The Curious Case of Lip Tongue Fusion: A Consequence of Suboptimal Oral Care.

Oral care is an often difficult and an unappreciated part of hospital life. Patients who are unable to provide their own care rely on assistance from hospital personnel. Most sequelae from suboptimal oral care often present over months if not years, in the form of dental caries and periodontal disease. We present an exception, where a 66-year-old patient who experienced widespread ulceration and necrosis from Capnocytophaga-related sepsis received suboptimal oral care, resulting in their tongue being fused to their lip. This was later divided by the oral and maxillofacial team resulting in restoration of full function. Future cases can be avoided in patients with similar symptoms, such as Stevens-Johnson syndrome or erythema multiforme, if rigorous oral care can be provided.

A chemoenzymatic strategy for site-selective functionalization of native peptides and proteins.

The emergence of new therapeutic modalities requires complementary tools for their efficient syntheses. Availability of methodologies for site-selective modification of biomolecules remains a long-standing challenge, given the inherent complexity and the presence of repeating residues that bear functional groups with similar reactivity profiles. We describe a bioconjugation strategy for modification of native peptides relying on high site selectivity conveyed by enzymes. We engineered penicillin G acylases to distinguish among free amino moieties of insulin (two at amino termini and an internal lysine) and manipulate cleavable phenylacetamide groups in a programmable manner to form protected insulin derivatives. This enables selective and specific chemical ligation to synthesize homogeneous bioconjugates, improving yield and purity compared to the existing methods, and generally opens avenues in the functionalization of native proteins to access biological probes or drugs.

Extensive bony sarcoidosis of the head and neck region: a rare presentation.

We present a rare case of sarcoidosis with extensive bony destruction of the maxillofacial and skull base bones. A 65-year-old woman was referred with an asymptomatic, non-healing dental socket. Examination revealed an oroantral fistula that was biopsied and repaired under general anaesthesia. Investigations included plain and cross-sectional imaging. Serological tests, in particular ACE, were normal. Histology showed benign florid granulomatous inflammation. At 6 months, the patient remained asymptomatic. She was re-referred 3 years later with further bony destruction of her maxilla and mandible. Repeat imaging showed intrathoracic lymphadenopathy and skull base involvement. Repeat biopsy confirmed granulomatous inflammation. Given the pulmonary, histological and radiological findings, a sarcoidosis diagnosis was made. Following multidisciplinary team meetings, the patient was treated with methotrexate and arrangements made for close monitoring. This case highlights the need for a consensus in identifying, treating and developing a follow-up protocol in such patients.

Rab-E and its interaction with myosin XI are essential for polarised cell growth.

The fundamental process of polarised exocytosis requires the interconnected activity of molecular motors trafficking vesicular cargo within a dynamic cytoskeletal network. In plants, few mechanistic details are known about how molecular motors, such as myosin XI, associate with their secretory cargo to support the ubiquitous processes of polarised growth and cell division. Live-cell imaging coupled with targeted gene knockouts and a high-throughput RNAi assay enabled the first characterisation of the loss of Rab-E function. Yeast two-hybrid and subsequent in silico structural prediction uncovered a specific interaction between Rab-E and myosin XI that is conserved between P. patens and A. thaliana. Rab-E co-localises with myosin XI at sites of active exocytosis, and at the growing tip both proteins are spatiotemporally coupled. Rab-E is required for normal plant growth in P. patens and the rab-E and myosin XI phenotypes are rescued by A. thaliana's Rab-E1c and myosin XI-K/E, respectively. Both PpMyoXI and AtMyoXI-K interact with PpRabE14, and the interaction is specifically mediated by PpMyoXI residue V1422. This interaction is required for polarised growth. Our results suggest that the interaction of Rab-E and myosin XI is a conserved feature of polarised growth in plants.

Glandular Odontogenic Cyst with Metaplastic Cartilage: Report of an Unusual Case and Literature Review.

Glandular odontogenic cysts are rare odontogenic cysts with a wide range of histopathological features. In this paper we describe the clinical and pathological features of an unusual case of a glandular odontogenic cyst with metaplastic cartilage. The previous literature of odontogenic cysts presenting with metaplastic cartilage is reviewed alongside a discussion of the differential diagnoses. To our knowledge this is the first reported case of a glandular odontogenic cyst with metaplastic cartilage.

Standard Operating Procedures for Biospecimen Collection, Processing, and Storage: From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer.

