Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes.

BACKGROUND: Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT. METHODS: To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion. RESULTS: Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion. CONCLUSION: We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy.

Intra-operative enteroscopy for the identification of obscure bleeding source caused by gastrointestinal angiodysplasias: through a balloon-tip trocar is better.

AIM: Intra-operative enteroscopy (IE) is a valid diagnostic tool which can be adopted in order to identify the precise location of bleeding gastrointestinal angiodysplasias (GIADs) of the small bowel. We describe a novel IE technique that may increase the diagnostic yield by maintaining a steady distension of the bowel and that prevents microtrauma to the intestinal mucosa and spillage of enteric content into the operative field. METHODS: After laparotomy, a centimetric transverse enterotomy is performed approximately at the middle of the small bowel. A 12-mm trocar with balloon is then introduced and insufflated. The small bowel is gently distended by carbon dioxide insufflation. Through the trocar, a paediatric colonscope is then inserted and the enteroscopy is performed either retrogradely to the duodenum or anterogradely to the caecum. Once located, surgery is tailored to the precise site of bleeding, with a consequent sparing of intestinal resection. RESULTS: IE with 12-mm trocar with balloon was adopted in four elderly patients undergoing surgery for bleeding GIADs. The length of small bowel resection ranged from 10 to 200 cm, depending on the number of GIADs. Operating time ranged from 210 to 275 min. Intra-operative blood loss was nil. No patient developed organ-space or wound infections. There was no recurrence of bleeding from the midgut. CONCLUSION: Performing IE through a balloon trocar may increase the diagnostic accuracy of the procedure with the benefit of reducing the risk of traumatic injury to the bowel and the risk of surgical site infection.

European Society of Endodontology position statement: the use of antibiotics in endodontics.

This position statement represents a consensus of an expert committee convened by the European Society of Endodontology (ESE) on Antibiotics in Endodontics. The statement is based on current scientific evidence as well as the expertise of the committee. The goal is to provide dentists and other healthcare workers with evidence-based criteria for when to use antibiotics in the treatment of endodontic infections, traumatic injuries of the teeth, revascularization procedures in immature teeth with pulp necrosis, and in prophylaxis for medically compromised patients. It also highlights the role that dentists and others can play in preventing the overuse of antibiotics. A recent review article provides the basis for this position statement and more detailed background information (International Endodontic Journal, 2017, https://doi.org/10.1111/iej.12741). Given the dynamic nature of research in this area, this position statement will be updated at appropriate intervals.

Engineering the Structural and Electronic Phases of MoTe2 through W Substitution.

MoTe2 is an exfoliable transition metal dichalcogenide (TMD) that crystallizes in three symmetries: the semiconducting trigonal-prismatic 2H- or α-phase, the semimetallic and monoclinic 1T'- or ß-phase, and the semimetallic orthorhombic γ-structure. The 2H-phase displays a band gap of ∼1 eV making it appealing for flexible and transparent optoelectronics. The γ-phase is predicted to possess unique topological properties that might lead to topologically protected nondissipative transport channels. Recently, it was argued that it is possible to locally induce phase-transformations in TMDs, through chemical doping, local heating, or electric-field to achieve ohmic contacts or to induce useful functionalities such as electronic phase-change memory elements. The combination of semiconducting and topological elements based upon the same compound might produce a new generation of high performance, low dissipation optoelectronic elements. Here, we show that it is possible to engineer the phases of MoTe2 through W substitution by unveiling the phase-diagram of the Mo1-xWxTe2 solid solution, which displays a semiconducting to semimetallic transition as a function of x. We find that a small critical W concentration xc ∼ 8% stabilizes the γ-phase at room temperature. This suggests that crystals with x close to xc might be particularly susceptible to phase transformations induced by an external perturbation, for example, an electric field. Photoemission spectroscopy, indicates that the γ-phase possesses a Fermi surface akin to that of WTe2.

Antibiotics in Endodontics: a review.

