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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Longitudinal Changes in Brain Diffusion MRI Indices during and after Proton Beam Therapy in a Child with Pilocytic Astrocytoma: A Case Report

Proton beam therapy (PBT) is an effective pediatric brain tumor treatment. However, the resulting microstructural changes within and around irradiated tumors are unknown. We retrospectively applied diffusion tensor imaging (DTI) and free-water imaging (FWI) on diffusion-weighted magnetic resonance imaging (dMRI) data to monitor microstructural changes during the PBT and after 8 months in a pilocytic astrocytoma (PA) and normal-appearing white matter (NAWM). We evaluated the conventional MRI- and dMRI-derived indices from six MRI sessions (t0–t5) in a Caucasian child with a hypothalamic PA: at baseline (t0), during the PBT (t1–t4) and after 8 months (t5). The tumor voxels were classified as “solid” or “fluid” based on the FWI. While the tumor volume remained stable during the PBT, the dMRI analyses identified two different response patterns: (i) an increase in fluid content and diffusivity with anisotropy reductions in the solid voxels at t1, followed by (ii) smaller variations in fluid content but higher anisotropy in the solid voxels at t2–t4. At follow-up (t5), the tumor volume, fluid content, and diffusivity in the solid voxels increased. The NAWM showed dose-dependent microstructural changes. The use of the dMRI and FWI showed complex dynamic microstructural changes in the irradiated mass during the PBT and at follow-up, opening new avenues in our understanding of radiation-induced pathophysiologic mechanisms in tumors and the surrounding tissues

White matter connectivity between occipital and temporal regions involved in face and voice processing in hearing and early deaf individuals

Neuroplasticity following sensory deprivation has long inspired neuroscience research in the quest of understanding how sensory experience and genetics interact in developing the brain functional and structural architecture. Many studies have shown that sensory deprivation can lead to cross-modal functional recruitment of sensory deprived cortices. Little is known however about how structural reorganization may support these functional changes. In this study, we examined early deaf, hearing signer and hearing non-signer individuals using diffusion MRI to evaluate the potential structural connectivity linked to the functional recruitment of the temporal voice area by face stimuli in deaf individuals. More specifically, we characterized the structural connectivity between occipital, fusiform and temporal regions typically supporting voice- and face-selective processing. Despite the extensive functional reorganization for face processing in the temporal cortex of the deaf, macroscopic properties of these connections did not differ across groups. However, both occipito- and fusiform-temporal connections showed significant microstructural changes between groups (fractional anisotropy reduction, radial diffusivity increase). We propose that the reorganization of temporal regions after early auditory deprivation builds on intrinsic and mainly preserved anatomical connectivity between functionally specific temporal and occipital regions

Design and experimental validation of an optimized microalgae-bacteria consortium for the bioremediation of glyphosate in continuous photobioreactors

Glyphosate will be banned from Europe by the end of 2022, but its widespread use in the last decades and its persistence in the environment require the development of novel remediation processes. In this work, a bacterial consortium was designed de novo with the aim to remove glyphosate from polluted water, supported by the oxygen produced by a microalgal species. To this goal, bioinformatics tools were employed to identify the bacterial strains from contaminated sources (Pseudomonas stutzeri; Comamonas odontotermitis; Sinomonas atrocyanea) able to express enzymes for glyphosate degradation, while the microalga Chlorella protothecoides was chosen for its known performances in wastewater treatment. To follow a bioaugmentation approach, the designed consortium was cultivated in continuous photobioreactors at increasing glyphosate concentrations, from 5 to 50 mg L-1, to boost its acclimation to the presence of the herbicide and its capacity to remove it from water. C. protothecoides tolerance to glyphosate was verified through batch experiments. Remarkably, steady state conditions were reached and the consortium was able to live as a community in the reactor. The consortium activity was validated in both synthetic and real wastewater, where glyphosate concentration was reduced by about 53% and 79%, respectively, without the detection of aminomethylphosphonic acid formation

