Faculty Bibliography

Background/Purpose: Intraoral myomucosal flaps such as the facial artery myomucosal (FAMM) flap and the buccal flap can provide effective palatal lengthening for the management of velopharyngeal insufficiency (VPI). This surgical approach is not without limitations and can result in increased postoperative burden to the patient and caregiver and frequently involves a second anesthetic event for pedicle division and flap inset. We sought to analyze the postoperative speech and functional outcomes of patients undergoing such procedures at our institution. Methods/Description: A retrospective assessment of all patients undergoing intraoral myomucosal flaps by a single surgeon at a tertiary academic institution was conducted. Only patients undergoing bilateral FAMM or buccal flaps for VPI were included. Data included demographic characteristics, flap-related complications, and postoperative speech and oral function. Results were compared between 2 age groups (group 1: <13, group 2: >=13). Analysis was performed over 5 clinical time points: preoperatively (T0), and postoperatively at 1 to 4 weeks (T1), 3 to 6 months (T2), and 1 to 3 years (T3).
Result(s): Of 54 patients reviewed, 24 met inclusion criteria: fourteen (58.3%) underwent bilateral FAMM flaps and 10 (41.7%) buccal flaps. Group 1 included 15 (62.5%) patients (median age: 6; range: 4-12) and group 2 included 9 (37.5%; median age: 23; range: 13-52). Group 1 patients were more likely to undergo buccal (60%), whereas group 2 were more likely to undergo FAMM flaps (88.9%). No intraor postoperative donor site complications, bleeding, flap necrosis, or dehiscence were noted. Subsequent pedicle division was performed in 66.7% of patients in group 1 (median: 35 days, range: 18-174) and 55.6% in group 2 (median: 46 days, range: 35-980) for interference with mastication in 10 (41.7%) patients, timing with other elective procedures in 3 (12.5%), or molar eruption in 1 patient. Ten (41.7%) patients had longitudinal speech follow-up, 70% of which were from group 1. Structural hypernasality had completely resolved in 80% of patients at T1, and in the rest by T3. At T1, >50% displayed abnormal occlusion or tongue placement and weak articulatory contact, which subsequently resolved. Dysphagia, drooling, or reduced oral opening were noted at T1 in most patients but had largely resolved on follow-up.
Conclusion(s): FAMM and buccal flaps are effective palatal lengthening procedures with 100% resolution of structural hypernasality and minimal complications in our series. Patient age and timing of division of flap pedicles may have an effect on postoperative oral function. Our findings support the early division of FAMM and buccal flap pedicles

Background/Purpose: Cleft deformities of the lip and palate affect nearly one in 500 to 700 births and lead to increased morbidity and mortality if untreated. Nevertheless, significant global disparities in access to timely and appropriate care still exist. The relatively basic infrastructure required to surgically correct these deformities and large unmet disease burden have resulted in a significant number of foundation-based cleft care initiatives focused toward developing countries. In this study, we evaluate the peer-reviewed literature generated by these foundations in an attempt to assess their clinical, scientific, educational, and economic impact. Methods/Description: A comprehensive review of the literature was performed using key search terms, and the level of evidence of identified articles was determined. Data were then analyzed to determine the different models of foundation-based cleft care in developing countries, as well as their clinical, scientific, educational, and economic impact.
Result(s): A total of 244 articles were identified through our search and reviewed. The levels of evidence of these articles were also determined, and included 3 (1.2%) level I, 62 (25.4%) level II, 11 (4.5%) level III, 59 (24.2%) level IV, 53 (21.7%) level V, and 56 (23.0%) articles that were not gradable. Foundation-based cleft care initiatives in developing countries have significantly contributed to a better understanding of disease epidemiology, barriers to care, safety considerations, complications and outcomes, as well as international and local cleft surgery education. The cleft care center model is more cost-effective than the surgical mission model and provides more sustainable care.
Conclusion(s): Foundation-based cleft care prevents significant morbidity in developing countries and has provided valuable resources for capacity building. The surgical mission model should be considered as a transitory conduit for establishing the more effective and sustainable cleft care center model of care

