New method for analysing spatial relationships of facial muscles on MRI: a pilot study.

Dysfunction of the facial musculature can have significant physical, social, and psychological consequences. In surgeries such as cleft surgery or craniofacial bimaxillary osteotomies, the perioral facial muscles may be detached or severed, potentially altering their functional vectors and mimicry capabilities. Ensuring correct reconstruction and maintenance of anatomical sites and muscle vectors is crucial in these procedures. However, a standardized method for perioperative assessment of the facial musculature and function is currently lacking. The aim of this study was to develop a workflow to analyse the three-dimensional vectors of the facial musculature using magnetic resonance imaging (MRI) scans. A protocol for localizing the origins and insertions of these muscles was established. The protocol was implemented using the 3DMedX computer program and tested on 7 Tesla MRI scans obtained from 10 healthy volunteers. Inter- and intra-observer variability were assessed to validate the protocol. The absolute intra-observer variability was 2.6 mm (standard deviation 2.0 mm), and absolute inter-observer variability was 2.6 mm (standard deviation 1.5 mm). This study presents a reliable and reproducible method for analysing the spatial relationships and functional significance of the facial muscles. The workflow developed facilitates perioperative assessment of the facial musculature, potentially aiding clinicians in surgical planning and potentially enhancing the outcomes of midface surgery.

Multimodal Precision Prevention - A New Direction in Alzheimer's Disease.

At least 40% of all dementia has been linked to modifiable risk factors suggesting a clear potential for preventative approaches targeting these factors. Despite the recent promising findings from anti-amyloid monoclonal antibodies, a limited proportion of patients are expected to be eligible for these novel AD treatments. Given the heterogeneous nature of AD and the complex multi-level pathological processes leading to dementia (involving, e.g., shared risk factors, interaction of different pathology mechanisms, and their putative synergistic effects on cognition), targeting a single pathology may not be sufficient to halt or significantly impact disease progression. With exponentially increasing numbers of patients world-wide, in parallel to the unprecedented population ageing, new multimodal therapy approaches targeting several modifiable risk factors and disease mechanisms simultaneously are urgently required. Developing the next generation of combination therapies with lifestyle intervention and pharmacological treatments, implementing the right interventions for the right people at the right time, and defining accessible and sustainable strategies worldwide are crucial. Here, we summarize the state-of-the-art multimodal lifestyle-based approaches, especially findings and lessons learned from the FINGER trial, for prevention and risk reduction of cognitive impairment and dementia. We also discuss some emerging underlying biological mechanisms and the current development of precision prevention approaches. We present an example of a novel trial design combining healthy lifestyle changes with a repurposed putative disease-modifying drug and place this study in the context of the World-Wide FINGERS, the first interdisciplinary network of multimodal trials dedicated to the prevention and risk reduction of cognitive impairment and dementia.

[Is there more to hypodontia then missing teeth?] / Ernstige hypodontie: meer dan alleen ontbrekende gebitselementen?

Dental care professionals regularly see patients with hypodontia. Hypodontia can be acquired, for example through chemotherapy or radiation at a young age, but is hereditary in most patients. Due to an error (pathogenic variant) in one of the many genes that control odontogenesis, the formation of the tooth germ is disrupted at an early stage. The genes involved are not only crucial for tooth development, but they also play an important role in other physical processes. This article provides background information on hypodontia. Based on an inventory of gastrointestinal complaints in patients with hypodontia and a case description of the simultaneous occurrence of a coagulation disorder and hypodontia, the importance of a broad view of this patient group is illustrated. It is concluded that, in addition to a dental assessment, examination of these patients should include a limited physical examination and the medical history of the patient and his close relatives.

A multicenter, open-label, randomized, phase II study of cediranib with or without lenalidomide in iodine 131-refractory differentiated thyroid cancer.

