Systematic Review of Postoperative Velopharyngeal Insufficiency: Incidence and Association With Palatoplasty Timing and Technique.

Cleft palate is among the most common congenital disorders worldwide and is correctable through surgical intervention. Sub-optimal surgical results may cause velopharyngeal insufficiency (VPI). When symptomatic, VPI can cause hypernasal or unintelligible speech. The postoperative risk of VPI varies significantly in the literature but may be attributed to differences in study size, cleft type, surgical technique, and operative age. To identify the potential impact of these factors, a systematic review was conducted to examine the risk of VPI after primary palatoplasty, accounting for operative age and surgical technique. A search of PubMed, Embase, and Web of Science was completed for original studies that examined speech outcomes after primary palatoplasty. The search identified 4740 original articles and included 35 studies that reported mean age at palatoplasty and VPI-related outcomes. The studies included 10,795 patients with a weighted mean operative age of 15.7 months (range: 3.1-182.9 mo), and 20% (n=2186) had signs of postoperative VPI. Because of the heterogeneity in reporting of surgical technique across studies, small sample sizes, and a lack of statistical power, an analysis of the VPI risk per procedure type and timing was not possible. A lack of data and variable consensus limits our understanding of optimal timing and techniques to reduce VPI occurrence. This paper presents a call-to-action to generate: (1) high-quality research from thoughtfully designed studies; (2) greater global representation; and (3) global consensus informed by high-quality data, to make recommendations on optimal technique and timing for primary palatoplasty to reduce VPI.

High prevalence of deleterious mutations in concomitant nonsyndromic cleft and outflow tract heart defects.

Our previous work demonstrating enrichment of outflow tract (OFT) congenital heart disease (CHD) in children with cleft lip and/or palate (CL/P) suggests derangements in common underlying developmental pathways. The current pilot study examines the underlying genetics of concomitant nonsyndromic CL/P and OFT CHD phenotype. Of 575 patients who underwent CL/P surgery at Children's Hospital Los Angeles, seven with OFT CHD, negative chromosomal microarray analysis, and no recognizable syndromic association were recruited with their parents (as available). Whole genome sequencing of blood samples paired with whole-blood-based RNA sequencing for probands was performed. A pathogenic or potentially pathogenic variant was identified in 6/7 (85.7%) probands. A total of seven candidate genes were mutated (CHD7, SMARCA4, MED12, APOB, RNF213, SETX, and JAG1). Gene ontology analysis of variants predicted involvement in binding (100%), regulation of transcription (42.9%), and helicase activity (42.9%). Four patients (57.1%) expressed gene variants (CHD7, SMARCA4, MED12, and RNF213) previously involved in the Wnt signaling pathway. Our pilot analysis of a small cohort of patients with combined CL/P and OFT CHD phenotype suggests a potentially significant prevalence of deleterious mutations. In our cohort, an overrepresentation of mutations in molecules associated with Wnt-signaling was found. These variants may represent an expanded phenotypic heterogeneity within known monogenic disease genes or provide novel evidence of shared developmental pathways. The mechanistic implications of these mutations and subsequent developmental derangements resulting in the CL/P and OFT CHD phenotype require further analysis in a larger cohort of patients.

Predictors of Complication Following Cleft Lip and Palate Surgery in a Low-Resource Setting: A Prospective Outcomes Study in Nicaragua.

BACKGROUND: Higher rates of postoperative complication following cleft lip or palate repair have been documented in low resource settings, but their causes remain unclear. This study sought to delineate patient, surgeon, and care environment factors in cleft complications in a low-income country. DESIGN: Prospective outcomes study. SETTING: Comprehensive Cleft Care Center. PATIENTS: Candidate patients presenting for cleft lip or palate repair or revision. INTERVENTIONS: Patient anthropometric, nutritional, environmental and peri- and post-operative care factors were collected. Post-operative evaluation occurred at standard 1-week and 2-month postoperative intervals. MAIN OUTCOME MEASURES: Complication was defined as fistula, dehiscence and/or infection. RESULTS: Among 408 patients enrolled, 380 (93%) underwent surgery, of which 208 (55%) underwent lip repair (124) or revision (84), and 178 (47%) underwent palate repair (96) or revision (82). 322 (85%) were evaluated 1 week and 166 (44%) 2 months postoperatively. 50(16%) complications were identified, including: 25(8%) fistulas, 24(7%) dehiscences, 17(5%) infections. Mid-upper arm circumference (MUAC) ≤12.5 cm was associated with dehiscence after primary lip repair (OR = 28, p = 0.02). Leukocytosis ≥11,500 on pre-operative evaluation was associated with dehiscence (OR = 2.51, p = 0.04) or palate revision fistula (OR = 64, p < 0.001). Surgeons who performed fewer previous-year palate repairs had higher likelihood of palate complications, (OR = 3.03, p = 0.01) although there was no difference in complication rate with years of surgeon experience or duration of surgery. CONCLUSIONS: Multiple patient, surgeon, and perioperative factors are associated with higher rates of complication in a low-resource setting, and are potentially modifiable to reduce complications following cleft surgery.

