How accurate are medical CT and micro-CT techniques compared to classical histology when addressing the growth of the internal rib parameters?

Rib internal anatomy and its cross-sectional morphology inform about important biomechanical or even evolutionary aspects. Classic histological studies require destructive techniques that are reprehensible depending on the case (e.g., fossils). In the last years, non-destructive CT-based methods are contributing to complementing previous knowledge without damaging the bone. Even though these methods have been proved to be useful to understand adult variation, we do not know whether these methods are useful to cover ontogenetic variation. This work compares classical histological methods with medical- and micro-CT to quantify the amount of mineral area at the rib midshaft (% Min. Ar.), a proxy for bone density. We compared cross-sections from an ontogenetic sample of 14 human first ribs ranging from perinates to adults using a) classical histology, b) HD (9-17 microns) and SD micro-CT (90 microns), and c) standard medical-CT (0.66 mm). We found that all the CT-based methods provide a larger % Min. Ar. compared to the histological techniques, but the HD micro-CT resolution is the only capable of producing results comparable to classical histology (p > 0.01), with the SD micro-CT and the medical-CT producing statistically larger results compared to classical histology (p < 0.01). In addition, it is important to state that the resolution of a standard medical-CT is not high enough to differentiate between mineral and non-mineral areas of the cross-sections for perinates and infants. These results could have important implications to avoid (when necessary) destructive techniques that are not appropriate in the case of highly valuable specimens such as fossils.

[Blue Lungs in Covid-19 Patients: A Step beyond the Diagnosis of Pulmonary Thromboembolism using MDCT with Iodine Mapping]. / Pulmones azules en pacientes COVID-19: un paso más allá del diagnóstico de tromboembolismo pulmonar mediante TCMD con mapa de yodo.

OBJECTIVE: To evaluate the diagnostic capacity of pulmonary angiography with multidetector computed tomography (MDCT) and iodine mapping in the diagnosis of pulmonary thromboembolism (PTE) in patients with Covid-19 disease. METHODS: Retrospective observational study of 81 consecutive patients admitted with Covid-19 respiratory infection who underwent MDCT for clinical suspicion of PTE (sudden dyspnea, chest pain, hemoptysis, severe respiratory failure (SRF) not corrected with high O2 flow) and/or raised D-dimer. RESULTS: Of the 81 patients studied [64 (79.01%) men], acute PTE was identified in 22 (27.16%), bilaterally in 13 (59.09%), and 13 (59,09%) showed areas of hypoperfusion. Of the 59 (72.83%) patients without PTE, hypoperfusion was observed in 41 (69.49%) (attributable in one case to pulmonary emphysema). In 18 (22.2%) of the total number of patients, neither PTE nor hypoperfusion were seen. A crazy paving pattern is a risk factor for developing PTE (OR 1.94; 95% CI 0.28-13.57), as are consolidations (OR 1.44; 95% CI 0.24-8.48) and septal thickening/bronchiectasis (OR 1.47; 95% CI 0.12-17.81).Patients with O2-refractory SRF showed a 6.36-fold higher risk for hypoperfusion on the iodine map. CONCLUSION: By adding the functional image to the anatomical image, pulmonary angiography with MDCT and iodine mapping can demonstrate not only PTE in main, lobar and segmental arteries, but also the presence of hypoperfusion in distal vessels. This makes it a highly useful tool for the accurate diagnosis and therapeutic orientation of patients with Covid-19 lung involvement.

An Unusual Case of Hypopituitarism as an Adverse Effect of Vandetanib and Remission of Breast Metastases in a Patient with Medullary Thyroid Cancer.

INTRODUCTION: Tyrosine kinase inhibitors have been a breakthrough in the treatment of advanced medullary thyroid cancer (MTC), and they can prolong progression-free survival (PFS). CASE PRESENTATION: A patient with MTC and metastatic spread to the lymph nodes, lungs, bones, breast, and cerebellum started treatment with vandetanib. During treatment, she developed secondary adrenal insufficiency and hypogonadotropic hypogonadism. After 9 years of vandetanib therapy, the disease has not progressed and the patient maintains a complete response of the breast metastases and a partial response of the other metastatic lesions. CONCLUSION: To our knowledge, this is the first reported case of secondary adrenal insufficiency and hypogonadotropic hypogonadism related to therapy with vandetanib. Moreover, the prolonged PFS and the complete disappearance of some of the metastatic lesions in this patient are truly unusual.

