Rotationplasty outcomes assessed by gait analysis following resection of lower extremity bone neoplasms.

Aims: The standard of surgical treatment for lower limb neoplasms had been characterized by highly interventional techniques, leading to severe kinetic impairment of the patients and incidences of phantom pain. Rotationplasty had arisen as a potent limb salvage treatment option for young cancer patients with lower limb bone tumours, but its impact on the gait through comparative studies still remains unclear several years after the introduction of the procedure. The aim of this study is to assess the effect of rotationplasty on gait parameters measured by gait analysis compared to healthy individuals. Methods: The MEDLINE, Scopus, and Cochrane databases were systematically searched without time restriction until 10 January 2022 for eligible studies. Gait parameters measured by gait analysis were the outcomes of interest. Results: Three studies were eligible for analyses. Compared to healthy individuals, rotationplasty significantly decreased gait velocity (-1.45 cm/sec; 95% confidence interval (CI) -1.98 to -0.93; p < 0.001), stride length (-1.20 cm; 95% CI -2.31 to -0.09; p < 0.001), cadence (-0.83 stride/min; 95% (CI -1.29 to -0.36; p < 0.001), and non-significantly increased cycle time (0.54 sec; 95% CI -0.42 to 1.51; p = 0.184). Conclusion: Rotationplasty is a valid option for the management of lower limb bone tumours in young cancer patients. Larger studies, with high patient accrual, refined surgical techniques, and well planned rehabilitation strategies, are required to further improve the reported outcomes of this procedure.

Deep Learning for Lung Cancer Diagnosis, Prognosis and Prediction Using Histological and Cytological Images: A Systematic Review.

Lung cancer is one of the deadliest cancers worldwide, with a high incidence rate, especially in tobacco smokers. Lung cancer accurate diagnosis is based on distinct histological patterns combined with molecular data for personalized treatment. Precise lung cancer classification from a single H&E slide can be challenging for a pathologist, requiring most of the time additional histochemical and special immunohistochemical stains for the final pathology report. According to WHO, small biopsy and cytology specimens are the available materials for about 70% of lung cancer patients with advanced-stage unresectable disease. Thus, the limited available diagnostic material necessitates its optimal management and processing for the completion of diagnosis and predictive testing according to the published guidelines. During the new era of Digital Pathology, Deep Learning offers the potential for lung cancer interpretation to assist pathologists' routine practice. Herein, we systematically review the current Artificial Intelligence-based approaches using histological and cytological images of lung cancer. Most of the published literature centered on the distinction between lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung carcinoma, reflecting the realistic pathologist's routine. Furthermore, several studies developed algorithms for lung adenocarcinoma predominant architectural pattern determination, prognosis prediction, mutational status characterization, and PD-L1 expression status estimation.

Prosthetic reconstruction following resection of lower extremity bone neoplasms: A systematic review and meta-analysis.

Prosthetic reconstructive procedures have become the mainstay in contemporary surgical treatment following resection of extremity bone neoplasms. Given that these patients are of young age most of the time, achievement of robust functional outcomes is of paramount importance. The aim of this study is to assess the impact of this procedure on the gait parameters of cancer patients compared to healthy individuals. The Medline, Scopus and Cochrane databases were systematically searched until January 2022 for eligible studies. Gait parameters measured by gait analysis after prosthetic reconstruction were the outcomes of interest. Eight cohort studies were included in our analysis. From these, seven studied prosthetic reconstruction of the knee (distal femur or proximal tibia) and only one exclusively studied prostetic reconstructions of the proximal femur. Compared to healthy individuals a significant decrease was evident in gait velocity (-0.16 m/sec, 95 %CI: -0.23 to -0.09, p-value < 0.001), in stride length (-6.07 %height, 95 %CI: -9,36 to -2.78, p-value < 0.001), in cadence (-3.96 stride/min, 95 %CI: -5.41 to -2.51, p-value < 0.001) and significant increase in cycle time (0.10 s, 95 %CI: 0.03 to 0.17, p-value = 0.005). Prosthetic reconstruction following lower limb tumor resection significantly affects the gait of patients. This knowledge can be utilized for further refinement of surgical techniques, rehabilitation strategies and follow-up programming.

