The Tumor Risk Score (TRS) - next level risk prediction in head and neck tumor surgery.

PURPOSE: Head and neck cancer surgery often requires postoperative monitoring in an intensive care unit (ICU) or intermediate care unit (IMC). With a variety of different risk scores, it is incumbent upon the investigator to plan a risk-adapted allocation of resources. Tumor surgery in the head and neck region itself offers a wide range of procedures in terms of resection extent and reconstruction methods, which can be stratified only vaguely by a cross-disciplinary score. Facing a variety of different risk scores we aimed to develop a new Tumor Risk Score (TRS) enabling anterograde preoperative risk evaluation, resource allocation and optimization of cost and outcome measurements in tumor surgery of the head and neck. METHODS: A collective of 547 patients (2010-2021) with intraoral tumors was studied to develop the TRS by grading the preoperative tumor size and location as well as the invasiveness of the planned surgery by means of statistical modeling. Two postoperative complications were defined: (1) prolonged postoperative stay in IMC/ICU and (2) prolonged total length of stay (LOS). Each parameter was analyzed using TRS and all preoperative patient parameters (age, sex, preoperative hemoglobin, body-mass-index, preexisting medical conditions) using predictive modeling design. Established risk scores (Charlson Comorbidity Index (CCI), American Society of Anesthesiologists risk classification (ASA), Functional Comorbidity Index (FCI)) and Patient Clinical Complexity Level (PCCL) were used as benchmarks for model performance of the TRS. RESULTS: The TRS is significantly correlated with surgery duration (p < 0.001) and LOS (p = 0.001). With every increase in TRS, LOS rises by 9.3% (95%CI 4.7-13.9; p < 0.001) or 1.9 days (95%CI 1.0-2.8; p < 0.001), respectively. For each increase in TRS, the LOS in IMC/ICU wards increases by 0.33 days (95%CI 0.12-0.54; p = 0.002), and the probability of an overall prolonged IMC/ICU stay increased by 32.3% per TRS class (p < 0.001). Exceeding the planned IMC/ICU LOS, overall LOS increased by 7.7 days (95%CI 5.35-10.08; p < 0.001) and increases the likelihood of also exceeding the upper limit LOS by 70.1% (95%CI 1.02-2.85; p = 0.041). In terms of predictive power of a prolonged IMC/ICU stay, the TRS performs better than previously established risk scores such as ASA or CCI (p = 0.031). CONCLUSION: The lack of a standardized needs assessment can lead to both under- and overutilization of the IMC/ICU and therefore increased costs and losses in total revenue. Our index helps to stratify the risk of a prolonged IMC/ICU stay preoperatively and to adjust resource allocation in major head and neck tumor surgery.

Implicit visuospatial sequence representations are accessible in both the practice and the transfer hand.

A serial reaction time task was used to test whether the representations of a probabilistic second-order sequence structure are (i) stored in an effector-dependent, effector-independent intrinsic or effector-independent visuospatial code and (ii) are inter-manually accessible. Participants were trained either with the dominant or non-dominant hand. Tests were performed with both hands in the practice sequence, a random sequence, and a mirror sequence. Learning did not differ significantly between left and right-hand practice, suggesting symmetric intermanual transfer from the dominant to the non-dominant hand and vice versa. In the posttest, RTs were shorter for the practice sequence than for the random sequence, and longest for the mirror sequence. Participants were unable to freely generate or recognize the practice sequence, indicating implicit knowledge of the probabilistic sequence structure. Because sequence-specific learning did not differ significantly between hands, we conclude that representations of the probabilistic sequence structure are stored in an effector-independent visuospatial code.

Individual differences in sensory processing sensitivity amplify effects of post-learning activity for better and for worse.

Sensory processing sensitivity (SPS) is a biologically-based trait associated with greater reactivity to both positive and negative environments. Recent studies suggest that the activity following learning can support or hinder memory retention. Here, we employed a within-subject experiment to examine whether and how individual differences in SPS contribute to differences in memory retention. Sixty-four participants encoded and immediately recalled two word lists: one followed by 8-min of eyes-closed, wakeful resting; and the other by a distraction task. After 7 days, participants completed a surprise free recall test for both word lists. If participants wakefully rested after encoding, memory retention increased as a function of higher SPS. However, in the distraction condition, a negative curvilinear relationship indicated that memory retention was especially hindered for highly sensitive individuals. These results suggest that individual differences in SPS are an important factor to consider when examining the effects of environmental conditions on learning and memory.