Pulmones azules en pacientes COVID-19: un paso más allá del diagnóstico de tromboembolismo pulmonar mediante TCMD con mapa de yodo / Blue Lungs in Covid-19 Patients: A Step beyond the Diagnosis of Pulmonary Thromboembolism using MDCT with Iodine Mapping

OBJETIVO: Evaluar la capacidad diagnóstica de la angiografía pulmonar con tomografía computarizada multidetector (TCMD) y mapa de yodo en el diagnóstico del tromboembolismo pulmonar (TEP), en pacientes con enfermedad por coronavirus COVID-19. MÉTODOS: Estudio observacional retrospectivo sobre 81 pacientes consecutivos ingresados con infección respiratoria por COVID-19, a los que se realizó TCMD ante la sospecha clínica de TEP [disnea súbita, dolor torácico, hemoptisis, insuficiencia respiratoria grave (IRG) que no corrige con flujo elevado de O2] y/o elevación del D-dímero. RESULTADOS: De los 81 pacientes estudiados, 64 (79,01%) varones, identificamos TEP agudo en 22 (27,16%), en 13 (59,09%) bilateral y en 13 (59,09%) con áreas de hipoperfusión. De los 59 (72,83%) pacientes sin TEP en 41 (69,49%) se observó hipoperfusión (en un caso atribuible a enfisema pulmonar). En 18 (22,2%) del total de pacientes no se vio ni TEP ni hipoperfusión. El patrón «crazy paving» es un factor de riesgo para desarrollar TEP (OR1,94; IC95% 0,28-13,57), así como los patrones «consolidaciones» (OR 1,44; I C95% 0,24-8,48) y «engrosamiento septos/bronquiectasias» (OR 1,47; IC 95% 0,12-17,81). Los pacientes con IRG refractaria al O2 mostraron un riesgo 6,36 veces superior para el hallazgo de hipoperfusión en el mapa de yodo. CONCLUSIÓN: La angiografía pulmonar con TCMD y mapa de yodo, al añadir la imagen funcional a la anatómica, es capaz de demostrar, además del TEP en arterias principales, lobares y segmentarias, la presencia de hipoperfusión en vasos distales, lo cual la convierte en una herramienta de gran utilidad para la adecuada orientación diagnóstica y terapéutica de los pacientes con afectación pulmonar por COVID-19

OBJECTIVE: To evaluate the diagnostic capacity of pulmonary angiography with multidetector computed tomography (MDCT) and iodine mapping in the diagnosis of pulmonary thromboembolism (PTE) in patients with Covid-19 disease. METHODS: Retrospective observational study of 81 consecutive patients admitted with Covid-19 respiratory infection who underwent MDCT for clinical suspicion of PTE (sudden dyspnea, chest pain, hemoptysis, severe respiratory failure (SRF) not corrected with high O2 flow) and/or raised D-dimer. RESULTS: Of the 81 patients studied [64 (79.01%) men], acute PTE was identified in 22 (27.16%), bilaterally in 13 (59.09%), and 13 (59,09%) showed areas of hypoperfusion. Of the 59 (72.83%) patients without PTE, hypoperfusion was observed in 41 (69.49%) (attributable in one case to pulmonary emphysema). In 18 (22.2%) of the total number of patients, neither PTE nor hypoperfusion were seen. A crazy paving pattern is a risk factor for developing PTE (OR 1.94; 95% CI 0.28-13.57), as are consolidations (OR 1.44; 95% CI 0.24-8.48) and septal thickening/bronchiectasis (OR 1.47; 95% CI 0.12-17.81). Patients with O2-refractory SRF showed a 6.36-fold higher risk for hypoperfusion on the iodine map. CONCLUSION: By adding the functional image to the anatomical image, pulmonary angiography with MDCT and iodine mapping can demonstrate not only PTE in main, lobar and segmental arteries, but also the presence of hypoperfusion in distal vessels. This makes it a highly useful tool for the accurate diagnosis and therapeutic orientation of patients with Covid-19 lung involvement

Late subadult ontogeny and adult aging of the human thorax reveals divergent growth trajectories between sexes.