Background/Purpose: Identify components needed to create a sustainable model. Methods/Description: Global Smile Foundation (GSF) is a not-forprofit foundation whose volunteers have been providing outreach cleft care in Guayaquil, Ecuador, for over 3 decades. Building on GSF's efforts to provide comprehensive and multidisciplinary cleft care yearround, an advanced training program in NasoAlveolar Molding (NAM) therapy was started in 2012 as part of GSF's empowerment and sustainability initiative. Components needed in host country were (1) establishing infrastructure, (2) cleft team (including cleft surgeon, speech pathologist, dental and psychosocial health-care professionals), (3) training of qualified local cleft health-care providers to ensure continued treatment and follow up, (4) academic collaboration: provide qualified trainers for NAM (didactic, clinical, laboratory), (5) local ownership and leadership, (6) local empowerment and sustainability programs, (7) yearly Follow-up.
Result(s): Year 1 (2012): 3 months training of 2 NAM providers (prosthodontist, orthodontist) prior to yearly surgical mission. Twenty patients treated w/NAM, NAM center continued year round, new patients followed by local cleft surgeon. Year 2 (2013): Existing providers train additional new provider (orthodontist) under supervision of visiting trainers. Fifty-seven patients treated w/NAM for the cleft team. Year 3 (2014): under same model, 2 new NAM providers trained (pediatric dentists). Year 4 (2015): Both providers remain at center, one becomes cleft team coordinator. Official cleft team established. Year 5 (2016): 2 international providers (pediatric dentist, orthodontist) selected for training to integrate NAM into their comprehensive cleft care model. NAM training expanded to cover educational components needed to set up comprehensive cleft team and NAM clinic in home settings. Training timed during surgical mission to rotate in all specialties and expanded to include online modules. Year 6 (2017): 2 new providers trained (periodontist, dentist) to remain at cleft center year round. Year 7 (2018): 3 International GSF providers (dentist, orthodontists) trained to provide NAM treatment at their centers. Total of 175 patients treated w/NAM. 2012-2018: Twelve dental providers trained in presurgical NAM and comprehensive cleft care in an outreach setting (7 from Ecuador, 2 from Peru, 1 from Salvador, 1 from Nicaragua, 1 from Egypt). 2012 Fundacion Global Smile-Ecuador was founded to ensure sustainability of ongoing and expanding cleft care programs. 2015 Comprehensive Cleft Center officially established at Leon Becerra Hospital in Guayaquil, Ecuador. In addition to their support of GSF's surgical missions, the local governorship started funding a presurgical NAM position to deliver presurgical and dental care year-round. By 2018, 175 patients had received NAM therapy.
Conclusion(s): Over the 7 years, our experience has shown, in addition to academic training and follow-up, local empowerment is key for long-term sustainability of the model

BACKGROUND:mAb114 is a single monoclonal antibody that targets the receptor-binding domain of Ebola virus glycoprotein, which prevents mortality in rhesus macaques treated after lethal challenge with Zaire ebolavirus. Here we present expedited data from VRC 608, a phase 1 study to evaluate mAb114 safety, tolerability, pharmacokinetics, and immunogenicity. METHODS:In this phase 1, dose-escalation study (VRC 608), conducted at the US National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA), healthy adults aged 18-60 years were sequentially enrolled into three mAb114 dose groups of 5 mg/kg, 25 mg/kg, and 50 mg/kg. The drug was given to participants intravenously over 30 min, and participants were followed for 24 weeks. Participants were only enrolled into increased dosing groups after interim safety assessments. Our primary endpoints were safety and tolerability, with pharmacokinetic and anti-drug antibody assessments as secondary endpoints. We assessed safety and tolerability in all participants who received study drug by monitoring clinical laboratory data and self-report and direct clinician assessment of prespecified infusion-site symptoms 3 days after infusion and systemic symptoms 7 days after infusion. Unsolicited adverse events were recorded for 28 days. Pharmacokinetic and anti-drug antibody assessments were completed in participants with at least 56 days of data. This trial is registered with ClinicalTrials.gov, number NCT03478891, and is active but no longer recruiting. FINDINGS/RESULTS:Between May 16, and Sept 27, 2018, 19 eligible individuals were enrolled. One (5%) participant was not infused because intravenous access was not adequate. Of 18 (95%) remaining participants, three (17%) were assigned to the 5 mg/kg group, five (28%) to the 25 mg/kg group, and ten (55%) to the 50 mg/kg group, each of whom received a single infusion of mAb114 at their assigned dose. All infusions were well tolerated and completed over 30-37 min with no infusion reactions or rate adjustments. All participants who received the study drug completed the safety assessment of local and systemic reactogenicity. No participants reported infusion-site symptoms. Systemic symptoms were all mild and present only in four (22%) of 18 participants across all dosing groups. No unsolicited adverse events occurred related to mAb114 and one serious adverse event occurred that was unrelated to mAb114. mAb114 has linear pharmacokinetics and a half-life of 24·2 days (standard error of measurement 0·2) with no evidence of anti-drug antibody development. INTERPRETATION/CONCLUSIONS:mAb114 was well tolerated, showed linear pharmacokinetics, and was easily and rapidly infused, making it an attractive and deployable option for treatment in outbreak settings. FUNDING/BACKGROUND:Vaccine Research Center, US National Institute of Allergy and Infectious Diseases, and NIH.