The overuse of antibiotics and the emergence of antibiotic-resistant bacterial strains is a global concern. This concern is also of importance in terms of the oral microbiota and the use of antibiotics to deal with oral and dental infections. The aim of this paper was to review the current literature on the indications and use of antibiotics and to make recommendations for their prescription in endodontic patients. Odontogenic infections, including endodontic infections, are polymicrobial, and in most cases, the prescription of antibiotics is empirical. This has led to the increasing use of broad-spectrum antibiotics even in cases where antibiotics are not indicated, such as symptomatic irreversible pulpitis, necrotic pulps and localized acute apical abscesses. In case of discrete and localized swelling, the primary aim is to achieve drainage without additional antibiotics. Adjunctive antibiotic treatment may be necessary in the prevention of the spread of infection, in acute apical abscesses with systemic involvement and in progressive and persistent infections. Medically compromised patients are more susceptible to complication arising from odontogenic infections and antimicrobials have a more specific role in their treatment. Therefore, antibiotics should be considered in patients having systemic diseases with compromised immunity or in patients with a localized congenital or acquired altered defence capacity, such as patients with infective endocarditis, prosthetic cardiac valves or recent prosthetic joint replacement. Penicillin VK, possibly combined with metronidazole to cover anaerobic strains, is still effective in most cases. However, amoxicillin (alone or together with clavulanic acid) is recommended because of better absorption and lower risk of side effects. In case of confirmed penicillin allergy, lincosamides such as clindamycin are the drug of choice.

Acoustic schwannoma with intracochlear extension and primary intracochlear schwannoma: removal through translabyrinthine approach with facial bridge cochleostomy and transcanal approach.

Intracochlear schwannomas can occur either as an extension of a larger tumor from the internal auditory canal, or as a solitary labyrinthine tumor. They are currently removed via a translabyrinthine approach extended to the basal turn, adding a transotic approach for tumors lying beyond the basal turn. Facial bridge cochleostomy may be associated with the translabyrinthine approach to enable the whole cochlea to be approached without sacrificing the external auditory canal and tympanum. We describe seven cases, five of which underwent cochlear schwannoma resection with facial bridge cochleostomy, one case with the same procedure for a suspect tumor and one, previously subjected to radical tympanomastoidectomy, who underwent schwannoma resection via a transotic approach. Facial bridge cochleostomy involved removing the bone between the labyrinthine and tympanic portions of the fallopian canal, and exposing the cochlea from the basal to the apical turn. Patients' recovery was uneventful, and long-term magnetic resonance imaging showed no residual tumor. Facial bridge cochleostomy can be a flexible extension of the translabyrinthine approach for tumors extending from the internal auditory canal to the cochlea. The transcanal approach is suitable for the primary exclusive intralabyrinthine tumor. The indications for the different approaches are discussed.

Lower tract respiratory infection in children younger than 5 years of age and adverse pregnancy outcomes related to household air pollution in Bariloche (Argentina) and Temuco (Chile).

The main objective of this study was to evaluate the association between household air pollution with lower tract respiratory infection (LRTI) in children younger than 5 years old and adverse pregnancy outcomes. This retrospective cohort study took place in two cities in Patagonia. Using systemic random sampling, we selected households in which at least one child <5 years had lived and/or a child had been born alive or stillborn. Trained interviewers administered the questionnaire. We included 926 households with 695 pregnancies and 1074 children. Household cooking was conducted indoors in ventilated rooms and the use of wood as the principal fuel for cooking was lower in Temuco (13% vs. 17%). In exposed to biomass fuel use, the adjusted OR for LRTI was 1.87 (95% CI 0.98-3.55; P = 0.056) in Temuco and 1.12 (95% CI 0.61-2.05; P = 0.716) in Bariloche. For perinatal morbidity, the OR was 3.11 (95% CI 0.86-11.32; P = 0.084) and 1.41 (95% CI 0.50-3.97; P = 0.518), respectively. However, none of the effects were statistically significant (P > 0.05). The use of biomass fuel to cook in traditional cookstoves in ventilated dwellings may increase the risk of perinatal morbidity and LRTI.

Mesenchymal stem cells are enriched in head neck squamous cell carcinoma, correlates with tumour size and inhibit T-cell proliferation.

BACKGROUND: Cancer is a multifactorial disease not only restricted to transformed epithelium, but also involving cells of the immune system and cells of mesenchymal origin, particularly mesenchymal stem cells (MSCs). Mesenchymal stem cells contribute to blood- and lymph- neoangiogenesis, generate myofibroblasts, with pro-invasive activity and may suppress anti-tumour immunity. METHODS: In this paper, we evaluated the presence and features of MSCs isolated from human head neck squamous cell carcinoma (HNSCC). RESULTS: Fresh specimens of HNSCC showed higher proportions of CD90+ cells compared with normal tissue; these cells co-expressed CD29, CD105, and CD73, but not CD31, CD45, CD133, and human epithelial antigen similarly to bone marrow-derived MSCs (BM-MSCs). Adherent stromal cells isolated from tumour shared also differentiation potential with BM-MSCs, thus we named them as tumour-MSCs. Interestingly, tumour-MSCs showed a clear immunosuppressive activity on in vitro stimulated T lymphocytes, mainly mediated by indoelamine 2,3 dioxygenase activity, like BM-MSCs. To evaluate their possible role in tumour growth in vivo, we correlated tumour-MSC proportions with neoplasm size. Tumour-MSCs frequency directly correlated with tumour volume and inversely with the frequency of tumour-infiltrating leukocytes. CONCLUSIONS: These data support the concept that tumour-MSCs may favour tumour growth not only through their effect on stromal development, but also by inhibiting the anti-tumour immune response.