Sexual dimorphism is an important feature of adult thorax morphology, but when and how sex-related differences in the ribcage arise during ontogeny is poorly known. Previous research proposed that sex-related size differences in the nasal region arise during puberty. Therefore, we explore whether ribcage sexual dimorphism also arises at that time and whether this sexual dimorphism is maintained until old age. We measured 526 (semi)landmarks on 80 CT-based human ribcage reconstructions, on individuals ranging from 7 to 65 year-old. The 3D coordinates were submitted to the Procrustes superimposition and analyzed. Our results show that the trajectories of thorax size and shape between sexes diverge at around 12 years of age, and continue slightly diverging until old age. The differential ontogenetic trends cause adult male ribcages to become deeper, shorter, and wider than female. Our results are consistent with the evidence from the cranial respiratory system, with the development of sexual dimorphism probably related to changes in body composition during puberty combined with changes in the reproductive system.

Rib cage anatomy in Homo erectus suggests a recent evolutionary origin of modern human body shape.

The tall and narrow body shape of anatomically modern humans (Homo sapiens) evolved via changes in the thorax, pelvis and limbs. It is debated, however, whether these modifications first evolved together in African Homo erectus, or whether H. erectus had a more primitive body shape that was distinct from both the more ape-like Australopithecus species and H. sapiens. Here we present the first quantitative three-dimensional reconstruction of the thorax of the juvenile H. erectus skeleton, KNM-WT 15000, from Nariokotome, Kenya, along with its estimated adult rib cage, for comparison with H. sapiens and the Kebara 2 Neanderthal. Our three-dimensional reconstruction demonstrates a short, mediolaterally wide and anteroposteriorly deep thorax in KNM-WT 15000 that differs considerably from the much shallower thorax of H. sapiens, pointing to a recent evolutionary origin of fully modern human body shape. The large respiratory capacity of KNM-WT 15000 is compatible with the relatively stocky, more primitive, body shape of H. erectus.

Association between ribs shape and pulmonary function in patients with Osteogenesis Imperfecta.

The aim of the present study was to test the hypothesis that ribs shape changes in patients with OI are more relevant for respiratory function than thoracic spine shape. We used 3D geometric morphometrics to quantify rib cage morphology in OI patients and controls, and to investigate its relationship with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), expressed as absolute value and as percentage of predicted value (% pred). Regression analyses on the full sample showed a significant relation between rib shape and FEV1, FVC and FVC % pred whereas thoracic spine shape was not related to any parameter. Subsequent regression analyses on OI patients confirmed significant relations between dynamic lung volumes and rib shape changes. Lower FVC and FEV1 values are identified in OI patients that present more horizontally aligned ribs, a greater antero-posterior depth due to extreme transverse curve at rib angles and a strong spine invagination, greater asymmetry, and a vertically short, thoraco-lumbar spine, which is relatively straight in at levels 1-8 and shows a marked kyphosis in the thoraco-lumbar transition. Our research seems to support that ribs shape is more relevant for ventilator mechanics in OI patients than the spine shape.

Three-dimensional analysis of sexual dimorphism in ribcage kinematics of modern humans.

