Osteosarcoma derives from primitive bone-forming mesenchymal cells and is the most common primary bone malignancy. The incidence rates and 95% confidence intervals of osteosarcoma for all races and both sexes are 4.0 (3.5-4.6) for the range 0-14 years and 5.0 (4.6-5.6) for the range 0-19 years per year per million persons. Among childhood cancers, osteosarcoma occurs eighth in general incidence and in the following order: leukemia (30%), brain and other nervous system cancers (22.3%), neuroblastoma (7.3%), Wilms tumor (5.6%), Non-Hodgkin lymphoma (4.5%), rhabdomyosarcoma (3.1%), retinoblastoma (2.8%), osteosarcoma (2.4%), and Ewing sarcoma (1.4%). The incidence rates of childhood and adolescent osteosarcoma with 95% confidence intervals areas follows: Blacks, 6.8/year/million; Hispanics, 6.5/year/million; and Caucasians, 4.6/year/million. Osteosarcoma has a bimodal age distribution, having the first peak during adolescence and the second peak in older adulthood. The first peak is in the 10-14-year-old age group, coinciding with the pubertal growth spurt. This suggests a close relationship between the adolescent growth spurt and osteosarcoma. The second osteosarcoma peak is in adults older than 65 years of age; it is more likely to represent a second malignancy, frequently related to Paget's disease. The incidence of osteosarcoma has always been considered to be higher in males than in females, occurring at a rate of 5.4 per million persons per year in males vs. 4.0 per million in females, with a higher incidence in blacks (6.8 per million persons per year) and Hispanics (6.5 per million), than in whites (4.6 per million). Osteosarcoma commonly occurs in the long bones of the extremities near the metaphyseal growth plates. The most common sites are the femur (42%, with 75% of tumors in the distal femur), the tibia (19%, with 80% of tumors in the proximal tibia), and the humerus (10%, with 90% of tumors in the proximal humerus). Other likely locations are the skull or jaw (8%) and the pelvis (8%). Cancer deaths due to bone and joint malignant neoplasms represent 8.9% of all childhood and adolescent cancer deaths. Death rates for osteosarcoma have been declining by about 1.3% per year. The overall 5-year survival rate for osteosarcoma is 68%, without significant gender difference. The age of the patient is correlated with the survival, with the poorest survival among older patients. Complete surgical excision is important to ensure an optimum outcome. Tumor staging, presence of metastases, local recurrence, chemotherapy regimen, anatomic location, size of the tumor, and percentage of tumor cells destroyed after neoadjuvant chemotherapy have effects on the outcome.

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra-and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m 2 ). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.

Studies to determine the etiology of osteosarcoma involve epidemiologic and environmental factors and genetic impairments. Factors related to patient characteristics include age, gender, ethnicity, growth and height, genetic and familial factors, and preexisting bone abnormalities. Rapidly proliferating cells may be particularly susceptible to oncogenic agents and mitotic errors which lead to neoplastic transformation. Genetic aberrations that accompany osteosarcoma have received increasing recognition as an important factor in its etiology. Osteosarcoma tumor cells exhibit karyotypes with a high degree of complexity which has made it difficult to determine whether any recurrent chromosomal aberrations characterize osteosarcoma. Although extremely rare, osteosarcoma has occasionally been observed in several members of the same family. No other clinical abnormalities in the proband or the affected members were reported. Pathologic examination of the tumors revealed no unusual features. Genetic testing was not available in most of these reports. The patients generally responded to conventional therapy. A genetic predisposition to osteosarcoma is found in patients with hereditary retinoblastoma, characterized by mutation of the retinoblastoma gene RB1 on chromosome 13q14. The Rothmund-Thomson syndrome is an autosomal recessive disorder with a heterogeneous clinical profile. Patients may have a few or multiple clinical features including skin rash, small stature, skeletal dysplasias, sparse or absent scalp hair, eyebrows or eyelashes, juvenile cataracts, and gastrointestinal disturbance including chronic emesis and diarrhea; its molecular basis is the mutation in the RECQL4 gene in a subset of cases. The Li-Fraumeni syndrome is an autosomal dominant disorder characterized by a high risk of developing osteosarcoma and has been found in up to 3% of children with osteosarcoma. It is associated with a germline mutation of the p53, a suppressor gene. The following three criteria must be met for a diagnosis of Li-Fraumeni syndrome: (1) A proband diagnosed with sarcoma when younger than 45 years; (2) A first-degree relative with any cancer diagnosed when younger than 45 years; (3) Another first- or second-degree relative of the same genetic lineage with any cancer diagnosed when younger than 45 years or sarcoma diagnosed at any age. A second recessive p53 oncogene on chromosome 17p13.1 may also play a role in the development and progression of osteosarcoma. Osteosarcoma has also been associated with solitary or multiple osteochondroma, solitary enchondroma or enchondromatosis (Ollier's disease), multiple hereditary exostoses, fibrous dysplasia, chronic osteomyelitis, sites of bone infarcts, sites of metallic prostheses and sites of prior internal fixation. Ionizing radiation is a well-documented etiologic factor. Osteosarcoma has also been associated with the use of intravenous radium and Thorotrast. Exposure to alkylating agents may also contribute to its development ,and it is apparently independent of the administration ...