BACKGROUND: Multitargeted tyrosine kinase inhibitors (TKIs) of the vascular endothelial growth factor receptor (VEGFR) pathway have activity in differentiated thyroid cancer (DTC). Lenalidomide demonstrated preliminary efficacy in DTC, but its safety and efficacy in combination with VEGFR-targeted TKIs is unknown. We sought to determine the safety and efficacy of cediranib, a VEGFR-targeted TKI, with or without lenalidomide, in the treatment of iodine 131-refractory DTC. PATIENTS AND METHODS: In this multicenter, open-label, randomized, phase II clinical trial, 110 patients were enrolled and randomized to cediranib alone or cediranib with lenalidomide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, duration of response, toxicity, and overall survival (OS). Patients (≥18 years of age) with DTC who were refractory to further surgical or radioactive iodine (RAI) therapy as reviewed at a multispecialty tumor board conference, and evidence of disease progression within the previous 12 months and no more than one prior line of systemic therapy were eligible. RESULTS: Of the 110 patients, 108 started therapy and were assessable for efficacy. The median PFS was 14.8 months [95% confidence interval (CI) 8.5-23.8 months] in the cediranib arm and 11.3 months (95% CI 8.7-18.9 months) in the cediranib with lenalidomide arm (P = 0.36). The 2-year OS was 64.8% (95% CI 43.3% to 86.4%) and 75.3% (95% CI 59.4% to 91.0%), respectively (P = 0.80). The serious adverse event rate was 41% in the cediranib arm and 46% in the cediranib with lenalidomide arm. CONCLUSIONS: Single-agent therapy with cediranib showed promising efficacy in RAI-refractory DTC similar to other VEGFR-targeted TKIs, while the addition of lenalidomide did not result in clinically meaningful improvements in outcomes.

Hidradenitis suppurativa in Black and White patients - a clinical study.

OBJECTIVE: It is suggested that hidradenitis suppurativa (HS) is more prevalent and causes greater morbidity in Black patients than in White. Clinical data are however lacking. PATIENTS AND METHODS: We therefore describe HS risk factors, disease severity and clinical phenotypes in the Blacks and Whites. Patients referred for HS between 1984 and 2019 at the Johns Hopkins Hospital were identified using the Pathology Data System (PDS). Clinical and sociodemographic characteristics were extracted and the van der Zee & Jemec HS clinical phenotypes were recovered. RESULTS: A total of 278 patients were identified. Ethnically, 108 (38.8%) were White, and 170 (61.2%) Black. The following HS phenotypes were found: Regular (n=193, 69.4%), scarring folliculitis (n=40, 1.4%) frictional furuncle (11.2%), conglobata (n=9, 3.2%), syndromic (n=3, 1.1%) and ectopic (n=2, 0.7%). No statistically significant ethnic differences in clinical presentation were found. Blacks however had more severe diseases than Whites (p= 0.024 for trend). With multivariate logistic regression analysis, we found that male sex, disease duration, and smoking were independent predictors of regular HS phenotype. Major limitations are the limited number of cases studied and the lack of data regarding response to therapies. CONCLUSIONS: Demographics and phenotypical presentation of HS patients do not seem to be associated with Black ethnicity. However, there is a significant trend for Blacks to present with more Hurley stage 2 and 3 disease compared to White patients. It is speculated that ethnic differences are epiphenomena to social factors, highlighting the broader importance of ethnicity.

The average three-dimensional face for different sex and age groups in a Dutch population.

The increasing use of three-dimensional imaging calls for reference models representing large parts of the population. The aim of this prospective study was to create templates depicting facial maturation in the younger age groups. Healthy Dutch volunteers were captured, without selection of inclusions. Three-dimensional average faces were created using MATLAB, for both genders in four age groups (4-8 years, 8-12 years, 12-16 years, and ≥16 years). Variation within the groups was calculated and depicted on an average face with a green to red colour scale, corresponding to standard deviations between 0 and ≥ 3 mm, respectively. Measurements of the distances of eight peri-oral landmarks were provided as ratios. The statistical analysis was performed using ANOVA and Tukey's test. Three-dimensional reconstructions of the average face and their first principal component were created for each gender and age group. The first principal component comprised the facial width for each group, and the variation of landmarks was low. All ratios showed an increasing trend with increasing age, except for the ratio of philtrum width to mouth width. This study is novel in comparing facial morphology by means of ratios and in creating average faces for the different young age groups. These data provide useful insights into facial maturation, which might be beneficial for facial surgeons.

Sexual needs and sexual function of patients with Parkinson's disease.