The Role and Effectiveness of Photodynamic Therapy on Patients With Actinic Keratosis: A Systematic Review and Meta-Analysis.

Actinic keratoses (AKs) are the most common neoplastic lesions and are recognized as a precursor to squamous cell skin cancer. Photodynamic therapy (PDT) is a therapeutic option for multiple AKs in line with field cancerization. The aim of this study was to assess the effectiveness of PDT on patients with AKs using a meta-analysis, in order to evaluate the possible superiority of one treatment over the others. For this purpose, the PubMed, MEDLINE, Scopus, OVID, Science Direct, British Journal of Dermatology, Research Gate, and Embase databases were searched in March 2022. The search terms used were 'photodynamic therapy' and 'actinic keratosis'. We utilized the random-effects meta-analysis model to compare methyl aminolevulinate PDT (MAL-PDT) and the combination of a nanoscale-lipid vesicle formulation with the prodrug 5-aminolevulinic acid (BF-200 ALA) on a complete response (CR) of the lesions. Our meta-analysis indicated that the comparison of BF-200 ALA versus MAL-PDT showed marginally higher CRs than MAL-PDT.

Deep Learning on Histopathological Images for Colorectal Cancer Diagnosis: A Systematic Review.

Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men, with an increasing incidence. Pathology diagnosis complemented with prognostic and predictive biomarker information is the first step for personalized treatment. The increased diagnostic load in the pathology laboratory, combined with the reported intra- and inter-variability in the assessment of biomarkers, has prompted the quest for reliable machine-based methods to be incorporated into the routine practice. Recently, Artificial Intelligence (AI) has made significant progress in the medical field, showing potential for clinical applications. Herein, we aim to systematically review the current research on AI in CRC image analysis. In histopathology, algorithms based on Deep Learning (DL) have the potential to assist in diagnosis, predict clinically relevant molecular phenotypes and microsatellite instability, identify histological features related to prognosis and correlated to metastasis, and assess the specific components of the tumor microenvironment.

The Association between the Binding Processes of Working Memory and Vascular Risk Profile in Adults.

Episodic buffer (EB), a key component of working memory, seems to have a rather complicated function as part of binding processes. Recent papers on the field claim that binding processes of working memory (WM) are assisted by attention and executive functions. On the same page, vascular pathology is gaining more ground as the main underlying cause for many brain pathologies. Hypercholesterolemia, hypertension, obesity, diabetes, lack of exercise and smoking are the most common risk factors that people of all ages suffer from and constitute the main vascular risk factors responsible for a possible decline in executive functions and attention. Thus, this research is an attempt to examine the relation between the binding functions of WM and the existence of vascular risk factors via a computerized test focusing on feature binding. The study comprised adults (n = 229) with and without vascular risk factors. The main tools used were a biomarker questionnaire and a feature binding test (FBT). The results showed that participants who report suffering from one or more vascular risk factors had significantly lower performance on specific subtasks of the FBT in comparison to the participants who were healthy. This allows us to assume that there might be a positive association between feature binding and a vascular risk profile in adults, and such a test could be a useful diagnostic tool for early cognitive impairment due to incipient vascular pathology.

Cigarette Smoking, Coffee Consumption, Alcohol Intake, and Risk of Crohn's Disease and Ulcerative Colitis: A Mendelian Randomization Study.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are widely associated with smoking in epidemiological studies, whereas there are conflicting results for the association between CD and UC for both coffee and alcohol consumption. Herein, we aimed to investigate whether cigarette smoking and alcohol and coffee consumption are causally associated with either CD or UC. METHODS: We utilized 540 genome-wide significant single-nucleotide polymorphisms for 3 potentially addictive substances-nicotine, alcohol, and caffeine-to assess the association of smoking, coffee, and alcohol consumption with CD and UC (12,194 CD cases, 12,366 UC cases, and 25,042 controls of European ancestry), using Mendelian randomization analysis. Mendelian randomization estimates were used to evaluate the effect of the exposure factors on CD and UC risk. Sensitivity analysis was employed to test for any directional pleiotropy. RESULTS: We found evidence for a positive causal association between the age of smoking initiation and UC risk and between alcohol consumption and CD risk, which disappeared after sensitivity analysis for both associations (P > 0.05). No evidence for a causal association between cigarettes per day, smoking initiation, smoking cessation, and coffee consumption variables and UC or CD was found. CONCLUSIONS: We found no clear evidence that either genetically predicted smoking, coffee consumption, or alcohol consumption are causally associated with the risk for CD or UC, although our findings indicate a potential positive association between the age of smoking and UC and between alcohol consumption and CD.

