Making Sense of Composite Endpoints in Clinical Research.

Multiple drugs currently used in clinical practice have been approved by regulatory agencies based on studies that utilize composite endpoints. Composite endpoints are appealing because they reduce sample size requirements, follow-up periods, and costs. However, interpreting composite endpoints can be challenging, and their misuse is not uncommon. Incorrect interpretation of composite outcomes can lead to misleading conclusions that impact patient care. To correctly interpret composite outcomes, several important questions should be considered. Are the individual components of the composite outcome equally important to patients? Did the more and less important endpoints occur with similar frequency? Do the component endpoints exhibit similar relative risk reductions? If these questions receive affirmative answers, the use and interpretation of the composite endpoint would be appropriate. However, if any component of the composite endpoint fails to satisfy the aforementioned criteria, interpretation can become difficult, necessitating additional steps. Regulatory agencies acknowledge these challenges and have specific considerations when approving drugs based on studies employing composite endpoints. In conclusion, composite endpoints are valuable tools for evaluating the efficacy and net clinical benefit of interventions; however, cautious interpretation is advised.

Intraparenchymal Meningioma.

Meningiomas have been described as the most frequent extra-axial tumor in the brain. Most are benign and correspond to World Health Organization (WHO) grade I; however, there are some reports of cases that shows atypical locations, like subcortical intra-axial meningiomas. This represents a challenge in radiological diagnosis because it could be taken as a metastasis tumor or vascular malformations. The authors bring a case report of a previously healthy patient who presents a traumatic brain injury with no traumatic lesions. A computed tomography (CT) evidenced a left frontal rounded subcortical lesion surrounded by large vasogenic edema. The first diagnostic impression was a metastasis tumor. During surgery, a total resection was completed, and the appearance of the tumor was meningioma. This was later confirmed by histological analysis. The literature was reviewed in order to determine the importance of including intraparenchymal meningiomas in the differential diagnosis of intracranial lesions.

Characterization of Progesterone Receptor Expression in Intracranial Meningiomas of Patients Treated in a High-Complexity Hospital in Bogota, Colombia.

Background Meningiomas are the single most common brain tumor. The incidence of these tumors increases with age; different studies have shown that meningiomas usually appear after the age of 50. These tumors are more common in women than in men, and women are twice as likely to suffer from the condition. Surgery is the primary form of treatment, which can be curative with complete resection. If the tumor is unresectable or other treatments such as surgery and radiotherapy have failed, hormonal therapy or chemotherapy may be considered. There is limited information about the clinical, demographic, and histopathological characteristics of these tumors in the population of Bogotá, Colombia. Objective To evaluate the expression of progesterone receptors in patients over 18 years old who have been diagnosed with meningiomas in a high-complexity hospital in Bogota, Colombia, and to describe the demographic and histopathological characteristics of these patients. Methods This is a descriptive and retrospective case series. Patients with meningioma who underwent surgical resection at a high-complexity hospital in Bogota, Colombia, from 2016 to 2019 were retrospectively identified and studied. Demographic variables, such as age and gender, were extracted from the clinical chart. Indirect immunoperoxidase staining was carried out for the progesterone receptor (PR) and Ki67. PR is analyzed as positive and negative, and the Ki67 proliferation index was determined. Results Thirty-two meningiomas from patients who underwent surgery were available for analysis. Twenty-five (78.1%) were positive for PR, 71.8% were females, and 93% were World Health Organization (WHO) grade I. Meningothelial (28%), fibrous (25%), and transitional (25%) meningiomas were the most frequent subtypes, correspondingly. The Ki67 mean value was 1.14 (0.11-10.71). Conclusion Our case series showed a greater frequency of meningiomas in women, with a high PR expression and a low Ki67 proliferation rate. These data correlate with literature worldwide.

Association between Testicular Microlithiasis and Testicular Neoplasia: Large Multicenter Study in a Pediatric Population.

Purpose To retrospectively define the strength of association between testicular microlithiasis and testicular neoplasia in a large geographically diverse pediatric population. Materials and Methods Retrospective review of scrotal ultrasonographic (US) examination reports and pathology specimens obtained between January 2000 and May 2014 at six academic pediatric hospitals in North America was performed. Reported cases were reviewed to confirm microlithiasis. Radiology and pathology data bases were searched for pathology-proven testicular tumors (benign or malignant germ cell or stromal tumors). Association strength (risk) was expressed in terms of odds ratios (ORs) with and without adjustment for fixed study site effects based on logistic regression. Results A total of 37 863 individuals underwent scrotal US during the study period. Mean age was 11.1 years ± 4.7 [standard deviation] in boys with microlithiasis and 9.1 years ± 5.9 in boys without microlithiasis (P < .001). Microlithiasis was confirmed in 2.90% of patients (1097 of 37 863; range, 1.61%-5.25% across sites). It was unilateral in 21.97% (241 of 1097) of patients and bilateral in 78.0% (856 of 1097). Tumor was identified in 4.64% (51 of 1097) of boys with microlithiasis and 0.33% (122 of 36 766) of boys without (unadjusted OR, 14.65; 95% confidence interval [CI]: 10.29, 20.84; adjusted OR, 14.19). Malignant germ cell tumors were identified in 2.8% (31 of 1097) of boys with microlithiasis and 0.12% (45 of 36 766) of boys without microlithiasis (unadjusted OR, 17.26; 95% CI: 11.8, 25.25; adjusted OR, 22.37). Sex cord-stromal tumors were identified in 0.46% (five of 1097) of boys with microlithiasis and 0.079% (29 of 36 766) of boys without (unadjusted OR, 5.8; 95% CI: 2.1, 16; adjusted OR, 6.39). Conclusion There is a strong association between testicular microlithiasis and primary testicular neoplasia in this pediatric population. © RSNA, 2017.