The International Family Study of Nonsyndromic Orofacial Clefts: Design and Methods.

BACKGROUND: The majority of research to understand the risk factors of nonsyndromic orofacial clefts (NSOFCs) has been conducted in high-income populations. Although patients with NSOFCs in low- and middle-income countries (LMICs) are at the highest risk of not receiving care, global health infrastructure allows innovative partnerships to explore the etiologic mechanisms of cleft and targets for prevention unique to these populations. METHODS: The International Family Study (IFS) is an ongoing case-control study with supplemental parental trio data designed to examine genetic, environmental, lifestyle, and sociodemographic risk factors for NSOFCs in 8 LMICs (through August 2020). Interview and biological samples are collected for each family. The interview includes demographics, family history of cleft, diet and water sources, maternal pregnancy history, and other lifestyle and environmental factors. RESULTS: Seven of 8 countries are currently summarized (2012-2017) for a total of 2955 case and 2774 control families with 11 946 unique biological samples from Vietnam, Philippines, Honduras, Madagascar, Morocco, Democratic Republic of the Congo, and Nicaragua. The phenotype distribution was 1641 (55.5%) cases with cleft lip and palate, 782 (26.5%) with cleft lip (CL), and 432 (14.6%) with cleft palate (CP). DISCUSSION: The International Family Study is the largest case set of NSOFCs with an associated biobank in LMICs currently assembled. The biobank, family, and case-control study now include samples from 8 LMICs where local health care infrastructure cannot address the surgical burden of cleft or investigate causal mechanisms. The International Family Study can be a source of information and may collaborate with local public health institutions regarding education and interventions to potentially prevent NSOFCs.

Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

The Local Mission: Improving Access to Surgical Care in Middle-Income Countries.

BACKGROUND: Billions of people lack access to quality surgical care. Short-term missions are used to supplement the delivery of surgical care in regions with poor access to care. Traditionally known for using international teams, Operation Smile has transitioned to using a local mission model, where surgical service is delivered to areas of need by teams originating within that country. This study investigates the proportion and location of Operation Smile missions that use the local mission model. METHODS: A retrospective review was performed of the Operation Smile mission database for fiscal years 2014 to 2019. Missions were classified into local or international missions. Countries were also classified by their income levels as well as their specialist surgical workforce (SAO) density. As no individual patient or provider data was recorded, ethics board approval was not warranted. RESULTS: Between 2014 and 2019, Operation Smile held an average of 144.8 (range 135-154) surgical missions per year. Local missions accounted for 97 ± 5.6 (67%) of the missions. Of the 34 program countries, 26 (76%) used local missions. Of the countries that had only international missions, six (75%) were low-income countries and the average SAO density was 1.54 (range 0.19-5.88) providers per 100,000 people. Of the countries with local missions, 24 (92%) were middle-income, and the average SAO density was 30.9 (range 3.4-142.4). CONCLUSION: International investments may assist in the creation of local surgical teams. Once teams are established, local missions are a valuable way to provide specialized surgical care within a country's own borders.

The Use of Crowdsourcing Technology to Evaluate Preoperative Severity in Patients With Unilateral Cleft Lip in a Multiethnic Population.

