A deep learning model for accurately predicting cancer-specific survival in patients with primary bone sarcoma of the extremity: a population-based study.

PURPOSE: Primary bone and joint sarcomas of the long bone are relatively rare neoplasms with poor prognosis. An efficient clinical tool that can accurately predict patient prognosis is not available. The current study aimed to use deep learning algorithms to develop a prediction model for the prognosis of patients with long bone sarcoma. METHODS: Data of patients with long bone sarcoma in the extremities was collected from the Surveillance, Epidemiology, and End Results Program database from 2004 to 2014. Univariate and multivariate analyses were performed to select possible prediction features. DeepSurv, a deep learning model, was constructed for predicting cancer-specific survival rates. In addition, the classical cox proportional hazards model was established for comparison. The predictive accuracy of our models was assessed using the C-index, Integrated Brier Score, receiver operating characteristic curve, and calibration curve. RESULTS: Age, tumor extension, histological grade, tumor size, surgery, and distant metastasis were associated with cancer-specific survival in patients with long bone sarcoma. According to loss function values, our models converged successfully and effectively learned the survival data of the training cohort. Based on the C-index, area under the curve, calibration curve, and Integrated Brier Score, the deep learning model was more accurate and flexible in predicting survival rates than the cox proportional hazards model. CONCLUSION: A deep learning model for predicting the survival probability of patients with long bone sarcoma was constructed and validated. It is more accurate and flexible in predicting prognosis than the classical CoxPH model.

Estimation of sex from the osteometric measurements of the femur in a contemporary Sri Lankan population / Estimación del sexo a partir de las medidas osteométricas del fémur en una población contemporánea de Sri Lanka

SUMMARY: Sex estimation from human skeletal remains is of vital importance in the buildup of a biological profile of an individual in medico-legal and bioarchaeological studies. The present study is focused on the estimation of sex from osteometric measurements of the complete femur and its fragmentary parts, and the development of a web based application related to this. Fifteen osteometric measurements were taken from 78 dry cadaveric femurs from the Faculty of Medicine, University of Kelaniya. Using R software, linear discriminant analysis and logistic regression methods were applied to build classification models with the help of the application of a stepwise procedure, to identify the best combination of measurements to estimate the sex of the femur. A cross-validation method was applied to estimate the predictive accuracy of each model. Since the linear discriminant analysis model gave more predictive accuracy than the regression model, we suggest using linear discriminant analysis to estimate the sex using osteometric measurements of the femur. From the whole femur measurements, a formula to determine sex was developed with highest total accuracy of 83 % using four parameters; epicondylar breadth, anteroposterior mid-shaft diameter, bi-trochanter length, and maximum shaft diameter. Similarly, measurements of transverse head diameter and bi-trochanter length with a total accuracy of 76 % for the proximal part of the femur, measurements of anteroposterior mid-shaft diameter with a total accuracy of 77 % for the mid-shaft, and measurements of epicondylar breadth and maximum length of the lateral condyle with a total accuracy of 70 % for the distal part of the femur were identified as significant discriminants to determine sex, and formulae were written accordingly. Average accuracy ranged from 83 % to 70 %, with male accuracy slightly higher than that of females. A web application to estimate the sex of femur using these formulae was developed and this will be of great importance for forensic medicine and bio-archaeological research in Sri Lanka.