Task-synchronized eye blink modulation neither requires visual stimulation nor active motor response and is modulated by task predictability.

It has been repeatedly shown that temporal task features are reflected in eye blink dynamics during attention tasks. Eye blinks occur with increased likeliness particularly when demands on external attention allocation are low. Both predictive, top-down and reactive, bottom-up processes were shown to be involved in blink regulation. However, whether temporal stimulus prediction is a generally active component of the attention system or rather specific to the visual domain has not been fully elaborated yet. By monitoring eye blinking of 99 students during an auditory attention task and analyzing particularly the dynamics of eye blink onsets relative to stimuli timings, we show here that prediction does, in principle, not require visual stimulation, and is also not merely a consequence of the involvement of manual responses during the task. We further show that both the inclusion of manual response to stimuli and elevated task predictability enhance the prediction component reflected in eye blink dynamics, whereas for the latter we experimentally manipulate objective task predictability by adjusting the frequency dependence of the power spectral densities of the series of inter-stimulus time intervals. This allows us finally to explain why, for specific choices of experimental conditions, the generally active and present prediction component involved in attention can become difficult to detect in non-visual, auditory tasks. Conversely, this comes with the important implication that, if tasks aim for elaborating particularly temporal prediction, distributing stimuli over time such that inter-stimulus-intervals conform to a sample of Gaussian noise represents a specifically unfavorable choice.

Wakeful resting and listening to music contrast their effects on verbal long-term memory in dependence on word concreteness.

Wakeful resting and listening to music are powerful means to modulate memory. How these activities affect memory when directly compared has not been tested so far. In two experiments, participants encoded and immediately recalled two word lists followed by either 6 min wakefully resting or 6 min listening to music. The results of Experiment 1 show that both post-encoding conditions have a similar effect on memory after 1 day. In Experiment 2, we explored the possibility that less concrete words, i.e. lower in imageability than in Experiment 1, are differently affected by the two post-encoding conditions. The results of Experiment 2 show that, when words are less concrete, more words are retained after 1 day when encoding is followed by wakeful resting rather than listening to music. These findings indicate that the effects of wakeful resting and listening to music on memory consolidation are moderated by the concreteness of the encoded material.

Patterns of eye blinks are modulated by auditory input in humans.

Previous studies could elaborate a link between attentional processes and eye blinking in both visual and auditory attention tasks. Here we show that this link is active at a fundamental level of perception: presentation of a series of bare sine tones is sufficient to induce a modulation of temporal blink patterns, allowing to determine which series was presented to participants even when they are not required to interactively engage in processing the auditory input. In particular, we monitored eye blinking during an auditory attention task using two series of sine tones, differing in the predictability of the timing of tone onsets. Whereas inter-onset intervals in one tone series corresponded to uncorrelated samples from a normal distribution, they were distributed according to a Gaussian random walk in the other tone series. We find that blink patterns are dynamically modulated by both purely auditory inputs. The magnitude, form, and coherence of the temporal associations between tone onsets and blink events depend strongly on the requirement to respond to the presented stimuli. The predictability of the tone series appears to modulate pre-stimulus blink inhibition given that a response is required. Altogether, these findings suggest eye blink as a readily available, non-invasive behavioral marker for context-sensitive, moment-to-moment allocation of attention.

Individual differences in working memory capacity moderate effects of post-learning activity on memory consolidation over the long term.

Similar to sleeping after learning, a brief period of wakeful resting after encoding new information supports memory retention in contrast to task-related cognition. Recent evidence suggests that working memory capacity (WMC) is related to sleep-dependent declarative memory consolidation. We tested whether WMC moderates the effect of a brief period of wakeful resting compared to performing a distractor task subsequent to encoding a word list. Participants encoded and immediately recalled a word list followed by either an 8 min wakeful resting period (eyes closed, relaxed) or by performing an adapted version of the d2 test of attention for 8 min. At the end of the experimental session (after 12-24 min) and again, after 7 days, participants were required to complete a surprise free recall test of both word lists. Our results show that interindividual differences in WMC are a central moderating factor for the effect of post-learning activity on memory retention. The difference in word retention between a brief period of wakeful resting versus performing a selective attention task subsequent to encoding increased in higher WMC individuals over a retention interval of 12-24 min, as well as over 7 days. This effect was reversed in lower WMC individuals. Our results extend findings showing that WMC seems not only to moderate sleep-related but also wakeful resting-related memory consolidation.