A genome-wide scan for pleiotropy between bone mineral density and nonbone phenotypes.

Osteoporosis is the most common metabolic bone disorder globally and is characterized by skeletal fragility and microarchitectural deterioration. Genetic pleiotropy occurs when a single genetic element is associated with more than one phenotype. We aimed to identify pleiotropic loci associated with bone mineral density (BMD) and nonbone phenotypes in genome-wide association studies. In the discovery stage, the NHGRI-EBI Catalog was searched for genome-wide significant associations (P value < 5 × 10-8), excluding bone-related phenotypes. SNiPA was used to identify proxies of the significantly associated single nucleotide polymorphisms (SNPs) (r 2 = 1). We then assessed putative genetic associations of this set of SNPs with femoral neck (FN) and lumbar spine (LS) BMD data from the GEFOS Consortium. Pleiotropic variants were claimed at a false discovery rate < 1.4 × 10-3 for FN-BMD and < 1.5 × 10-3 for LS-BMD. Replication of these genetic markers was performed among more than 400 000 UK Biobank participants of European ancestry with available genetic and heel bone ultrasound data. In the discovery stage, 72 BMD-related pleiotropic SNPs were identified, and 12 SNPs located in 11 loci on 8 chromosomes were replicated in the UK Biobank. These SNPs were associated, in addition to BMD, with 14 different phenotypes. Most pleiotropic associations were exhibited by rs479844 (AP5B1, OVOL1 genes), which was associated with dermatological and allergic diseases, and rs4072037 (MUC1 gene), which was associated with magnesium levels and gastroenterological cancer. In conclusion, 12 BMD-related genome-wide significant SNPs showed pleiotropy with nonbone phenotypes. Pleiotropic associations can deepen the genetic understanding of bone-related diseases by identifying shared biological mechanisms with other diseases or traits.

The effectiveness of photodynamic therapy and cryotherapy on patients with basal cell carcinoma: A systematic review and meta-analysis.

Basal cell carcinoma (BCC) is known as the most common type of nonmelanoma skin cancer worldwide. The aim of this study is to show the effectiveness of photodynamic therapy and cryotherapy in patients with BCCs with the use of meta-analyses in order to see if there is a possible superiority of one treatment over the other. We searched the databases PubMed, MEDLINE, CINAHL, Scopus, OVID, Embase, Science Direct, JAMA Dermatology, and Research Gate in April 2020. The search combined related terms for cryotherapy, BCC, cryosurgery, cryoablation, laser and photodynamic therapy. The comparison of photodynamic therapy (PDT) vs cryotherapy on recurrence rate yielded no statistically significant results (Figure 2; N = 3 randomized control trials [RCTs]; Summary Random Effects OR = 4.99; P = .212). We observed large heterogeneity (I2 = 87.3%), but no indication for small study effects (Egger's test, P = .02). Regarding the comparison of PDT vs cryotherapy on complete response, again no statistically significant results were observed (Figure 3; N = 2 RCTs; Summary Fixed Effects OR = 0.83; P = .538) and no indication of heterogeneity (I2 = 0%). Our meta-analyses indicated that the comparison of PDT vs cryotherapy has no statistically significant results. Therefore, these therapies seem to have similar therapeutic effects.

Association of low Syndecan-1 expression with adverse histopathological parameters in gastric carcinomas.

