Subphenotyping and Classification of Cleft Lip and Alveolus in Adult Unoperated Patients: A New Embryological Approach.

OBJECTIVE: Previously, a new embryological classification was introduced subdividing oral clefts into fusion and/or differentiation defects. This subdivision was used to classify all subphenotypes of cleft lip with or without alveolus (CL±A). Subsequently, it was investigated whether further morphological grading of incomplete CLs is clinically relevant, and which alveolar part is deficient in fusion/differentiation defects. DESIGN: Observational cohort study. SETTING: Three hundred fifty adult unoperated Indonesian cleft patients presented themselves for operation. Cephalograms, dental casts, and intraoral and extraoral photographs-eligible for the present study-were used to determine morphological severity of CL±A. PATIENTS: Patients with unilateral or bilateral clefts of the primary palate only were included. MAIN OUTCOME MEASURES: Clefts were classified-according to developmental mechanisms and timing in embryogenesis-as fusion and/or differentiation defects. Grades of incomplete CLs were related to the severity of alveolar clefts (CAs) and hypoplasia, and permanent dentition was used to investigate which alveolar part is deficient in fusion/differentiation defects. RESULTS: One hundred eight adult patients were included. All subphenotypes-96 unilateral and 12 bilateral clefts-could be classified into differentiation (79%), fusion (17%), fusion-differentiation (2%), or fusion and differentiation (2%) defects. The various grades of incomplete CLs were related to associated CAs and hypoplasia, and all alveolar deformities were located in the premaxillae. CONCLUSIONS: This study showed that all CL±A including the Simonart bands can be classified, that further morphological grading of incomplete CLs is clinically relevant, and that the premaxilla forms the deficient part in alveolar deformities.

Classifying common oral clefts: a new approach after descriptive registration.

OBJECTIVE: Using the Dutch Oral Cleft Registration, which records the morphology and topography of common oral clefts, a new classification based on the (patho)embryology of the primary and secondary palates was tested. DESIGN: Prospective observational study. SETTING: The fifteen cleft palate teams in the Netherlands register patients to the national registry. PATIENTS: All unoperated patients with common oral clefts reported between 1997 and 2006 inclusive were included. MAIN OUTCOME MEASURES: The classification is based on the pathoembryological events that ultimately result in various subphenotypes of common oral clefts. PATIENTS within the three categories cleft lip/alveolus (CL/A), cleft lip/alveolus and palate (CL/AP), and cleft palate (CP) were divided into three subgroups: fusion defects, differentiation defects, and fusion and differentiation defects. A timetable was constructed to relate the type of clefting to the time of derailment during embryonic development. RESULTS: 3512 patients were included. PATIENTS with CL/A showed 22% fusion defects, 75% differentiation defects, and 3% fusion and differentiation defects. CL/AP patients and CP patients mostly showed fusion defects (70% and 89%, respectively). We were able to relate almost all (over 90%) cleft subphenotypes to specific weeks in embryonic development. CONCLUSIONS: This classification provides new cleft subgroups that may be used for clinical and fundamental research. The subphenotypes of these subgroups originate from different time frames during embryonic development and different cell biological mechanisms, thereby enabling more accurate data for, e.g., gene identification and/or environmental factors.

Mental health is strongly associated with capability after lower extremity injury treated with free flap limb salvage or amputation.

BACKGROUND: Knowledge about factors associated with long-term outcomes, after severe traumatic injury to the lower extremity, can aid with the difficult decision whether to salvage or amputate the leg and improve outcome. We therefore studied factors independently associated with capability at a minimum of 1 year after amputation or free flap limb salvage. METHODS: We included 135 subjects with a free flap lower extremity reconstruction and 41 subjects with amputation, between 1991 and 2021 at two urban-level 1 trauma centers with a mean follow-up of 11 ± 7 years. Long-term physical functioning was assessed using the Physical Component Score (PCS) of the Short-Form 36 (SF36) and the Lower Extremity Functional Scale (LEFS) questionnaires. Independent variables included demographics, injury characteristics, and the Mental Component Score (MCS) of the SF36. RESULTS: Greater mental health was independently and strongly associated with greater capability, independent of amputation or limb reconstruction. Mental health explained 33% of the variation in PCS and 57% of the variation in LEFS. Injury location at the knee or leg was associated with greater capability, compared to the foot or ankle. Amputation or limb reconstruction was not associated with capability. DISCUSSION: This study adds to the growing body of knowledge that physical health is best regarded through the lens of the bio-psycho-social model in which mental health is a strong determinant. This study supports making mental health an important aspect of rehabilitation after major lower extremity injury, regardless of amputation or limb salvage.

Validation of the Dutch registry of common oral clefts: quality of recording specific oral cleft features.