Factors modulating the effects of waking rest on memory.

Study results indicate that moments of unoccupied rest immediately after learning serve an essential cognitive function: memory consolidation. However, there also are findings suggesting that waking rest after learning has similar effects on delayed memory performance as an active wake condition, where participants work on a cognitive distractor task. Based on these studies, we highlight several potentially modulating factors of the so-called resting effect.

Predictability of pharyngeal airway space dimension changes after orthognathic surgery in class II patients: A mathematical approach.

INTRODUCTION: Angle Class II malocclusion due to mandibular retrognathia is a common dentofacial deformity. It is well known that mandibular advancement increases pharyngeal airway dimensions. The aim of this study was to evolve a mathematical method for predicting posterior pharyngeal airway space (PAS) changes based on 2D lateral cephalographic radiographs (LCRs) and expected extent of mandibular advancement prior to BSSO. MATERIALS AND METHODS: Linear regression analyses were performed in order to investigate the relation between the posterior airway space and mandibular advancement. LCRs where carried out to assess skeletal landmarks and pharyngeal airway space pre- (T0) and postoperatively (T1). To detect changes postoperatively, the posterior airway space was divided into three units: nasopharyngeal airway space (superior airway space - SPAS), oropharyngeal airway space (mid airway space - MAS) and hypopharyngeal airway space (inferior airway space - IAS). The differences between the distances of distinct measurement points (DIFF) were measured pre- and postoperatively. DOA referred to the distance of mandibular advancement and DP to the distance between the measurement points preoperatively. The parameters a, b1 and b2 were the regression coefficients that were determined separately for each unit (SPAS, MAS, and IAS). RESULTS: 49 patients (16 male and 33 female) with a mean age of 27.2 years (SD: 10.09), ranging from 18 to 51 years, who underwent mandibular advancement surgery (BSSO) were enrolled in this study. The mean distance of mandibular advancement was 5.05 mm (SD: 1.63). Regarding SPAS and IAS, mandibular advancement did not affect dimensions significantly: SPAS DIFF, 0.33 mm ± 1.13 mm (b1, p = 0.0881; b2, p = 0.087); IAS DIFF, 0.66 mm ± 2.45 mm (b1, p = 0.342; b2, p = 0.765). DOA and DP did not influence DIFF significantly in both sections. Regarding MAS, the mean effect of mandibular advancement was an expansion of 2.47 mm ± 2.24. The linear regression model showed a statistically significant (b1, p = 0.0064; b2, p = 0.0240) influence of DOA and DP on DIFF in posterior airway dimensions pre- and postoperatively. DISCUSSION: Based on preoperative LCR imaging data, a linear regression model was developed as a mathematical approach to allow prediction of PAS development in patients with Angle Class II malocclusions of different degrees. Increasing mandibular advancement was shown to be linked to increasing PAS, while a greater distance between the measuring points preoperatively led to smaller predicted PAS increases postoperatively. CONCLUSION: Predicting pharyngeal airway space (PAS) development after mandibular advancement by analysing lateral cephalometric radiographs (LCR) may be useful in the screening and treatment of obstructive sleep apnea syndrome (OSAS) patients. Our mathematical approach is a simple and sustainable prediction tool based on LTR data for patients with Class II malocclusions.

Follow-up study to investigate symmetry and stability of cranioplasty in craniosynostosis - Introduction of new pathology-specific parameters and a comparison to the norm population.