ABSTRACT: Crowd sourcing has been used in multiple disciplines to quickly generate large amounts of diverse data. The objective of this study was to use crowdsourcing to grade preoperative severity of unilateral cleft lip phenotype in a multiethnic cohort with the hypothesis that crowdsourcing could efficiently achieve similar rankings compared to expert surgeons. Deidentified preoperative photos were collected for patients with primary, unilateral cleft lip with or without cleft palate (CL ±â€ŠP). A platform was developed with C-SATS for pairwise comparisons utilizing Elo rankings by crowdsource workers through Amazon Mechanical Turk. Images were independently ranked by 2 senior surgeons for comparison. Seventy-six patients with varying severity of unilateral (CL ±â€ŠP) phenotype were chosen from Operation Smile missions in Bolivia, Madagascar, Vietnam, and Morocco. Patients were an average of 1.2 years' old, ranging from 3 months to 3.3 years. Each image was compared with 10 others, for a total of 380 unique pairwise comparisons. A total of 4627 total raters participated with a median of 12 raters per pair. Data collection was completed in <20 hours. The crowdsourcing ranking and expert surgeon rankings were highly correlated with Pearson correlation coefficient of R = 0.77 (P = 0.0001). Crowdsourcing provides a rapid and convenient method of obtaining preoperative severity ratings, comparable to expert surgeon assessment, across multiple ethnicities. The method serves as a potential solution to the current lack of rating systems for preoperative severity and overcomes the difficulty of acquiring large-scale assessment from expert surgeons.

Factors Associated With Delay in Cleft Surgery at a Tertiary Children's Hospital in a Major US Metropolitan City.

OBJECTIVE: To identify factors associated with late cleft repair at a US tertiary children's hospital. DESIGN: Retrospective study of children with CL/P using Children's Hospital Los Angeles (CHLA) records. SETTING: US tertiary children's hospital. PATIENTS/PARTICIPANTS: Patients undergoing primary CL or CP repair at CHLA from 2009 to 2018. MAIN OUTCOME MEASURES: Proportion of children who had delayed primary CL repair or CP repair using CHLA and American Cleft Palate-Craniofacial Association (ACPA) guidelines and factors associated with late surgery. RESULTS: In total, 805 patients-503 (62.5%) who had CL repair, 302 (37.5%) CP repair-were included. Using CHLA protocol, 14.3% of patients seeking CL repair had delayed surgery. Delay was significantly associated with female gender, non-Hispanic ethnicity, Spanish primary language, government insurance, bilateral cleft, cleft lip and palate (CLP), and syndromic diagnosis. Using ACPA guidelines, 5.4% had delayed surgery. Female gender and syndromic diagnosis were significantly associated with delay and remained significant after adjustment for confounders in multivariate models. For CP repair, 60.3% of patients had delayed surgery using CHLA protocol. Cleft lip and palate diagnosis, complete cleft, syndromic diagnosis, and longer travel distance were significantly associated with delay. Using ACPA guidelines, 28.5% had delayed surgery; however, significant association with patient variables was not consistently observed. CONCLUSIONS: Delay in cleft surgery occurs most often for patients seeking CP repair and is associated with female gender, non-Hispanic ethnicity, Spanish language, government insurance, and bilateral CL, CLP, or syndromic diagnoses. Initiatives should aim to optimize cleft surgery delivery for these subpopulations.

The experiences of female surgeons around the world: a scoping review.

INTRODUCTION: The Lancet Commission for Global Surgery identified an adequate surgical workforce as one indicator of surgical care accessibility. Many countries where women in surgery are underrepresented struggle to meet the recommended 20 surgeons per 100,000 population. We evaluated female surgeons' experiences globally to identify strategies to increase surgical capacity through women. METHODS: Three database searches identified original studies examining female surgeon experiences. Countries were grouped using the World Bank income level and Global Gender Gap Index (GGGI). RESULTS: Of 12,914 studies meeting search criteria, 139 studies were included and examined populations from 26 countries. Of the accepted studies, 132 (95%) included populations from high-income countries (HICs) and 125 (90%) exclusively examined populations from the upper 50% of GGGI ranked countries. Country income and GGGI ranking did not independently predict gender equity in surgery. Female surgeons in low GGGI HIC (Japan) were limited by familial support, while those in low income, but high GGGI countries (Rwanda) were constrained by cultural attitudes about female education. Across all populations, lack of mentorship was seen as a career barrier. HIC studies demonstrate that establishing a critical mass of women in surgery encourages female students to enter surgery. In HICs, trainee abilities are reported as equal between genders. Yet, HIC women experience discrimination from male co-workers, strain from pregnancy and childcare commitments, and may suffer more negative health consequences. Female surgeon abilities were seen as inferior in lower income countries, but more child rearing support led to fewer women delaying childbearing during training compared to North Americans and Europeans. CONCLUSION: The relationship between country income and GGGI is complex and neither independently predict gender equity. Cultural norms between geographic regions influence the variability of female surgeons' experiences. More research is needed in lower income and low GGGI ranked countries to understand female surgeons' experiences and promote gender equity in increasing the number of surgical providers.