BACKGROUND: Sexual dysfunction (SD) is a frequent non-motor symptom in Parkinson's disease (PD) that is rarely addressed, and sexual counseling is sporadic. OBJECTIVES: To investigate PD patients' SD and sexual counseling motivation and to propose an interventional strategy for movement disorder specialists. METHODS: All consecutive PD patients who presented to a movement disorder unit between 2018 and 2019 completed anonymous questionnaires containing the Female Sexual Function Index, the International Index of Erectile Function, and a questionnaire on sexual needs and motivation to receive sexual counseling. RESULTS: The age range of the 100 recruited patients (78 men) was 40-80 years, and the mean disease duration was 8.64 ± 6.84 years. SD appeared at all PD stages. The presence of SD pre-PD diagnosis significantly predicted SD post-diagnosis in men. Erectile dysfunction was the most common male SD (70%). Women reported frequent SD before PD diagnosis and currently. More than half of the responders (74% of the men and 40% of the women) were motivated to receive sexual counseling. Most of them (77.4%) were in a relationship. CONCLUSIONS: The findings of this analysis revealed that most PD patients had experienced SD before being diagnosed with PD and were interested in receiving sexual counseling. We propose a six-step intervention strategy for the management of SD in PD designed for application in a movement disorder unit. We also recommend that neurologists and other healthcare providers undergo training to provide basic sexual counseling tailored to the needs of PD patients.

Value of cone beam computed tomography for detecting bone invasion in squamous cell carcinoma of the maxilla.

OBJECTIVE: To determine the diagnostic value of cone beam computed tomography (CBCT) in detecting bone invasion in maxillary squamous cell carcinoma (MSCC). STUDY DESIGN: In this retrospective cohort study, preoperative CBCT scans were independently assessed by a single surgeon in imaging assessment 1 (IA 1) and by 1 surgeon with 2 dentists in consensus (IA 2) for the presence of bone invasion in MSCC. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, area under the receiver operating characteristic curve (AUC), and Cohen's κ were calculated. Histopathologic results of resection specimens served as the reference standard. RESULTS: Of 27 patients, 19 (70%) had proven bone invasion. IA 1 yielded 68.4% sensitivity, 75.0% specificity, 86.7% PPV, 50.0% NPV, 70.4% accuracy, and 0.717 AUC. All results of IA 2 were true-positive and true-negative, resulting in 100% sensitivity, specificity, PPV, NPV, accuracy, and AUC. The assessments differed in 6 cases. Interobserver κ was fair (0.38, 95% CI 0.04-0.72, P = .038). There was a significant association between CBCT detection of bone invasion and extent of surgical treatment (P = .006) CONCLUSIONS: The diagnostic accuracy of CBCT was high but observer-dependent. CBCT examination may be useful in surgical treatment planning.

[Reconstruction of the mandible after loss of the middle segment due to an odontogenic myxoma]. / Reconstructie van de mandibula na verlies van het middensegment door een odontogeen myxoom.

In an 18-year-old boy, the middle segment of the mandible was removed because of a locally aggressive tumour. The reconstruction became infected and was lost, resulting in 2 separately-moving mandible parts and oral disability. For the second reconstruction, skeletal fixation with osteosynthesis plates, dental fixation with a stabilization frame and intermaxillary fixation were used. Preparation for returning the jaws to their original position was facilitated by three-dimensional simulation software. After a successful second reconstruction, an implant-supported removable bridge was eventually placed.

Multimodal Preventive Trial for Alzheimer's Disease: MIND-ADmini Pilot Trial Study Design and Progress.

BACKGROUND: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer's disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. OBJECTIVES: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. METHODS: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. RESULTS: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. CONCLUSIONS: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).

Zygomaticomaxillary complex fracture repair with intraoperative CBCT imaging. A prospective cohort study.

The aim of this study was to evaluate the value of intraoperative conebeam computed tomography (CBCT) imaging in the treatment of zygomaticomaxillary complex (ZMC) fractures. A prospective single center cohort study was performed. Included were consecutive patients who underwent surgery for a unilateral ZMC fracture. An intraoperative CBCT scan was performed after reduction of the ZMC fracture. Revision reduction was performed of the ZMC and/or orbital floor (OF) on indication. The preoperative and postoperative asymmetry of the outer surface of the ZMC was measured on digital 3D-models of CBCT scans, using a mirroring and surface-based matching technique. The postoperative asymmetry of the ZMC in the study group was compared to the asymmetry of the ZMC in the control group with healthy individuals. A total of 38 patients with a unilateral ZMC fracture were included. The mean postoperative asymmetry in the study group (1.67 mm, SD 0.89) was less than the mean preoperative asymmetry (2.69 mm, SD 0.95) (paired samples T-test p < 0.01) but showed no statistically significant difference with the mean asymmetry in the healthy control group (1.40 mm, SD 0.54) (independent samples T-test p = 0.31). Revision reduction of the ZMC and/or OF fracture had been performed in 11 cases after malalignment was noted on the intraoperative CBCT. The indication for intraoperative revision reduction was associated with comminuted ZMC fractures and/or fractures with indication for OF reduction (Pearson Chi Square p < 0.01). Within the limitations of the study, intraoperative CBCT imaging seemed to have a positive influence on ZMC fracture treatment, especially in the case of comminuted ZMC fractures and/or fractures with indication for OF treatment.