The trigemino-cardiac reflex (TCR) is clinically defined as the sudden onset of parasympathetic activity, sympathetic hypotension, apnea, or gastric hypermotility during central or peripheral stimulation of any of the sensory branches of the trigeminal nerve. Clinically, the TCR has been reported to occur during craniofacial surgery, manipulation of the trigeminal nerve/ganglion and during surgery for lesion in the cerebellopontine angle, cavernous sinus, and the pituitary fossa. Apart from the few clinical reports, the physiologic function of this brainstem reflex has not yet been fully explored. The manifestation of the TCR can vary from bradycardia and hypotension to asystole. From the experimental findings, the TCR represents an expression of a central reflex leading to rapid cerebrovascular vasodilatation generated from excitation of oxygen-sensitive neurons in the rostral ventro-lateral medulla oblongata. By this physiologic response, the systemic and cerebral circulations may be adjusted in a way that augments cerebral perfusion. This review summarizes the current state of knowledge about TCR.

BackgroundTraditionally, physicians have believed that limb‐salvage surgery has functional and cosmetic advantages over amputation, yet the literature is equivocal. Therefore, we sought to compare the psychosocial and functional outcomes in osteosarcoma survivors after limb‐salvage surgery and amputation. We hypothesized there to be neither psychosocial nor functional outcome differences between groups.ProcedureParticipants received treatment of extremity osteosarcoma, had received their cancer diagnosis at least 2 years prior, and were at least 16 years old. A comprehensive set of validated psychosocial and functional measures was used to assess outcome.ResultsFifty‐seven patients participated in this study (33 who underwent limb‐salvage surgery and 24 who underwent amputation). Participants had gone 12–24 years since diagnosis and were 16–52 years old at study participation. We used multiple linear regression models to examine differences in quality of life, body image, self‐esteem, and social support between the two groups and found no differences. Lower limb function was a significant predictor of quality of life (P < 0.001), whereas surgery type did not impact this relationship. Body image was rated significantly worse by those who underwent late amputation, amputation after failed limb salvage, than by those who did not.ConclusionsParticipants with more functional lower limbs had better quality of life than did those with less functional lower limbs regardless of whether they underwent amputation or limb‐salvage surgery. Pediatr Blood Cancer 2010;54:990–999 © 2010 Wiley‐Liss, Inc.

Abstract:Complete examination of the brainstem involves transverse serial 5-m sections made throughout the entire brainstem. The number of serial sections varies from 360 in sudden intrauterine unexplained death (SIUD) to 600 in term fetuses to over 1400 sections in sudden infant death syndrome (SIDS) victims. The procedure is not applicable in all histopathological laboratories, owing to the need for additional technical personnel. The simplified procedure allows a remarkable reduction of the number of sections. The brainstem is divided into 3 blocks. The first, cranial block, extends from the border between the medulla oblongata and pons up to the upper pole of the olivary nucleus. The second, intermediate block, corresponding to the submedian area of the inferior olivary nucleus, has as reference point the obex and extends 2 to 3 mm above and below the obex itself. The third, caudal block, includes the lower pole of the inferior olivary nucleus and the lower adjacent area of the medulla oblongata. Examinations of the brainstems from 106 SIDS victims, 30 controls, and 51 stillborns underlined a remarkable variability, particularly of the arcuate nucleus. The simplified examination of the brainstem makes it possible to evaluate the structures, examining 3 specific levels, defined by morphologic reference points.

Our hybrid Ilizarov method combined with minimal internal fixation enables excellent to good results in most cases of complex tibial plateau fractures.

BACKGROUND:To the best of the authors' knowledge, there has been relatively little research published to date regarding very longterm survivors of childhood and adolescent osteosarcoma. In the current study, the authors compared the very long-term survival outcomes of patients with osteosarcoma who were treated with either limb salvage procedures or amputation. METHODS: A total of 38 patients with osteosarcoma who survived 20 years from the time of diagnosis were divided into 2 groups according to whether they underwent amputation or limb salvage. Participants were asked to complete a questionnaire concerning their education, employment, annual income, marital status, health insurance, lifestyle, siblings, and all current and past health issues. RESULTS: Education, employment, marital status, and health insurance were not found to differ significantly between the 2 groups of survivors, who described themselves as being similar to their siblings. Eight percent of survivors underwent secondary amputation because of complications with an endoprosthesis. The cumulative incidence of second primary neoplasms was 13%, and this finding was significantly higher in females and in survivors who underwent radiotherapy and had a genetic predisposition. The second primary malignancies were breast cancer (ductal invasive carcinoma, ductal in situ carcinoma, and leiomyosarcoma), mediastinal leiomyosarcoma, and squamocellular carcinoma of the oral cavity and the uterine cervix. Amputees required more assistive walking support than survivors who received limb salvage treatment (P <.05, chi-square test). CONCLUSIONS: Despite the many challenges that osteosarcoma survivors face, patients who survived 20 years after their initial diagnosis reported having overall adjusted well to their physical limitations and were productive individuals.