Longitudinal Changes in Brain Diffusion MRI Indices during and after Proton Beam Therapy in a Child with Pilocytic Astrocytoma: A Case Report

Proton beam therapy (PBT) is an effective pediatric brain tumor treatment. However, the resulting microstructural changes within and around irradiated tumors are unknown. We retrospectively applied diffusion tensor imaging (DTI) and free-water imaging (FWI) on diffusion-weighted magnetic resonance imaging (dMRI) data to monitor microstructural changes during the PBT and after 8 months in a pilocytic astrocytoma (PA) and normal-appearing white matter (NAWM). We evaluated the conventional MRI- and dMRI-derived indices from six MRI sessions (t0–t5) in a Caucasian child with a hypothalamic PA: at baseline (t0), during the PBT (t1–t4) and after 8 months (t5). The tumor voxels were classified as “solid” or “fluid” based on the FWI. While the tumor volume remained stable during the PBT, the dMRI analyses identified two different response patterns: (i) an increase in fluid content and diffusivity with anisotropy reductions in the solid voxels at t1, followed by (ii) smaller variations in fluid content but higher anisotropy in the solid voxels at t2–t4. At follow-up (t5), the tumor volume, fluid content, and diffusivity in the solid voxels increased. The NAWM showed dose-dependent microstructural changes. The use of the dMRI and FWI showed complex dynamic microstructural changes in the irradiated mass during the PBT and at follow-up, opening new avenues in our understanding of radiation-induced pathophysiologic mechanisms in tumors and the surrounding tissues

Investigating the spatial pattern of structural changes of the Optic Radiation in early blind individuals

Synopsis The study of sensory deprived individuals shows the capability of the brain to massively reorganize. Previous studies show that the optic tract of early blind individuals undergoes structural changes, but little is known about their spatial distribution. We investigated the spatial profile of the structural changes occurring along tractography reconstruction from diffusion MRI data of the optic radiations in early blind individuals compared to age- and gender-matched healthy sighted controls. Introduction Early blindness (EB) affects the optic radiation (OR), the component of the visual pathway conveying signals from the lateral geniculate nucleus (LGN) of the thalamus to the occipital cortex. Previous diffusion MRI studies showed that the OR of EB individuals presents lower fractional anisotropy (FA) values compared to matched sighted controls. However, these studies either (i) averaged FA along the OR tract, or (ii) considered voxel-based analyses. As a result, the spatial distribution of FA changes along the OR in EB remains not well characterized. Here we investigate whether the FA profile along the OR is affected by blindness relative to sighted controls. The possible detection of localised patterns of changes might provide new insights into the mechanisms of plasticity in sensory-deprived individuals. Methods A group of 16 early-blind subjects (8 males, mean age 33.9, onset ≤ 3 years old) was investigated in comparison with a gender- and age-matched group of healthy sighted controls. A 4T Bruker Medspec MRI scanner was used to acquire diffusion (2.3mm isotropic voxel, 60 DW and 10 b0 volumes, b =1500s/mm2 , TE = 99ms) and T1 anatomical (MPRAGE, 1 mm isotropic) data. Diffusion data were corrected for eddy currents and head motion (FSL) followed by bias field correction and global intensity normalization in MrTrix3 . Diffusion profiles (FODs) were estimated on upsampled DWI data from the group-specific average response function. Anatomically-constrained probabilistic tractography (ACT) was performed at following parameters: 0.5 mm step size, 45° maximum angle threshold, 1000 seeds/voxel. Tracking was randomly initiated from each voxel in the LGN and the primary visual cortex (V1) was used as target. The LGN was extracted from the Juelich atlas (threshold=25%), inflated (2mm) to account for inter-subject variability, and non-linearly registered to the subject’s diffusion space in FSL(FNIRT). V1 was automatically parcellated in Freesurfer(v5.3.0). Parcellations were visually inspected and, manually edited by an expert operator (author H.T.). Resulting tractograms were then filtered and transformed into TrackVis file format using nipype. The Along-Tract-Statistic Toolkit was used to estimate FA at multiple locations along the tract length: each tract streamlines were reoriented to a common origin and re-parameterized with cubic B-splines, resampled to new vertices in such a way that each streamline’s point closest to the midpoint vertex of the calculated mean tract streamline was identified, and each half of each streamline’s restant vertices fell respectively on their side of the midpoint vertex. The number of new vertices was calculated by dividing the length of each tract mean streamline by the voxel resolution, and then averaging it across subjects. Each subject’s FA map was then sampled at these new vertices and FA values were collapsed across streamlines at each group of correspondent vertices in order to get mean (M) and standard deviation (SD) FA estimates along the length of the tract. FA was also extracted by collapsing each individual’s along-tract FA values to compare Hedges’s g in this condition with Hedges’s g for each vertex showing significant FA differences between groups. Results For both hemispheres, significant effects of group (left: p=0.004, right: p=0.005) and vertex (left: p<0.001, right: p<0.001) were observed across all the tract length. Significant interactions of vertex and group were found for the right hemisphere (p<0.001, figure 1). Post-hoc t-tests show that verteces presenting significant group interactions (p<0.05, corr.) are segregated in two distinct segments along the tract course, and that they are localized respectively in the postero-central and posterior regions of the OR (figure 2, 3). Discussion and Conclusion These results confirm previous findings for decreased FA values within the OR of early-blind people, and shed new light on the spatial pattern characterizing such changes. Interestingly, FA changes appear to mainly affect two distinct segments of the tract course, and this might point to the occurrence of focal patterns of white matter reorganization occurring in specific tract positions. The localization of such phenomenon might provide new understandings of mechanisms of plasticity in sensory-deprived individuals, and might represent new valuable opportunities in the assessment of suitability of sight restoration