Temporal bone carcinoma. Current diagnostic, therapeutic, and prognostic concepts.

Temporal bone carcinoma is an uncommon aggressive malignancy. Its low incidence and the absence of a globally accepted staging system still make it difficult to compare different centers' approaches and results. In this review of the main available studies dealing with temporal bone carcinoma since 1995, we consider its rational preoperative staging and assessment, compare the effectiveness of different treatments by tumor stage, and outline the main actuarial prognostic factors.

Toward the Development of User-Centered Neurointegrated Lower Limb Prostheses.

The last few years witnessed radical improvements in lower-limb prostheses. Researchers have presented innovative solutions to overcome the limits of the first generation of prostheses, refining specific aspects which could be implemented in future prostheses designs. Each aspect of lower-limb prostheses has been upgraded, but despite these advances, a number of deficiencies remain and the most capable limb prostheses fall far short of the capabilities of the healthy limb. This article describes the current state of prosthesis technology; identifies a number of deficiencies across the spectrum of lower limb prosthetic components with respect to users' needs; and discusses research opportunities in design and control that would substantially improve functionality concerning each deficiency. In doing so, the authors present a roadmap of patients related issues that should be addressed in order to fulfill the vision of a next-generation, neurally-integrated, highly-functional lower limb prosthesis.

Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver transplant surgery: a prospective randomized control study.

BACKGROUND: Although orthotopic liver transplantation (OLT) is nowadays considered standard practice at experienced centres, it can still be affected by a significant risk of massive bleeding and its related complications. Solvent/detergent plasma (S/D Plasma) has been proposed as an alternative to fresh frozen plasma (FFP) to curtail such complications. This study aimed at evaluating the efficacy of S/D Plasma in OLT patients by comparing it to FFP. MATERIALS AND METHODS: Sixty-three OLT patients were randomized into two groups depending on whether they were transfused with FFP or S/D plasma. A thromboelastography-based protocol aimed at achieving and maintaining predetermined coagulation goals was used to guide plasma transfusions. At the beginning and the end of surgery, standard laboratory coagulation tests were performed together with the assessment of the VII, VIII, V, XII factors and S protein blood levels. RESULTS: The two study groups equally achieved the thromboelastography goals but with a reduced amount of transfusions in the S/D plasma group (P < 0.0001). At the end of surgery, factors V and XII and S protein blood levels were lower in the S/D plasma patients who also showed lower INR, aPTT and antithrombin III levels. CONCLUSION: In cirrhotic patients undergoing OLT, the use of S\D plasma associated with thromboelastography allows the same clinical results but with a significant reduction in the amount of plasma transfusions.

The epidemiology of life-threatening complications associated with reproductive process in public hospitals in Argentina.

OBJECTIVE: To analyse life-threatening obstetric complications that occurred in public hospitals in Argentina. DESIGN: Multicentre collaborative cross-sectional study. SETTING: Twenty-five hospitals included in the Perinatal Network of Buenos Aires Metropolitan Area. POPULATION: Women giving birth in participating hospitals during a 1-year period. METHODS: All cases of severe maternal morbidity (SMM) and maternal mortality (MM) during pregnancy (including miscarriage and induced abortion), labour and puerperium were included. Data were collected prospectively. MAIN OUTCOME MEASURES: Identification criteria, main causes and incidence of SMM; case-fatality rates, morbidity-mortality index and effective intervention's use rate. RESULTS: A total of 552 women with life-threatening conditions were identified: 518 with SMM, 34 with MM. Identification criteria for SMM were case-management (48.9%), organ dysfunction (15.2%) and mixed criteria (35.9%). Incidence of SMM was 0.8% (95% confidence interval [95% CI] 0.73-0.87%) and hospital maternal death ratio was 52.3 per 100 000 live births (95% CI 35.5-69.1). Main causes of MM were abortion complications and puerperal sepsis; main causes of SMM were postpartum haemorrhage and hypertension. Overall case-fatality rate was 6.2% (95% CI 4.4-8.6): the highest due to sepsis (14.8%) and abortion complications (13.3%). Morbidity-mortality index was 15:1 (95% CI 7.5-30.8). Use rate of known effective interventions to prevent or treat main causes of MM and SMM was 52.3% (95% CI 46.9-57.7). CONCLUSIONS: This study describes the importance of life-threatening obstetric complications that took place in public hospitals with comprehensive obstetric care and the low utilisation of known effective interventions that may decrease rates of SMM and MM. It also provides arguments that justify the need to develop a surveillance system for SMM.