High-quality and well-annotated biorepositories are needed to better understand the pathophysiology and biologic mechanisms of chronic pancreatitis (CP) and its consequences. We report a methodology for the development of a robust standard operating procedure (SOP) for a biorepository based on the experience of the clinical centers within the consortium to study Chronic Pancreatitis, Diabetes and Pancreas Cancer Clinical Centers (CPDPC), supported by the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases as a unique multidisciplinary model to study CP, diabetes, and pancreatic cancer in both children and adults. Standard operating procedures from the CPDPC centers were evaluated and consolidated. The literature was reviewed for standard biorepository operating procedures that facilitated downstream molecular analysis. The existing literature on biobanking practices was harmonized with the SOPs from the clinical centers to produce a biorepository for pancreatic research. This article reports the methods and basic principles behind the creation of SOPs to develop a biorepository for the CPDPC. These will serve as a guide for investigators developing biorepositories in pancreas research. Rigorous and meticulous adherence to standardized biospecimen collection will facilitate investigations to better understand the pathophysiology and biologic mechanisms of CP, diabetes, and pancreatic cancer.

Development of a stereoselective and scalable process for the preparation of a methylcyclobutanol-pyridyl ether.

The evolution of a scalable process for the preparation of methylcyclobutanol-pyridyl ether 1 is described. Key aspects of this development including careful control of the stereochemistry, elimination of chromatography, and application to kilogram-scale synthesis are addressed.

Predisposing Characteristics of Adjacent Segment Disease After Lumbar Fusion.

STUDY DESIGN: Retrospective Review. OBJECTIVE: The aim of this study was to determine medical, radiographic, and surgical risk factors for the development of adjacent segment disease (ASD) after lumbar fusion. SUMMARY OF BACKGROUND DATA: ASD is a recognized outcome of spinal fusion that leads to increased costs and debilitating symptoms for patients. However, a comprehensive understanding of risk factors for the development of this surgical outcome does not exist. METHODS: The medical records of patients who received their first lumbar fusion for any indication were retrospectively examined for preoperative medical comorbidities and medications, as well as surgical approach and perioperative complications. A blinded reviewer assessed radiographs for each patient to examine sagittal alignment after fusion. Multivariable logistic regression was used to model the risk of developing ASD on the basis of one or more predictors. RESULTS: A total of 137 patients fit the inclusion criteria; 9% required a follow-up operation for degeneration at segments adjacent to the fusion. The ASD group had a mean follow-up of 21.1 months prior to revision surgery and an overall follow-up of 41.0 months. The average follow-up in the control group was 14.0 months. Statistically significant independent predictors of developing ASD included antidepressant use [odds ratio (OR) = 5.4], diagnosis of degenerative scoliosis (OR = 34.2), fusion of L4-S1 (OR = 56.5), having no decompressions adjacent to the fusion, and low sacral slope (OR = 0.9). No patient who developed ASD received a decompression adjacent to the fusion such that an OR could not be generated for this independent predictor. CONCLUSION: This study is the first to use a combination of medical, surgical, and postoperative sagittal balance as risk factors for the development of adjacent segment disease after lumbar fusion. The awareness of these risk factors may allow for better patient selection and surgical technique to decrease the probability of acquiring this adverse outcome. LEVEL OF EVIDENCE: 4.

Diagnosis of giant cell arteritis: when should we biopsy the temporal artery?

Giant cell arteritis (GCA) can be diagnosed histopathologically by biopsy of the temporal artery, and clinically using the 5-point score of the 1990 American College of Rheumatology (ACR) classification. We aimed to find out whether some patients are referred for biopsy unnecessarily. We audited all referrals (n=100) made to the Department of Oral and Maxillofacial Surgery over 34 months, and used the ACR classification to find out whether patients had had a clinical diagnosis of GCA at referral (ACR score: 3 or more). We then compared them with the result of the biopsy. Of the 100 referred, 98 had a biopsy, and of them, 15 were diagnosed with GCA (2 results were not included). Thirteen of the 15 had already been diagnosed clinically (based on the ACR classification) at referral. Our results gave an ACR specificity of 96% (95% CI: 85% to 99%) but only 20% sensitivity (95% CI: 11% to 32%). There was a linear correlation of high ACR scores with histopathological confirmation. Biopsy is most beneficial when there is a degree of diagnostic uncertainty (ACR: 1 or 2), an atypical presentation, or when steroids may be relatively contraindicated. On the basis of our study, we designed a new referral form for biopsy based on the ACR criteria.

The long and winding road part 2. The CLP patient's journey, 0-21 years.