OBJECTIVE: Since 1997, common oral clefts in the Netherlands have been recorded in the national oral cleft registry using a unique descriptive recording system. This study validates data on the topographic-anatomical structure, morphology, and side of individual anomalies of the primary palate and secondary palate that form the oral cleft. DESIGN: Validation study. SETTING: All 15 Dutch cleft palate teams reporting presurgery oral cleft patients to the national registry. PATIENTS: A random sample of 250 cases registered in the national database with oral clefts from 1997 through 2003; of these, 13 cases were excluded. MAIN OUTCOME MEASURES: By linking registry data with clinical data, we identified differential recording rates by comparing the prevalence, and we measured the degree of agreement by computing validity and reliability statistics. RESULTS: The topographic-anatomical structures (lip, alveolus, and hard and soft palates) of the anomalies had near-perfect interdatabase agreement with a sensitivity of 88% to 99%. However, when analyzing the individual anomalies in detail (morphology and side), validity decreased and depended on morphological severity. This association was most evident for anomalies of the secondary palate. For example, sensitivity was higher for "complete cleft hard palate" (92%) than for "submucous cleft hard/soft palate" (69%). CONCLUSIONS: Overall, the validity of Dutch registry data on oral clefts is good, supporting the feasibility of this unique recording system. However, when analyzing oral cleft data in detail, the quality appears to be related to anatomical location and morphological severity. This might have implications for etiologic research based on registry data and for guidelines on neonatal examination.

Ten years recording common oral clefts with a new descriptive system.

OBJECTIVE: After introducing a new descriptive recording system for congenital craniofacial abnormalities in The Netherlands, common oral clefts are highlighted. DESIGN: Prospective observational study. SETTING: Fifteen cleft palate teams, united in the Dutch Association for Cleft Palate and Craniofacial Anomalies, registered patients from 1997 to 2006. PATIENTS: All unoperated patients with a common oral cleft were included. MAIN OUTCOME MEASURES: Detailed information and birth prevalence rates of cleft lip/alveolus, cleft lip/alveolus and palate, and cleft palate were provided, relating referral age, gender, family history, additional congenital abnormalities, and syndrome diagnoses to these three categories. RESULTS: This study included 3512 patients, resulting in an overall prevalence of 16.6 per 10,000 live births. Patients showed a cleft lip/alveolus (28%), a cleft lip/alveolus and palate (39%), or a cleft palate (33%). The three categories exhibited very heterogeneous cleft types. Mean referral age was 5.8 months (median 3 weeks). Birth weight was the lowest in cleft palate patients (3238 g; p < .001 to .009). Cleft palate patients showed less positive family history concerning congenital anomalies (23%, p < .001 to .013), but more syndrome diagnoses were established in this category (24%, p < .001). Ten percent of all cleft patients showed additional abnormalities of the head and neck area, and 13% displayed congenital anomalies of other systems. CONCLUSIONS: This new recording method allows adequate description of common oral clefts. Many cleft types exist within these three categories and should be differentiated, because they originate from different time frames and/or cell biological mechanisms during embryogenesis.

Validation of the NVSCA registry for common oral clefts: study design and first results.

OBJECTIVE: Since 1997 the Dutch Association for Cleft Palate and Craniofacial Anomalies (NVSCA) has maintained a national registry of congenital craniofacial anomalies. This study validates data on three common oral cleft categories (cleft lip/alveolus = CL/A; cleft lip/alveolus and palate = CL/AP; and cleft palate = CP) and general items. DESIGN: Retrospective observational study. SETTING: All 15 Dutch cleft palate teams registered presurgery patients with common oral clefts (n = 2553) from 1997 to 2003. PATIENTS: A random sample of 250 cases was used; 13 cases were excluded. MAIN OUTCOME MEASURES: The corresponding medical data were reviewed; these medical data served to validate the NVSCA registry data. Prevalence comparisons, 2 x 2 tables and validity measures were performed. RESULTS: The cleft categories most accurately recorded were CL/A and CP. Both categories had an observed agreement of 98%, kappa of 0.94, and a sensitivity and specificity of 97%. Cleft lip/alveolus and palate had an observed agreement of 95%, kappa of 0.89, a sensitivity of 90%, and a specificity of 99%. Regarding the general items, observed agreement and kappa were highest for adoption/foster child (99%; 0.76) and lowest for remarks about pregnancy (63%; 0.20). Sensitivity ranged from 25% (consanguinity) to 97% (white mother) and specificity was high for all items (>93%) except for white father and mother (approximately 35%). CONCLUSIONS: The NVSCA registry is a valuable tool for quality improvement and research because validity on all three common oral cleft categories is very good. Validity on the general items is reasonable to satisfying and appears to be related to the type of information.