Diffusion-Tensor Imaging of the Physes: A Possible Biomarker for Skeletal Growth-Experience with 151 Children.

Purpose To determine the changes of diffusion-tensor imaging (DTI) and tractography in the distal femur and proximal tibia related to age, sex, and height. Materials and Methods Following institutional review board approval, with waiver of consent and with HIPAA compliance, the authors retrospectively analyzed DTI images of the knee in 151 children, 73 girls (median age, 14.1 years; range, 6.5-17.8 years) and 78 boys (median age, 16.6 years; range, 6.9-17.9 years), studied from January 2013 to October 2014. At sagittal echo-planar DTI (20 directions, b values of 0 and 600 sec/mm2), regions of interest were placed in the tibial and femoral physes. Using a fractional anisotropy threshold of 0.15 and an angle threshold of 40°, the authors performed tractography and measured apparent diffusion coefficient (ADC) and tract length and volume. Changes related to age, sex, and height were evaluated by using fitted nonlinear polynomial functions on bootstrapped samples. Results Femoral tract volume and length increased and then decreased with age (P < .001); the peaks of femoral tract volume are consistent with the growth spurt, occurring earlier in girls (10.8 years) than in boys (13.0 years) (P < .001). Girls had smaller tract volumes in comparison to boys (P = .013). ADC peaks 2 years earlier than tract volume (girls at 9.3 years, boys at 11.0 years). Girls with greater than 50th percentile of height had longer tracts and greater tract volumes compared with girls with less than 50th percentile (P < .020). DTI parameters of boys do not correlate with percentile of height (P > .300). Conclusion DTI of the physis and metaphysis shows greater tract length and volumes in subjects who are at ages when the growth is fastest. ADC and tract length and volume have an earlier and smaller peak in girls than in boys. Femoral tract length and volume are larger in taller girls. © RSNA, 2017.

Bioquímica en la vida diaria: el equilibrio químico y la función transportadora de la hemoglobina / Biochemistry Applied to Everyday Life: Chemical Equilibrium and the Transporting Function of the Hemoglobin

La hemoglobina es una proteína sanguínea que puede transportar oxígeno, un gas insoluble en medio acuoso, llevándolo a las diferentes partes del organismo en donde es requerido para su buen funcionamiento, así como productos metabólicos como el CO2 y el hidrógeno, para su excreción. Estos procesos se ven condicionados por factores como el pH, la concentración de BPG, las presiones parciales de O2 y CO2, la cooperatividad de la unión entre la hemoglobina y esos compuestos y los cambios conformacionales que la hemoglobina debe sufrir para captar y soltar eficientemente estas moléculas en el sitio del organismo donde son requeridos. Cambios abruptos en la presión atmosférica ligados a la altura, y la exposición a altas concentraciones de otros gases afines a la hemoglobina como el monóxido de carbono, presente en vehículos o recintos cerrados, pueden comprometer el funcionamiento normal del organismo precisamente porque causan efectos sobre esa función transportadora de la hemoglobina. En este escrito, se explicarán fenómenos de la vida diaria relacionados con el transporte de gases por la hemoglobina, como una demostración de que los conocimientos bioquímicos comienzan a ser útiles desde ahora para entender situaciones cotidianas y a dejarnos la expectativa de su valor para entender muchos de los problemas de salud que tendremos en nuestras manos.

The hemoglobin is a blood protein which can transport oxygen, a gas insoluble in water, to different organs where it is required for the proper function; this protein also transports the metabolic products, CO2 and H+ for their excretion. This process depends on pH, the BPG concentration, pO2 and pCO2. The cooperative binding between hemoglobin and those compounds and the conformational changes necessary for oxygen and CO2 uptake and release in the specific place where they are required. Abrupt changes of atmospheric pressure associated with height and the exposure to other gases such as CO present in vehicles and closed rooms could compromise the normal functioning of the organism because their presence affects the transport function of the hemoglobin. In this paper, we will explain everyday phenomena related to the transport of gases through hemoglobin as a demonstration that a knowledge of biochemistry begins to be useful from now on to understand everyday situations and give us an expectation of their value to comprehend many health problems that would be faced in the future.