transepithelial protrusions by DC was less efficient in var DC compared to wt. In accordance, antigen uptake and processing by DC derived from var patients was decreased significantly in the in vitro model of antigen sampling through the intestinal barrier. Conclusion: DCs of pediatric CD patients showed a marked impairment of bacterial uptake and antigen processing, as well as a decreased maturation. Moreover autophagy is involved in the proper interactions between DC and intestinal epithelium. Our results indicate that an autophagy defect is associated with an impairment of intestinal innate immunity in pediatric CD.
had multiple episodes of catheter-related sepsis. Two patients required admission for dehydratation and metabolic acidosis secondary to an intercurrent GI infection. Currently median weight’s centile is 28.7 and height’s centile is 27.2 (range 3–75). Conclusions: The rate of complications such as infections and allergic reactions in our case series is reduced compare to what published in literature. However we observed an high rate of surgical complications (intestinal obstruction) requiring new interventions. The mean time of PN weaning was 13.5 months with the vast majority of patients weaned using an hydrolyzed formula. The current growth status is satisfactory in most of the patients.
PO43 PO42 SHORT BOWEL DISEASE IN INFANTS: STATE OF ART IN OUR CENTER
SEVERITY OF HISTOLOGICAL DAMAGE IN CELIAC DISEASE AND CORRELATION WITH SERUM ANTITRANSGLUTAMINASE ANTIBODY LEVELS
L. Tonelli 1 , S. Gatti 1 , R. Annibali 1 , M. Rossi 1 , V. Albano 1 , G. Cobellis 2 , C. Catassi 1
L. Tonelli, S. Gatti, R. Annibali, M. Rossi, V. Albano, C. Catassi
1
Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy
Department of Pediatrics, Università Politectinica delle Marche, Ancona, Italy 2 Department of Pediatric Surgery, Università Politectinica delle Marche, Ancona, Italy Introduction: Short bowel syndrome (SBS) is clinically defined by malabsorption, diarrhea and malnutrition related to functional or anatomical loss of small bowel (>50%). In children the main causes are necrotizing enterocolitis (NEC) and intestinal atresia (IA). The incidence is about 24.5/100,000 newborns. Patients often require parenteral nutrition (PN) to allow a long term proper nutrition. A large proportion receive Home Parenteral Nutrition (HPN) with variable and not always successful weaning from PN. There’s no consensus on the optimal feeding formula for infants affected by SBS during the weaning from PN, usually an hydrolyzed formula (HF) or an aminoacid based formula (AAF) are required. Complications such as infections, mechanical catheteral insertion, and intestinal occlusion may occur. A long term growth and nutritional follow up of these patients is mandatory. Case series: We present 7 cases of patients affected by SBS who were referred to the our center in the last 3 years. The study population include 5 males and 2 females with a current mean age of 3 years. Main clinical characteristics are reported in the Table 1. Five of them (71%) had NEC in their first days of life, while in the remaining (29%) congenital intestinal atresia was diagnosed. The median residual bowel length was 67.2 cm and 4 of them had ileocecal valve resected. All the patients had an ileostomy and subsequent re-anastomosis, after a variable period of time ranging from 2 to 25 months. All of them required PN with a mean duration of 13.5 months, 5 were discharged on HPN. Five patients (71%) were weaned from PN using a HF and the remaining 2 with an AAF. In terms of complications 5 patients required further surgery and intestinal resection for a secondary intestinal occlusion. One patient