PURPOSE: Cranioplasty and modulation of frontoorbital advancement (FOA) in children with craniosynostosis aims to achieve an attractive aesthetic and functional rehabilitation of the forehead area, comparable to that in unaffected children. Based on a three-dimensional surface scan, a cephalometric data evaluation with new parameters for the quantification of physiological and pathological cranial morphologies, and objective evaluation of postoperative follow-up in comparison to an age-equivalent standard population, were performed. MATERIALS AND METHODS: In a prospective study, 80 children were operated on with non-syndromic craniosynostosis (trigonocephalus, n = 30; plagiocephalus, n = 10; scaphocephalus, n = 38; brachycephalus, n = 2) and pre- and 3, 6, 12, 18 and 30 months postoperative three-dimensional surface scans were obtained (3DShape, Erlangen, Germany) and morphometrically measured (Onyx Ceph, Image Instruments, Chemnitz, Germany). In addition, 49 healthy children who were not operated on were measured at equivalent ages (n = 25 [6 months]; n = 20 [9 months]; n = 4 [12 months]). RESULTS: All patient groups showed stable long-term results with regard to shaping of the forehead. Cranioplasty in patients with scaphocephalus resulted in a significant widening of the anterior (73.9 ± 3.5 mm; p < 0.001) and posterior (132.2 ± 5.2 mm; p < 0.001) cranial width, with no significant difference from the norm population 1 year after surgery (p = 0.6597). As parameters for the correction of trigonocephaly, the frontal angle showed significant improvement (145.9 ± 3.7°; p < 0.001). While the parietal angle 12 months after surgery showed similar values as the norm population, the frontal angle was about 10° smaller than in healthy children (p = 0.0055), despite a clinically inconspicuous physiognomy. As part of the correction of plagiocephaly, the patients tended to relapse in the postoperative course, although there was no statistically significant difference in the frontal angle compared to that in the norm population (153.3 ± 3.9°; p = 0.06). While 6 months after surgery all patients showed a normal cranial volume development compared to healthy children of the same age, the volumes of brachycephalic patients remained below the norm (1244.2 ± 153.2 cm3; p = 0.0244). Overall, the analysis of the norm population showed a growing dispersion of measurement values with increasing age, which was observed to be more concentrated in the operated cranial morphologies. CONCLUSION: The determination of new pathology-specific morphometric parameters on the three-dimensional surface scan enables an objective quantification of physiological and pathological cranial morphologies of children. A comparison of operated children with a healthy, age-appropriate comparison group showed that preoperative and statistically significant deviations of the new measuring parameters in long-term follow-up could be normalized through surgical intervention, although this does not apply without limitations to children with coronary suture synostosis.

Postoperative Medical Complications and Intermediate Care Unit/Intensive Care Unit Admission in Joint Replacement Surgery: A Prospective Risk Model.

BACKGROUND: Postoperative complications are the main consumers of technical, medical, and human resources. Especially in the field of elective joint replacement surgery, a specialized, easy-to-obtain, and cost-efficient preoperative stratification and risk-estimation model is missing. METHODS: With preoperatively surveyed patient parameters, we identified the most relevant parameters to predict postoperative medical complications. We devised a prospective risk model, measuring the individual probability for intermediate care unit (IMC) or intensive care unit (ICU) admission. The study includes all patients (n = 649) treated with primary or revision total knee arthroplasty in our clinic from 2008 to 2012. RESULTS: The association between general comorbidity scores and mortality risk is well known. Among different comorbidity scores, the Charlson Comorbidity Index is not only relevant for overall postoperative complications (odds ratios [OR] = 2.20) but also predictive of specific complications such as the postoperative need for blood transfusion (OR = 1.94) and unexpected adverse events (OR = 1.74). Considering adverse events, c-reactive protein and leukocyte levels are also highly relevant. Upon predicting a necessary postoperative transfer to an IMC or ICU, the preoperative hemoglobin level, the Charlson Comorbidity Index, and the Index of Coexistent Disease stood out. The latter indicates an increased rate for an IMC/ICU stay by 341% per point. Condensing the most influential predictors, the probability for postoperative IMC/ICU transfer can be calculated for each individual patient. Using the routinely assessed patient's variables, no steadier prediction is possible. CONCLUSION: The introduced risk-estimation model offers a specialized preoperative resource-stratification method in knee joint replacement surgery. It condenses the most influential, individual risk factors to avoid clinical test redundancy and improve resource efficiency and presurgical care planning. A prospective follow-up study could help validating the risk model in clinical routine.

A mathematical approach improves the predictability of length of hospitalization due to acute odontogenic infection: A retrospective investigation of 303 patients.

