Aebele B. Mink van der Molen

Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2

The alveolar cleft in patients with clefts of lip, alveolus and palate (CLAP) is usually reconstructed with an autologous bone graft. Harvesting of autologous bone grafts is associated with more or less donor site morbidity. Donor site morbidity could be eliminated if bone is fabricated by growth factor-aided tissue engineering. The objective of this review was to provide an oversight on the current state of the art in growth factor-aided tissue engineering with regard to reconstruction of the alveolar cleft in CLAP. Medline, Embase and Central databases were searched for articles on bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 7, transforming growth factor beta, platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, vascular endothelial growth factor and platelet-rich plasma for the reconstruction of the alveolar cleft in CLAP. Two-hundred ninety-one unique search results were found. Three articles met our selection criteria. These three selected articles compared BMP-2-aided bone tissue engineering with iliac crest bone grafting by clinical and radiographic examinations. Bone quantity appeared comparable between the two methods in patients treated during the stage of mixed dentition, whereas bone quantity appeared superior in the BMP-2 group in skeletally mature patients. Favourable results with BMP-2-aided bone tissue engineering have been reported for the reconstruction of the alveolar cleft in CLAP. More studies are necessary to assess the quality of bone. Advantages are shortening of the operation time, absence of donor site morbidity, shorter hospital stay and reduction of overall cost.

A systematic review of associated structural and chromosomal defects in oral clefts: when is prenatal genetic analysis indicated?

Background Oral clefts—comprising cleft lip (CL), cleft lip with cleft palate (CLP), and cleft palate (CP)—are being diagnosed prenatally more frequently. Consequently, the need for accurate information on the risk of associated anomalies and chromosomal defects to aid in prenatal counselling is rising. This systematic review was conducted to investigate the prenatal and postnatal prevalence of associated anomalies and chromosomal defects related to cleft category, thereby providing a basis for prenatal counselling and prenatal invasive diagnostics. Methods Online databases were searched for prenatal and postnatal studies on associated anomalies and chromosomal defects in clefts. Data from the literature were complemented with national validated data from the Dutch Oral Cleft Registry. Results Twenty studies were included: three providing prenatal data, 13 providing postnatal data, and four providing both. Data from prenatal and postnatal studies showed that the prevalence of associated anomalies was lowest in CL (0–20.0% and 7.6–41.4%, respectively). For CLP, higher frequencies were found both prenatally (39.1–66.0%) and postnatally (21.1–61.2%). Although CP was barely detectable by ultrasound, it was the category most frequently associated with accompanying defects in postnatal studies (22.2–78.3%). Chromosomal abnormalities were most frequently seen in association with additional anomalies. In the absence of associated anomalies, chromosomal defects were found prenatally in CLP (3.9%) and postnatally in CL (1.8%, 22q11.2 deletions only), CLP (1.0%) and CP (1.6%). Conclusions Prenatal counselling regarding prognosis and risk of chromosomal defects should be tailored to cleft category, and more importantly to the presence/absence of associated anomalies. Irrespective of cleft category, clinicians should advise invasive genetic testing if associated anomalies are seen prenatally. In the absence of associated anomalies, prenatal conventional karyotyping is not recommended in CL, although array comparative genomic hybridisation should be considered. In presumed isolated CLP or CP, prenatal invasive testing, preferably by array based methods, is recommended.

Transverse Plane Tendon and Median Nerve Motion in the Carpal Tunnel : Ultrasound Comparison of Carpal Tunnel Syndrome Patients and Healthy Volunteers

Background The median nerve and flexor tendons are known to translate transversely in the carpal tunnel. The purpose of this study was to investigate these motions in differential finger motion using ultrasound, and to compare them in healthy people and carpal tunnel syndrome patients. Methods Transverse ultrasounds clips were taken during fist, index finger, middle finger and thumb flexion in 29 healthy normal subjects and 29 CTS patients. Displacement in palmar-dorsal and radial-ulnar direction was calculated using Analyze software. Additionally, the distance between the median nerve and the tendons was calculated. Results We found a changed motion pattern of the median nerve in middle finger, index finger and thumb motion between normal subjects and CTS patients (p<0.05). Also, we found a changed motion direction in CTS patients of the FDS III tendon in fist and middle finger motion, and of the FDS II and flexor pollicis longus tendon in index finger and thumb motion, respectively (p<0.05). The distance between the median nerve and the FDS II or FPL tendon is significantly greater in patients than in healthy volunteers for index finger and thumb motion, respectively (p<0.05). Conclusion Our results suggest a changed motion pattern of the median nerve and several tendons in carpal tunnel syndrome patients compared to normal subjects. Such motion patterns may be useful in distinguishing affected from unaffected individuals, and in studies of the pathomechanics of carpal tunnel syndrome.