Active application of liquid etching agent improves adhesion of fibre posts to intraradicular dentine.

AIM: To assess the effectiveness of an active application of liquid etching, compared with the standard gel formulation on smear layer removal from post space walls and push-out bond strength of luted fibre posts. METHODOLOGY: Human extracted teeth were collected and root filled. After post space preparation and cleaning with 10% ethylenediaminetetraacetic acid for 30 s, teeth were assigned to four groups (n = 11) according to etching procedure: (i) 37% phosphoric acid (H3 PO4 ) gel; (ii) 37% H3 PO4 liquid applied with an endodontic needle; (iii) 37% H3 PO4 liquid applied with an Endovac; (iv) no etching procedure (control group). Three teeth per group were sectioned longitudinally and prepared for SEM examination to evaluate the presence of smear layer, debris, sealer/gutta-percha remnants, and the number of open tubules. Eight teeth per group were bonded with an etch-and-rinse adhesive, and fibre posts were luted with a resin-based cement. After cutting, specimens were prepared for a push-out test. Data were analysed by anova and post hoc tests (P < 0.05). RESULTS: Improved smear layer removal was obtained in Group 2, followed by Group 1, Group 3, and the control group (P < 0.05). The mean values for the bond strength of the push-out test were: Group 1, 8.3 ± 2.9 MPa (coronal); 7.7 ± 3.0 (middle); 3.3 ±1.9 MPa (apical); Group 2, 7.8 ± 2.1 MPa (coronal); 6.9 ± 3.9 MPa (middle); 3.7 ± 1.3 MPa (apical); Group 3, 9.7 ± 2.8 MPa (coronal); 8.6 ± 2.1 MPa (middle); 6.9 ± 2.3 MPa (apical); and Group 4, 2.9 ± 3.0 MPa (coronal); 2.6 ± 2.0 MPa (middle); 1.1 ± 2.0 MPa (apical). CONCLUSIONS: Liquid phosphoric acid applied with an endodontic needle yielded better canal wall smear layer removal and higher bond strength values when an etch-and-rinse system was used.

Progress in Dental Adhesive Materials.

There have been significant advances in adhesive dentistry in recent decades, with efforts being made to improve the mechanical and bonding properties of resin-based dental adhesive materials. Various attempts have been made to achieve versatility, introducing functional monomers and silanes into the materials' composition to enable the chemical reaction with tooth structure and restorative materials and a multimode use. The novel adhesive materials also tend to be simpler in terms of clinical use, requiring reduced number of steps, making them less technique sensitive. However, these materials must also be reliable and have a long-lasting bond with different substrates. In order to fulfill these arduous tasks, different chemical constituents and different techniques are continuously being developed and introduced into dental adhesive materials. This critical review aims to discuss the concepts behind novel monomers, bioactive molecules, and alternative techniques recently implemented in adhesive dentistry. Incorporating monomers that are more resistant to hydrolytic degradation and functional monomers that enhance the micromechanical retention and improve chemical interactions between adhesive resin materials and various substrates improved the performance of adhesive materials. The current trend is to blend bioactive molecules into adhesive materials to enhance the mechanical properties and prevent endogenous enzymatic degradation of the dental substrate, thus ensuring the longevity of resin-dentin bonds. Moreover, alternative etching materials and techniques have been developed to address the drawbacks of phosphoric acid dentin etching. Altogether, we are witnessing a dynamic era in adhesive dentistry, with advancements aiming to bring us closer to simple and reliable bonding. However, simplification and novelty should not be achieved at the expense of material properties.

Microbial contamination of resin composites inside their dispensers: An increased risk of cross-infection?