Congenital Heart Disease in Patients With Cleft Lip/Palate and Its Impact on Cleft Management.

OBJECTIVE: To evaluate characteristics of congenital heart disease (CHD) in patients with cleft lip and/or palate (CL/P) and assess potential associations with cleft outcomes. DESIGN: Retrospective review of all patients with CL/P who underwent primary cleft treatment from 2009 to 2015. SETTING: Children's Hospital Los Angeles, a tertiary hospital. PATIENTS: Exclusion criteria included microform cleft lip diagnosis, international patients, and patients presenting for secondary repair or revision after primary repair at another institution. MAIN OUTCOMES MEASURED: Patient demographics, prenatal and birth characteristics, CL/P characteristics, syndromic status, postoperative complications, and other outcomes were analyzed relative to CHD diagnoses and management. Patients with CL/P with (+CHD) were compared to those without (-CHD) CHD using χ2 tests and analysis of variance. RESULTS: Among 575 patients with CL/P, 83 (14.4%) had CHD. Congenital heart disease rates were significantly higher in patients with cleft palate (CP) compared to other cleft types (χ2, P = .009). Eighty-one (97.6%) out of 83 +CHD patients were diagnosed prior to initial CL/P surgical assessment. Twenty-three (27.7%) +CHD patients required surgical repair of 10 cardiac anomalies prior to cleft care. Congenital heart disease was associated with delayed CP repair and increased rates of fistula in isolated patients with CP. CONCLUSIONS: Congenital heart disease is known to be more prevalent in patients with CL/P. These data suggest the condition is particularly increased in patients with CP. Severe forms of CHD are diagnosed and treated prior to cleft care however postoperative fistula may be more common in patients with CHD. Therefore, careful attention is required for patient optimization and palatal flap dissection in patients with coexisting CHD and CL/P.

Alternatives to Autologous Bone Graft in Alveolar Cleft Reconstruction: The State of Alveolar Tissue Engineering.

Alveolar cleft reconstruction has historically relied on autologous iliac crest bone grafting (ICBG), but donor site morbidity, pain, and prolonged hospitalization have prompted the search for bone graft substitutes. The authors evaluated bone graft substitutes with the highest levels of evidence, and highlight the products that show promise in alveolar cleft repair and in maxillary augmentation. This comprehensive review guides the craniofacial surgeon toward safe and informed utilization of biomaterials in the alveolar cleft.A literature search was performed to identify in vitro human studies that fulfilled the following criteria: Level I or Level II of evidence, ≥30 subjects, and a direct comparison between a autologous bone graft and a bone graft substitute. A second literature search was performed that captured all studies, regardless of level of evidence, which evaluated bone graft substitutes for alveolar cleft repair or alveolar augmentation for dental implants. Adverse events for each of these products were tabulated as well.Sixteen studies featuring 6 bone graft substitutes: hydroxyapatite, demineralized bone matrix (DBM), ß-tricalcium phosphate (TCP), calcium phosphate, recombinant human bone morphogenic protein-2 (rhBMP-2), and rhBMP7 fit the inclusion criteria for the first search. Through our second search, the authors found that DBM, TCP, rhBMP-2, and rhBMP7 have been studied most extensively in the alveolar cleft literature, though frequently in studies using less rigorous methodology (Level III evidence or below). rhBMP-2 was the best studied and showed comparable efficacy to ICBG in terms of volume of bone regeneration, bone density, and capacity to accommodate tooth eruption within the graft site. Pricing for products ranged from $290 to $3110 per 5 mL.The balance between innovation and safety is a complex process requiring constant vigilance and evaluation. Here, the authors profile several bone graft substitutes that demonstrate the most promise in alveolar cleft reconstruction.

Patient Barriers to Accessing Surgical Cleft Care in Vietnam: A Multi-site, Cross-Sectional Outcomes Study.

