The importance of predicting patient responses to monoclonal antibodies for Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a chronic immune-mediated inflammatory bowel disease that results in relapsing and remitting symptoms but progressive transmural bowel damage leading to significant morbidity. CD results from dysregulation of the immune system related to genetic and environmental factors. While the use of monoclonal antibodies targeting cytokines and adhesion molecules has been shown to improve outcomes in CD patients, their widespread use has been limited due to high costs as well as variable access. Here, we summarize the factors that have been shown to correlate with responsiveness to biologic agents for use in practice. AREAS COVERED: We summarize the current literature regarding factors that have been shown to influence patient response to various biologic agents including: patient-related factors (e.g. age, gender, weight smoking history); disease-specific factors (e.g. disease duration, location/extension, behavior/phenotype, severity); genetic markers; transcription factors, and the gut microbiome. Finally, we review the utility of prediction models and present data supporting the use of recently developed decision support tools. EXPERT OPINION: Clinical decision support tools developed by machine learning are currently available for the selection of biologic agents in CD patients. We expect these models to become an integral tool for clinicians in the treatment of CD in the coming years.

Dental students' perception of a blended learning approach to clinic orientation.

PURPOSE/OBJECTIVES: The pandemic presented a big challenge to dental education: rapid conversion of a hands-on, experiential learning program to a virtual environment. The objectives of this study are to examine the conventional approaches of facilitating the transition from pre-clinic to clinic, to analyze how a blended learning approach including virtual learning modules facilitated this transition, and to assess the benefits of virtual learning in the future of dental school curriculum. METHODS: Rising third-year dental students in 2020 (n = 134) were engaged in a three-month (from the end of May to the end of August 2020) clinic orientation consisting of virtual didactic and clinic simulated activities. Part I consisted of didactic courses presented virtually. Part II consisted of simulated clinical activities for operative and radiology along with 3-week virtual treatment planning (TP) sessions with quizzes for each week. Part III consisted of clinical assisting and shadowing activities in the clinic on restorative procedures and TP sessions with senior students. Surveys were administered before and after each part of the orientation program. RESULTS: Data confirmed that 1) virtually-delivered didactic materials increased students' knowledge in learning relevant key topics of clinic transition and 2) virtual TP sessions increased students' perceived confidence and knowledge in assessment and TP. CONCLUSION: Despite challenges faced during school closure, most dental students positively valued the virtual orientation methods of learning. Integrating a virtual mode of didactic can serve as a new methodology of the dental school curriculum in preparation for the clinic.

Assessment of the radiant emittance of damaged/contaminated dental light-curing tips by spectrophotometric methods.

OBJECTIVES: This study investigated the effects of physically damaged and resin-contaminated tips on radiant emittance, comparing them with new undamaged, non-contaminated tips using 3 pieces of spectrophotometric laboratory equipment. MATERIALS AND METHODS: Nine tips with damage and/or resin contaminants from actual clinical situations were compared with a new tip without damage or contamination (control group). The radiant emittance was recorded using 3 spectrophotometric methods: a laboratory-grade thermopile, a laboratory-grade integrating sphere, and a portable light collector (checkMARC). RESULTS: A significant difference between the laboratory-grade thermopile and the laboratory-grade integrating sphere was found when the radiant emittance values of the control or damaged/contaminated tips were investigated (p < 0.05), but both methods were comparable to checkMARC (p > 0.05). Regardless of the method used to quantify the light output, the mean radiant emittance values of the damaged/contaminated tips were significantly lower than those of the control (p < 0.05). The beam profile of the damaged/contaminated tips was less homogeneous than that of the control. CONCLUSIONS: Damaged/contaminated tips can reduce the radiant emittance output and the homogeneity of the beam, which may affect the energy delivered to composite restorations. The checkMARC spectrophotometer device can be used in dental offices, as it provided values close to those produced by a laboratory-grade integrated sphere spectrophotometer. Dentists should assess the radiant emittance of their light-curing units to ensure optimal curing in photoactivated, resin-based materials.