OBJECTIVES: Sexual dimorphism is an important biological factor underlying morphological variation in the human skeleton. Previous research found sex-related differences in the static ribcage, with males having more horizontally oriented ribs and a wider lower ribcage than females. Furthermore, a recent study found sex-related differences in the kinematics of the human lungs, with cranio-caudal movements of the caudal part of the lungs accounting for most of the differences between sexes. However, these movements cannot be quantified in the skeletal ribcage, so we do not know if the differences observed in the lungs are also reflected in sex differences in the motion of the skeletal thorax. MATERIALS AND METHODS: To address this issue, we quantified the morphological variation of 42 contemporary human ribcages (sex-balanced) in both maximal inspiration and expiration using 526 landmarks and semilandmarks. Thoracic centroid size differences between sexes were assessed using a t test, and shape differences were assessed using Procrustes shape coordinates, through mean comparisons and dummy regressions of shape on kinematic status. A principal components analysis was used to explore the full range of morphological variation. RESULTS: Our results show significant size differences between males and females both in inspiration and expiration (p < .01) as well as significant shape differences, with males deforming more than females during inspiration, especially in the mediolateral dimension of the lower ribcage. Finally, dummy regressions of shape on kinematic status showed a small but statistically significant difference in vectors of breathing kinematics between males and females (14.78°; p < .01). DISCUSSION: We support that sex-related differences in skeletal ribcage kinematics are discernible, even when soft tissues are not analyzed. We hypothesize that this differential breathing pattern is primarily a result of more pronounced diaphragmatic breathing in males, which might relate to differences in body composition, metabolism, and ultimately greater oxygen demand in males compared to females. Future research should further explore the links between ribcage morphological variation and basal metabolic rate.

Ribcage measurements indicate greater lung capacity in Neanderthals and Lower Pleistocene hominins compared to modern humans.

Our most recent fossil relatives, the Neanderthals, had a large brain and a very heavy body compared to modern humans. This type of body requires high levels of energetic intake. While food (meat and fat consumption) is a source of energy, oxygen via respiration is also necessary for metabolism. We would therefore expect Neanderthals to have large respiratory capacities. Here we estimate the pulmonary capacities of Neanderthals, based on costal measurements and physiological data from a modern human comparative sample. The Kebara 2 male had a lung volume of about 9.04 l; Tabun C1, a female individual, a lung volume of 5.85 l; and a Neanderthal from the El Sidrón site, a lung volume of 9.03 l. These volumes are approximately 20% greater than the corresponding volumes of modern humans of the same body size and sex. These results show that the Neanderthal body was highly sensitive to energy supply.

3D analysis of sexual dimorphism in size, shape and breathing kinematics of human lungs.

Sexual dimorphism in the human respiratory system has been previously reported at the skeletal (cranial and thoracic) level, but also at the pulmonary level. Regarding lungs, foregoing studies have yielded sex-related differences in pulmonary size as well as lung shape details, but different methodological approaches have led to discrepant results on differences in respiratory patterns between males and females. The purpose of this study is to analyse sexual dimorphism in human lungs during forced respiration using 3D geometric morphometrics. Eighty computed tomographies (19 males and 21 females) were taken in maximal forced inspiration (FI) and expiration (FE), and 415 (semi)landmarks were digitized on 80 virtual lung models for the 3D quantification of pulmonary size, shape and kinematic differences. We found that males showed larger lungs than females (P < 0.05), and significantly greater size and shape differences between FI and FE. Morphologically, males have pyramidal lung geometry, with greater lower lung width when comparing with the apices, in contrast to the prismatic lung shape and similar widths at upper and lower lungs of females. Multivariate regression analyses confirmed the effect of sex on lung size (36.26%; P < 0.05) and on lung shape (7.23%; P < 0.05), and yielded two kinematic vectors with a small but statistically significant angle between them (13.22°; P < 0.05) that confirms sex-related differences in the respiratory patterns. Our 3D approach shows sexual dimorphism in human lungs likely due to a greater diaphragmatic action in males and a predominant intercostal muscle action in females during breathing. These size and shape differences would lead to different respiratory patterns between sexes, whose physiological implications need to be studied in future research.

3D geometric morphometrics of thorax variation and allometry in Hominoidea.