PURPOSE: Increasing rates of hospitalization of patients diagnosed with acute odontogenic infection have become a burden for public health care, with significant economic concerns. The aim of this study was to investigate factors that tend to prolong hospital length of stay (LOS) in the treatment of severe infections. We present a statistical model that enables the prediction of LOS by exposing the feasibility of the essential statistical determinants. MATERIALS AND METHODS: A 5-year retrospective study investigated records of 303 in-hospital patients with abscess of odontogenic origin. Time-to-event models were used to analyse data where the outcome variable is the time to the occurrence of a specific event. Here, the focus is on a statistical model for the prediction of LOS of patients. RESULTS: The group of all patients (n = 303) was analysed by considering seven characteristics of the patients (age, gender, spreading of infection, localization of infection focus, type of administered antibiotics, diagnosed diabetes mellitus, and existence of a remaining infection focus). Age (p = 0.049; rc = -0.007) and spreading of infection (p < 0.001; rc = -0.965) showed a significant impact on the LOS. Subjects were divided into two groups. Group A (n = 185) consisted of patients who presented with a severe odontogenic infection and not yet removed infection focus; group B were patients having undergone outpatient operative tooth removal (n = 118). To group A patients' data, two new risk factors ("days between abscess incision and removal of infection focus" = dbir and "removal of infection focus during the same stay as abscess incision" = riss) replaced the risk factors "remaining infection focus." A significant impact on the LOS was detected for dbir (p < 0.001; rc = -0.15) and riss (p < 0.001; rc = -1.76). Our statistical model explicitly describes how the probability for discharge depends on the time and how specific characteristics affect the LOS. We observed a significantly higher LOS in older patients and subjects with infection spreading. In group A patients, dbir and riss had a highly significant impact on the LOS. CONCLUSION: Predicting the LOS may promote transparency to costs and management of patients under inpatient treatment. Our statistical model describes the probability of a discharge at time t compared to a discharge later than t (a LOS longer than t). Furthermore, the model enables a prediction of the LOS of each patient for practitioners in an easy way.

The role of immediate versus secondary removal of the odontogenic focus in treatment of deep head and neck space infections. A retrospective analysis of 248 patients.

OBJECTIVES: Aim of this study was to investigate conditions and predisposing factors for head and neck infection progress regarding the length of stay (LOS) in hospital, with special emphasis on the time of removal of the odontogenic infection focus. MATERIAL AND METHODS: A 3-year retrospective study reviewed hospital records of 248 subjects who were treated under inpatient conditions with severe odontogenic infections who received surgical incisions, drainage, and intravenous (IV) antibiotics. Outcomes measured included age, gender, involved fascial spaces, LOS, number of infected spaces, antibiotics administered, and comorbidities. We precisely recorded the time between abscess incision and focus extraction. RESULTS: Removal of infection focus (tooth) in the same stay (1 stay, n = 106; group 1; mean 6.5 days ± 3) showed significantly higher (p = 0.042) LOS than extraction in a second stay (2 stays, n = 46; group 2; 5.3 ± 3.1). Group 3 patients showed infection after removal of teeth in outpatient management (1 stay ex-op, n = 96) and presented significantly lower LOS (5.6 ± 2.5) compared to group 1 (p = 0.0216). LOS of group 3 to group 2 patients showed no significance (p = 0.668). Infection expansion and diabetes showed a significant increase of LOS. CONCLUSION: Simultaneous removal of infection focus and abscess incision leads to the lowest LOS. If tooth extraction is performed after incision, subsequent focus extraction performed in a second stay shows lower overall-LOS than extraction at the same stay at later stage. CLINICAL RELEVANCE: Multiple factors tend to increase the LOS of patients with severe head and neck infections of odontogenic origin. Our data reveals the role of removal of odontogenic focus and additionally ranks further parameters that influence the LOS. Based on our findings, decisions regarding the surgical treatment can be recommended.

Wakeful resting and memory retention: a study with healthy older and younger adults.

Studies indicate that a brief period of wakeful rest after learning supports memory retention, whereas distraction weakens it. It is open for investigation whether advanced age has a significant effect on the impact of post-learning wakeful rest on memory retention for verbal information when compared to a cognitively demanding distraction task. In this study, we examined (1) whether post-learning rest promotes verbal memory retention in younger and older adults and (2) whether the magnitude of the rest benefit changes with increasing age. Younger adults and older adults learned and immediately recalled two consecutive word lists. After one word list, participants rested wakefully for 8 min; after the other list, they solved matrices. Memory performance was again tested in a surprise free recall test at the end of the experimental session. We found that, overall, younger adults outperformed older adults. Also, memory retention was higher following a wakeful rest phase compared to distraction. A detailed analysis revealed that this wakeful rest benefit was significant for the older adults group, whereas the younger adults group retained a similar amount of information in both post-encoding conditions. We assume that older adults can profit more from a wakeful rest phase after learning and are more prone to distraction than younger adults. With increasing age, a short break immediately after information uptake may help better retain the previously learned information, while distraction after learning tends to weaken memory retention.