In Search of the Optimal Surgical Treatment for Velopharyngeal Dysfunction in 22q11.2 Deletion Syndrome: A Systematic Review

Background Patients with the 22q11.2 deletion syndrome (22qDS) and velopharyngeal dysfunction (VPD) tend to have residual VPD following surgery. This systematic review seeks to determine whether a particular surgical procedure results in superior speech outcome or less morbidity. Methodology/ Principal Findings A combined computerized and hand-search yielded 70 studies, of which 27 were deemed relevant for this review, reporting on a total of 525 patients with 22qDS and VPD undergoing surgery for VPD. All studies were levels 2c or 4 evidence. The methodological quality of these studies was assessed using criteria based on the Cochrane Collaborations tool for assessing risk of bias. Heterogeneous groups of patients were reported on in the studies. The surgical procedure was often tailored to findings on preoperative imaging. Overall, 50% of patients attained normal resonance, 48% attained normal nasal emissions scores, and 83% had understandable speech postoperatively. However, 5% became hyponasal, 1% had obstructive sleep apnea (OSA), and 17% required further surgery. There were no significant differences in speech outcome between patients who underwent a fat injection, Furlow or intravelar veloplasty, pharyngeal flap pharyngoplasty, Honig pharyngoplasty, or sphincter pharyngoplasty or Hynes procedures. There was a trend that a lower percentage of patients attained normal resonance after a fat injection or palatoplasty than after the more obstructive pharyngoplasties (11–18% versus 44–62%, p = 0.08). Only patients who underwent pharyngeal flaps or sphincter pharyngoplasties incurred OSA, yet this was not statistically significantly more often than after other procedures (p = 0.25). More patients who underwent a palatoplasty needed further surgery than those who underwent a pharyngoplasty (50% versus 7–13%, p = 0.03). Conclusions/ Significance In the heterogeneous group of patients with 22qDS and VPD, a grade C recommendation can be made to minimize the morbidity of further surgery by choosing to perform a pharyngoplasty directly instead of only a palatoplasty.

Median Nerve Deformation in Differential Finger Motions: Ultrasonographic Comparison of Carpal Tunnel Syndrome Patients and Healthy Controls

We investigated the median nerve deformation in the carpal tunnel in patients with carpal tunnel syndrome and controls during thumb, index finger, middle finger, and a four finger motion, using ultrasound. Both wrists of 29 asymptomatic volunteers and 29 patients with idiopathic carpal tunnel syndrome were evaluated by ultrasound. Cross‐sectional images during motion from full extension to flexion were recorded. Median nerve cross‐sectional area, perimeter, aspect ratio of the minimal enclosing rectangle, and circularity in extension and flexion positions were calculated. Additionally, a deformation index was calculated. We also calculated the intra‐rater reliability. In both controls and patients, the median nerve cross‐sectional area became significantly smaller from extension to flexion in all finger motions (p < 0.05). In flexion and extension, regardless of the specific finger motion, the median nerve deformation, circularity and the change in perimeter were all significantly greater in CTS patients than in controls (p < 0.05). We found excellent intra‐rater reliability for all measurements (ICC > 0.84). With this study we have shown that it is possible to assess the deformation of the median nerve in carpal tunnel syndrome with ultrasonography and that there is more deformation of the median nerve in carpal tunnel syndrome patients during active finger motion. These parameters might be useful in the evaluation of kinematics within the carpal tunnel, and in furthering our understanding of the biomechanics of carpal tunnel syndrome in the future.

Increase of prevalence of craniosynostosis

INTRODUCTION Craniosynostosis represents premature closure of cranial sutures. Prevalence is approximately 3.1-6.4 in 10.000 live births, which is reportedly rising. This epidemiologic study aims to provide insight into this rise through an accurate description of the prevalence, exploring regional variation and change over time. METHODS The Dutch Association for Cleft Palate and Craniofacial Anomalies was consulted to identify patients with craniosynostosis born between 2008 and 2013. Data were verified using data provided by all hospitals that treated these patients. The following data were collected: date of birth, gender, diagnosis and postal code. Previously reported data from 1997 until 2007 were included to assess for change in prevalence over the years. RESULTS Between 2008 and 2013 759 patients with craniosynostosis were born in the Netherlands. Prevalence of craniosynostosis was 7.2 per 10.000 live births. Sagittal synostosis was the most common form (44%). Poisson regression analysis showed a significant mean annual increase of prevalence of total craniosynostosis (+12.5%), sagittal (+11.7%) and metopic (+20.5%) synostosis from 1997 to 2013. CONCLUSION The prevalence of craniosynostosis is 7.2 per 10.000 live born children in the Netherlands. Prevalence of total craniosynostosis, sagittal and metopic suture synostosis has risen significantly from 1997 until 2013, without obvious cause.

