The Influence of Sidedness in Unilateral Cleft Lip and Palate on Mid Facial Growth at Five Years of Age.

OBJECTIVE: To determine whether facial growth at five years is different for children with a left versus right sided cleft lip and palate. DESIGN: Retrospective cohort study. SETTING: Seven UK regional cleft centres. PATIENTS: Patients born between 2000-2014 with a complete unilateral cleft lip and palate (UCLP). MAIN OUTCOMES MEASURE: 5-Year-Old's Index scores. RESULTS: 378 children were included. 256 (68%) had a left sided UCLP and 122 (32%) had a right sided UCLP. 5-Year-Old's index scores ranged from 1 (good) to 5 (poor). There was a higher proportion of patients getting good scores (1 and 2) in left UCLP (43%) compared to right UCLP (37%) but there was weak evidence for a difference (Adjusted summary odds ratio 1.27, 95% CI 0.87 to 1.87; P = .22). CONCLUSIONS: Whilst maxillary growth may be different for left versus right sided UCLP, definitive analysis requires older growth indices and arch forms.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naïve (AMBER) and virologically suppressed (EMERALD) participants with neurological and/or psychiatric comorbidities: Week 96 subgroup analysis.

OBJECTIVE: Our objective was to evaluate the prevalence of pre-existing neurological and/or psychiatric comorbidities (NPCs) and efficacy/safety outcomes for participants with versus without baseline NPCs in AMBER and EMERALD. METHODS: AMBER (treatment-naïve population) and EMERALD (virologically suppressed population) were phase III randomized studies of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg. The primary objective of this post hoc analysis was to assess virological response (HIV-1 RNA <50 copies/mL) at week 48 by intent-to-treat US Food and Drug Administration snapshot analysis comparing participants with and without baseline NPCs. RESULTS: Among participants in AMBER, 88/362 (24%) in the D/C/F/TAF arm and 99/363 (27%) in the control arm had baseline NPCs; in EMERALD, 294/763 (39%; D/C/F/TAF) and 166/378 (44%; control) participants had baseline NPCs. At baseline, psychiatric NPCs were more common than neurological NPCs in both studies; the most common of each type were depression and headache, respectively. High virological response rates were achieved with D/C/F/TAF across studies regardless of baseline NPCs at weeks 48 (range 86%-95%) and 96 (range 80%-91%). No participants in either study with a baseline NPC prematurely discontinued because of a study drug-related neurological or psychiatric adverse event. CONCLUSION: D/C/F/TAF may be a suitable treatment option for individuals with HIV-1 and NPCs.

Prevalence and clinical features of hemicrania continua in clinic-based studies: A systematic review and meta-analysis.

OBJECTIVE: To estimate the relative frequencies of hemicrania continua and its clinical features in adult patients who were evaluated for headache in a clinic-based setting. METHODS: PubMed and Embase were searched for observational, clinic-based studies published between 1 January 2004 and 1 February 2022, that reported on the relative frequencies of hemicrania continua and its clinical features. Two independent investigators (HMA and SA-K) screened titles, abstracts, and full text-articles. A random-effects meta-analysis was conducted to estimate pooled relative frequencies of hemicrania continua and its clinical features across clinic-based studies. RESULTS: Eleven clinic-based studies were deemed eligible for inclusion. Of these, eight studies reported on the relative frequency of hemicrania continua among adult patients (n = 9854) who were evaluated for headache in a tertiary care unit. The pooled relative frequency of hemicrania continua was found to be 1.8% (95% CI; 1.0-3.3). Considerable heterogeneity was noted across studies (I2 = 89.8%). The three most common symptoms associated with hemicrania continua were lacrimation (72.3%), conjunctival injection (69.8%), and restlessness/agitation (60.2%). CONCLUSION: The findings of this meta-analysis suggest that there is limited epidemiologic data on the relative frequencies of hemicrania continua and its clinical features. Standardized data acquisition and reporting are needed to estimate prevalence rates more accurately and to better understand epidemiologic patterns. This, in turn, should increase awareness of the impact that hemicrania continua has in clinical practice.

New malic acid producer strains of Saccharomyces cerevisiae for preserving wine acidity during alcoholic fermentation.