Post-encoding wakeful resting supports the retention of new verbal memories in children aged 13-14 years.

Evidence primarily exists in adults that engaging in task-related mental activity after new learning results in increased forgetting of learned information, compared with quietly resting in the minutes that follow learning, where less forgetting is observed. The current study investigated whether the beneficial effect of post-encoding rest can be observed in children aged 13-14 years. Each child (N = 102) encoded two word lists. After the presentation and immediate recall of one word list, children wakefully rested for 10 min (resting condition), after presentation and immediate recall of the other word list, they solved visuo-spatial problems for 10 min (problem-solving condition). Seven days later, a surprise free recall test for the two word lists took place. Our results showed that children retained more words over 7 days in the resting condition than with the problem-solving condition. Post-hoc analyses revealed that the resting effect was a function of the number of words recollected during the immediate recall. Specifically, those children who recalled fewest words (≤ 13/30 words) in the immediate recall showed a significant resting effect. There was no resting effect in those who recalled a mid-range (14-16/30 words) or a high number (>16/30 words) of words. These results provide new insights into the factors that influence memory in children, and suggest that a few minutes of wakeful rest benefits memory, relative to engaging in an ongoing task. Statement of contribution What is already known on this subject? Task-related mental activity after encoding weakens memory retention more than wakeful resting. Beneficial effect of resting after encoding was found primarily in younger and older adults. What does this study add? We investigated children at the age of 13-14 years. 8-min post-encoding wakeful resting supports memory retention over 7 days. Individuals differ in the impact of a brief period of wakeful resting after learning. Only children with lower immediate memory performances profited from wakeful resting.

The role of C-reactive protein and white blood cell count in the prediction of length of stay in hospital and severity of odontogenic abscess.

INTRODUCTION: Odontogenic infections and subsequent developing abscess remain to be a potentially life-threatening event, due to septicemia, airway compression and spreading into sensitive anatomic tissues. C-reactive proten (CRP) and white blood cell (WBC) count are routinely blood-measured indicators for inflammation. Are CRP-levels and WBC-count predictive factors of the developement of odontogenic abscess? METHODS: A 4-year retrospective study evaluated hospital records of 218 patients, diagnosed and inpatiently treated for acute odontogenic abscess. They received surgical incision, drainage and intravenous antibiotics. CRP-levels and WBC-counts were measured preoperativly. RESULTS: 218 subjects were enrolled in this study. Patients hospitalized 10 days or more showed significantly higher CRP-levels (p = < 0.001) and WBC-counts (p = 0.006) on admission day than patients with lower LOS. CRP-levels of patients with LOS from 7-9 days were significantly lower (p = 0.47) than in people hospitalized 10 days or more. Abscess focus in the mandible shows significantly higher WBC-counts (p = 0.014). Multiple space infections present a significantly higher CRP (p = 0.003) and WBC (p < 0.001) on admission day. DISCUSSION: According to the presented data, CRP-levels and WBC-count can be regarded as predictive factors for LOS (length of stay in hospital) in patients with long term hospitalization (CRP:7-9 days and > 10 days; WBC: > 10 days). Further WBC and CRP are suitable to predict multiple space infections and localisation of the abscess (WBC) in certain limits. CONCLUSION: In predicting the developement of odontogenic abscess, CRP is more capable in providing exact statements regarding the LOS. However, WBC-counts are more suitable in predicting multiple space infections and localization of infection.

Fibrous dysplasia imitating malignancy.

Fibrous dysplasia is a benign bone disease, presenting as monostotic or polyostotic lesions, or as part of a syndrome (McCune-Albright/Mazabraud). Its clinical course shows a variegated picture and the progression of its growth is unpredictable. In the workup of 39 fibrous dysplasia cases in the cranio-facial area, four cases presented fast growth tendencies, of which two patients with McCune-Albright syndrome showed malignant-like rapid growth. This local aggressive form is extremely rare, and the concept of this issue has not been clearly defined. With regard to the speed of growth a volumetric-time analysis in one of our cases demonstrated a 74 days tumor doubling rate with an exponential growth curve. According to the literature the aggressive form presented extra-cranially mainly at an adult age, whereas its appearance in our cranio-facial patient collective was much younger. Distinguishing nonmalignant and malignant aggressive forms is difficult and highly inconsistent in the literature. We therefore implemented a quantitative growth measure analysis to define aggressive forms based on progression and speed of growth and impartial of type of FD, localization or functional incapacity. Due to our study findings and literature review we state a prevalence of an aggressive form might be possibly about 5 %.