Ever since the seminal papers of Keith and Schultz, hominoid primate ribcages have been described as either "funnel-" or "barrel-shaped." Following this dichotomic typology, it is currently held that Homo sapiens and hylobatids (gibbons and siamangs) share a barrel-shaped ribcage and that they are more similar to each other than to the funnel-shaped thoraces of great apes (Gorilla, Pan, and Pongo). Other researchers hypothesized that thoracic width and the invagination of the thoracic spine into the thorax are related to allometry. However, analyses that take into account the complex three-dimensional (3D) shape of the ribcage are lacking. Here, we address hypotheses about thorax shape and evolution using 3D morphometrics of thoraces in anatomical connection obtained by computed tomography scans of 23 hominoid cadavers and 10 humans and examining thorax compartments composed of seven ribs (1-7 thorax) and of 11 ribs (1-11 thorax). In the 1-7 thorax analyses, the human thorax is uniquely flat because of torsion of the upper and central ribs, differing from all non-human hominoids including hylobatids. In the 1-11 thorax analyses, humans are markedly different from African great apes, with hylobatids and orangutans intermediate. In full shape space analyses, affinities between orangutans and humans on the one hand and between hylobatids and African great apes on the other are evident. Therefore, we reject the hypothesis that humans and hylobatids bear any special affinities in overall 3D thorax shape to each other. We find that larger thoraces are wider and flatter, with a more invaginated spine, supporting the allometric hypothesis. Hominoid thorax variation shows complex interactions between allometry, rib curves, torsion, and declination, and the morphology of the costo-vertebral joint and the thoracic vertebral column. When considering functional specializations alongside phylogenetic relationships, an overly simplistic dichotomy between funnel-shaped and barrel-shaped thoraces is not supported.

In Vivo 3D Analysis of Thoracic Kinematics: Changes in Size and Shape During Breathing and Their Implications for Respiratory Function in Recent Humans and Fossil Hominins.

The human ribcage expands and contracts during respiration as a result of the interaction between the morphology of the ribs, the costo-vertebral articulations and respiratory muscles. Variations in these factors are said to produce differences in the kinematics of the upper thorax and the lower thorax, but the extent and nature of any such differences and their functional implications have not yet been quantified. Applying geometric morphometrics we measured 402 three-dimensional (3D) landmarks and semilandmarks of 3D models built from computed tomographic scans of thoraces of 20 healthy adult subjects in maximal forced inspiration (FI) and expiration (FE). We addressed the hypothesis that upper and lower parts of the ribcage differ in kinematics and compared different models of functional compartmentalization. During inspiration the thorax superior to the level of the sixth ribs undergoes antero-posterior expansion that differs significantly from the medio-lateral expansion characteristic of the thorax below this level. This supports previous suggestions for dividing the thorax into a pulmonary and diaphragmatic part. While both compartments differed significantly in mean size and shape during FE and FI the size changes in the lower compartment were significantly larger. Additionally, for the same degree of kinematic shape change, the pulmonary thorax changes less in size than the diaphragmatic thorax. Therefore, variations in the form and function of the diaphragmatic thorax will have a strong impact on respiratory function. This has important implications for interpreting differences in thorax shape in terms of respiratory functional differences within and among recent humans and fossil hominins. Anat Rec, 300:255-264, 2017. © 2016 Wiley Periodicals, Inc.

Cavitación de adenocarcinoma de pulmón como respuesta al tratamiento con bevacizumab / Cavitating lung cancer as response to bevacizumab treatment

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Morphological and functional implications of sexual dimorphism in the human skeletal thorax.

OBJECTIVES: The human respiratory apparatus is characterized by sexual dimorphism, the cranial airways of males being larger (both absolutely and relatively) than those of females. These differences have been linked to sex-specific differences in body composition, bioenergetics, and respiratory function. However, whether morpho-functional variation in the thorax is also related to these features is less clear. We apply 3D geometric morphometrics to study these issues and their implications for respiratory function. MATERIAL AND METHODS: Four hundred two landmarks and semilandmarks were measured in CT-reconstructions of rib cages from adult healthy subjects (Nmale = 18; Nfemale = 24) in maximal inspiration (MI) and maximal expiration (ME). After Procrustes registration, size and shape data were analyzed by mean comparisons and regression analysis. Respiratory function was quantified through functional size, which is defined as the difference of rib cage size between MI and ME. RESULTS: Males showed significantly larger thorax size (p < .01) and functional size (p < .05) than females. In addition, the 3D-shape differed significantly between sexes (p < .01). Male rib cages were wider (particularly caudally) and shorter, with more horizontally oriented ribs when compared to females. While thorax widening and rib orientation were unrelated to allometry, thorax shortening showed a slight allometric signal. CONCLUSIONS: Our findings are in line with previous research on sexual dimorphism of the respiratory system. However, we add that thorax shortening observed previously in males is the only feature caused by allometry. The more horizontally oriented ribs and the wider thorax of males may indicate a greater diaphragmatic contribution to rib cage kinematics than in females, and differences in functional size fit with the need for greater oxygen intake in males.

