Patrícia Andrade

Is it Possible to Change Phenotype Progression in Crohn's Disease in the Era of Immunomodulators? Predictive Factors of Phenotype Progression

OBJECTIVES:Crohns disease (CD) induces cumulative structural damage, initially characterized by a non-stenosing non-penetrating behavior (B1) with progression over time to a fibro-stenosing (B2) and/or penetrating phenotype (B3). Our aim was to assess the long-term evolution of disease behavior of CD and determine what factors predict phenotype progression.METHODS:This was a study based on prospectively collected data from a CD database in an inflammatory bowel disease outpatient clinic. B1 corresponds to a non-stenosing non-penetrating disease, B2 to a stenosing behavior, and B3 to a penetrating one.RESULTS:Seven hundred and thirty-six patients with CD (368 female) were followed up for 12.3 years (±8.4), with 87.0% of them exhibiting B1 phenotype at diagnosis. Of these patients, 28.5% progressed to B2 phenotype and 23.5% to B3. Fifty percent of the patients started azathioprine treatment before phenotype change and 13.9% started anti-tumor necrosis factor-α (anti-TNFα) treatment before phenotype change. Monotherapy with azathioprine before phenotype change as well as combination therapy with azathioprine/anti-TNFα before phenotype change delayed disease progression (B1–B2 or B3) in comparison with patients who did not receive treatment (P<0.001). The hazard ratio (HR) for disease progression was lower for both monotherapy with azathioprine (HR: 0.15, P<0.001) or combination therapy with anti-TNFα (HR: 0.33, P<0.001). Upper gastrointestinal tract involvement, male gender, and steroid use were associated with an early progression of phenotype from B1 to B2 or B3 (P<0.001). The HR for disease progression was higher in patients who used steroids without criteria of dependence or resistance (HR: 2.67, P<0.001) and was even higher in patients with criteria of dependence or resistance (HR: 6.44, P<0.001). Longer delays between CD diagnosis and beginning of therapy with azathioprine and/or anti-TNFα were associated with disease progression. The longer the duration of treatment, the less likely the disease progression.CONCLUSIONS:Monotherapy with azathioprine before behavior change as well as combination therapy with azathioprine and anti-TNFα before behavior change delays phenotype progression of CD, whereas upper gastrointestinal tract involvement, male gender, and steroid use with or without criteria of steroid dependence are associated with a higher risk for disease progression.

High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis

Please cite this article as: Cardoso, H., Vale, A.M., Rodrigues, S., Gonçalves, R., Albuquerque, A., Pereira, P., Lopes, S., Silva, M., Andrade, P., Morais, R., Coelho, R., Macedo, G., High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis, Journal of Hepatology (2016), doi: http://dx.doi.org/10.1016/j.jhep.2016.07.027

Comparison between two surgical techniques for root coverage with an acellular dermal matrix graft.

AIM The aim of this randomized, controlled, clinical study was to compare two surgical techniques with the acellular dermal matrix graft (ADMG) to evaluate which technique could provide better root coverage. MATERIAL AND METHODS Fifteen patients with bilateral Miller Class I gingival recession areas were selected. In each patient, one recession area was randomly assigned to the control group, while the contra-lateral recession area was assigned to the test group. The ADMG was used in both groups. The control group was treated with a broader flap and vertical-releasing incisions, and the test group was treated with the proposed surgical technique, without releasing incisions. The clinical parameters evaluated before the surgeries and after 12 months were: gingival recession height, probing depth, relative clinical attachment level and the width and thickness of keratinized tissue. RESULTS There were no statistically significant differences between the groups for all parameters at baseline. After 12 months, there was a statistically significant reduction in recession height in both groups, and there was no statistically significant difference between the techniques with regard to root coverage. CONCLUSIONS Both surgical techniques provided significant reduction in gingival recession height after 12 months, and similar results in relation to root coverage.

