Quantification of the visceral and subcutaneous fat by computed tomography: Interobserver correlation of a single slice technique

AbstractPurposeTo assess the interobserver reproducibility of the quantification of the visceral and subcutaneous fat by computed tomography from an umbilical slice and study the effect of the level of the slice (slice going through the navel versus a slice going through disc L3–L4).Materials and methodsForty-four breast cancer patients who had a CT-scan were included in this study. This is a double blind (junior versus senior) retrospective study to determine the interobserver reproducibility. A junior observer studied the variation between two levels of slice by selecting an image going through L3–L4 and the navel.ResultsThe measurement of the fat obtained from an umbilical slice seemed to be well correlated and consistent with that obtained from a slice with a disc reference (L3–L4). The interobserver reproducibility is good for the quantification of the umbilical fat (Spearman and Lin at 0.9921 and 0.985 [P<0.001] for the visceral fat).ConclusionThe interobserver reproducibility of the single slice CT-scan measurement going through the navel (easily detected) is excellent and may therefore be used in oncology as a predictive tool to measure a characteristic of the host and not the tumor

HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation.

Activation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the kinase client itself. Removal of regulatory phosphorylation from client kinases and their release from the HSP90-CDC37 system depends on the Ser/Thr phosphatase PP5, which associates with HSP90 via its N-terminal TPR domain. Here, we present the cryoEM structure of the oncogenic protein kinase client BRAFV600E bound to HSP90-CDC37, showing how the V600E mutation favours BRAF association with HSP90-CDC37. Structures of HSP90-CDC37-BRAFV600E complexes with PP5 in autoinhibited and activated conformations, together with proteomic analysis of its phosphatase activity on BRAFV600E and CRAF, reveal how PP5 is activated by recruitment to HSP90 complexes. PP5 comprehensively dephosphorylates client proteins, removing interaction sites for regulatory partners such as 14-3-3 proteins and thus performing a 'factory reset' of the kinase prior to release

Impact of the COVID-19 pandemic on the care of cancer patients in Spain

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer; EspanyaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cáncer; EspañaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cancer; SpainBackground Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. Materials and methods This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. Results Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. Conclusions This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.This work was supported by funding from the AECC, a non-profit organization, whose medical department funded the study and the medical writing (no grant number)

Endometrial carcinoma: molecular alterations involved in tumor development and progression

In the western world, endometrial carcinoma (EC) is the most common cancer of the female genital tract. The annual incidence has been estimated at 10-20 per 100 000 women. Two clinicopathological variants are recognized: the estrogen related (type I, endometrioid) and the non-estrogen related (type II, non-endometrioid).The clinicopathological differences are paralleled by specific genetic alterations, with type I showing microsatellite instability and mutations in phosphatase and tensin homologue deleted on chromosome 70, PIK3CA, K-RAS and CTNNB1 (beta-catenin), and type II exhibiting TP53 mutations and chromosomal instability. Some non-endometrioid carcinomas probably arise from pre-existing endometrioid carcinomas as a result of tumor progression and, not surprisingly, some tumors exhibit combined or mixed features at the clinical, pathological and molecular levels. In EC, apoptosis resistance may have a role in tumor progression. Understanding pathogenesis at the molecular level is essential in identifying biomarkers for successful targeted therapies. In this review, the genetic changes of endometrial carcinogenesis are discussed in the light of the morphological features of the tumors and their precursors

Traumatismo de la fisis distal de la tibia: tratamiento y resultados

Hemos realizado un estudio retrospectivo de 206 fracturas fisiarias distales de tibia. Se excluyeron las lesiones fisiarias aisladas de peroné y los arrancamientos óseos de tibia o peroné sin afectación de la placa fisiaria. Se recopilaron variables de 199 casos relativas al diagnóstico, tratamiento y evolución. La clasificación utilizada fue la de Salter y Harris para los traumatismos fisiarios. El tiempo de seguimiento medio fue de 7,73 meses (rango de 1,36 a 126 meses). Se trataba de 115 varones y 84 hembras. El tipo más frecuente fue el II (n=82, 41,2%). La media de edad fue de 12,1 ± 2,6 años. La causa más frecuente fue el accidente casual. Se realizó tratamiento conservador en 121 casos (60,8%). Los resultados se valoraron en función de las complicaciones aparecidas. En 169 casos (90,7%) el resultado fue satisfactorio, encontrando sólo 17 casos (9,3%) de malos resultados por presentar desalineación de los ejes (de 5 o más grados) y/o acortamiento (de 1 cm o más). Se presentó malposición en 9 casos (12%) en el tipo II, 4 casos (10,8%) en el tipo III, 1 caso (4%) en el tipo IV y 3 casos (100%) en el tipo V. La relación entre el grado de reducción obtenido y aparición de malposición sólo presentó diferencias significativas en los casos aparecidos del tipo II. La aparición de alteraciones de crecimiento en los tipos III y IV suele tener poca trascendencia clínica por ocurrir en pacientes con cartílagos en fase avanzada de cierre, no así en el tipo II donde pueden estar asociadas lesiones de tipo V, aconsejando realizar reducciones mediante maniobras cuidadosas para intentar evitar alteraciones.This is a retrospective study of 206 physeal fractures of the distal tibia. Isolated physeal injuries to the fibula and dislocations of the tibia or fibula without involvement of the growth plate were excluded. Variables from 199 cases relative to the diagnosis, treatment and evolution were recorded. The Salter-Harris classification was used for physeal fractures. The mean follow-up period was 7.73 months (range: 1.36 to 126 months), and 115 male and 84 female patients were treated. The most frequented type of fracture was type II (n=82, 41.2%). The mean age of the patients was 12.1 ± 2.6 years. The most frequented cause of injury was accident. In 121 cases (60.8%) the injury was treated conservatively. The results were evaluated in terms of subsequent complications. In 169 cases (90.7%) the results were satisfactory, and in only 17 cases (9.3%) the results were poor as a consequence of misalignment of the axes (5 or more degrees) and/or shortening (1 cm or more). Misalignment was found in 9 cases (12%) of type II, 4 cases (10.8%) of type III, 1 case (4%) of type IV and 3 cases (100%) of type V. The correlation between the degree of reduction obtained and the appearance of misalignment was statistically significant only in the cases of type II fracture. The appearance of growth disturbance in type III and type IV fractures is usually of minor clinical importance because it occurs in patients whose cartilage is at an advanced stage of closure, unlike type II fractures, which may be associated with type V injuries. In these cases reduction must be performed with special care in order to avoid growth disturbance

Proposal for the creation of a national strategy for precision medicine in cancer: a position statement of SEOM, SEAP, and SEFH

Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational, and knowledge-related challenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals, and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology, Pathology, and Hospital Pharmacy, we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cancer

Thermal activation of ferroelectric switching

By applying the theory of thermally activated nucleation to the switching of ferroelectric domains, a method is developed to experimentally obtain the value of both the activation enthalpy, ΔH, and activation volume, V*, for the thermally activated process involved in ferroelectric switching. The method was applied to the switching of a soft lead zirconate titanate and values of ΔH = (0.16±0.02) eV and V* = (1.62±0.16)×10−25 m3 were obtained at the coercive field. These values imply that the energy, ΔU, required for the formation of switching nuclei is mainly supplied by the work done by the electric field. A comparison of these values with those obtained from theoretical considerations suggests that the switching is achieved by the sideways expansion of nuclei formed at the domain boundaries in the form of low amplitude and long wavelength fluctuations of the domain walls