BACKGROUND: Most people who lack adequate access to surgical care reside in low- and lower-middle-income countries. Few studies have analyzed the barriers that determine the ability to access surgical treatment. We seek to determine which barriers prevent access to cleft care in a resource-limited country to potentially enable barrier mitigation and improve surgical program design. METHODS: A cross-sectional, multi-site study of families accessing care for cleft lip and palate deformities was performed in Vietnam. A survey instrument containing validated demographic, healthcare service accessibility, and medical/surgical components was administered. The main patient outcome of interest was receipt of initial surgical treatment prior to 18 months of age. RESULTS: Among 453 subjects enrolled in the study, 216 (48%) accessed surgical care prior to 18 months of age. In adjusted regression models, education status of the patient's father (OR 1.64; 95% CI 1.1-2.5) and male sex (OR 1.61; 95% CI 1.1-2.4) were both associated with timely access to care. Distance and associated cost of travel, to either the nearest district hospital or to the cleft surgical mission site, were not associated with timing of access. In a sensitivity analysis considering care received prior to 24 months of age, cost to attend the surgical mission was additionally associated with timely access to care. CONCLUSIONS: Half of the Vietnamese children in our cohort were not able to access timely surgical cleft care. Barriers to accessing care appear to be socioeconomic as much as geographical or financial. This has implications for policies aimed at reaching vulnerable patients earlier.

The Prevalence of Congenital Heart Disease in Nonsyndromic Cleft Lip and/or Palate: A Systematic Review of the Literature.

BACKGROUND: Life-threatening anomalies, such as congenital heart disease (CHD) must be identified in patients with cleft lip and/or palate (CL/P) to minimize perioperative risk. Nevertheless, screening practices vary highly among cleft teams and programs, and little is known about the prevalence and clinical significance of CHD in nonsyndromic CL/P patients. Through a systematic literature review, this study examines the demographics and severity of CHD in the nonsyndromic CL/P population. The implications of concomitant CHD in providing safe and comprehensive cleft care both in the United States and abroad are discussed. METHODS: A systematic review of PubMed literature from 1980 to September 2015 was performed following PRISMA guidelines. Studies describing rates of CHD and severity of lesions specifically in nonsyndromic and all CL/P patients were included. Analysis of cumulative data was performed according to nonsyndromic status and cleft type. RESULTS: Twelve studies were found to meet inclusion criteria. Of the 4055 nonsyndromic CL/P patients who met inclusion criteria, 7.42% (n=301) had CHD, which was significantly greater than the general population (~1%; odds ratio [OR], 7.94; P<0.0001). Congenital heart disease was significantly more common in cleft palate (CP) (OR, 15.1), combined CL and palate (CL+P) (OR, 13.5), and CL (OR, 4.23) compared with the general population. Palatal clefts (CP and CL+P) had significantly increased odds of CHD compared with CL (OR, 3.58 and 3.19, respectively, both P<0.0001). The most common forms of CHD were atrial or ventricular septal defects (n=210, 74.2%), which typically do not require surgical intervention in the general population. Clinical significance of these CHD lesions in CL/P patients is not fully known. CONCLUSIONS: Cleft management programs aim to maximize the number of patients receiving care while maintaining patient safety. Appropriate evaluation of perioperative risk necessitates understanding the prevalence of CHD in CL/P patients and the severity of those lesions. Patients with CL/P, particularly patients with palatal clefts, have significantly higher odds of having CHD than the general population. Congenital heart disease is most likely to present as atrial or ventricular septal defects, which are lesions that are unlikely to impact safety during cleft repair surgery.

The effect of short-term preoperative nutritional intervention for cleft surgery eligibility.

BACKGROUND: Children with orofacial clefts are highly susceptible to malnutrition, with severe malnutrition restricting their eligibility to receive safe surgery. Ready-to-use therapeutic foods (RUTF) are an effective treatment for malnutrition; however, the effectiveness has not been demonstrated in this patient population prior to surgery. We studied the effectiveness of short-term RUTF use in transitioning children with malnutrition, who were initially ineligible for surgery, into surgical candidates. METHODS: A cohort of patients from Ghana, Honduras, Malawi, Madagascar, Nicaragua, and Venezuela enrolled in a nutrition program were followed by Operation Smile from June 2017 to January 2020. Age, weight, and length/height were tracked at each visit. Patients were included until they were sufficiently nourished (Z > = -1) with a secondary outcome of receiving surgery. The study was part of a collaborative program between Operation Smile (NGO), Birdsong Peanuts (peanut shellers and distributors), and MANA Nutrition (RUTF producer). RESULTS: A total of 556 patients were recruited between June 2017 and January 2020. At baseline 28.2% (n = 157) of patients were diagnosed with severe, 21.0% (n = 117) moderate, and 50.7% (n = 282) mild malnutrition. 324 (58.3%) presented for at least one return visit. Of those, 207 (63.7%) reached optimal nutrition status. By visit two, the mean z-score increased from -2.5 (moderate) to -1.7 (mild) (p < 0·001). The mean time to attain optimal nutrition was 6 weeks. There was a significant difference in the proportion of patients who improved by country(p < 0.001). CONCLUSION: Malnutrition prevents many children with orofacial clefts in low- and middle-income countries from receiving surgical care even when provided for free. This creates an even larger disparity in access to surgery. In an average of 6 weeks with an approximate cost of $25 USD per patient, RUTF transitioned over 60% of patients into nutritionally eligible surgical candidates, making it an effective, short-term preoperative nutritional intervention. Through unique partnerships, the expansion of cost-effective, large-scale nutrition programs can play a pivotal role in ensuring those at the highest risk of living with unrepaired orofacial clefts receive timely and safe surgical care.

