Results of a phase I trial with Haploidentical mbIL-21 ex vivo expanded NK cells for patients with multiply relapsed and refractory AML.

Natural killer (NK)-cells have potent anti-tumor effects, yet it remains unclear if they are effective for patients with relapsed acute myeloid leukemia (AML). In a phase I clinical trial, we treated 12 patients (median age 60 years) with refractory AML (median 5 lines of prior therapy, median bone marrow blast count of 47%) with fludarabine/cytarabine followed by 6 infusions of NK-cells expanded from haploidentical donors using K562 feeder cells expressing membrane-bound IL21 and 4-1BBL. Patients received 106-107/kg/dose. No toxicity or graft-versus-host disease (GVHD) was observed and MTD was not reached. Seven patients (58.3%) responded and achieved a complete remission (CR) with/without count recovery. Median time to best response was 48 days. Five responding patients proceeded to a haploidentical transplant from the same donor. After a median follow-up of 52 months, 1-year overall survival (OS) for the entire group was 41.7%, better for patients who responded with CR/CRi (57.14%), and for patients who responded and underwent transplantation (60%). Persistence and expansion of donor-derived NK-cells were identified in patients' blood, and serum IFNγ levels rose concurrently with NK cell infusions. A higher count-functional inhibitory KIR was associated with higher likelihood of achieving CR/CRi. In conclusion, we observed a significant response to ex vivo expanded NK-cell administration in refractory AML patients without adverse effects.

Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome.

CTNND1 encodes the p120-catenin (p120) protein, which has a wide range of functions, including the maintenance of cell-cell junctions, regulation of the epithelial-mesenchymal transition and transcriptional signalling. Due to advances in next-generation sequencing, CTNND1 has been implicated in human diseases including cleft palate and blepharocheilodontic (BCD) syndrome albeit only recently. In this study, we identify eight novel protein-truncating variants, six de novo, in 13 participants from nine families presenting with craniofacial dysmorphisms including cleft palate and hypodontia, as well as congenital cardiac anomalies, limb dysmorphologies and neurodevelopmental disorders. Using conditional deletions in mice as well as CRISPR/Cas9 approaches to target CTNND1 in Xenopus, we identified a subset of phenotypes that can be linked to p120-catenin in epithelial integrity and turnover, and additional phenotypes that suggest mesenchymal roles of CTNND1. We propose that CTNND1 variants have a wider developmental role than previously described and that variations in this gene underlie not only cleft palate and BCD but may be expanded to a broader velocardiofacial-like syndrome.

Pre-eruptive coronal resorption of unerupted molar teeth in orthodontic patients.

Pre-eruptive coronal resorption (PCR) is a rare phenomenon affecting unerupted permanent teeth. The aetiology of PCR is unknown and is often detected as an incidental finding. The prognosis of affected teeth can be extremely variable and may involve multidisciplinary management. The lower second permanent molars are commonly affected. The following is a description of three clinical cases of PCR affecting lower permanent molars in orthodontic patients.

Patient's experience of treatment for sleep apnoea with a mandibular advancement splint.

BACKGROUND AND AIMS: Obstructive sleep apnoea (OSA) is a well recognised clinical disorder in which there is narrowing and repeated collapse of the upper airway during sleep resulting in the cessation of breathing. Patients with mild to moderate sleep apnoea are often provided with mandibular advancement splint (MAS) therapy as a form of first line or definitive treatment. The aims of this audit were to evaluate patient satisfaction and success of MAS therapy. METHODS: 93 patients diagnosed with sleep apnoea and suitable for a splint were recruited prospectively at Queen Victoria Hospital, East Grinstead between January 2009 and October 2010. A patient satisfaction questionnaire was developed by health professionals involved in the care of patients with sleep apnoea and assessed for face and content validity and reliability. Participants completed the questionnaire six weeks after the splint was fitted. RESULTS: 44% who previously experienced snoring now reported no snoring and 47% reported less snoring since wearing the MAS appliance. 69% reported complete resolution of sleep apnoea symptoms. 37% experienced aching teeth and 33% experienced having a dry throat when wearing the appliance. 86% of sleeping partners felt that their quality of sleep was improved following their partners treatment. CONCLUSIONS: The standards set for each criteria in this audit were met. MAS treatment has a key role to play in the management of obstructive sleep apnoea with high rates of patient satisfaction and the majority of patients partners reporting a significant improvement in their own and their partners sleep quality.