Regeneration of class II furcation defects: determinants of increased success

One of the most important indications for guided tissue regeneration (GTR) treatment is class II furcation lesion. However, periodontal regeneration of this type of defect, although possible, is not considered totally predictable, especially in terms of complete bone fill. Many factors may account for variability in the response to regenerative therapy in class II furcation. The purpose of this review is to assess the prognostic significance of factors related to the patient (smoking, stress, diabetes mellitus, acquired immunodeficiency syndrome and other acute and debilitating diseases, and the presence of multiple deep periodontal pockets), local factors (furcal anatomy, defect morphology, thickness of gingival tissue and tooth mobility), surgical treatment (infection control, bone replacement grafts combined with barriers or GTR alone, type of barrier and surgical technique), and postoperative period (plaque control, membrane exposure, membrane retrieval and a regular supportive periodontal care program) for successful of GTR in class II furcations.

Correlation Between Calprotectin and Modified Rutgeerts Score.

Background:Endoscopic recurrence after surgery for Crohns disease (CD) is high, and it has important prognostic value. Crohns disease will recur in the majority of patients after surgery. Fecal calprotectin (FC) and lactoferrin (FL) have attracted interest in the postoperative setting for predicting relapse. We have evaluated the accuracy of FC and FL in diagnosing endoscopic recurrence (ER) using the modified Rutgeerts score (MRS) compared with the Rutgeerts score (RS). Methods:A series of consecutive patients who underwent ileocolonic resection for Crohns disease were evaluated. Biomarkers, clinical indexes, and fecal markers were recorded on the day of ileocolonoscopy. ER was defined as a MRS ≥ i2b or a RS ≥ i2. Results:Ninety-nine patients were included in this prospective cohort. The median time between surgery and colonoscopy was 87.5 months (IQR, 31–137). FC and FL levels were higher in patients with ER than in those in remission (Median FC, 196.5 &mgr;g/g [IQR, 96–634 &mgr;g/g] versus 42.1 &mgr;g/g [IQR 19–91.60 &mgr;g/g; P < 0.001]; Median FL, 23.27 &mgr;g/g [IQR 8.9–47.8 &mgr;g/g] versus 2 &mgr;g/g [IQR 0.9–7.26 &mgr;g/g; P < 0.001]). Using the MRS, 34% of patients presented with ER compared with 76% if the RS was used. The RS performed worse than the MRS with a decrease in sensitivity (74% versus 48% for FC and 85% versus 55% for FL) and in NPV (91% versus 33% for FC, and 90% versus 37% for FL). Furthermore, the accuracy of the MRS was higher than that of the RS (75% versus 55%). Conclusions:Both FC and FL proved to correlate well with endoscopic findings in the evaluation of Crohns disease after surgery. Both markers predicted recurrence with greater accuracy when the MRS was used. Fecal markers can be used to monitor disease recurrence after intestinal resection, with patients being selected to undergo further endoscopic evaluation.

Disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under azathioprine and steroids: First case report and literature review

Immunosuppressive treatments used in the management of Inflammatory Bowel Disease, namely steroids, thiopurines and anti-TNF drugs, raise the risk of acquiring opportunistic infections. However, most of these infections are mild and self-limited, not requiring specific therapy or suspension of the immunosuppressors. We report a case of disseminated cutaneous herpes simplex infection in a patient with Crohns disease under steroids and azathioprine.

Potential of Bioactive Glass Particles of Different Size Ranges to Affect Bone Formation in Interproximal Periodontal Defects in Dogs

BACKGROUND The aim of this study was to compare the potential of bioactive glass particles of different size ranges to affect bone formation in periodontal defects, using the guided tissue regeneration model in dogs. METHODS In six dogs, 2-wall intrabony periodontal defects were surgically created and chronified on the mesial surfaces of mandibular third premolars and first molars bilaterally. After 1 month, each defect was randomly assigned to treatment with bioabsorbable membrane in association with bioactive glass with particle sizes between 300 and 355 microm (group 1) or between 90 and 710 microm (group 2), membrane alone (group 3), or negative control (group 4). The dogs were sacrificed 12 weeks after surgeries, and histomorphometric measurements were made of the areas of newly formed bone, new mineralized bone, and bioactive glass particle remnants. RESULTS With regard to the area of bioactive glass particle remnants, there was a statistically significant difference between groups 1 and 2, favoring group 1. There were greater areas of mineralized bone in groups 1 and 2 compared to groups 3 and 4 (P <0.05). CONCLUSION The bioactive glass particles of small size range underwent faster resorption and substitution by new bone than the larger particles, and the use of bioactive glass particles favored the formation of mineralized bone.

