Evolutionary dynamics at the tumor edge reveal metabolic imaging biomarkers.

Human cancers are biologically and morphologically heterogeneous. A variety of clonal populations emerge within these neoplasms and their interaction leads to complex spatiotemporal dynamics during tumor growth. We studied the reshaping of metabolic activity in human cancers by means of continuous and discrete mathematical models and matched the results to positron emission tomography (PET) imaging data. Our models revealed that the location of increasingly active proliferative cellular spots progressively drifted from the center of the tumor to the periphery, as a result of the competition between gradually more aggressive phenotypes. This computational finding led to the development of a metric, normalized distance from 18F-fluorodeoxyglucose (18F-FDG) hotspot to centroid (NHOC), based on the separation from the location of the activity (proliferation) hotspot to the tumor centroid. The NHOC metric can be computed for patients using 18F-FDG PET-computed tomography (PET/CT) images where the voxel of maximum uptake (standardized uptake value [SUV]max) is taken as the activity hotspot. Two datasets of 18F-FDG PET/CT images were collected, one from 61 breast cancer patients and another from 161 non-small-cell lung cancer patients. In both cohorts, survival analyses were carried out for the NHOC and for other classical PET/CT-based biomarkers, finding that the former had a high prognostic value, outperforming the latter. In summary, our work offers additional insights into the evolutionary mechanisms behind tumor progression, provides a different PET/CT-based biomarker, and reveals that an activity hotspot closer to the tumor periphery is associated to a worst patient outcome.

International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: Diagnosis, treatment and follow up.

Phosphomannomutase 2 (PMM2-CDG) is the most common congenital disorder of N-glycosylation and is caused by a deficient PMM2 activity. The clinical presentation and the onset of PMM2-CDG vary among affected individuals ranging from a severe antenatal presentation with multisystem involvement to mild adulthood presentation limited to minor neurological involvement. Management of affected patients requires a multidisciplinary approach. In this article, a systematic review of the literature on PMM2-CDG was conducted by a group of international experts in different aspects of CDG. Our managment guidelines were initiated based on the available evidence-based data and experts' opinions. This guideline mainly addresses the clinical evaluation of each system/organ involved in PMM2-CDG, and the recommended management approach. It is the first systematic review of current practices in PMM2-CDG and the first guidelines aiming at establishing a practical approach to the recognition, diagnosis and management of PMM2-CDG patients.

Is video-assisted thoracoscopic diaphragmatic plication a widespread technique for diaphragmatic hernia in adults? Review of the literature and results of a national survey.

Diaphragmatic plication is the most accepted treatment for symptomatic diaphragmatic hernia in adults. The fact that this pathology is infrequent and this procedure not been widespread means that this is an exceptional technique in our field. To estimate its use in the literature, we carried out a review in English and Spanish, to which we added our series. We found only six series that contribute 59 video-assisted mini-thoractomy for diaphragmatic plications in adults, and none in Spanish. Our series will be the second largest with 18 cases. Finally, we conducted a survey in all the Spanish Thoracic Surgery units in Spain: none reported more than 10 cases operated by thoracoscopy in the last 8 years (except our series) and most continue employing thoracotomy as the main approach. We believe that many patients with symptomatic diaphragmatic hernia could benefit from the use of such techniques.

Universal scaling laws rule explosive growth in human cancers.

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.

[Bilateral Chylothorax after delivery: an infrequent case treated with videothoracoscopic talc pleurodesis]. / Quilotórax bilateral posparto: un caso infrecuente resuelto mediante pleurodesis con talco por videotoracoscopia.

Bilateral chylothorax after delivery is a highly infrequent entity. We present the case of a 28-year-old woman who developed progressive dyspnea due to bilateral milky pleural effusion several months after delivery. The effusion was found to contain chylomicrons in the biochemical analysis. Initial conservative treatment failed twice and the chylothorax was successfully treated through sequential bilateral videothoracoscopy with an interval of 6 days between the two interventions and pleurodesis with spray talc.