UNLABELLED: Patients with a cleft lip and palate (CLP) deformity require the highest standard of care that the NHS can provide and this requires multidisciplinary care from teams located in regional cleft centres. Care of these cases is from birth to adulthood and requires several phases of intervention, corresponding to the stages of facial and dental development. Management ideally starts pre-natally, following the initial diagnosis, and occasionally pre-surgical appliances are prescribed. The lip is ideally repaired within three months, followed by palate closure between 12 and 18 months. Careful monitoring is required in the first few years and ENT referral, where necessary, will diagnose middle ear infection, which commonly affects CLP patients. Speech therapy is an integral part of the ongoing care. Excellent oral hygiene is essential and preventive dietary advice must be given and regularly reinforced. Orthodontic expansion is often needed at 9 years of age in preparation for a bone graft and, once the permanent dentition erupts, definitive orthodontic treatment will be required. Maxillary forward growth may have been constrained by scarring from previous surgery, so orthognathic correction may be required on growth completion. Final orthodontic alignment and high quality restorative care will allow the patients to have a pleasing aesthetic result. CLP patients and their families will need continuing support from medical and dental consultants, specialist nurses, health visitors, speech and language specialists and, perhaps, psychologists. The first article in this series of two outlined the principles of care for the CLP patient and this second part illustrates this with a case report, documenting one patient's journey from birth to 21 years of age. CLINICAL RELEVANCE: A successful outcome for CLP patients requires a sound dentition.The general dental practitioner role is vital to establish and maintain excellent oral hygiene, a healthy diet and good routine preventive and restorative care. Understanding the total needs of CLP patients can help the dentist to provide high quality care as part of the multidisciplinary management.

Incidence and outcome of graft resorption in anterior lumbar interbody fusion: using femoral ring allografts and recombinant human bone morphogenetic protein-2.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To determine the incidence of resorption after anterior lumbar interbody fusion (ALIF) and its effect on outcome. SUMMARY OF BACKGROUND DATA: Recombinant human bone morphogenetic protein-2 (rhBMP-2) used in ALIF has been associated with a 0.5% to 82% incidence of resorption. This has been described as either a complication or part of the natural history. We postulate that early resorption (≤4 mo) in ALIF using femoral ring allograft augmented with rhBMP-2 supplemented with posterior instrumentation has no effect on outcome. METHODS: Institutional review board-approved retrospective 60 chart cohort study of ALIF using femoral ring allograft-augmented rhBMP-2 supplemented with posterior instrumentation from May 5, 2005, to April 6, 2010. Two groups were based upon the presence or absence of early graft resorption (≤4 mo). Patients were seen prior to surgery and postoperatively until 29 ± 20 months (last visit). Follow-up visual analogue scale pain scores and radiographical evidence of fusion were measured and compared between the 2 groups. RESULTS: Sixty patients, 27 females and 33 males had follow-up for 29 ± 20 months. Group 1 (33 patients, 45 levels) and group 2 (27 patients, 36 levels) were identical in age (P = 0.62), sex distribution (P = 0.43), preoperative pain score (P = 0.63), and in the rhBMP-2 dose per level (P = 0.77). There were no significant group differences in postoperative visual analogue scale scores but a trend to higher fusion rate in group 1 was seen (P = 0.07) at 6 months. There was a 40% incidence of early resorption with no significant differences in visual analogue scale scores or fusion rate between both groups. CONCLUSION: There is a 40% incidence of early resorption (≤4 mo) that had no significant effect on pain score or fusion rate. Resorption should be considered part of the fusion process and not necessarily a complication. LEVEL OF EVIDENCE: 3.

Sclerosing odontogenic carcinoma in the maxilla: a rare primary intraosseous carcinoma.

Sclerosing Odontogenic Carcinoma (SOC) was first described by Koutlas et al. in 2008. SOC is a low-grade odontogenic carcinoma, which presents as an expansile radiolucency that causes tooth displacement and root resorption. It is locally aggressive but reports suggest a very low probability of regional or distant metastasis. SOC contains small nests and thin cords of small cuboidal or polygonal epithelial cells with cytoplasmic clearing. Pleomorphism and mitoses are not prominent. Skeletal muscle and perineural infiltration with stromal sclerosis is characteristic. Immunohistochemically, SOC stains for cytokeratins (CK) 5/6 and 19, and e-cadherin. Nuclear staining with p63 is also positive. CK20, carcinoembryonic antigen and CAM 5.2 are negative. We report a rare entity of primary intraosseous carcinoma of the maxilla which has the clinical and histological markers of SOC. Occurrence in the maxilla has been reported only once before in the literature.

The long and winding road--the journey of a cleft lip and palate patient part 1.