Treatment with infliximab or azathioprine negatively impact the efficacy of hepatitis B vaccine in inflammatory bowel disease patients

Immunization against hepatitis B virus (HBV) infection is recommended in patients with inflammatory bowel disease (IBD), particularly in those under immunosuppressive therapy. Limited data are available about IBD patients response to HBV vaccination. We assessed the response rate to HBV vaccination in IBD patients and evaluated the impact of different factors on the efficacy of HBV vaccination.

Adjunct effect of the antimicrobial photodynamic therapy to an association of non-surgical and surgical periodontal treatment in modulation of gene expression: A human study

BACKGROUND This study has evaluated the effect of antimicrobial photodynamic therapy (aPDT) used in conjunction with non-surgical and surgical periodontal treatment (PT) in modulating gene expression during periodontal wound healing. METHODS Fifteen patients with chronic periodontitis, presenting bilaterally lower molars with class III furcation lesions and scheduled for extraction, were selected. In initial therapy, scaling and root planing (SRP) was performed in the Control Group (CG), while SRP+aPDT were performed in the Test Group (TG). 45days later, flap surgery plus SRP, and flap surgery plus SRP+aPDT were performed in the CG and TG, respectively. At 21days post-surgery, the newly formed granulation tissue was collected, and Real-time PCR evaluated the expression of the genes: tumor necrosis factor-α, interleukin-1β, interleukin-4, interleukin-10, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), type I collagen, alkaline phosphatase, osteopontin, osteocalcin, and bone sialoprotein. RESULTS There were statistically significant differences between the groups in relation to mRNA levels for MMP-2 (TG=3.26±0.89; CG=4.23±0.97; p=0.01), TIMP-2/MMP-2 ratio (TG=0.91±0.34; CG=0.73±0.32; p=0.04), OPG (TG=0.84±0.45; CG=0.30±0.26; p=0.001), and OPG/RANKL ratio (TG=0.60±0.86; CG=0.23±0.16; p=0.04), favoring the TG. CONCLUSION The present data suggest that the aPDT associated to nonsurgical and surgical periodontal therapy may modulate the extracellular matrix and bone remodeling by up regulating the TIMP- 2/MMP-2 and OPG/RANKL mRNA ratio, but the clinical relevance needs to be evaluated in further studies.

Antimicrobial photodynamic therapy associated to nonsurgical periodontal treatment in smokers: Microbiological results

BACKGROUND Studies suggest that smokers present more or greater numbers of potential periodontal pathogens than non-smokers. The aim of this study was to investigate the microbiologic effects of adjunctive aPDT on nonsurgical periodontal treatment in smokers with chronic periodontitis (CP). METHODS Twenty smokers with CP had two contralateral teeth randomly assigned in a split-mouth design to receive SRP (CG) or SRP + a single episode of aPDT (TG), with a diode laser and a phenothiazine photosensitizer. Levels of 40 subgingival species were measured using checkerboard DNA-DNA hybridization at baseline and 1, 4 and 12 weeks after periodontal treatment. RESULTS All 40 bacterial species evaluated were detected in different levels at baseline, with no statistic significant differences between groups. After periodontal treatment, the levels of some bacterial species decreased, while some other species presented an increase. Despite this variation, the statistical analysis was not able to identify significant differences neither at intragroup nor at intergroup comparisons. CONCLUSION Periodontal treatment with SRP or SRP + aPDT was not able to reduce levels of 40 subgingival species in smokers with CP. These outcomes indicate that smoking impairs periodontal healing after nonsurgical treatment even associated with aPDT.