Background: Celiac disease (CD) is a autoimmune disorder triggered by gluten ingestion. According to the new European guidelines, biopsy can be avoided in children with typical symptoms, high titre antibodies and HLA-DQ2/DQ8 genotypes. Objectives: To evaluate the correlation between serological data, histological changes and clinical findings in children with CD. To analyze the temporal trend of upper endoscopy performed for diagnosis of CD in children referred to our centre and to compare features of children diagnosed with and without biopsy. Patients and methods: Data from 125 children with CD were retrospectively reviewed. During the study period (Jan 2011–Jun 2013) the new diagnostic criteria for diagnosis of CD were applied. Clinical presentation, levels of serum IgA-anti-transglutaminase (tTG), IgG-deamidated-gliadin-peptides (DGP) and antiendomisialantibodies (EMA), histological findings (Marsh classification) and HLA DQ2-DQ8 were collected. Correlations between levels of antibodies, Marsh grade and clinical presentation (atypical, typical, silent) were identified. Moreover clinical, serological and histological findings were compared between 2 groups (children with a biopsy-proven diagnosis and without biopsy). The temporal trend of biopsy/diagnosis ratio was analyzed. Results: One hundred twenty-five patients (mean age 7.32 years ± 4.26, F/M: 2.47) were diagnosed with CD. The majority (47.2%) presented with typical symptoms, 28.8% had atypical presentation and 24% were asymptomatic. Diagnosis of CD was confirmed in 116 (92.8%). HLA DQ2-cis was found to be the most prevalent haplotype (31%). Seventy-five (60%) underwent biopsy and the remaining 50 (40%) did not require histological
Table 1
Patient (male: M; female: F)
Gestat. age
Underlying disease
GL(M) AA(M) RC(M) LG(M) VL(F) MS(F) OA(M)
Preterm (33w) Preterm (32w) Preterm (34w) Term Term Preterm (34w) Preterm (34w)
NEC NEC NEC NEC IA NEC IA
Residual bowel (cm) 120 60 70 47.5 40 65 68
Residual ileo-cecal valve
Timing of stoma closure (months)
PN total duration (months)
Current age and growth status (centiles)
Yes No Yes Yes No No Yes
2 2 4 10 8 5 25
4 3 6 36 24 Currently on PN 3
3 yrs w 50◦ ; h 3◦ 12 mo w 75◦ ; h 50◦ 5 yrs w 10◦ ; h 25◦ 4 yrs w 10◦ ; h 10◦ 5 yrs w 50◦ ; h 75◦ 18 mo w 3◦ ; h 3◦ 6 mo w 3◦ ; h 25◦
Abstracts / Digestive and Liver Disease 45 (2013) e263–e311
confirmation. Of those that underwent endoscopy 66 had major intestinal changes (Marsh 2–3). The remaining 9 patients (Marsh 0–1) were considered as having potential-CD. Increasing Marsh score was positively correlated with mean values of tTG (p = 0.040) and DGP (p = 0.057), but no correlation was found either with EMA (semi-quantitative parameter) or clinical presentation. Patients requiring biopsy were found to be 4-years older (p = 0.001) and to have lower values of tTG (p = 0.05) and DGP (p = 0.001) compared to those in which biopsy has been avoided. A trend toward an increasing proportion of patients requiring endoscopy and histological confirmation has been observed, despite a reduction in the number of total diagnosis. Conclusions: This data confirm that increased levels of tTG and DGP antibodies in CD are correlated with increasing severity of the histological lesions. This finding further support the validity of the new guidelines. We recently observed an increase in the relative number of upper endoscopies performed for confirmation of CD in our centre. This data could simply reflect a recent change in clinical presentation, with a trend toward more atypical and complex cases referred to our service, therefore a longer period of observation is needed.