OBJECTIVES: To evaluate the effects of microorganisms' contamination inside the dispensing syringes of different types of resin-based composites (RBCs). METHODS: This study encompassed two sections. First, an anonymous electronic survey was submitted via Google forms to Italian dentists to acquire information about composite handling during clinical procedures. Then, a bench test was performed on nanohybrid RBCs differing in matrix chemistry and fillers [FiltekTM Supreme XTE (3MTM); Venus Pearl (Kulzer GmbH); Admira Fusion x-tra (Voco)] to evaluate the microbial viability on their surfaces with/out photocuring. Uncured RBCs were exposed to standardized inocula of Streptococcus Mutans, Candida Albicans, Lactobacillus Rhamnosus, or mixt plaque in an in vitro model reproducing clinical restorative procedures. Half of the RBC specimens were cured after exposure. Microbial viability was assessed using an MTT-based test. Statistical analysis included three-way ANOVA and Tukey's tests (p<0.05). RESULTS: Among 300 dentists completing the survey, the majority declared to use the spatula to carry the RBCs from the syringe to the dental cavity (50% same spatula; 35% two spatulas). However, 80% of respondents had personal feelings that using one spatula could be a source of cross-contamination. In vitro results using one spatula showed microbial contamination of all RBCs after one hour of storage. The contamination levels depended on the used strain and RBC type (p<0.0001), but photocuring did not reduce contamination (p = 0.2992). CONCLUSIONS: Microbial species' viability on uncured RBCs and after photocuring shows the existence of a considerable risk of cross-infection. Clinical procedures in Restorative Dentistry need to acknowledge and to reduce such risk during RBCs handling. CLINICAL SIGNIFICANCE: Dentists must be aware of the possibility of cross-infection during restorative procedures, especially when the same spatula is repeatedly used for placing RBC in the cavity.

Women's preference for caesarean section: a systematic review and meta-analysis of observational studies.

BACKGROUND: The striking increase in caesarean section rates in middle- and high-income countries has been partly attributed to maternal request. We conducted a systematic review and meta-analysis of women's preferences for caesarean section. OBJECTIVES: To review the published literature on women's preferences for caesarean section. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE, LILACS and PsychINFO was performed. References of all included articles were examined. SELECTION CRITERIA: We included studies that quantitatively evaluated women's preferences for caesarean section in any country. We excluded articles assessing health providers' preferences and qualitative studies. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened abstracts of all identified citations, selected potentially eligible studies, and assessed their full-text versions. We conducted a meta-analysis of proportions, and a meta-regression analysis to determine variables significantly associated with caesarean section preference. MAIN RESULTS: Thirty-eight studies were included (n = 19,403). The overall pooled preference for caesarean section was 15.6% (95% CI 12.5-18.9). Higher preference for caesarean section was reported in women with a previous caesarean section versus women without a previous caesarean section (29.4%; 95% CI 24.4-34.8 versus 10.1%; 95% CI 7.5-13.1), and those living in a middle-income country versus a high-income country (22.1%; 95% CI 17.6-26.9 versus 11.8%; 95% CI 8.9-15.1). AUTHORS' CONCLUSIONS: Only a minority of women in a wide variety of countries expressed a preference for caesarean delivery. Further research is needed to better estimate the contribution of women's demand to the rising caesarean section rates.

The combination of immunosuppressive drugs with 8-methoxypsoralen and ultraviolet a light modulates the myeloid-derived dendritic cell function.