A Novel Method for Quantitative Three-Dimensional Analysis of Zygomatico-Maxillary Complex Symmetry.

OBJECTIVE: To develop a reliable and accurate method to quantify the symmetry of the zygomaticomaxillary complex (ZMC). METHODS: Virtual three-dimensional models were created from 53 computed-tomography scans: 15 healthy cases without maxillofacial disorders and 38 patients with ZMC fractures requiring surgical treatment.Asymmetry of the ZMC was measured using a mirroring and surface-based matching technique that uses the anterior cranial fossa as reference to determine the symmetrical position of the ZMC. The measure for ZMC asymmetry was defined as mean surface distance (MSD) between the ZMC-surface and the symmetrical position.Reliability of the method was tested in the 15 healthy cases. Inter-and intra-observer correlation coefficients (Ce) and variabilities were assessed. Accuracy was assessed by comparing ZMC asymmetry between healthy and ZMC fracture cases, and by assessing correlation of ZMC fracture severity with ZMC asymmetry. RESULTS: The average MSD of the 15 healthy cases was 1.40 ± 0.54 mm and the average MSD of the 38 ZMC fracture cases was 2.69 ± 0.95 mm ( P < 0.01). Zygomaticomaxillary complex asymmetry correlated with fracture severity ( P = 0.01). Intra-rater CC was 0.97 with an intra-rater variability of 0.09 ± 0.11 mm. Inter-rater Ce was 0.95 with an inter-rater variability of 0.12 ± 0.13 mm. CONCLUSIONS: Our method is reliable and accurate for quantitative three-dimensional analysis of ZMC-symmetry. It takes into account asymmetry caused by the shape of the ZMC as well as asymmetry caused by the position of the ZMC. CLINICAL RELEVANCE: This method is useful for the evaluation of ZMC asymmetry associated with congenital and acquired disorders of craniofacial skeleton, for surgical planning and for evaluation of postoperative results.

Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies in multiple myeloma patients.

Autologous stem cell transplant (aHSCT) is associated with improved survival for multiple myeloma (MM) patients but may be associated with second primary malignancy (SPM) development. Using the California Cancer Registry linked to statewide hospitalization data, we determined the cumulative incidence (CMI) of SPMs more than 1 year after MM diagnosis, accounting for the competing risk of death. AHSCT recipients were matched 1:2 to non-aHSCT patients. Adjusted hazard ratios (aHR) were estimated using the Fine and Gray method. Among 16,331 patients, 933 (5.7%) developed a SPM more than 1 year after diagnosis. The 10-year CMI of developing any SPM was 6.6%, 5.7% for solid tumor SPM and 0.9% for hematologic malignancies. The 10-year CMI of developing any SPM was similar among aHSCT [9.1% (7.7-10.7%)] and non-aHSCT [7.5% (6.5-8.6%)] (P = 0.26) recipients and there was no difference in solid-tumor SPMs (P = 0.98). The 10-year CMI of hematologic SPMs was higher among aHSCT recipients [2.1% (1.4-2.9%) vs. 0.8% (0.5-1.2%); P = 0.005], corresponding to a 1.3% absolute increase and an aHR of 1.51 (1.01-2.27). Ten-year myeloma-specific and non-cancer mortality rates were 59% (58.2-60.0%) and 18.1% (17.4-18.8%), respectively. Although aHSCT was associated with a small increase in hematologic SPMs, mortality was driven by MM and non-cancer causes.

