Artificial intelligence technologies for the detection of colorectal lesions: The future is now

Several studies have shown a significant adenoma miss rate up to 35% during screening colonoscopy, especially in patients with diminutive adenomas. The use of artificial intelligence(AI) in colonoscopy has been gaining popularity by helping endoscopists in polyp detection, with the aim to increase their adenoma detection rate(ADR) and polyp detection rate(PDR) in order to reduce the incidence of interval cancers. The efficacy of deep convolutional neural network(DCNN)-based AI system for polyp detection has been trained and tested in ex vivo settings such as colonoscopy still images or videos. Recent trials have evaluated the real-time efficacy of DCNN-based systems showing promising results in term of improved ADR and PDR. In this review we reported data from the preliminary ex vivo experiences and summarized the results of the initial randomized controlled trials.     

An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1

Recent studies suggest that Cu/Zn superoxide dismutase (SOD1) could be pathogenic in both familial and sporadic amyotrophic lateral sclerosis (ALS) through either inheritable or nonheritable modifications. The presence of a misfolded WT SOD1 in patients with sporadic ALS, along with the recently reported evidence that reducing SOD1 levels in astrocytes derived from sporadic patients inhibits astrocyte-mediated toxicity on motor neurons, suggest that WT SOD1 may acquire toxic properties similar to familial ALS-linked mutant SOD1, perhaps through posttranslational modifications. Using patients' lymphoblasts, we show here that indeed WT SOD1 is modified posttranslationally in sporadic ALS and is iper-oxidized (i.e., above baseline oxidation levels) in a subset of patients with bulbar onset. Derivatization analysis of oxidized carbonyl compounds performed on immunoprecipitated SOD1 identified an iper-oxidized SOD1 that recapitulates mutant SOD1-like properties and damages mitochondria by forming a toxic complex with mitochondrial Bcl-2. This study conclusively demonstrates the existence of an iper-oxidized SOD1 with toxic properties in patient-derived cells and identifies a common SOD1-dependent toxicity between mutant SOD1-linked familial ALS and a subset of sporadic ALS, providing an opportunity to develop biomarkers to subclassify ALS and devise SOD1-based therapies that go beyond the small group of patients with mutant SOD1.     

Reduction of volumetric bone mineral density in postmenopausal women with hepatitis C virus-correlated chronic liver disease: A peripheral quantitative computed tomography (pQCT) study

BackgroundThe prevalence of osteoporosis in chronic liver disease (CLD) varies considerably among the studies, depending on patient selection and diagnostic criteria. We aimed to measure bone turnover markers and volumetric bone mineral density (BMD) in a group of postmenopausal women with CLD using both dual energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT), in comparison with age-matched healthy subjects.MethodsThirty-five postmenopausal patients with HCV-correlated CLD and 35 healthy postmenopausal women, as controls, underwent a DXA scan at lumbar and femoral level and a pQCT measurement of the nondominant forearm. Serum concentrations of biochemical markers relevant to bone turnover were also measured.ResultsPatients showed no differences in DXA values either at lumbar or femoral level compared to controls. On the contrary, pQCT geometrical (cortical cross-sectional area) and volumetric (total and trabecular volumetric BMD) parameters were significantly reduced in the CLD women. Also the Strength–Strain Index (SSI), an estimate of diaphyseal bone resistance to bending and torsion, was significantly lower in patients than in controls. Patients with CLD presented an unbalanced bone turnover, with increased bone resorption markers.ConclusionsThe bone geometrical and volumetric parameters measured in our CLD postmenopausal women, by pQCT, show a reduced bone mineral quality and stiffness. Conversely, DXA-measurements seem unable to appreciate the bone alterations in these patients. This would encourage further studies to validate pQCT analysis as a diagnostic tool for a correct estimate of bone involvement in CLD.     

Microglial polarization and plasticity: Evidence from organotypic hippocampal slice cultures

Increasing evidence indicates that “functional plasticity” is not solely a neuronal attribute but a hallmark of microglial cells, the main brain resident macrophage population. Far from being a univocal phenomenon, microglial activation can originate a plethora of functional phenotypes, encompassing the classic M1 proinflammatory and the alternative M2 anti‐inflammatory phenotypes. This concept overturns the popular view of microglial activation as a synonym of neurotoxicity and neurogenesis failure in brain disorders. The characterization of the alternative programs is a matter of intense investigation, but still scarce information is available on the course of microglial activation, on the reversibility of the different commitments and on the capability of preserving molecular memory of previous priming stimuli. By using organotypic hippocampal slice cultures as a model, we developed paradigms of stimulation aimed at shedding light on some of these aspects. We show that persistent stimulation of TLR4 signaling promotes an anti‐inflammatory response and microglial polarization toward M2‐like phenotype. Moreover, acute and chronic preconditioning regimens permanently affect the capability to respond to a later challenge, suggesting the onset of mechanisms of molecular memory. Similar phenomena could occur in the intact brain and differently affect the vulnerability of mature and newborn neurons to noxious signals. GLIA 2013;61:1698–1711     

Why do studies show different associations between intrauterine exposure to maternal smoking and age at menarche?

Purpose

Studies suggests that intrauterine exposure to maternal smoking both accelerates or delays age at menarche. We hypothesize that these opposing findings relate to different infant and childhood growth patterns across cohorts.