RESUMEN: La estimación del sexo a partir de restos óseos humanos en los estudios médico-legales y bioarqueológicos es de vital importancia en la construcción de un perfil biológico de un individuo. El objetivo de este estudio fue la estimación del sexo a partir de medidas osteométricas del fémur completo y sus partes fragmentarias, y el desarrollo de una aplicación web relacionada con esto. Se tomaron quince medidas osteométricas de 78 fémures cadavéricos secos de la Facultad de Medicina de la Universidad de Kelaniya. Utilizando el software R, se aplicaron métodos de análisis discriminante lineal y regresión logística para construir modelos de clasificación con la aplicación de un procedimiento por pasos, para identificar la mejor combinación de medidas y estimar el sexo a partir del fémur. Se aplicó un método de validación cruzada para estimar la precisión predictiva de cada modelo. Dado que el modelo de análisis discriminante lineal proporcionó una mayor precisión predictiva que el modelo de regresión, sugerimos su utilización para estimar el sexo mediante mediciones osteométricas del fémur. A partir de las mediciones del fémur completo, se desarrolló una fórmula para determinar el sexo con la mayor precisión total del 83 % utilizando cuatro parámetros; anchura del epicóndilo, diámetro anteroposterior del tercio medio de la diáfisis, longitud bitrocánter y diámetro máximo de la diáfisis. De manera similar, utilizamos las mediciones del diámetro transversal de la cabeza del fémur y la longitud del bitrocánter con una precisión del 76 % para la parte proximal del hueso, las mediciones del diámetro anteroposterior del tercio medio de la diáfisis se obtuvo con una precisión del 77 %. El ancho del epicóndilo y la longitud máxima del cóndilo lateral con una precisión del 70 % para la parte distal del fémur se identificaron como discriminantes significativos para determinar el sexo y se escribieron fórmulas. La precisión promedio osciló entre el 83 % y el 70 %, siendo la precisión en los hombres ligeramente superior al de las mujeres. Se desarrolló una aplicación web para estimar el sexo del fémur utilizando estas fórmulas y creemos será importante para la medicina forense y la investigación bioarqueológica en Sri Lanka.

Effect of Dietary Growth Promoter Supplementations on the Serum Biochemistry and Morphometric Characteristics of Tibia Bone in Broiler Chicken

Bone mineralization is considered an essential source of minerals for metabolic needs that provide strength and hardness to the bone tissues and in birds its development can be enhanced by the use of dietary supplements. The present study was executed to evaluate the influence of prebiotic, probiotic and antibiotic on the morphometric aspects of tibia bone in broilers. One-hundred and sixty-one-day-old broiler chick were divided randomly into four groups (n=40) with 4 replicates (n=10 in each replicate). Group-I fed with only corn based basal diet and served as controlled group. Group-II with antibiotic supplement (Zinc bacitracin 0.04%), Group-III with probiotic supplement (lactobacillus 0.1%) & Group-IV with prebiotic supplement (mannan oligosaccharide 0.1%). On the 35th day, two birds were selected randomly from each replicate and slaughtered to record the morphometric parameters of both right and left tibia bones from each bird. The findings showed that the length, weight, thickness of lateral and medial wall, tibiotarsal index of bone and bone ash percentage of supplemented groups have had significant (p<0.05) difference when compared to that of the controlled group. The weight/length index in birds supplemented with prebiotic and probiotic was significantly higher (p<0.05) than in the antibiotic supplemented and control group. Medullary canal diameter of all the supplemented groups was significantly lower (p<0.05) than the control group. No significant (p>0.05) difference of robusticity index and diaphysis diameter was observed among various groups. A significant (p<0.05) low level of Alkaline Phosphatase while higher level of Calcium and Phosphorus was recorded in the supplemented groups compared to that of the control group. In conclusion, the use of prebiotic and probiotic as growth promoter can exhibit some underline mechanisms in the form of enhancement of bone quality, density and characteristics in broiler chicks as compared to common antibiotics.(AU)

[Nailing of long bone fractures in precarious situations: focus on the Surgical Implant Generation Network (SIGN) nail]. / Enclouage des os longs en situation précaire: intérêt du clou SIGN (Surgical Implant Generation Network).

Economic development in low-income countries has led to a considerable increase in motor vehicles, in particular motorcycles. Traffic accident-related fractures are therefore increasing. The treatment of long bone fractures is, in the majority of cases, based on locked intramedullary nailing, a procedure which is rarely available in countries with poor sanitary conditions. To provide optimal treatment to these countries, the SIGN (Surgical Implant Generation Network) nail was developed in 1999 by Lewis Zirkle. It is currently used free of charge in 53 countries. In return, an international database must be completed in order to assess and develop it. In the light of our experiences in Haiti and Burundi and on the basis of a literature review, we here highlight the conceptual and technical features of SIGN nail whose implant in French-speaking countries is still limited.

Sex differences in diet and life conditions in a rural Medieval Islamic population from Spain (La Torrecilla, Granada): An isotopic and osteological approach to gender differentiation in al-Andalus.