In the context of climate change, the chemical composition of wines is characterized by a massive drop of malic acid concentration in grape berries. Then wine professionals have to find out physical and/or microbiological solutions to manage wine acidity. The aim of this study is to develop wine Saccharomyces cerevisiae strains able to produce significant amount of malic acid during the alcoholic fermentation. By applying a large phenotypic survey in small scale fermentations, the production level of malic acid in seven grape juices confirmed the importance of the grape juice in the production of malic acid during the alcoholic fermentation. Beside the grape juice effect, our results demonstrated that extreme individuals able to produce up to 3 g/L of malic acid can be selected by crossing together appropriate parental strains. A multivariate analysis of the dataset generated illustrate that the initial the amount of malic acid produced by yeast is a determining exogenous factor for controlling the final pH of wine. Interestingly most of the acidifying strains selected are particularly enriched in alleles that have been previously reported for increasing the level of malic acid at the end of the alcoholic fermentation. A small set of acidifying strains were compared with strains able to consume a large amount of malic acid previously selected. The total acidity of resulting wines was statistically different and a panelist of 28 judges was able to discriminate the two groups of strains during a free sorting task analysis.

Sidedness in Unilateral Orofacial Clefts: A Systematic Scoping Review.

OBJECTIVE: An overview of the literature relating to the sidedness of unilateral cleft lip with or without cleft palate to map current knowledge on the cause and impact of directional asymmetry. DESIGN: Scoping review with a systematic search of Medline and Embase from inception to May 2023. PATIENTS, PARTICIPANTS: Humans born with a left or right unilateral cleft lip with or without a cleft palate. MAIN OUTCOME MEASURES: Cleft sidedness as a co-occurrence, an outcome or an exposure. RESULTS: Forty studies were eligible for inclusion and confirmed the predilection for the occurrence of left sided cleft lips; 12 studies reported cleft sidedness co-occurring with another phenotype, 11 studies report sidedness as an outcome and 17 studies as an exposure. Phenotypes which were reported to co-occur with either left or right sided clefts included congenital dental anomalies, handedness and additional congenital anomalies. Variables investigated as a potential cause of left or right sided clefts as an outcome included chromosomal anomalies, genetic variants and environmental factors. Outcomes investigated in relation to cleft sidedness as an exposure included facial anatomical features, facial growth, educational attainment, functional and psychological characteristics. More studies showed worse outcomes in right sided clefts versus left sided clefts than vice versa, although studies were inconsistent, and a quality assessment was not performed. CONCLUSIONS: The field of cleft sidedness research is expanding and there are promising early findings to differentiate cause and outcome by sidedness of the cleft.

Paradoxical eczema in patients with psoriasis receiving biologics: a case series.

Atopic eczema and psoriasis are chronic, inflammatory dermatoses that can significantly affect the quality of life of those affected. Although both diseases are common, they rarely occur together. Severe psoriasis can be treated with biologic therapies targeting specific cytokine pathways involved in disease pathogenesis. There are reports of paradoxical eczema developing in biologic-treated patients with psoriasis, sometimes necessitating treatment discontinuation and thus leading to poor disease control. This retrospective case series identified 36 such events occurring in 23 patients. All currently available biologic classes were implicated. Eosinophilia (n = 19) and elevated serum IgE (n = 3) were identified in some cases. Treatment strategies included no treatment, topical corticosteroids, broad-acting systemic agents, and discontinuation or switch of biologic therapy. Two patients had persistent eczema and psoriasis despite discontinuation of all biologic therapies.

The Method of Surgical Lip Repair Affects Speech Outcomes in Children With Bilateral Cleft Lip and Palate.

OBJECTIVE: It was hypothesized that lip repair protocols in children with bilateral cleft lip and palate (BCLP) would affect development of bilabial consonants /m/ /b/ /p/. This study compared speech outcomes in 2 surgical groups. DESIGN: A retrospective case note investigation. SETTING: UK Cleft Centre (2000-2009). PATIENTS: Forty-nine children with complete BCLP, of whom 26 had a 1-stage and 23 a 2-stage bilateral cleft lip repair. INTERVENTIONS: One-stage cleft lip repair versus a 2-staged cleft lip repair. MAIN OUTCOME MEASURES: Bilabial consonant production at 18 months, 3 and 5 years of age. Cleft Speech Characteristics (CSCs) at age 5. RESULTS: At age 18 months, 81% of the 1-stage lip repair group and 4% of the 2-stage lip repair group produced bilabial consonants (P <·0001, Fisher test). At age 3 years, 81% of the 1-stage and 26% of the 2-stage lip repair groups produced bilabial consonants (P =·0133, Fisher test). At age 5 years, both groups had similar bilabial consonant production, but children in the 2-stage lip repair group had more frequent and severe CSCs (P = ·0037, χ2). CONCLUSION: A 1-stage lip repair for children with complete BCLP resulted in better bilabial consonant production at 18 months and 3 years of age than a 2-stage lip repair. At age 5 years both groups had bilabial consonants but children in the 2-stage lip repair group had worse CSCs. The surgical protocol for bilateral cleft lip repair affected speech outcome in children with BCLP.

