Association of candidate pharmacogenetic markers with platinum-induced ototoxicity:PanCareLIFE dataset

Genetic association studies suggest a genetic predisposi- tion for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase ( TPMT ) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross- sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnos- tic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes ( ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2 ) were genotyped. The genotype and phenotype data represent a resource for conducting meta- analyses to derive a more precise pooled estimate of the ef- fects of genes on the risk of hearing loss due to platinum treatment

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Recursive segmentation based on higher order statistics in thermal imaging pedestrian detection

Automatic pedestrian detection based on thermal imaging is currently performed in two steps. The segmentation step subdivides the image into multiple regions of interest (ROIs) discarding background regions, while the classification step discriminates pedestrians from non pedestrians in each candidate ROI. In this paper a computationally inexpensive new method is proposed for the segmentation step, which recursively subdivides the image into smaller and smaller rectangular ROIs until a candidate pedestrian is identified. ROI boundaries are found on the base of an adaptive threshold updated at each step of the algorithm, while threshold tuning relies on higher order statistics of gray level histograms. Tests performed on OTCBVS database demonstrate significant improvement over a recent literature method in terms of accuracy and efficiency of segmentation

Low-level multimodal integration on Riemannian manifolds for automatic pedestrian detection

In Computer Vision, automated pedestrian detection is surely one of the hottest topics, with important applications in surveillance and security. To this end, information integration from different imaging modalities, such as thermal infrared and visible spectrum, can significantly improve the detection rate with respect to monomodal strategies. A common scheme consists of extracting two sets of features, from thermal and visible images of the same scene respectively, and stacking them together into a single feature set, ignoring possible and meaningful inter-media dependencies. Here we propose a fusion scheme which acts at the feature-level, taking standard pixel characteristics (such as first/second order spatial derivatives or Local Binary Pattern) and designing a composite descriptor that, at the same time, encodes the information coming from the separate modalities, as well as the cross-modal mutual relationships in the form of covariances. The descriptor, which lies on a Riemannian manifold, is projected onto a Euclidean tangent space and then fed into a Support Vector Machine classifier. Experiments performed on the OTCBVS dataset [1], and validated statistically, demonstrate that our method outperforms significantly the single modality policies as well as different fusion schemes at the pixel, feature and decision level

The Network Of Cities Of The Espírito Santo: Polarization And Challenges For Public Policy

This article assesses the current cities network in the state of Espírito Santo, showing its rigidity and polarization. To identify and simulate this network was chosen the use of a gravity model. From this methodology, was examined a portfolio investment and its possible impacts on the territorial organization of the state. The assessment is that the portfolio is still very concentrated in Grande Vitória, but major investments begin to spread along the coast (both north and south), which opens the possibility of performance of public policies for strengthening alternative regional hubs and better distributed by this state. This policy, to be most effective, should also focus on the change in the profile of the investments in the state, still concentrated mainly in the production of commodities

GH deficiency in cancer survivors in the transition age: diagnosis and therapy

Background: Survival rates among childhood cancer survivors (CCSs) have significantly risen in the last 40 years due to substantial improvements in treatment protocols. However, this improvement has brought with it serious late effects that frequently involve the endocrine system. Of the endocrine disorders, GH deficiency (GHD) is the most common among CCSs as a consequence of a history of cancers, surgery, and/or radiotherapy involving the hypothalamo-pituitary region. Methods: A comprehensive search of English language articles regardless of age was conducted in the MEDLINE database between December 2018 and October 2019. We selected all studies on GH therapy in CCSs during the transition age regarding the most challenging topics: when to retest; which diagnostic tests and cut-offs to use; when to start GH replacement therapy (GHRT); what GH dose to use; safety; quality of life, compliance and adherence to GHRT; interactions between GH and other hormonal replacement treatments. Results: In the present review, we provide an overview of the current clinical management of challenges in GHD in cancer survivors in the transition age. Conclusions: Endocrine dysfunction among CCSs has a high prevalence in the transition age and increase with time. Many endocrine disorders, including GHD, are often not diagnosed or under-diagnosed, probably due to the lack of specialized centers for the long-term follow-up. Therefore, it is crucial that transition specialized clinics should be increased in terms of number and specific skills in order to manage endocrine disorders in adolescence, a delicate and complex period of life. A multidisciplinary approach, also including psychological counseling, is essential in the follow-up and management of these patients in order to minimize their disabilities and maximize their quality of life

Zonulin as a Biomarker for the Development of Celiac Disease

Objectives: Increased intestinal permeability seems to be a key factor in the pathogenesis of autoimmune diseases, including celiac disease (CeD). However, it is unknown whether increased permeability precedes CeD onset. This study's objective was to determine whether intestinal permeability is altered before celiac disease autoimmunity (CDA) in at-risk children. We also examined whether environmental factors impacted zonulin, a widely used marker of gut permeability. Methods: We evaluated 102 children in the CDGEMM study from 2014-2022. We included 51 CDA cases and matched controls, who were enrolled for 12 months or more and consumed gluten. We measured serum zonulin from age 12 months to time of CDA onset, and the corresponding time point in controls, and examined clinical factors of interest. We ran a mixed-effects longitudinal model with dependent variable zonulin. Results: Children who developed CDA had a significant increase in zonulin in the 18.3 months (range 6-78) preceding CDA compared to those without CDA (slope differential = β = 0.1277, 95% CI: 0.001, 0.255). Among metadata considered, zonulin trajectory was only influenced by increasing number of antibiotic courses, which increased the slope of trajectory of zonulin over time in CDA subjects (P = .04). Conclusions: Zonulin levels significantly rise in the months that precede CDA diagnosis. Exposure to a greater number of antibiotic courses was associated with an increase in zonulin levels in CDA subjects. This suggests zonulin may be used as a biomarker for preclinical CeD screening in at-risk children, and multiple antibiotic courses may increase their risk of CDA by increasing zonulin levels

Laparoscopic placement of "self-locating catheter": our experience and a review of literature

Among the available devices for peritoneal dialysis, the Di Paolo self-locating catheter (SLC) represents a milestone using to its ability to ensure a permanent reliable means of access to the peritoneum. Our experience included 20 laparoscopic peritoneal catheter placements from 2008 to 2011. We performed the laparoscopic surgical technique using 3 trocars: 2 10 mm and 1 5 mm. The technique allows catheter introduction into the pouch of Douglas under direct vision. Among 20 treated patients, 1 died due to causes unrelated to peritoneal dialysis; 1 underwent transplantation, and 1 was switched to hemodialysis because of ultrafiltration failure. The complications included 2 catheter displacements, only 1 of them needing repositioning by open laparotomy, and 1 case of peritonitis. No infection in the subcutaneous tunnel or obstruction and malfunction occurred among our patients. The Di Paolo SLC is similar to Tenckhoff catheter but includes a small tungsten cylinder at the tip that engenders continuous gravity in the peritoneal cavity, producing a reduced risk of dislocation. In a large series of cases, Di Paolo et al. reported a 0.8% dislocation rate after SLC placement compared with 12% using Tenckhoff catheters. They also demonstrated a reduced risk of other complications, such as peritonitis, infection, obstruction, and failure. These data have been confirmed by other authors with smaller case series. Thus, introduction of the SLC and improved surgical techniques result in better efficiency of peritoneal dialysis