Assessing the benefit of reoperations in patients who suffer from fecal incontinence after repair of their anorectal malformation.

BACKGROUND AND AIM: Patients with a previously repaired anorectal malformation (ARM) can suffer from complications which lead to incontinence. Reoperation can improve the anatomic result, but its impact on functional outcomes is unclear. METHODS: We performed a retrospective cohort study of patients with a previously repaired ARM who underwent redo PSARP at our Center and compared results at initial assessment and 12 months after redo. RESULTS: One hundred fifty-three patients underwent a redo PSARP for anoplasty mislocation (n=93, 61%), stricture (n=55, 36%), remnant of the original fistula (n=28, 18%), or rectal prolapse (n=11, 7%). Post-redo complications included stricture (n=33, 22%) and dehiscence (n=5, 3%). At 1-year post-redo, 75/153 (49%) are on laxatives only, of whom 57 (76%) are continent of stool. Of the remaining 78 (51%) patients, 61 (78%) are clean (≤1 accident per week) on enemas. Interestingly, 16/79 (20%) of patients with expected poor continence potential were continent of stool on laxatives. Overall, 118/153 (77%) are clean after their redo. Quality of life (76.7 vs. 83.8, p=0.05) and Baylor continence (29.2 vs. 17.7, p=<0.0001) scores improved. CONCLUSION: Patients with fecal incontinence after an ARM repair can, with a reoperation, have their anatomy corrected which can restore continence for many, and improve their quality of life. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective cohort study.

Role of proNGF/p75 signaling in bladder dysfunction after spinal cord injury.

Loss of bladder control is a challenging outcome facing patients with spinal cord injury (SCI). We report that systemic blocking of pro-nerve growth factor (proNGF) signaling through p75 with a CNS-penetrating small-molecule p75 inhibitor resulted in significant improvement in bladder function after SCI in rodents. The usual hyperreflexia was attenuated with normal bladder pressure, and automatic micturition was acquired weeks earlier than in the controls. The improvement was associated with increased excitatory input to the spinal cord, in particular onto the tyrosine hydroxylase-positive fibers in the dorsal commissure. The drug also had an effect on the bladder itself, as the urothelial hyperplasia and detrusor hypertrophy that accompany SCI were largely prevented. Urothelial cell loss that precedes hyperplasia was dependent on p75 in response to urinary proNGF that is detected after SCI in rodents and humans. Surprisingly, death of urothelial cells and the ensuing hyperplastic response were beneficial to functional recovery. Deleting p75 from the urothelium prevented urothelial death, but resulted in reduction in overall voiding efficiency after SCI. These results unveil a dual role of proNGF/p75 signaling in bladder function under pathological conditions with a CNS effect overriding the peripheral one.

Implications of phase variation of a gene (pgtA) encoding a pilin galactosyl transferase in gonococcal pathogenesis.

The pilin glycoprotein (PilE) is the main building block of the pilus of Neisseria gonorrhoeae (gonococcus [GC]). GC pilin is known to carry a disaccharide O-glycan, which has an alphaGal attached to the O-linked GlcNAc by a 1-3 glycosidic bond. In this report, we describe the cloning and characterization of the GC gene, pilus glycosyl transferase A (pgtA), which encodes the galactosyl transferase that catalyzes the synthesis of this Gal-GlcNAc bond of pilin glycan. A homopolymeric tract of Gs (poly-G) is present in the pgtA gene of many GC strains, and this pgtA with poly-G can undergo phase variation (Pv). However, in many other GC, pgtA lacks the poly-G and is expressed constitutively without Pv. Furthermore, by screening a large number of clinical isolates, a significant correlation was observed between the presence of poly-G in pgtA and the dissemination of GC infection. Poly-G was found in pgtA in all (24 out of 24) of the isolates from patients with disseminated gonococcal infection (DGI). In contrast, for the vast majority (20 out of 28) of GC isolated from uncomplicated gonorrhea (UG) patients, pgtA lacked the poly-G. These results indicate that Pv of pgtA is likely to be involved in the conversion of UG to DGI.