Caso de atresia bronquial / A case of bronchial atresia

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Utilidad de la PAAF guiada por TC en el diagnóstico de lesiones mediastínicas / Usefulness CT-guided F.N.A.C. in the Diagnosis of Mediastinal Lesions

ObjetivosEvaluar la validez diagnóstica de la punciónaspiración con aguja fina (PAAF) percutánea en lesiones mediastínicas considerando la biopsia o el seguimiento clínico como patrón de referencia.Pacientes y métodosSe realizó PAAF percutánea guiada por TC a 131 pacientes con lesiones mediastínicas. Se usó un TC helicoidal con cortes de 3–10mm y baja dosis de radiación (40mAs, 120kV). Las muestras fueron examinadas in situ por un citólogo para determinar su validez. Se obtuvo comprobación histológica mediante biopsia o estudio de pieza quirúrgica en 73 pacientes y seguimiento clínico en 50, comparándose los resultados globales y en subgrupos.ResultadosEn 126 pacientes (96,2%) el material fue válido para diagnóstico. Ciento tres lesiones (78,6%) fueron consideradas malignas (62 tumores primarios y 41 metástasis) y 23 (17,6%) benignas. En los 123 pacientes de los que se dispuso de seguimiento clínico o patológico, la PAAF permitió identificar malignidad con una sensibilidad del 95,2% (IC95%: 89,2–97,9%), especificidad 84,2% (IC95%: 62,4–94,5%), valor predictivo positivo 97,1% (IC95%: 91,7–99,0%), valor predictivo negativo 76,2% (IC95%: 54,9–89,4%), razón de verosimilitud positiva 6,03 (IC95%: 2,13–17,05) y exactitud 93,5% (IC95%: 87,7–96,7%). La complicación más frecuente fue el neumotórax (3 casos). La correlación citohistológica fue elevada tanto en las lesiones malignas (kappa 0,641) como en las benignas (kappa 0,607).ConclusionesLa PAAF percutánea guiada por TC es una técnica segura y eficaz para el diagnóstico de masas mediastínicas con alta rentabilidad para la detección de malignidad(AU)

ObjectiveTo evaluate the diagnostic accuracy of the percutaneous fine needle aspiration cytology (FNAC) for mediastinal lesions by using histology or follow-up clinical diagnosis as gold standard.Patients and MethodsCT-guided percutaneous FNAC was performed on 131 patients with mediastinal lesions. Helical CT was used with 3–10mm image thickness range and low radiation dose (40mAs, 120kV). Samples were immediately examined by a cytologist to determine if they were representative. Histological samples were obtained by means of biopsy or resection specimens in 73 patients and clinical follow-up in 50.ResultsThe material was satisfactory for diagnosis in 126 patients (95.2 %), in whom 103 lesions (78.6%) were considered malignant (62 primary tumours and 41 metastases) and 23 (17.6%) benign. In the 123 patients with clinical monitoring or pathological diagnosis, using FNAC led to the identification of malignancy with a sensitivity of 95.2 % (95%CI: 89.2–97.9%), specificity 84.2% (95%CI: 62.4–94.5%), positive predictive value 97.1% (95%-CI: 91.7–99.0%), negative predictive value 76.2% (95%CI: 54.9–89.4%), likelihood-ratio positive 6.03 (95%CI: 2.13–17.05) and accuracy 93.5% (95%CI: 87.7–96.7%). Pneumothorax was the most frequent complication (3 cases). There was good agreement between the cytological findings and the histological findings, not only for malignant lesions (kappa coefficient: 0.641) but also for benign (kappa 0.607).ConclusionsCT-guided percutaneous FNAC is a safe and effective technique for the diagnosis of the mediastinal masses, with a high diagnostic yield for malignancy depicting(AU)