Lip asymmetry and smile aesthetics.

Objective : To determine if lip asymmetry can affect lip aesthetics. Setting and Participants : A group of dentists (n = 40) and cleft patients (n = 40) were recruited from the dental hospital and cleft service. Interventions : Still photographic digital images of lips and teeth were manipulated to produce a computerized gradient of smile appearance with different degrees of upper-lip vertical asymmetry. These five photographs (with 0 mm representing "symmetry," and 1, 2, 2.5, and 3 mm, asymmetries) were assessed by participants using a 5-point Likert scale. Statistics : Descriptive statistics in addition to chi-square test were used to analyze the data. In order to satisfy the requirement of the chi-square test, the five smile ratings were reduced to three. Results : Lip asymmetry did affect relative smile aesthetics, as determined by dentists and cleft patients. Both the dentists and cleft patients rated the 0-mm photograph more attractive than the 2.5-mm and 3-mm smiles (P < .05). The 0-, 1-, and 2-mm smiles were indistinguishable for both dentists and cleft patients. Conclusion : Lip asymmetry affects smile aesthetics. However, cleft patients and dentists were tolerant of minor asymmetries. This suggests that small degrees of lip asymmetry do not affect relative smile aesthetics as much as large degrees of lip asymmetry (2.5 mm or more).

Assessment of slot sizes in self-ligating brackets using electron microscopy.

OBJECTIVE: To measure the slot dimensions of 0.022 inch self-ligating upper central incisor brackets from six manufacturers using electron microscopy, to compare the measured dimensions with the manufacturers' published dimensions, and to determine if the walls of the slots were parallel. MATERIALS: Six self-ligating upper central incisor brackets from four manufacturers (SmartClip and Clarity SL, 3M Unitek, Monrovia, CA, USA; Speed, Strite Industries Ontario, Canada; Damon MX, Ormco, Orange, CA, USA; In-Ovation R and In-Ovation C, Dentsply GAC, Bohemia NY, USA) were imaged with a scanning electron microscope and the slots heights measured. Intra-operator repeatability and accuracy were determined. RESULTS: All brackets had slot sizes that were significantly larger (p < 0.05) than the stated 0.022 inch. Speed brackets were 5.1 per cent larger (0.02311 inch) and the closest to the published dimension. The SmartClip brackets were 14.8 per cent larger (0.02526 inch) than the quoted slot size of 0.022 inch. In most brackets the distances between the slot walls was generally greater further from the bracket bases. CONCLUSIONS: The actual measurements of upper central incisor self-ligating brackets from six manufacturers were larger than the manufacturers' stated dimension, and the walls of the slots diverged from the bracket bases.

Presurgical cleft lip and palate orthopedics: an overview.

Patients with cleft lip and/or palate go through a lifelong journey of multidisciplinary care, starting from before birth and extending until adulthood. Presurgical orthopedic (PSO) treatment is one of the earliest stages of this care plan. In this paper we provide a review of the PSO treatment. This review should help general and specialist dentists to better understand the cleft patient care path and to be able to answer patient queries more efficiently. The objectives of this paper were to review the basic principles of PSO treatment, the various types of techniques used in this therapy, and the protocol followed, and to critically evaluate the advantages and disadvantages of some of these techniques. In conclusion, we believe that PSO treatment, specifically nasoalveolar molding, does help to approximate the segments of the cleft maxilla and does reduce the intersegment space in readiness for the surgical closure of cleft sites. However, what we remain unable to prove equivocally at this point is whether the reduction in the dimensions of the cleft presurgically and the manipulation of the nasal complex benefit our patients in the long term.