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Rapid-Initiation Model of Care for Human Immunodeficiency Virus Type 1 Infection: Primary Analysis of the DIAMOND Study.

BACKGROUND: Most guidelines recommend rapid treatment initiation for patients with newly diagnosed human immunodeficiency virus type 1 (HIV-1) infection, but prospective US data are limited. The DIAMOND (NCT03227861) study using darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is a phase 3 prospective study evaluating efficacy/safety of a single-tablet regimen in a rapid-initiation model of care. METHODS: Adults aged ≥18 years began D/C/F/TAF ≤14 days from diagnosis without screening/baseline results; as results became available, participants not meeting predefined safety/resistance stopping rules continued. Primary endpoint was virologic response (HIV-1 RNA <50 copies/mL; intent-to-treat; US Food and Drug Administration [FDA] snapshot) at week 48; participant satisfaction was measured via the HIV Treatment Satisfaction Questionnaire status version (HIVTSQs). RESULTS: Of 109 participants, 87% were male, 32% black/African American, median (range) age was 28 (range, 19-66) years, 25% of participants had HIV-1 RNA ≥100 000 copies/mL, 21% had CD4+ cell count <200 cells/µL, and 31% enrolled ≤48 hours from diagnosis. At week 48, 97 (89%) participants completed the study and 92 (84%) achieved HIV-1 RNA <50 copies/mL (FDA snapshot). There were no protocol-defined virologic failures; incidences of adverse events (AEs) and adverse drug reactions (33%) were low, no serious AEs were study drug related, and 1 (<1%) participant discontinued due to study drug related AE(s). The overall HIVTSQs score at week 48 was 58 (maximum: 60). CONCLUSIONS: At week 48, a high proportion of participants starting D/C/F/TAF achieved HIV-1 RNA <50 copies/mL and very few discontinued therapy. D/C/F/TAF was well tolerated, no participants discontinued due to baseline resistance stopping criteria, and high treatment satisfaction among participants was recorded. CLINICAL TRIALS REGISTRATION: NCT03227861.

Closer to the Truth on National Fistula Prevalence After Unilateral Complete Cleft Lip and Palate Repair? The Cleft Care UK Study.

OBJECTIVES: To (1) determine the prevalence of nonperialveolar palatal fistula up to age 5 following repair of unilateral cleft lip and palate (UCLP) in the United Kingdom, (2) examine the association of palatoplasty techniques with fistula occurrence, and (3) describe the frequency of fistula repairs and their success. DESIGN: Cross-sectional study. SETTING: All 11 centralized regional cleft centers in the United Kingdom. PARTICIPANTS: Two hundred sixty-eight children born between 2005 and 2007 recruited by Cleft Care UK, a nationwide cross-sectional study of all 5-year-old children born with nonsyndromic UCLP. MAIN OUTCOME MEASURE: Nonperialveolar palatal fistula prevalence up to age 5. RESULTS: Fistulas were found in 72 children (31.3%, 95% confidence interval: 25.4%-37.7%) and had no significant association with palate repair sequences. Twenty-four fistulas were repaired by age 5, 12 of which had data showing 10 (83.3%) successful repairs. CONCLUSION: The prevalence of nonperialveolar fistulas following primary palatoplasty of UCLP in the United Kingdom was higher than previously reported. This information should be part of the preoperative discussion with families. Prospective collection of the presence of fistulas will be necessary before we can associate the occurrence of fistulas with a surgeon, institution, surgical technique, or protocol of care.

Is There a Correlation Between Nasolabial Appearance and Dentoalveolar Relationships in Patients With Repaired Unilateral Cleft Lip and Palate?

OBJECTIVE: To determine whether a relationship exists between the aesthetic scores given to photographic records of the nasolabial region of patients with repaired unilateral cleft lip and palate (UCLP) and the 5-Year Olds' Index scores of study models for the same participants. DESIGN: Retrospective study. SETTING: University of Bristol Dental Hospital, United Kingdom. PARTICIPANTS: Patients with nonsyndromic UCLP previously enrolled in the Cleft Care UK (CCUK) Study. METHODS: The CCUK participants, who had both study models and photographs (frontal and worm's eye view), were identified and their records retrieved. These were rated by 2 consultants and 2 senior registrars in orthodontics. The 5-Year Olds' Index was used to score the study models, and at a separate sitting, a 5-point Likert scale was used to score the cropped frontal and worm's eye view photographs of the same children. The results were analyzed using intraclass correlation coefficients and Cohen κ. MAIN OUTCOME MEASURES: Correlation between the aesthetic scores of the photographic views and the concordant 5-Year Olds' Index scores of the study models. RESULTS: The intraclass correlation coefficient scores showed very poor agreement between the photographic views and their concordant study models. The level of inter- and intra-rater reliability was strongest when scoring the study models. CONCLUSIONS: There was no agreement between the scores given to various photographic views and their corresponding study models. Scoring the study models using the 5-Year Olds' Index was the most reliable outcome measure for this age-group.

