Rethinking PICO in the Machine Learning Era: ML-PICO

Background  Machine learning (ML) has captured the attention of many clinicians who may not have formal training in this area but are otherwise increasingly exposed to ML literature that may be relevant to their clinical specialties. ML papers that follow an outcomes-based research format can be assessed using clinical research appraisal frameworks such as PICO (Population, Intervention, Comparison, Outcome). However, the PICO frameworks strain when applied to ML papers that create new ML models, which are akin to diagnostic tests. There is a need for a new framework to help assess such papers. Objective  We propose a new framework to help clinicians systematically read and evaluate medical ML papers whose aim is to create a new ML model: ML-PICO (Machine Learning, Population, Identification, Crosscheck, Outcomes). We describe how the ML-PICO framework can be applied toward appraising literature describing ML models for health care. Conclusion  The relevance of ML to practitioners of clinical medicine is steadily increasing with a growing body of literature. Therefore, it is increasingly important for clinicians to be familiar with how to assess and best utilize these tools. In this paper we have described a practical framework on how to read ML papers that create a new ML model (or diagnostic test): ML-PICO. We hope that this can be used by clinicians to better evaluate the quality and utility of ML papers.     

Annulo-aortic ectasia with DeBakey type II dissecting aneurysm in Gaucher's disease

Annulo-aortic ectasia is an extremely rare complication of Gaucher's disease. We report successful surgery in a patient with Gaucher's disease complicated by annulo-aortic ectasia and aortic dissection. Cabrol's operation was accomplished without bleeding or sternal adaptation problems.     

Subcutaneous phaeohyphomycosis of the right thumb

Black fungi are a group of fungi that are characterized by the development of a pale brown to black color in the cell walls of their vegetative cells, conidia, or both. A mycotic infection caused by a member of black fungi can be subdivided into three clinical entities: phaeohyphomycosis, chromoblastomycosis, and mycetoma. Phaeohyphomycosis is distinguished from mycetoma by the absence of grain (organized, interwoven mycelial aggregates) formation, and from chromoblastomycosis by the absence of sclerotic bodies (thick-walled muriform cells). Phaeohyphomycosis is a rare disease and has been sporadically reported. In the present report, phaeohyphomycosis of the right thumb of a 72-year-old man was presented. A precipitating trauma of two months earlier at the site was recalled. A solitary mass, 10 mm in diameter, was gradually formed in the palm side of the distal right thumb and finally resected. Histological examination disclosed a solitary granulomatous lesion surrounded by an incomplete fibrous capsule. The lesion mainly involved subcutaneous tissue and was composed of multiple pyogranulomas. Pigmented branched septate hyphae and yeast-like cells were sparsely found in the periphery of the abscess and within histiocytic cells of the granulomas. No sclerotic cells were detected. When pigmentation of black fungi in tissue is as faint as in the present case, Fontana-Masson staining is useful to accentuate the presence of melanin-like pigment of fungal cell walls.     

Changes in the incidence and duration of ventricular fibrillation in dependence on the extraneuronal accumulation of isoprenaline in the perfused rat heart

Summary The relationship between the accumulation of isoprenaline and the incidence and duration of ventricular fibrillation was investigated in the perfused rat heart. Isolated rat hearts were perfused with ³H-isoprenaline (1 mol/l) for 30 min at a constant flow rate of 6.5 ml/min at a temperature between 40 and 41° C. Electrocardiograms were recorded during the perfusion period and the isoprenaline content of the tissue was measured after the perfusion. The accumulation of isoprenaline was significantly increased and the duration of ventricular fibrillation was significantly prolonged by the presence of tropolone (100 mol/l). When extraneuronal uptake inhibitors such as normetanephrine (100 mol/l), 3-O-methylisoprenaline (100 mol/l) or phenoxybenzamine (1 mol/l) were added to the perfusion fluid containing ³H-isoprenaline (1 mol/l) and tropolone (100 mol/l), the accumulation of isoprenaline was sifnificantly decreased, the incidence of ventricular fibrillation was significantly reduced and the duration of ventricular fibrillation was significantly shortened. There was a significant correlation for dependence of duration of ventricular fibrillation on the isoprenaline content of rat hearts perfused with various extraneuronal uptake inhibitors in the presence of tropolone (correlation coefficient [r]=0.62, P<0.001).These results indicate that the accumulation of isoprenaline in perfused rat hearts relates to the occurrence and duration of ventricular fibrillation.This study was supported in part by a Grant-in-Aid for Scientific Research (59570980) from the Ministry of Education, Science and Culture, Japan     