Chronic diseases are strongly associated with sickness absences in a sample of Italian public employees

Objectives

Data on the prevalence of chronic diseases and their relationship with sickness absence in the Italian public employees are rather scarce. Therefore, in the first place, we assessed the distribution of chronic diseases in the employees of the University of Ferrara. As a next step, we investigated the possible associations between each chronic disease and cumulative days of all-cause sickness absence, and finally we investigated the odds ratio of each single chronic disease on sickness absence.

Material and Methods

A total of 514 employees, 269 sick-listed and 245 not sick-listed in 2012, were studied. Demographical/clinical characteristics and chronic diseases were obtained from all study participants during medical surveillance procedures. Sickness absence days and job seniority data were obtained from the administrative office.

Results

Gastrointestinal and psychiatric diseases were the most reported in the sick-listed sample (p = 0.01 and p = 0.02, respectively, compared to the not sick-listed). In the interquantile regression analysis, the sickness absence days were as?sociated with psychiatric diseases (β = 65.1, 95% CI: 13.2-117.1, p = 0.01) and with the presence of 2 or more chronic diseases (β = 23.3, 95% CI: 4.5–42, p = 0.02). Furthermore, the logistic regression analysis showed that the odds of sickness absence were increased 2 fold by psychiatric diseases (OR = 2.2, 95% CI: 1.01–4.93, p = 0.04), and gastrointestinal diseases (OR = 1.9, 95% CI: 1.07–3.42, p = 0.02) and, to a lesser extent, by high body mass index (OR = 1.05, 95% CI: 1–1.11, p = 0.03). Conversely, female gender reduced by half the odds of sickness absence (OR = 0.5, 95% CI: 0.3–0.8, p = 0.04).

Conclusions

This study highlights the relevant association between chronic diseases and sickness absence in Italian public employees. Our findings indicate the importance of considering the health status when designing preventive interventions aimed at decreasing sickness absences in this population.     

Radiation effects on development of HER2-positive breast carcinomas.

PURPOSE: Neither hormone-related nor genetics risk factors have been associated with the development of highly proliferative HER2-positive breast carcinomas. Because the majority of HER2-positive tumors present the amplification of the oncogene, we asked whether genomic instability triggered by irradiation might be involved in the induction of HER2-overexpressing breast carcinomas. EXPERIMENTAL DESIGN: Sixty-six infiltrating breast carcinomas from patients treated with radiation therapy for Hodgkin's lymphoma or other pediatric solid tumors and a control series of 61 consecutive sporadic breast tumors were analyzed by immunohistochemistry for HER2 expression with HercepTest. A panel of antibodies against estrogen receptor, progesterone receptor, c-kit, cytokeratin 5/6, p53, and ki67 antigen was also used to identify differentiation subsets and molecular characteristics of the analyzed breast carcinomas. RESULTS: Although no differences between the two tumor series were found with respect to HER2 expression scored 2+ and 3+, the percentage of 3+ HER2-positive tumors was significantly higher in patients irradiated during breast maturation compared with patients irradiated after breast maturation (35.3% versus 12.5%, P = 0.046). In the latter group, 52.5% of the breast carcinomas showed basal-like differentiation (estrogen receptor, progesterone receptor, and HER2 negative) versus only 5.9% in the group irradiated during breast development (P < 0.0001). Analysis adjusted for age confirmed the significant increase in basal-like tumor development in patients irradiated within 4 years of menarche, but also showed that the differences between patients irradiated before and after puberty in HER2 3+ tumor frequencies are due to age-related differences in HER2 3+ tumor onset. CONCLUSION: Together, our data indicate that the development of HER2-positive tumors correlates with timing rather than type of carcinogenic hits and provide clear evidence that radiation is a risk factor for breast carcinomas showing basal-like differentiation.     

Risk of second cancer in nongastric marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue: a population-based study from northern Italy.

PURPOSE: The aim of this study was to define the risk of second cancer in nongastric marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). EXPERIMENTAL DESIGN: We considered for the analysis 157 patients with a confirmed histology of marginal zone B-cell lymphoma of MALT, presenting with a clinically prevalent extranodal site of disease, except for stomach. All patients came from two hematologic institutions of Northern Italy. We compared the occurrence of second cancer with respect to the general population by calculating the standardized incidence ratio, with the age- and sex-specific incidence rates of a cancer registry of Northern Italy (Lombardia) as a reference. RESULTS: A history of solid neoplasia was present in 29 (18%) patients for a total number of 30 neoplasms: 25 solid tumors, 2 hematologic diseases (1 Hodgkin's lymphoma and 1 essential thrombocythemia), and 3 nonmelanoma in situ skin cancers. In 4 patients, the site of cancer and lymphoma was the same. In 21 cases the solid tumor preceded the MALToma, in 3 the neoplasm was concomitant, whereas in 6 it was subsequent. For the entire group, the standardized incidence ratio of an additional malignancy was 0.8 [95% confidence interval (95% CI), 0.55-1.17; P = 0.2]. After excluding nonmelanoma skin cancer, the standardized incidence ratio of a second tumor was 0.75 (95% CI, 0.5-1.12; P = 0.2). After excluding all previous malignancies, the standardized incidence ratio of a second cancer was 1.32 (95% CI, 0.69-2.55; P = 0.4). The comparison of risks between males and females was not significant in each group analysis. CONCLUSIONS: Patients with nongastric MALT lymphomas are not at increased risk for other neoplasms compared with the general population of the same geographic area.