Genome Analysis Using Whole-Exome Sequencing of Non-Syndromic Cleft Lip and/or Palate from Malagasy Trios Identifies Variants Associated with Cilium-Related Pathways and Asian Genetic Ancestry.

BACKGROUND: Orofacial clefts (OFCs) are common congenital disabilities that can occur as isolated non-syndromic events or as part of Mendelian syndromes. OFC risk factors vary due to differences in regional environmental exposures, genetic variants, and ethnicities. In recent years, significant progress has been made in understanding OFCs, due to advances in sequencing and genotyping technologies. Despite these advances, very little is known about the genetic interplay in the Malagasy population. METHODS: Here, we performed high-resolution whole-exome sequencing (WES) on non-syndromic cleft lip with or without palate (nCL/P) trios in the Malagasy population (78 individuals from 26 families (trios)). To integrate the impact of genetic ancestry admixture, we computed both global and local ancestries. RESULTS: Participants demonstrated a high percentage of both African and Asian admixture. We identified damaging variants in primary cilium-mediated pathway genes WNT5B (one family), GPC4 (one family), co-occurrence in MSX1 (five families), WDR11 (one family), and tubulin stabilizer SEPTIN9 (one family). Furthermore, we identified an autosomal homozygous damaging variant in PHGDH (one family) gene that may impact metabiotic activity. Lastly, all variants were predicted to reside on local Asian genetic ancestry admixed alleles. CONCLUSION: Our results from examining the Malagasy genome provide limited support for the hypothesis that germline variants in primary cilia may be risk factors for nCL/P, and outline the importance of integrating local ancestry components better to understand the multi-ethnic impact on nCL/P.

Cleft Lip and Palate Research in Low- and Middle-income Countries: A Scientometric Analysis.

Cleft lip and palate (CLP) comprise over 90% of the world's congenital anomalies and cause significant disability worldwide, while disproportionally burdening low- and middle-income countries (LMICs). Research can help inform strategies that reduce disparities in accessing CLP care. We performed a scientometric analysis of CLP research in LMICs to identify influential contributors and themes. METHODS: The authors searched seven citation databases accessed via Web of Science, from inception to March 2, 2021. Social network analysis was done using VOSviewer. The Kruskal-Wallis test and linear regression were used. RESULTS: In total, 1561 articles authored by 6414 researchers affiliated with 2113 organizations in 119 countries were included. Most authors (n = 6387, 99.6%) had published two or more articles. The USA (454 articles), Brazil (211 articles), China (175 articles), and India (127 articles) published the most. The most prolific institutions were the University of Sao Paulo (94 articles), the University of Pittsburgh (57 articles), and the University of Iowa (55 articles). Marazita ML (33 articles), Shi B (27 articles), and Murray JC (22 articles) had the highest number of publications. An estimated 510 articles (32.7%) were focused on epidemiology, 240 (15.4%) on management, and 54 (3.5%) on global plastic surgery for CLP. CONCLUSIONS: LMICs are disproportionally burdened by CLP, but research is limited and often produced by high-income countries. This study elucidates partnership and health system strengthening opportunities to improve LMIC research capacity and ultimately informs the management and outcomes for patients with CLP.

The influence of an all-female healthcare environment on mentorship and empowerment of female healthcare professionals.