OBJECTIVES: Gender differentiation can influence the diet, physical activity, and health of human populations. Multifaceted approaches are therefore necessary when exploring the biological consequences of gender-related social norms in the past. Here, we explore the links between diet, physiological stress, physical activity, and gender differentiation in the Medieval Islamic population of La Torrecilla (Granada, Spain, 13th-15th century AD), by analyzing stable isotope patterns, stature, and long bone diaphyseal measurements. MATERIALS AND METHODS: The sample includes 96 individuals (48 females, 48 males) classified as young and middle adults (20-34 and 35-50 years of age respectively). Diet was reconstructed through the analysis of δ13 C and δ15 N. Stature, humeral and femoral diaphyseal shape and product of diaphyseal diameters served as proxies of physiological stress and physical activity. RESULTS: Isotopic ratios suggest a substantial dietary contribution of C4 plants (e.g., sorghum, millet), a variable access to animal proteins, and no differences between the sexes. Sexual dimorphism in stature derives from a markedly low female stature. Long bone diaphyseal properties suggest that men performed various physically stressful activities, whereas women were involved in less physically demanding activities (possibly related to household work). DISCUSSION: Gender differentiation in La Torrecilla was expressed by a possibly differential parental investment in male versus female offspring and by culturally sanctioned gender differences in the performance of physical tasks. Diet was qualitatively homogenous between the sexes, although we cannot rule out quantitative differences. Our results shed new light on the effects of gender-related social norms on human development and lifestyle.

Genetically-achieved disturbances to the expression levels of TNFSF11 receptors modulate the effects of zoledronic acid on growing mouse skeletons.

Zoledronic acid (ZOL), a nitrogen bisphosphonate (N-BP), is currently used to treat and control pediatric osteolytic diseases. Variations in the intensity of the effects and side effects of N-BPs have been reported with no clear explanations regarding their origins. We wonder if such variations could be associated with different levels of RANKL signaling activity in growing bone during and after the treatment with N-BPs. To answer this question, ZOL was injected into neonate C57BL/6J mice with different genetically-determined RANKL signaling activity levels (Opg+/+\RankTg-, Opg+/+\RankTg+, Opg+/-\RankTg-, Opg+/-\RankTg+, Opg-/-\RankTg- and Opg-/-\RankTg+ mice) following a protocol (4 injections from post-natal day 1 to 7 at the dose of 50 µg/kg) that mimics those used in onco-pediatric patients. At the end of pediatric growth (1 and half months) and at an adult age (10 months), the bone morphometric and mineral parameters were measured using µCT in the tibia and skull for the different mice. A histologic analysis of the dental and periodontal tissues was also performed. At the end of pediatric growth, a delay in long bone and skull bone growth, a blockage of tooth eruption, some molar root alterations and a neoplasia-like structure associated with incisor development were found. Interestingly, the magnitude of these side effects was reduced by Opg deficiency (Opg-/-) but increased by Rank overexpression (RankTg). Analysis of the skeletal phenotype at ten months confirmed respectively the beneficial and harmful effects of Opg deficiency and Rank overexpression. These results validated the hypothesis that the RANKL signaling activity level in the bone microenvironment is implicated in the modulation of the response to ZOL. Further studies will be necessary to understand the underlying molecular mechanisms, which will help decipher the variability in the effects of N-BPs reported in the human population. SIGNIFICANT STATEMENTS: The present study establishes that in mice the RANKL signaling activity level is a major modulator of the effects and side-effects of bisphosphonates on the individual skeleton during growth. However, the modulatory actions are dependent on the ways in which this level of activity is increased. A decrease in OPG expression is beneficial to the skeletal phenotype observed at the end of growth, while RANK overexpression deteriorates it. Far removed from pediatric treatment, in adults, the skeletal phenotypes initially observed at the end of growth for the different levels of RANKL signaling activity were maintained, although significant improvement was associated only with reductions in OPG expression.

Growth plate stress distribution implications during bone development: a simple framework computational approach.

Mechanical stimuli play a significant role in the process of long bone development as evidenced by clinical observations and in vivo studies. Up to now approaches to understand stimuli characteristics have been limited to the first stages of epiphyseal development. Furthermore, growth plate mechanical behavior has not been widely studied. In order to better understand mechanical influences on bone growth, we used Carter and Wong biomechanical approximation to analyze growth plate mechanical behavior, and explore stress patterns for different morphological stages of the growth plate. To the best of our knowledge this work is the first attempt to study stress distribution on growth plate during different possible stages of bone development, from gestation to adolescence. Stress distribution analysis on the epiphysis and growth plate was performed using axisymmetric (3D) finite element analysis in a simplified generic epiphyseal geometry using a linear elastic model as the first approximation. We took into account different growth plate locations, morphologies and widths, as well as different epiphyseal developmental stages. We found stress distribution during bone development established osteogenic index patterns that seem to influence locally epiphyseal structures growth and coincide with growth plate histological arrangement.

