Automated classification of depression from structural brain measures across two independent community‐based cohorts

Major depressive disorder (MDD) has been the subject of many neuroimaging case–control classification studies. Although some studies report accuracies ≥80%, most have investigated relatively small samples of clinically‐ascertained, currently symptomatic cases, and did not attempt replication in larger samples. We here first aimed to replicate previously reported classification accuracies in a small, well‐phenotyped community‐based group of current MDD cases with clinical interview‐based diagnoses (from STratifying Resilience and Depression Longitudinally cohort, ‘STRADL’). We performed a set of exploratory predictive classification analyses with measures related to brain morphometry and white matter integrity. We applied three classifier types—SVM, penalised logistic regression or decision tree—either with or without optimisation, and with or without feature selection. We then determined whether similar accuracies could be replicated in a larger independent population‐based sample with self‐reported current depression (UK Biobank cohort). Additional analyses extended to lifetime MDD diagnoses—remitted MDD in STRADL, and lifetime‐experienced MDD in UK Biobank. The highest cross‐validation accuracy (75%) was achieved in the initial current MDD sample with a decision tree classifier and cortical surface area features. The most frequently selected decision tree split variables included surface areas of bilateral caudal anterior cingulate, left lingual gyrus, left superior frontal, right precentral and paracentral regions. High accuracy was not achieved in the larger samples with self‐reported current depression (53.73%), with remitted MDD (57.48%), or with lifetime‐experienced MDD (52.68–60.29%). Our results indicate that high predictive classification accuracies may not immediately translate to larger samples with broader criteria for depression, and may not be robust across different classification approaches.     

Surgery for Ventricular Tachycardia

The treatment of drug-refractory chronic ventricular tachycardia (VT) has undergone a revolution over the last 50 years. We now have automatic implantable cardioverter defibrillator therapy with pace-terminating capabilities, and catheter ablation of VT has refined mapping and improved methods of lesion generation. Between 1980 and 1993, Houston Methodist Hospital became a leader in the diagnosis and surgical ablation of VT and other arrhythmias. This is a brief account of that period and some of the experiences and lessons that have led to significant advances used today.     

Potential impact of PD-L1 (SP-142) immunohistochemical heterogeneity in clear cell renal cell carcinoma immunotherapy

Intratumor heterogeneity (ITH) detection remains a challenge in modern oncology because it can have a direct impact on the success of new therapies. Anti-PD-1/PD-L1 immunotherapy is an emerging treatment modality that is showing great promise for clear cell renal cell carcinoma (CCRCC) patients with advanced disease. Patient selection for such therapy relies upon the immunohistochemical detection of PD-1/PD-L1, however the degree of ITH for these markers among tumor cells and/or inflammatory mononuclear infiltrates remains unknown. Therefore, we analyzed PD-L1 (SP-142) expression in the tumor inflammatory cells of 22 CCRCC cases with the aim to define the pattern of PD-L1 expression, and to compare the reliability of current tumor sampling protocols (RS) with a multisite tumor sampling strategy (MSTS). While the RS protocol identified 5/22 (22.7%) of cases that were positive for PD-L1 expression, MSTS identified 10/22 (45.45%) of cases. This suggests that RS may miss a proportion of CCRCC patients that might benefit from immunotherapy. In addition, MSTS demonstrated that positive and negative regions of PD-L1 expression are very variable within each tumor.     

MicroRNAs in hematological malignancies

MicroRNAs (miRNAs) have become one of the hottest topics in biology over recent years, but remarkably have only been formally recognized for just over 10 years. These endogenously produced short (19–24 nt) non-coding RNAs have introduced an entirely new paradigm in our understanding of gene control and it is now evident that miRNAs play a crucial regulatory role in many, if not all, physiological and pathological processes. In this review we provide an overview of the role and potential clinical utility for miRNAs in hematological malignancies and their function in normal hematopoiesis. Although still in its infancy, the miRNA field has already added much to our understanding of hematological processes, and provides us with novel tools as both biomarkers and therapeutic agents for hematological malignancies.     

Abnormal blood vessels in the gastric antrum

Three patients who bled from curious vascular lesions of the gastric antrum are described. Each presented with an iron-deficiency anemia. Histological examination in two of the patients demonstrated numerous ectatic submucosal vessels in the antrum, the appearances being somewhat similar to angiodysplasia of the colon. The gastric lesions were not shown by barium meal examination or angiography but gave characteristic appearances on endoscopy. We believe that Billroth I partial gastrectomy is the treatment of choice for this condition.     

Valve Strain Quantitation in Normal Mitral Valves and Mitral Prolapse With Variable Degrees of Regurgitation

ObjectivesThe aim of this study was to quantitate patient-specific mitral valve (MV) strain in normal valves and in patients with mitral valve prolapse with and without significant mitral regurgitation (MR) and assess the determinants of MV strain.BackgroundFew data exist on MV deformation during systole in humans. Three-dimensional echocardiography allows for dynamic MV imaging, enabling digital modeling of MV function in health and disease.MethodsThree-dimensional transesophageal echocardiography was performed in 82 patients, 32 with normal MV and 50 with mitral valve prolapse (MVP): 12 with mild mitral regurgitation or less (MVP ? MR) and 38 with moderate MR or greater (MVP + MR). Three-dimensional MV models were generated, and the peak systolic strain of MV leaflets was computed on proprietary software.ResultsLeft ventricular ejection fraction was normal in all groups. MV annular dimensions were largest in MVP + MR (annular area: 13.8 ± 0.7 cm²) and comparable in MVP ? MR (10.6 ± 1 cm²) and normal valves (10.5 ± 0.3 cm²; analysis of variance: p < 0.001). Similarly, MV leaflet areas were largest in MVP + MR, particularly the posterior leaflet (8.7 ± 0.5 cm²); intermediate in MVP ? MR (6.5 ± 0.7 cm²); and smallest in normal valves (5.5 ± 0.2 cm²; p < 0.0001). Strain was overall highest in MVP + MR and lowest in normal valves. Patients with MVP ? MR had intermediate strain values that were higher than normal valves in the posterior leaflet (p = 0.001). On multivariable analysis, after adjustment for clinical and MV geometric parameters, leaflet thickness was the only parameter that was retained as being significantly correlated with mean MV strain (r = 0.34; p = 0.008).ConclusionsMVs that exhibit prolapse have higher strain compared to normal valves, particularly in the posterior leaflet. Although higher strain is observed with worsening MR and larger valves and annuli, mitral valve leaflet thickness—and, thus, underlying MV pathology—is the most significant independent determinant of valve deformation. Future studies are needed to assess the impact of MV strain determination on clinical outcome.