PURPOSE: Since syndecan-1 is an adhesion molecule involved in tumor invasion and metastasis, we evaluated the relationship between syndecan-1 expression and histopathological features of gastric carcinomas. METHODS: Syndecan-1 expression was evaluated in 104 gastric carcinomas using immunohistochemistry. RESULTS: High, moderate and low syndecan-1 expression in carcinoma cells was observed in 17/104, 25/104 and 62/104 cases, respectively. High, moderate and low syndecan-1 expression in stromal cells was observed in 5/104, 22/104 and 77/104 cases, respectively. Low epithelial syndecan-1 expression was significantly associated with increased depth of invasion (p=0.034) and lymph vessel invasion (p=0.035). Low stromal syndecan-1 expression was significantly associated with histologic type (intestinal vs diffuse/mixed; p=0.04), increased histologic grade (p=0.04) and large tumor size (p=0.026). CONCLUSION: Low levels of tumor and stromal syndecan- 1 expression were associated with adverse histopathological parameters in gastric carcinoma. This suggests that syndecan-1 expression may be helpful for assessing the aggressiveness of gastric carcinomas.

Prediction of Melanoma Risk in a Southern European Population Based on a Weighted Genetic Risk Score.

Many single nucleotide polymorphisms (SNPs) have been described as putative risk factors for melanoma. The aim of our study was to validate the most prominent genetic risk loci in an independent Greek melanoma case-control dataset and to assess their cumulative effect solely or combined with established phenotypic risk factors on individualized risk prediction. We genotyped 59 SNPs in 800 patients and 800 controls and tested their association with melanoma using logistic regression analyses. We constructed a weighted genetic risk score (GRSGWS) based on SNPs that showed genome-wide significant (GWS) association with melanoma in previous studies and assessed their impact on risk prediction. Fifteen independent SNPs from 12 loci were significantly associated with melanoma (P < 0.05). Risk score analysis yielded an odds ratio of 1.36 per standard deviation increase of the GRSGWS (P = 1.1 × 10(-7)). Individuals in the highest 20% of the GRSGWS had a 1.88-fold increase in melanoma risk compared with those in the middle quintile. By adding the GRSGWS to a phenotypic risk model, the C-statistic increased from 0.764 to 0.775 (P = 0.007). In summary, the GRSGWS is associated with melanoma risk and achieves a modest improvement in risk prediction when added to a phenotypic risk model.

Exposure to pesticides and diabetes: A systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus has a multifactorial pathogenesis with a strong genetic component as well as many environmental and lifestyle influences. Emerging evidence suggests that environmental contaminants, including pesticides, might play an important role in the pathogenesis of diabetes. OBJECTIVES: We performed a systematic review and meta-analysis of observational studies that assessed the association between exposure to pesticides and diabetes and we examined the presence of heterogeneity and biases across available studies. METHODS: A comprehensive literature search of peer-reviewed original research pertaining to pesticide exposure and diabetes, published until 30st May 2015, with no language restriction, was conducted. Eligible studies were those that investigated potential associations between pesticides and diabetes without restrictions on diabetes type. We included cohort studies, case-control studies and cross-sectional studies. We extracted information on study characteristics, type of pesticide assessed, exposure assessment, outcome definition, effect estimate and sample size. RESULTS: We identified 22 studies assessing the association between pesticides and diabetes. The summary OR for the association of top vs. bottom tertile of exposure to any type of pesticide and diabetes was 1.58 (95% CI: 1.32-1.90, p=1.21×10(-6)), with large heterogeneity (I(2)=66.8%). Studies evaluating Type 2 diabetes in particular (n=13 studies), showed a similar summary effect comparing top vs. bottom tertiles of exposure: 1.61 (95% CI 1.37-1.88, p=3.51×10(-9)) with no heterogeneity (I(2)=0%). Analysis by type of pesticide yielded an increased risk of diabetes for DDE, heptachlor, HCB, DDT, and trans-nonachlor or chlordane. CONCLUSIONS: The epidemiological evidence, supported by mechanistic studies, suggests an association between exposure to organochlorine pesticides and Type 2 diabetes.