BACKGROUND:The principle of relative motion has allowed patients to regain a higher degree of hand function, while protecting extensor tendon repairs. The purpose of this study was to determine whether the principle of relative motion could be a viable method to protect a flexor tendon repair. METHODS:Four fresh-frozen cadaver arms were each mounted on a testing apparatus (wrist in 30° of extension, metacarpophalangeal [MCP] joints blocked to 70°-80°). A minimum of 11 N was used to cyclically load the flexor digitorum profundus and extensor digitorum communis tendons to maximum allowable flexion and extension for 25 cycles. Measurements of elongation of the tendons were obtained through the use of differential variable reluctance transducers. Testing was performed in both intact and repaired (single 6-0 nylon suture) middle finger tendons (zone 3) with and without a relative motion flexion splint (RMFS), which placed the affected finger in 15° to 25° of relative flexion at the MCP joint. RESULTS:In all 4 hands, elongation was restricted to less than 1.3 mm in repaired tendon in the RMFS compared with elongation >2 mm in the nonsplinted condition. Average elongation was 0.86 mm (SD = 0.45). Visual examination of the tendons demonstrated no gapping with the use of the RMFS in any of the hands. All repairs had suture breakage and repair rupture without the RMFS. CONCLUSIONS:This study demonstrates that the RMFS decreases elongation and eliminates tendon-repair gapping after flexion/extension cycling in a cadaver model. It provides proof of concept that the RMFS may be a viable protective mechanism for flexor tendon repairs in zone 3.

Pressure injuries/ulcers are a global health issue, and there is a need for clinicians from many countries and continents to express their opinions on the terminology change (pressure ulcer to injury) and revised staging definitions. A convenience, opinion survey sample of clinicians from the Western Asia Gulf Region enrolled in a yearlong wound care course participated by expressing their opinion about these changes. Results reveal support for the pressure injury terminology and the revised staging definitions.

Bone cancer metastasis is extremely painful and decreases the quality of life of the affected patients. Available pharmacological treatments are not able to sufficiently ameliorate the pain and as cancer patients are living longer new treatments for pain management are needed. Decitabine (5-aza-2'-deoxycytidine), a DNA methyltransferases inhibitor, has analgesic properties in pre-clinical models of post-surgical and soft tissue oral cancer pain by inducing an up-regulation of endogenous opioids. In this study, we report that daily treatment with decitabine (2µg/g, i.p.) attenuated nociceptive behavior in the 4T1-luc2 mouse model of bone cancer pain. We hypothesized that the analgesic mechanism of decitabine involved activation of the endogenous opioid system through demethylation and reexpression of the transcriptionally silenced endothelin B receptor gene, Ednrb. Indeed, Ednrb was hypermethylated and transcriptionally silenced in the mouse model of bone cancer pain. We demonstrated that expression of Ednrb in the cancer cells lead to release of β-endorphin in the cell supernatant which reduced the number of responsive DRG neurons in an opioid-dependent manner. Our study supports a role of demethylating drugs, such as decitabine, as unique pharmacological agents targeting the pain in the cancer microenvironment.

BACKGROUND:Single-stage primary cleft lip and palate (PCLP) repair is controversial in the United States, and most patients are treated with a staged approach. In this study, early postoperative complications of the single-stage approach as compared to primary cleft lip (PCL) or primary cleft palate (PCP) alone were evaluated. This study represents the largest cohort of patients undergoing combined cleft lip and palate repair. METHODS:The American College of Surgeons National Surgical Quality Improvement Program-Pediatric database was used to identify patients undergoing single-stage PCLP, PCL, or PCP repairs. Preoperative factors and postoperative outcomes were compared between the 3 groups, as well as within the PCLP group between patients with and without complications. Univariate and multivariate analyses were performed. RESULTS:A TOTAL OF:: 181 patients were included in the single-stage PCLP group, 1007 in the PCP group and 783 in the PCL group. There was no difference in the rates of early complications between the 3 groups. Within the PCLP group, cardiac risk factors (β = 35.19; 95% confidence interval [CI] 7.88-75.21; P = 0.04) and complications (β = 77.31; 95% CI 35.82-118.79; P < 0.001) were significant risk factors for longer operative time. CONCLUSION/CONCLUSIONS:Analysis of a national database showed that single-stage PCLP repair is not associated with increased risk of early postoperative complications as compared to primary lip or palate repair alone. In-depth long-term analyses of craniofacial morphology, fistulae rate, speech, and dental outcomes are essential for a comprehensive assessment of the effects of combined cleft lip and palate repair.