Inhibition of growth and induction of apoptosis by all-trans retinoic acid in lymphoid cell lines transfected with the PML/RARα fusion gene

The interaction of an exogenous PML/RARα fusion gene associated with acute promyelocytic leukaemia, with all- trans retinoic acid (ATRA) was examined in two lymphoid cell lines. L1210 and MOLT-4 cells were transfected with PML/RARα cDNA in the expression vector pGD and stable transformants (L1210 PML/RAR α and MOLT-4 PML/RAR α) were selected with G418. ATRA inhibited the growth of these stable transformants, as assessed by [³H]thymidine incorporation, in a dose-dependent manner, but had no effect on the growth of control cells stably transformed with neomycin resistant gene alone. ATRA also induced apoptosis, as assessed by fragmentation of genomic DNA, in L1210 PML/RAR α and MOLT-4 PML/RAR α cells but not in control cells. The exogenous PML/RARα fusion gene therefore probably mediates the effects of ATRA on cell growth and apoptosis in these cell lines.     

Accessory mitral valve leaflet causing aortic regurgitation and left ventricular outflow tract obstruction. Case report and review of published reports

Arrhythmias, aortic regurgitation, and symptoms of severe intermittent ventricular outflow obstruction developed in a 14 year old boy with a heart murmur who had been followed from infancy. These were caused by an accessory mitral leaflet, which was successfully removed at open heart operation. A review of 21 previously reported cases found a high incidence of associated cardiac malformations, appreciable subaortic obstruction in most patients, and a consistent attachment of the accessory tissue to the ventricular aspect of the anterior mitral leaflet. The characteristic echocardiographic appearance of a mobile mass arising from the area of aortic-mitral continuity is sufficient for the diagnosis of accessory mitral leaflet and echocardiographic examination will facilitate the surgical management of this condition.     

Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis

4-Hydroxy-2-hexenal (HHE) is a toxic, reactive aldehydic intermediate formed by nonenzymatic peroxidation of n-3 polyunsaturated fatty acids. The aim of this study was to determine the implication for HHE in the pathomechanism of amyotrophic lateral sclerosis (ALS) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) techniques using a mouse monoclonal IgG(1) antibody mAbHHE53 specific for protein-bound HHE. Immunohistochemical analysis on formalin-fixed, paraffin-embedded sections and frozen sections of spinal cords obtained at autopsy from 10 sporadic ALS patients and 10 age-matched control subjects demonstrated that protein-bound HHE immunoreactivity was seen and was prominent in the entire gray matter in the ALS cases and localized in the neurons, reactive astrocytes, microglial cells, and the surrounding neuropil, while the immunoreactivity was obscure or undetectable in the control cases. No significant protein-bound HHE immunoreactivity was seen in sections processed with omission of mAbHHE53 or in sections incubated with the antibody with an excess of the respective antigen. Competitive ELISA analysis on trypsin-digested protein extracts of fresh-frozen spinal cord samples disclosed a significant increase in protein-bound HHE level in the ALS cases compared with the control cases. Our results indicate that enhanced HHE formation occurs in the entire gray matter of sporadic ALS spinal cords and suggest that the selective vulnerability of motor neurons to HHE mediates the pathomechanism of this disease.     

The clinical criteria for Carpentier-Edwards bioprosthesis in the mitral position

This is a comparative study of late results of mitral valve replacement between Carpentier-Edwards (C-E) and Bj?rk-Shiley (B-S) valve prosthesis. The purpose of this study is to clarify the clinical criteria for C-E valve. C-E valve was implanted in 202 patients. The mean follow up period was 5.8 years and the longest one was 11 years. For B-S valve, it was 132 patients, 5.3 years and 17 years, respectively. With respect to the incidence of thromboembolic episodes, in spite of no anticoagulant therapy in the C-E group, there was no statistical difference between the C-E and the B-S groups. The incidence of valve related complication in the C-E group was significantly lower than that in the B-S group 5 years postoperatively. But that in the B-S group was significantly low 10 years postoperatively. Since the over 60 years old patients in the C-E group had low incidence of primary tissue failure, over ten years durability might be secured. In conclusion, the present clinical criteria for C-E valve should be as follows: 1) the patient older than 65 years, 2) the patient with contraindication for anticoagulant therapy, 3) the woman who desires pregnancy and 4) the patient with hemorrhagic diathesis caused by cardiac cachexia, liver cirrhosis and so on.