Low- and middle-income countries (LMICs) have the greatest need for additional healthcare providers, and women outside the workforce help address the need. Women in healthcare need more mentorship and leadership training to advance their careers due to systemic barriers. This study evaluates how women working together on a medical team influences mentorship, leadership and empowerment. A single all-female volunteer team participating in a cleft surgery mission in Oujda, Morocco were surveyed before and after the mission. Statistical analysis with student's t-test or chi-squared were performed. 95 female volunteers from 23 countries participated on this team and 85% completed surveys. Volunteers from high-income countries (32%) and LMICs (68%) had similar mission roles (p = 0.58). Experience as a mission volunteer (p = 0.47), team leader (p = 0.28), and educator (p = 0.18) were equivalent between cohorts. 73% of women had previously received mentorship but 98% wanted more. 75% had previously mentored others, but 97% wanted to be mentors. 73% of volunteers who had no prior mentorship found their first mentor during the mission. All participants found a long-term peer relationship and felt motivated to mentor women at home. 95% were inspired to pursue leadership positions, advance professionally, and continue working with other women. This population of female healthcare professionals overwhelmingly desired more mentorship than is felt to be available. An all-female healthcare environment appears to provide opportunities for mentorship and create lasting motivation to teach, lead, and advance professionally. Findings raise the potential that increasing visibility of female professionals may effectively empower women in healthcare.

The Smile Index: Part 3. A Simple, Prognostic Severity Scale for Unilateral Cleft Palate.

BACKGROUND: Unilateral cleft palates have a large spectrum of variability. Key morphologic factors such as cleft width and palatal length are not represented in current classification systems. Palate length and velopharyngeal port size are clinically linked to speech outcomes, as the soft palate must close the posterior pharynx for proper phonation. This study investigates the relationship between objective preoperative measures and postoperative velopharyngeal port size, to define a reproducible severity scale. METHODS: Surgical data were prospectively collected from unilateral cleft palate patients in Morocco, Bolivia, Vietnam, and Madagascar. Key measurements were cleft width and palate width at the hard-soft palate junction, alveolar cleft width, vertical alveolar discrepancy, velopharyngeal port size. Cleft width ratio (CWR) was defined as the width of the cleft at the hard-soft junction, divided by the palate width. RESULTS: Seventy-six patients were evaluated. Thirty-one had complete clefts and average age at surgical repair was 2.9 years. Mean CWR was 0.50 ± 0.12. Palate length was increased by an average of 2.2 mm (11%) after palatoplasty. Multivariate analysis determined greater CWR and larger preoperative velopharyngeal ports were significantly correlated with a smaller percent change in palate length after palatoplasty (P < 0.01). CONCLUSIONS: A wider palatal cleft decreases the surgeon's ability to decrease velopharyngeal port size through palatoplasty. Given the ease of measurement even in low-resource settings, CWR may be a valuable tool for setting expectations for speech results, modifying surgical technique, and correlating future speech outcomes in evidence-based cleft care.

Convolutional Neural Network Models for Automatic Preoperative Severity Assessment in Unilateral Cleft Lip.

BACKGROUND: Despite the wide range of cleft lip morphology, consistent scales to categorize preoperative severity do not exist. Machine learning has been used to increase accuracy and efficiency in detection and rating of multiple conditions, yet it has not been applied to cleft disease. The authors tested a machine learning approach to automatically detect and measure facial landmarks and assign severity grades using preoperative photographs. METHODS: Preoperative images were collected from 800 unilateral cleft lip patients, manually annotated for cleft-specific landmarks, and rated using a previously validated severity scale by eight expert reviewers. Five convolutional neural network models were trained for landmark detection and severity grade assignment. Mean squared error loss and Pearson correlation coefficient for cleft width ratio, nostril width ratio, and severity grade assignment were calculated. RESULTS: All five models performed well in landmark detection and severity grade assignment, with the largest and most complex model, Residual Network, performing best (mean squared error, 24.41; cleft width ratio correlation, 0.943; nostril width ratio correlation, 0.879; severity correlation, 0.892). The mobile device-compatible network, MobileNet, also showed a high degree of accuracy (mean squared error, 36.66; cleft width ratio correlation, 0.901; nostril width ratio correlation, 0.705; severity correlation, 0.860). CONCLUSIONS: Machine learning models demonstrate the ability to accurately measure facial features and assign severity grades according to validated scales. Such models hold promise for the creation of a simple, automated approach to classifying cleft lip morphology. Further potential exists for a mobile telephone-based application to provide real-time feedback to improve clinical decision making and patient counseling.