What We Do: Greater Palatine Medializing Foraminal Osteotomy for Repair of the Wide Cleft Palate.

Wide cleft palates (>15-mm gap) present a number of challenges to the surgeon tasked with their repair ( Bardach, 1999 ). Eliminating the need for secondary surgery due to fistula formation can reduce additional anesthetic and scarring risks and optimize early speech development. Greater palatine foraminal osteotomy is a useful surgical adjunct that allows additional medial movement of oral mucoperiosteal flaps to aid in tension-free closure of the oral layer. We use a technique similar to that described by Seibert in 1995 with a few modifications. Closure of the nasal layer in these wide clefts can be achieved using a sphenoid flap, a technique recently published by our unit ( Khan et al, 2018 ).

Defining the Aesthetic Range of Normal Symmetry for Lip and Nose Features in 5-Year-Old Children Using the Computer-Based Program SymNose.

OBJECTIVE: To provide a normal comparison group against which to judge symmetry results after cleft surgery and to introduce the thin lip correction (TLC) feature in SymNose. A lip-aspect ratio algorithm has been added to the latest version of SymNose to compensate for the higher degree of overlap in thicker lips when compared to thin lips. DESIGN: Retrospective analysis of symmetry in healthy participants, using the computer-based program SymNose on both anteroposterior (AP) and base view images. Photographs of 91 noncleft children were traced twice by 3 independent investigators experienced with SymNose. PARTICIPANTS: Five-year-old healthy participants from a local state school in Tavistock (West Devon, United Kingdom). MAIN OUTCOME MEASURE: Asymmetry expressed as the perimeter mismatch percentage for nose and lip features on AP view images and for nose features on base view images. RESULTS: The perimeter mismatch reference range for the nose (AP view) was 2.65% to 30.91%, for the lip 2.13% to 15.44%, for the nose (base view) 1.69% to 14.84%, for the nostrils 4.68% to 26.6%, and for the width-height ratio 1.15% to 1.80%. The perimeter mismatch percentage for the lip without TLC was significantly higher compared to the perimeter mismatch percentage with TLC (P < .001). CONCLUSION: This article provides a noncleft reference range for all perimeters drawn from SymNose against which to compare results after cleft surgery at 5 years of age. Furthermore, it shows the importance of correcting for variance in lip volume per child.

Use of the Sphenoid Flap in Repair of the Wide Cleft Palate.

OBJECTIVE: In wide palatal defects, closure of the nasal layer can prove a considerable challenge. Mobilizing nasal flaps posteriorly usually facilitates soft palate closure. However, the defect is often too wide within the hard palate; hence, bilateral vomerine flaps are frequently required. Despite this, there is often a small defect in the nasal layer at the posterior septum (typically equating to the hard-soft palate junction), which has to be left to heal by secondary intention with the resulting increased risk of fistula formation and the potential deleterious long-term effect on speech due to cicatricial migration of the reconstructed levator sling anteriorly. We describe our experience in the use of the sphenoid flap to obtain tension-free primary closure of the nasal layer. METHODS: A retrospective multi-center study assessing all sphenoid flap procedures undertaken at both Birmingham Children's Hospital and Great Ormond Street Hospital. Key demographic and medical data was collected pre-, peri-, and postoperatively across the 2 sites. RESULTS: A total of 66 patients underwent the use of a sphenoid flap to aid closure of the nasal layer. The average age at time of repair was 9.7 months. More than half (55%, n = 36) were isolated cleft palates, and 35% (n = 23) were BCLPs. Forty-two percent of all patients had Robin sequence. The average cleft width was 14.4 mm. The overall fistula rate was 25.8% (n = 17). CONCLUSIONS: We describe the operative technique, indications, and our experience in the use of the sphenoid flap in wide cleft palate repair.

Congenital cutaneous lymphadenoma.