Sonographic measurements of subsynovial connective tissue thickness in patients with carpal tunnel syndrome.

A major pathologic finding in patients with idiopathic carpal tunnel syndrome is noninflammatory fibrosis and thickening of the subsynovial connective tissue. The objective of this study was to determine the ability of sonography to depict this thickening by comparing subsynovial connective tissue thickness in patients with carpal tunnel syndrome and healthy control participants.

Prenatal Screening for Orofacial Clefts in the Netherlands: A Preliminary Report on the Impact of a National Screening System

In the Netherlands a new and countrywide routine screening system for physical congenital anomalies was introduced by legislation in 2007. The screening was aimed initially at Down syndrome, but under specific conditions secondary screening for cleft lip and palate and other congenital malformations is performed as well. This article gives an overview of the Dutch system, with a focus on cleft lip (and palate) and the report of one centers experience. In general, voluntary termination of pregnancy in the second trimester has increased slightly since the introduction of the current system, but the termination-of-pregnancy rate for isolated cleft lip and palate remains limited in the Netherlands.

Long-Term Results of Mandibular Distraction Osteogenesis with a Resorbable Device in Infants with Robin Sequence: Effects on Developing Molars and Mandibular Growth.

Background: Mandibular distraction osteogenesis with a unidirectional resorbable device is an effective treatment option for severe upper airway obstruction in infants with Robin sequence. Long-term effects, especially with regard to tooth development and mandibular outgrowth, are not known. Methods: Robin sequence infants with a follow-up of greater than or equal to 5 years were included. Baseline characteristics were extracted from medical records. Panoramic and lateral cephalometric radiographs were analyzed and patients were recalled for physical examination. Results: Ten infants underwent mandibular distraction osteogenesis at a mean age of 3.7 months (median, 19 months; range, 11 days to 27 months). Mean length of follow-up was 6.8 years (range, 5.0 to 7.9 years). Ten Robin sequence infants without mandibular distraction osteogenesis (mean length of follow-up, 7.4 years; range, 6.7 to 8.9 years) were the controls. Shape anomalies, positional changes, and root malformations of molars were seen significantly more often than in the control group (p = 0.007, p = 0.009, and p = 0.043, respectively). Mandibular length was shorter (p = 0.030), but mandibular ramus height was comparable (p = 0.838) with that of the non–mandibular distraction osteogenesis group. Compared with healthy controls, all Robin sequence infants had a significantly shorter mandible. Conclusions: Mandibular distraction osteogenesis with a resorbable system reveals overall good short- and long-term results, but the effects on developing molars and mandibular outgrowth likely necessitate secondary procedures. This factor should be considered when deciding on treatment options and counseling of parents. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Inhibited early immunologic response is associated with hypertrophic scarring.

This study aimed to examine changes in the inflammatory response in early hypertrophic compared to normal wound healing. The immune system is thought to be involved in hypertrophic scar formation. However, the exact mechanism and time of onset of the derailment remain unknown. In a prospective observational study, skin biopsies were taken directly postwounding and 3 hours later from patients who had elective cardiothoracic surgery. The skin biopsies were analysed for mRNA, proteins and cells involved in the early inflammatory phase of wound healing. The endpoint was scar outcome (hypertrophic (HTS) or normal (NTS)) at one year after surgery. There were significant differences between the NTS and HTS groups regarding the fold changes of mRNA expression of P‐selectin during surgery. Postoperative skin concentrations of inflammatory proteins IL‐6, IL‐8 and CCL2 were significantly lower in the HTS compared to the NTS group. Also, a trend of higher pre‐operative M2 macrophage numbers was observed in the HTS group. Neutrophil numbers increased equally during surgery in both groups. The increase of P‐selectin mRNA in hypertrophic wound healing could affect leucocyte migration. The decreased concentrations of inflammatory proteins in hypertrophic wound healing indicate a reduced inflammatory response, which has consequences for the treatment of hypertrophic scarring during the early inflammatory phase. In a conclusion, alterations of wound healing associated with hypertrophic scarring are visible as early as 3 hours postwounding and include a reduced rather than increased inflammatory protein response.