UNLABELLED: Patients with a cleft lip and palate (CLP) deformity require the highest standard of care that can be provided and this requires multidisciplinary care from teams located in regional cleft centres. Care of these cases is from birth to adulthood and requires several phases of intervention, corresponding to the stages of facial and dental development. Management ideally starts pre-natally, following the initial diagnosis, and occasionally pre-surgical appliances are prescribed. The lip is ideally repaired within three months, followed by palate closure between 12 and 18 months. Careful monitoring is required in the first few years and ENT referral, where necessary, will diagnose middle ear infection, which commonly affects CLP patients. Speech therapy is an integral part of the ongoing care. Excellent oral hygiene is essential and preventive dietary advice must be given and regularly reinforced. Orthodontic expansion is often needed at 9 years of age in preparation for a bone graft and, once the permanent dentition erupts, definitive orthodontic treatment will be required. Maxillary forward growth may have been constrained by scarring from previous surgery, so orthognathic correction may be required on growth completion. Final orthodontic alignment and high quality restorative care will allow the patients to have a pleasing aesthetic result. CLP patients and their families will need continuing support from medical and dental consultants, specialist nurses, health visitors, speech and language specialists and, perhaps, psychologists. These two articles outline the principles of care for the CLP patient and, secondly, illustrate this with a case report, documenting one patient's journey from birth to 21 years of age. CLINICAL RELEVANCE: A successful outcome for CLP patients requires a sound dentition.The general dental practitioner role is vital to establish and maintain excellent oral hygiene, a healthy diet and good routine preventive and restorative care. Understanding the total needs of CLP patients can help the dentist to provide high quality care as part of the multidisciplinary management.

Fibrin microthreads support mesenchymal stem cell growth while maintaining differentiation potential.

We developed a method to produce discrete fibrin microthreads, which can be seeded with human mesenchymal stem cells (hMSCs) and used as a suture to enhance the efficiency and localization of cell delivery. To assess the efficacy of fibrin microthreads to support hMSC attachment, proliferation, and survival, microthreads (100 µm diameter per microthread) were bundled together, seeded with 50,000 hMSCs for 2 h, and cultured for 5 days. Cell density on microthread bundles increased over time in culture to a maximum average density of 731 ± 101 cells/mm(2) after 5 days. A LIVE/DEAD assay confirmed that the cells were viable, and Ki-67 staining verified hMSC proliferation. In addition, functional differentiation assays demonstrated that hMSCs cultured on microthreads retained their ability to differentiate into adipocytes and osteocytes. The results of this study demonstrate that fibrin microthreads support hMSC viability and proliferation, while maintaining their multipotency. We anticipate that these cell-seeded fibrin microthreads will serve as a platform technology to improve localized delivery and engraftment of viable cells to damaged tissue.

Management of type II odontoid fractures in the geriatric population: outcome of treatment in a rigid cervical orthosis.

STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze geriatric patients with Type II odontoid fractures treated either with rigid cervical orthosis (CO) or surgery (Odontoid Screw or Transarticular screw). SUMMARY OF BACKGROUND DATA: Our literature search did not yield any studies on the outcome of Type II odontoid fractures in geriatric population treated with the rigid CO. We therefore designed a study to analyze geriatric patients with Type II odontoid fractures treated with either rigid cervical collar or surgery. MATERIALS AND METHODS: This is a retrospective chart review of patients with Type II odontoid fractures between July 1998 and June 2006. Inclusion criteria consists of males and females of 70 years of age or older with Type II odontoid fractures who were treated with rigid cervical collar or surgery. Exclusion criteria were displacement >4 mm, posteriorly displaced fracture, neurologic compromise, multilevel cervical spine injury, and treatment in a halo vest. Medical comorbidities were assessed using the Modified Cumulative Illness Rating Scale for Geriatrics. Primary outcomes were mortality and fusion (union, stable nonunion, nonunion). Minimum of 3 months follow-up was acceptable. RESULTS: One hundred eighty four odontoid fractures were identified in 8 years. Twenty patients met our inclusion criteria (9 treated in rigid collar and 11 treated surgically). Median follow-up was 5.5 months. Out of 20 patients, 4 patients died (1 treated in CO, 3 treated surgically). Cumulative Illness Rating Scale for Geriatrics index was highest in patient treated in CO. In the rigid collar group, 6 patients had union (66.6%), and 2 developed stable nonunion (22.2%); whereas in the surgically treated group, 7 patients had union (87.5%), and 1 patient developed nonunion (12.5%). CONCLUSIONS: Patients treated nonoperatively in rigid collar seem to have an overall favorable outcome. A well-designed prospective study, to compare the outcomes of surgical intervention with nonsurgical management of Type II odontoid in elderly is recommended.