Outcomes of long bone fractures treated by open intramedullary nailing at the St Ann's bay hospital, Jamaica / Resultados clínicos de las fracturas de huesos largos tratadas mediante enclavijado intramedular abierto en el hospital de Saint Ann's bay, Jamaica

Between May 2001 to August 2004, 35 patients had open nailing of long bones. There were 40 fractures fixed. Of these 40 fractures, there were 25 femoral fractures, 11 were tibial fractures and 4 were humeral fractures. There were 33 (82.5%) closed fractures and 7 (17.5%) open fractures. In the group of patients with open fractures, there were two Grade I, two Grade II and three Grade IIIB. Seven (20%) patients were lost to follow-up; all of whom had closed fractures. The final analysis as it relates to complications was done using 28 patients with 32 fractures. The majority of fractures healed without significant complication. All the patients with closed fractures went on to bony union. There was one non-union and three delayed unions. There were two infections (osteomyelitis) and this was from the open fracture cohort. This represents an infection rate of 28.6% in this cohort. Two (7.0%) patients had persistent pain and one (3.6%) patient had early removal of the nail because of failure of fixation. The mean time from injury to surgery for the fractured femur was 15.5 (range 0-49) days; fractured tibia 24.4 (range 0-40), days and fractured humerus 41.5 (20-81) days. The mean hospital stay was 18.9 (range 9-37) days for patients with fractured femur; for fractured tibia, it was 20.5 (range 3-82) days and for fractured humerus, it was 22.7 (range 3-82) days. The mean postoperative stay was 4.1 (range 1-14) days for fractured femur, 4.5 (range 1-14) days for fractured tibia and 4.0 (range 1-10) days for fractured humerus. The mean time to healing (consolidation) as defined by X-rays was 5.0 (range 3-11) months for fractured femur, 5.2 ( range 3-11) months for tibia and 7.0 (range 6- 8) months for fractured humerus.

Desde mayo de 2001 hasta agosto de 2004, 35 pacientes recibieron reducción de fracturas de huesos largos mediante enclavijado a cielo abierto. Se produjeron 40 fijaciones de fracturas. De estas 40 fracturas, 25 fracturas fueron del fémur, 11 fueron de la tibia, y 4 del húmero. Hubo 33 (82.5%) fracturas cerradas y 7 (17.5%) fracturas abiertas. En el grupo de pacientes con fracturas abiertas, hubo dos fracturas de grado I, dos de grado II y tres de grado IIIB. El análisis final en cuanto a las complicaciones, se realizó con 28 pacientes con 32 fracturas. La mayoría de las fracturas se curaron sin complicaciones significativas. Todos los pacientes con fracturas cerradas lograron finalmente la unión ósea. Hubo uno que no logró la unión y tres uniones retardadas. Se produjeron dos infecciones (osteomielitis), provenientes de la cohorte de fractura abierta. Esto representa una tasa de infección del 28.6% en dicha cohorte. Dos (7.0%) pacientes presentaban dolores persistentes, y a un (3.6%) paciente le fue retirado el clavo tempranamente debido a que la fijación falló. El tiempo promedio desde la lesión hasta la cirugía, fue de 15.5 días (rango 0-49) para la fractura del fémur; 24.4 días (rango 0-40) para la fractura de la tibia, y 41.5 días (20-81) para la fractura del húmero. La estancia promedio en el hospital fue de 18.9 días (rango 9-37) para los pacientes con el fémur fracturado; para la fractura de la tibia fue de 20.5 días (rango 3-82), y para el húmero fracturado fue 22.7 días (rango 3-82). La estadía postoperatoria promedio fue 4.1 días (rango 1-14) para el fémur fracturado, 4.5 días (rango 1-14) para la tibia fracturada, y 4.0 días (rango 1-10) días para los casos de fractura del húmero. El tiempo promedio de sanación (consolidación) tal como lo definieron los rayos X fue 5.0 meses (rango 3-11) para el fémur fracturado, 5.2 meses (rango 3-11) para la tibia y 7.0 meses (rango 6-8) para el húmero fracturado.