Current measures are not sufficient: an interview-based qualitative assessment of quality of life in cutaneous T-cell lymphoma.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) negatively impacts quality of life (QoL), but existing QoL questionnaires may not comprehensively reflect patients' experience. OBJECTIVES: To identify the aspects of QoL that are most meaningful to patients with CTCL and to evaluate existing QoL instruments in this context. METHODS: Semistructured interviews were conducted between May and June 2019 using purposive sampling of patients with CTCL. Data were analysed by an inductive thematic approach using Dedoose Version 8.0.35. RESULTS: One-on-one interviews lasting a median of 43 min were completed by 18 patients [median age 62 years (interquartile range 52-70); 39% advanced-stage (IIB-IV)]. Itch was the most common clinical symptom reported (16 of 18 patients), followed by pain (12 of 18), skin breaks (11 of 18) and skin flaking (10 of 18). Eleven patients reported that their symptoms interfered with sleep, which impacted daily functioning. Patients also noted a lack of understanding of the disease in the community and felt uncertain (12 of 18), depressed (11 of 18), suicidal (four of 18) and hopeless (nine of 18). Nearly all patients (17 of 18) reported a sense of 'otherness' (not feeling 'normal' or 'like themselves'), and most patients (16 of 18) specifically mentioned concern about their physical appearance. Patients also noted substantial treatment burden. Salient patient concerns, including individual clinical symptoms, concern about appearance and problems with sleep, were not adequately or consistently represented in generic, skin-specific or CTCL-specific QoL measures. CONCLUSIONS: Incorporating the concerns and priorities that distinguish patients with CTCL from other patient populations will be of paramount importance in developing a comprehensive CTCL-specific measure of QoL that adequately captures patients' experience.

Is low or high body mass index in patients operated for oral squamous cell carcinoma associated with the perioperative complication rate?

The aim of this study was to analyse the effect of body mass index (BMI), both low and high values, on the perioperative complication rate in patients with oral squamous cell carcinoma (OSCC). The medical records of 259 patients operated between 2014 and 2017 for OSCC were reviewed. Univariate and multivariate analyses were performed. Sixty of the 259 patients developed 87 complications. Low or high BMI was not associated with the perioperative complication rate. A longer operating time and increased blood loss were associated with a higher perioperative complication rate and higher Clavien-Dindo grade. Low BMI, American Society of Anesthesiologists score 2 and 3, a longer operating time, and increased blood loss were associated with a longer hospital stay. Low BMI was associated with a longer hospital stay. Neither low nor high BMI was associated with the perioperative complication rate. A longer operating time and increased blood loss were associated with a higher perioperative complication rate and higher Clavien-Dindo grade.

Influenza vaccine effectiveness against laboratory-confirmed influenza in a vaccine-mismatched influenza B-dominant season.

BACKGROUND: The 2017-2018 influenza season in Israel was characterized by the predominance of influenza B Yamagata, with a lesser circulation of influenza A(H1N1)pdm09 and influenza A(H3N2). We estimated vaccine effectiveness (VE) of the inactivated influenza vaccine which was selected for use that season. METHODS: End-of-season VE and 95% confidence intervals (CI) against laboratory-confirmed influenza-like illness (ILI) were estimated by means of the test-negative design. Age-specific VE analysis was carried out using a moving age interval. RESULTS: Specimen were obtained from 1,453 community ILI patients; 610 (42.0%) were influenza-positive, among which 69.7% were B, 17.2% A(H1N1)pdm09 and 13.4% A(H3N2). A 98.6% of molecularly characterized influenza B belonged to the Yamagata lineage. Of the sampled individuals, 1320 were suitable for VE analysis. Of those vaccinated, 90.6% received the inactivated trivalent influenza vaccine (TIV) containing a Victoria lineage influenza B-like virus. VE against influenza A differed by age, with the highest VE of 72.9% (95%CI 31.9-89.2%) observed in children 0.5-14 years old, while all ages VE was 46.6% (95%CI 10.4-68.2%). All ages VE against influenza B was 23.2% (95%CI -10.1-46.4%) with age-specific analysis showing non-significant VE estimates. Utilizing a moving age interval of 15 years, afforded a detailed age-specific insight into influenza VE against the influenza viruses circulating during the 2017-2018 season. CONCLUSIONS: The moderate-high 2017-2018 influenza A VE among children and adolescents, supports seasonal influenza vaccination at a young age. The low VE against influenza B in Israel, is most likely the result of influenza B/TIV-mismatch.

Pain in the Prehospital Setting in Rwanda: Results of a Mixed-Methods Quality Improvement Project.