Nonsyndromic cleft palate: An association study at GWAS candidate loci in a multiethnic sample.

BACKGROUND: Nonsyndromic cleft palate only (nsCPO) is a common and multifactorial form of orofacial clefting. In contrast to successes achieved for the other common form of orofacial clefting, that is, nonsyndromic cleft lip with/without cleft palate (nsCL/P), genome wide association studies (GWAS) of nsCPO have identified only one genome wide significant locus. Aim of the present study was to investigate whether common variants contribute to nsCPO and, if so, to identify novel risk loci. METHODS: We genotyped 33 SNPs at 27 candidate loci from 2 previously published nsCPO GWAS in an independent multiethnic sample. It included: (i) a family-based sample of European ancestry (n = 212); and (ii) two case/control samples of Central European (n = 94/339) and Arabian ancestry (n = 38/231), respectively. A separate association analysis was performed for each genotyped dataset, and meta-analyses were performed. RESULTS: After association analysis and meta-analyses, none of the 33 SNPs showed genome-wide significance. Two variants showed nominally significant association in the imputed GWAS dataset and exhibited a further decrease in p-value in a European and an overall meta-analysis including imputed GWAS data, respectively (rs395572: PMetaEU = 3.16 × 10-4 ; rs6809420: PMetaAll = 2.80 × 10-4 ). CONCLUSION: Our findings suggest that there is a limited contribution of common variants to nsCPO. However, the individual effect sizes might be too small for detection of further associations in the present sample sizes. Rare variants may play a more substantial role in nsCPO than in nsCL/P, for which GWAS of smaller sample sizes have identified genome-wide significant loci. Whole-exome/genome sequencing studies of nsCPO are now warranted.

Current concepts in cleft care: A multicenter analysis.

The current surgical techniques used in cleft repair are well established, but different centers use different approaches. To determine the best treatment for patients, a multi-center comparative study is required. In this study, we surveyed all craniofacial departments registered with the German Society of Maxillofacial Surgery to determine which cleft repair techniques are currently in use. Our findings revealed much variation in cleft repair between different centers. Although most centers did use a two-stage approach, the operative techniques and timing of lip and palate closure were different in every center. This shows that a retrospective comparative analysis of patient outcome between the participating centers is not possible and illustrates the need for prospective comparative studies to establish the optimal technique for reconstructive cleft surgery.

Head circumference - a useful single parameter for skull volume development in cranial growth analysis?

BACKGROUND: The measurement of maximal head circumference is a standard procedure in the examination of childrens' cranial growth and brain development. The objective of the study was to evaluate the validity of maximal head circumference to cranial volume in the first year of life using a new method which includes ear-to-ear over the head distance and maximal cranial length measurement. METHODS: 3D surface scans for cranial volume assessment were conducted in this method comparison study of 44 healthy Caucasian children (29 male, 15 female) at the ages of 4 and 12 months. RESULTS: Cranial volume increased from measurements made at 4 months to 12 months of age by an average of 1174 ± 106 to 1579 ± 79 ml. Maximal cranial circumference increased from 43.4 ± 9 cm to 46.9 ± 7 cm and the ear-to ear measurement increased from 26.3 ± 21 cm to 31.6 ± 18 cm at the same time points. There was a monotone association between maximal head circumference (HC) and increase in volume, yet a backwards inference from maximal circumference to the volume had a predictive value of only 78% (adjusted R2). Including the additional measurement of distance from ear to ear strengthened the ability of the model to predict the true value attained to 90%. The addition of the parameter skull length appeared to be negligible. CONCLUSION: The results demonstrate that for a distinct improvement in the evaluation of a physiological cranial volume development, the additional measurement of the ear-to ear distance using a measuring tape is expedient, and, especially for cases with pathological skull changes, such as craniosynostosis, ought to be conducted.