The functional properties of myeloid dendritic cells (DCs) differ, depending on microenvironmental factors as well as on their stage of maturation. The main approaches for the selective enhancement of the tolerogenic properties of DCs include the induction of a pharmacological arrest of the DCs maturation and the genetical engineering of DCs expressing immunosuppressive molecules. Several immunosuppressive/anti-inflammatory agents have been discovered that potentially inhibit DC maturation and immunogenicity. Photopheresis (ECP) is an immunomodulatory therapy in which leucocytes are exposed to 8-methoxypsoralen (8-MOP) and ultraviolet (UV) A radiation (PUVA). The combination of ECP with immunosuppressive agents has demonstrated efficacy in the management of transplanted patients by reducing either the incidence of organ rejection or the pharmacological toxicity. In particular, we have observed in hepatitis C virus (HCV)-positive patients that the same combination has reduced the immunosuppressive burden and improved sustainability and efficacy of pre-emptive antiviral therapy after liver transplantation. Therefore, in our work we investigated the in vitro effects of PUVA, combined with immunosuppressive drugs (IDs), on both in vitro human DC generation and maturation, in order to contribute to understanding the immunological mechanisms underlying this pharmacological combination. Monocyte PUVA-treatment was performed by using an in vitro experimental protocol that we previously described. PUVA-treated or -untreated highly purified CD14+ cells were incubated with the association of the immunosuppressive drugs, used in the management of liver transplantation, at two different concentrations, in the presence of IL-4 and GM-CSF. The treatment with IDs at the highest concentration (corresponding to that used in clinical practice), alone or in association with PUVA, induced an immunosuppressive effect, by impairing both DC generation and maturation. Neither immunosuppressive drugs at the lowest concentration nor their combination with PUVA affected myeloid DC generation, but modified DC functions, strengthening the induction of a tolerogenic pattern. As this ID concentration was arbitrarily chosen, further experiments could highlight whether lower concentrations than those used in clinical practice would elicit the same effect on DCs and potentially improve their functional properties. This work describes an original experimental approach exploring the in vitro mechanism of action of the combined procedure of PUVA with immunosuppressive drugs, used in liver transplantation, on DCs generation and function. Our results contribute to the knowledge of the mechanisms of action of this combined procedure on DCs, suggesting useful therapeutic implications for the in vivo therapy.

Dentin Cross-linking Effect of Carbodiimide After 5 Years.

Carbodiimide (EDC)-based dentin primers preserve hybrid layer (HL) integrity. However, aging >1 y has not been investigated. The present study examined whether the cross-linking effect of EDC was reflected in dentin bond strength, endogenous enzymatic activity, and the chemical profile of the HL after 5-y aging in artificial saliva. Noncarious human third molars (N = 42) were cut to expose middle/deep coronal dentin and treated as follows: group 1, dentin etched with 35% H3PO4, pretreated with a 0.3M aqueous EDC primer for 1 min and restored with XP Bond (Dentsply Sirona); group 2, as in group 1 but without EDC pretreatment; group 3, Clearfil SE Bond (Kuraray-Noritake) primer applied to dentin surface, followed by EDC pretreatment as in group 1 and application of bond; group 4, as in group 3 without EDC pretreatment. After composite buildup, the specimens were cut into sticks or slabs, depending on the experiment. All tests were performed at baseline (T0) and after 5 y of aging (T5) in artificial saliva at 37 °C. Microtensile bond strength (µTBS) was tested at a crosshead speed of 1 mm/min until failure. Endogenous enzymatic activity was investigated with in situ zymography. The chemical profile of HL was determined via Raman spectroscopy. Three-way analysis of variance and post hoc Tukey test were used to analyze µTBS and in situ zymography data (α = 0.05). EDC pretreatment and aging significantly influenced µTBS and in situ zymography results (P < 0.05). Higher bond strength and lower gelatinolytic activity were identified in the EDC-treated groups at T5 (P < 0.05), especially in the etch-and-rinse groups. Raman spectra revealed less defined amide III peaks in control specimens at T5. The EDC cross-linking effect persisted in the HL for 5 y in terms of bond strength, collagen structure preservation, and dentinal enzyme silencing.

Feasibility and safety of granulocytapheresis in Crohn's disease: a prospective cohort study.

BACKGROUND AND OBJECTIVE: This study evaluated the feasibility and safety of granulocytapheresis (GCAP) in inducing and maintaining remission in refractory Crohn's disease. The relationship between the clinical outcomes and the location (ileal or ileocolonic) of disease was also assessed. PATIENTS: We evaluated 16 patients with ileal location (group A), 14 with ileocolonic location (group B). The patients underwent five sessions (1 session/wk) of GCAP (Adacolumn(TM)). CDAI was measured at the end of the GCAP, at 6, 9 and 12 months. RESULTS AND CONCLUSIONS: No major complications were observed. At the end of GCAP, 19 (63.3%) patients showed a clinical remission: 10 (62.5%) in group A versus 9 (64.2%) in group B. At 6 months, 16 (53.3%) of the cases had maintained remission: 9 (56.2%) in group A versus 7 (50.0%) in group B. At 9 months, 13 (43.3%) patients had maintained remission: 7 (43.7%) in group A versus 6 (42.8%) in group B. At 12 months, 12 (40%) patients were still in clinical remission: 7 (43.7%) in group A versus 5 (35.7%) in group B. Risk of relapse was not related to disease location. The procedure was well tolerated and feasible in an important percentage of Crohn's disease patients.