Cutaneous lymphadenoma is an uncommon benign neoplasm often considered to be an adamantinoid variant of trichoblastoma. Lesions present in both sexes, between 14 and 87 years of age, and are mainly located on the head and neck. Cases in children are rare and there is only 1 previous case of a congenital lymphadenoma. An 8-year-old Asian girl presented with a congenital lesion on her forehead comprising 4 pink papules, the largest 5 mm in diameter. Microscopy revealed a well-circumscribed tumor within the dermis and subcutis comprising well-demarcated epithelial lobules of basaloid and clear cells with subtle peripheral palisading, growing in a collagenous stroma but lacking retraction artefact. A relatively dense accompanying predominantly lymphocytic inflammatory cell infiltrate including both T-cells (CD3+) and B-cells (CD20+) permeated the nodules and spilled into the stroma. CD68+ histiocytes and CD1a+ Langerhans cells were moderately numerous. This is the second case of congenital lymphadenoma which-in spite of its rarity in childhood-widens the diagnostic possibilities of cutaneous lymphoepithelial tumors in children.

Surrogate Outcome Measures for Corneal Neurotization in Infants and Children.

BACKGROUND: Corneal anesthesia is a rare and challenging condition, particularly in young children. The insensate cornea leads to abnormal epithelial cell metabolism and loss of trophic influences supplied by the corneal nerve fibers. This results in recurrent spontaneous epithelia erosion and eventual loss of sight. Corneal reinnervation is a definitive treatment option for neuropathic keratitis. The outcome measures in young children following corneal sensitization are different to adults as esthesiometry is unachievable. METHODS: The authors have undertaken corneal reinnervation in a young patient using a sural nerve graft. Surrogate measures suitable for pediatric patients were used for assessment of the outcome. RESULTS: Postoperatively there was evidence of improved corneal healing and function after 8 weeks. At 10 months postprocedure, the cornea was completely free of vascularization. CONCLUSION: Resensitization of the cornea using nerve grafts has previously been reported in older children and adults. This is the first time the procedure has been undertaken in a young child. Although the technique is still in its infancy with only 4 patients reported worldwide including our report, it seems to hold promise of improvement to this challenging cohort of patients.

Reporting of Randomized Controlled Trials in Cleft Lip and Palate: A 10-Year Review.

OBJECTIVES: Reviews of the quality of reporting of randomized controlled trials (RCTs) have recently been conducted in different surgical specialties. In this review of RCTs relating to cleft lip, cleft palate, and cleft lip and palate (CL/P), we investigate the quality of reporting against the Consolidated Standards of Reporting Trials (CONSORT) checklist. DESIGN: A systematic review of CL/P RCTs published from 2004 to 2013, with the included articles scored against the CONSORT checklist. PATIENTS, PARTICIPANTS: The literature search identified 174 articles. Studies were selected for participants with CL/P who were involved in an RCT with prospective data collection and reported in a full journal article. A total of 6352 participants were included from 65 CL/P RCTs during the study period. MAIN OUTCOME MEASURES: The methodological quality of RCTs was assessed using the CONSORT checklist and Jadad scale. RESULTS: The mean CONSORT score was 15.8, and the mean Jadad score was 3.3. There was a significant positive correlation between the CONSORT and Jadad score (P < .0001, ρ = .47). The only significant correlation showed that with an increasing number of authors, both the CONSORT and the Jadad score increased. CONCLUSION: This analysis has shown that that there are deficiencies in the transparent reporting of factors such as randomization implementation, blinding, and participant flow. Interventions, outcomes, and the interpretation of results are well presented. We would recommend that RCTs are conceived and undertaken using the CONSORT checklist and reported in a clear and reproducible manner.

Are cleft palate fistulae a cause of dental decay?

AIM: To investigate a possible correlation between fistula and dental decay in children at 5 years of age from a single-surgeon series of cleft palate repairs. METHODS: Retrospective review of data over a 9-year period between 2003 and 2011 of cleft palate repairs performed by the senior author at Birmingham Children's Hospital, U.K. Data collected on age, sex, age at repair, presence of fistula, and number of decayed, missing, or filled primary teeth (i.e., decayed, missing, and filled teeth score) at age 5 years. RESULTS: The overall fistula rate for this patient population was 24.1%. Fistulae were more common in the more severe forms of cleft type, as was frequency of dental decay. Comparison of fistula versus nonfistula groups showed a higher rate of dental decay (40%) in the fistula group, compared with only 20% in the nonfistula group (P = .036). CONCLUSION: A positive association was established between dental decay and the presence of a fistula. Although not proven as causative, possible reasons for this include nasal mucus retaining sugary food in the mouth and an overall prolonged food-clearance time. The known association between severity of cleft and an increased likelihood of a fistula and severity of cleft and increased dental decay were again demonstrated but were not found to be the exclusive explanation for the new finding of an association between fistulae and higher dental decay rates.