Introduction: Pain is a universal human experience tied to an individual's health but difficult to understand. It is especially important in health emergencies. We performed a two-step quality improvement project to assess pain management by the SAMU ambulance service in Kigali, Rwanda, examining how pain is assessed and treated by ambulance staff to facilitate development of standardized guidelines of pain management in the prehospital setting, which did not exist at the time of the study. Materials and Methods: Deidentified ambulance service records from December 2012 to May 2016 were analyzed descriptively for patient demographics, emergency conditions, pain assessment, and medications given. Then, anonymized, semistructured interviews of ambulance staff were conducted until thematic saturation was achieved. Data were analyzed using a grounded theory approach. Results: SAMU managed 11,161 patients over the study period, of which 6,168 (55%) were documented as reporting pain and 5,010 (45%) received pain medications. Men had greater odds of receiving pain medications compared to women (OR = 3.8, 95% CI (3.5, 4.1), p < 0.01). Twenty interviews were conducted with SAMU staff. They indicated that patients communicate pain in different ways. They reported using informal ways to measure pain or a standardized granular numeric scale. The SAMU team reviewed these results and developed plans to modify practices. Conclusions: We reviewed the existing quality of pain management in the prehospital setting in Kigali, Rwanda, assessed the SAMU staff's perceptions of pain, and facilitated standardization of prehospital pain management through context-specific guidelines.

Endochondral Bone Regeneration by Non-autologous Mesenchymal Stem Cells.

Mimicking endochondral bone formation is a promising strategy for bone regeneration. To become a successful therapy, the cell source is a crucial translational aspect. Typically, autologous cells are used. The use of non-autologous mesenchymal stromal cells (MSCs) represents an interesting alternative. Nevertheless, non-autologous, differentiated MSCs may trigger an undesired immune response, hampering bone regeneration. The aim of this study was to unravel the influence of the immune response on endochondral bone regeneration, when using xenogeneic (human) or allogeneic (Dark Agouti) MSCs. To this end, chondrogenically differentiated MSCs embedded in a collagen carrier were implanted in critical size femoral defects of immunocompetent Brown Norway rats. Control groups were included with syngeneic/autologous (Brown Norway) MSCs or a cell-free carrier. The amount of neo-bone formation was proportional to the degree of host-donor relatedness, as no full bridging of the defect was observed in the xenogeneic group whereas 2/8 and 7/7 bridges occurred in the allogeneic and the syngeneic group, respectively. One week post-implantation, the xenogeneic grafts were invaded by pro-inflammatory macrophages, T lymphocytes, which persisted after 12 weeks, and anti-human antibodies were developed. The immune response toward the allogeneic graft was comparable to the one evoked by the syngeneic implants, aside from an increased production of alloantibodies, which might be responsible for the more heterogeneous bone formation. Our results demonstrate for the first time the feasibility of using non-autologous MSC-derived chondrocytes to elicit endochondral bone regeneration in vivo. Nevertheless, the pronounced immune response and the limited bone formation observed in the xenogeneic group undermine the clinical relevance of this group. On the contrary, although further research on how to achieve robust bone formation with allogeneic cells is needed, they may represent an alternative to autologous transplantation.

The epidemiology and prehospital care of motorcycle crashes in a sub-Saharan African urban center.

OBJECTIVE: Road traffic crashes (RTCs) are common among motorcyclists in Kigali, Rwanda. The Service d'Aide Medicale Urgente (SAMU), a prehospital ambulance service, responds to many of these crashes. We aimed to describe motorcycle-related RTCs managed by SAMU. METHODS: SAMU clinical data including demographic information, injury characteristics, and management details were analyzed descriptively for all motorcycle crashes occurring between December 2012 and July 2016. RESULTS: Every patient included in this study was injured. These patients all called the ambulance for their injuries after a motorcycle crash. There were 2,912 motorcycle-related RTCs over the study period, representing 26% of all patients managed by SAMU. The incidence of motorcycle crashes in Kigali was 258 crashes per 100,000 people over the 3.5-year study period. The average age was 30 years and 80% were males. The most common injuries were to the lower extremities (n = 958, 33%), head (n = 878, 30%), or upper extremities (n = 453, 16%). Injuries often resulted in fractures of extremities (n = 740, 25%) and external hemorrhage anywhere in the body (unspecified region; n = 660, 23%), yet few were severe based on the Kampala Trauma Score (n = 23, 2%) and Glasgow Coma Scale (n = 42, 1.5%). The most common interventions were provision of diclofenac (n = 1,526, 52.5%), peripheral intravenous (IV) access (n = 1,217, 42%), and administration of IV fluids (n = 1,048, 36%). CONCLUSION: Motorcycle-related RTCs represent a large burden of disease for patients treated by SAMU in Kigali, Rwanda. Young men are most at risk of injury, which imposes a financial strain on society. Though injuries occurred frequently, critical trauma cases from motorcycle crashes were uncommon. This may be a result of several initiatives in Rwanda to improve road safety.