Is dangling of the lower leg after a free flap reconstruction necessary? Study protocol for a large multicenter randomized controlled study.

BACKGROUND: Within the field of plastic surgery, free tissue transfer is common practice for knee and lower leg defects. Usually, after such free flap reconstruction, patients undergo a dangling protocol in the postoperative phase. A dangling protocol is designed to gradually subject the free flap to increased venous pressure resulting from gravitational forces. Worldwide there are multiple variations of dangling protocols. However, there is no evidence available in the literature that supports the use of a dangling protocol. METHODS: This is a multicenter randomized controlled trial that includes patients with a free flap lower leg reconstruction. The primary outcome is to assess whether a no-dangling protocol is not inferior to a dangling protocol, in terms of proportion of partial flap loss, 6 months after surgery. Secondary objectives are to identify differences in major and minor complications, length of stay, and costs, and to objectify blood gaseous changes during dangling. Furthermore, at 2 years we will assess difference in physical function, infection rates, and osseous union rates. DISCUSSION: The primary outcome of this study will give a more decisive answer to the question of whether a dangling protocol is necessary after a free flap reconstruction of the lower leg. The secondary outcomes of this study will provide a better insight into the physical functions, infection rates, and union rates in these patients. TRIAL REGISTRATION: Central Committee on Research Involving Human Subjects (CCMO), NL63146.041.17. Registered on 11 July 2018. Netherlands Trial Register, NTR7545 . Registered on 10 October 2018.

Long-Term Patient-Reported Outcomes following Free Flap Lower Extremity Reconstruction for Traumatic Injuries.

BACKGROUND: Reconstruction of severe lower extremity injuries using free flaps has become a reliable approach. Knowledge of long-term surgical outcomes, limb function, and quality of life is limited. METHODS: Two hundred thirty-nine patients undergoing a free flap reconstruction of an open lower extremity fracture between 1993 and 2014 were divided into three groups and studied, as follows: group 1, early free flap reconstruction within 6 weeks; group 2, delayed reconstruction after 6 weeks; and group 3, delayed reconstruction with osteomyelitis. Patient-reported outcomes were assessed with the 36-Item Short-Form Health Survey and the Lower Extremity Functional Scale. Independent variables predicting outcomes were identified using multivariate analyses. RESULTS: Patients in group 3 significantly more often experienced delayed union. Questionnaires were completed by 108 patients (mean follow-up, 9.7 years). The 36-Item Short-Form Health Survey physical component scores were significantly lower in all three groups compared with Dutch norms, as was the mental health score in group 3. There were no significant differences in quality of life and lower limb function among the three groups. Chronic pain was an independent predictor for decreased quality of life and limb function in groups 1 and 2, as was delayed union for decreased limb function in group 3. CONCLUSIONS: After free flap reconstruction of severe lower extremity injuries, all patient groups showed significantly lower quality of life compared to the Dutch population; however, there were no significant differences between the groups. Predictors for poorer quality of life and limb function were chronic pain and delayed union.

Decreasing prevalence of oral cleft live births in the Netherlands, 1997-2006.

OBJECTIVES: The number of new oral cleft patients has fallen in the Netherlands. This may be explained by two hypotheses: (1) greater prenatal detection of congenital anomalies has led to more pregnancy terminations and (2) increased folic acid use has reduced the oral cleft risk. Both hypotheses would mainly apply to the category cleft lip/alveolus ± cleft palate (CL±P), since, unlike cleft palate only (CP), CL±P can be detected prenatally by two-dimensional (2D) ultrasound and develops during the period recommended for folic acid use. The authors aimed to determine trends in prevalence over 1997-2006 and to evaluate the hypotheses by stratifying trends by cleft category. METHODS: This study was a time-trend analysis of infants born alive with oral clefts in the Netherlands during 1997-2006 and registered in the national oral cleft registry. The authors calculated prevalence rates and the estimated annual percentage change (EAPC) for all oral clefts and the two categories. RESULTS: In 1997-2006, 3308 infants out of 1 970 872 live births had oral clefts, an overall prevalence per 10 000 live births of 16.8 (CL±P: 11.3; CP: 5.5). Time-trend analysis showed that the prevalence of all oral clefts decreased (EAPC -1.8%; 95% CI: -3.0% to -0.6%), as did the CL±P prevalence (EAPC -2.3%; 95% CI: -3.8% to -0.9%). No significant trends were found for the CP prevalence. CONCLUSIONS: Because the live-birth prevalence of CL±P decreased, that of all oral clefts decreased. These findings are in line with both hypotheses and may therefore have implications for prenatal counselling and folic acid policy.