PO44 AUTOIMMUNE ENTEROPATHY IN A 13 YEARS OLD CELIAC GIRL SUCCESSFULLY TREATED WITH INFLIXIMAB C.M. Trovato 1 , S. Leoni 1 , D. Iorfida 1 , I. Celletti 1 , S. Gatti 1 , P. Di Matteo 1 , G. Di Nardo 1 , A. Marchegiano 3 , F. Valitutti 1 , S. Cucchiara 1 , M. Barbato 2 1
Pediatric Sapienza University, Gastroenterology and Liver Unit, Rome, Italy 2 Sapienza University, Gastroenterology and Liver Unit, Rome, Italy 3 Clinic Sciences Department of Sapienza University, Gastroenterology Unit, Rome, Italy Autoimmune enteropathy is a rare cause of small bowel villous atrophy, characterized by malabsorption, unresponsiveness to dietary restriction, circulating autoantibodies to enterocytes and an overall predisposition to autoimmunity. Albeit mainly regarded as a disease of early childhood, several adult-onset autoimmune enteropathy cases have been identified. This report describes for the first time the life-threatening clinical presentation and the management of overlapping autoimmune enteropathy in a compliant-to-diet young celiac girl. A 13 years old celiac girl was admitted to our unit because of vomiting, weight loss, diarrhea, neurological disturbances such as head tremors, vertical nystagmus and lower limb hyperesthesia. She was on parenteral nutrition. After celiac disease diagnosis at 2 years old, according to espghan criteria, she had always been compliant on a strict gluten-free diet and her medical history was unremarkable. Blood tests showed hypoproteinemia (Albumin = 30 g/L) and hypokalemia (K = 3 mmol/L), the latter requiring strict daily correction. Total IgA count was within the normal range. Serologic testing for anti-tranglutaminase and anti-endomysial antibodies were both negative. To further investigate hypoproteinemia and malabsorption, anterograde enteroscopy was then performed under general anesthesia. Stomach biopsies revealed autoimmune atrophic fundic gastritis. Biopsies along the small bowel showed microerosions, atrophic mucosa, apoptotic bodies and crypt abscesses; the intraepithelial lymphocyte count was normal, whilst plasma cells and lymphocytes were markedly increased
e299
in the lamina propria. While she was still under general anesthesia, colonoscopy was also performed: large bowel biopsies highlighted microerosions and crypt abscesses, with an overall lymphocyte increase in both the epithelium and in the lamina propria. Direct immunofluorescence for serum anti-enterocyte antibody testing turned out to be positive. The diagnosis of autoimmune enteropathy was established on histological findings and on the presence of anti-enterocyte antibodies. She was treated with Azathioprine (75 mg per day), Methylprednisolone (60 mg per day) and group B vitamins, which brought clinical improvement with remission of neurological symptoms, vomiting and diarrhea. Afterwards, the girl was partially fed orally while continuing on parenteral nutrition. When Methylprednisolone was gradually reduced, watery diarrhea reappeared. Infliximab (5 mg/kg) was then commenced. After the second infusion, two weeks later, the girl tremendously improved, with remission of diarrhea, switch to exclusive oral nutrition and slight weight gain (0.470 kg). After six months on Infliximab (infusions at 0, 2, 6, 14, 22 weeks), the girl continued to gain weight and did not report any complaints; anti-enterocyte antibodies were negative, and a follow-up upper GI endoscopy revealed on histology a completely healed villous architecture.
PO45 A PROSPECTIVE, COMPARATIVE, RANDOMIZED, CONTROLLED STUDY ON THE EFFICACY OF THE TREATMENT WITH MAGNESIUM (MG-) ALGINATE IN INFANTS WITH GASTROESOPHAGEAL REFLUX D. Ummarino, E. Sciorio, F. Crocetto, E. Miele, A. Staiano Department of Pediatrics, University “Federico II”, Naples, Italy Aim: Gastroesophageal reflux (GER) is a frequent condition during the first year of life, that can be treated with lifestyle changes and reassurance. However, some children show distressing symptoms, which may require treatments that can improve the quality of life. The aim of our study was to evaluate the efficacy of Mgalginate in the treatment of GER in infant compared with rice starch thickened formula or with reassurance. Methods: This prospective, comparative, randomized, controlled trial was conducted in patients younger than 1 year, affected by suggestive symptoms of gastroesophageal reflux. All patients underwent a validate questionnaire for assessment of clinical score (I-GERQ). The patients were randomized for 8 weeks into 3 groups according to the treatment (Group A: Mg-alginate; Group B: tickened formula feeding; Group C: reassurance, that consist in lifestyle changes and reassurance on the goodness of the condition). A clinical evaluation and score of symptoms was practiced after one month (T1) and after two months (T2) of treatment. Results: We enrolled 35 patients (mean age 5.56 ± 2.34). Fourteen children were treated with Mg-alginate (Group A), 10 with thickened formula (Group B) and 11 were only reassured (Group C). The mean values of the results of the questionnaire I-GERQ at T0 were similar in the three groups. At the end of the study (T2) in Group A 12 patients (85.7%) out of 14 showed a resolution of the symptoms, while the patients healed in Group B and in Group C were 6/10 (60%) and 6/11 (54.5%), respectively (ORG-TF : 4; ORG-R : 5; p < 0.05). Moreover, patients treated with alginate showed a lower clinical score in T2 compared with the other groups (Group A: 2.36; Group B: 5.67; Group C: 7.18).