MicroRNA cloning and sequencing in osteosarcoma cell lines: Differential role of miR-93

Background Studies show that abnormalities in non-coding genes can contribute to carcinogenesis; microRNA levels may modulate cancer growth and metastatic diffusion. Method MicroRNA libraries were built and sequenced from two osteosarcoma cell lines (MG-63 and 143B), which differ in proliferation and transmigration. By cloning and transfection, miR-93, expressed in both cell lines, was then investigated for its involvement in osteosarcoma progression. Results Six of the 19 miRNA identified were expressed in both cell lines with higher expression levels of miR-93 in 143B and in primary osteosarcoma cultures compared to normal osteoblasts. Interestingly, levels of miR-93 were significantly higher in metastases from osteosarcoma than in paired primary tumours. When 143B and MG-63 were transfected with miR-93, clones appeared to respond differently to microRNA overexpression. Ectopic expression of miR-93 more significantly increased cell proliferation and invasivity in 143B than in MG-63 clones. Furthermore, increased mRNA and protein levels of E2F1, one of the potential miR-93 targets, were seen in osteosarcoma cellular clones and its involvement in 143B cell proliferation was confirmed by E2F1 silencing. Conclusion Although further studies are needed to evaluate miRNA involvement in osteosarcoma progression, miR-93 overexpression seems to play an important role in osteosarcoma cell growth and invasion. © International Society for Cellular Oncology 2011

The deaf graph: Structural brain networking in auditory deprivation

Introduction: Deafness is usually accompanied by functional brain alterations that may be thought as an alteration to connectome scaffolding [1,2,3]. The general goal of this study was to investigate brain structural network organization in early and profoundly deaf subjects (ED). The specif

Long-term potentiation-like plasticity is retained during relapse in patients with Multiple Sclerosis.

OBJECTIVE To investigate the degree of synaptic plasticity in Multiple Sclerosis (MS) patients during acute relapses compared to stable MS patients and healthy controls (HCs) and to analyze its functional relevance. METHODS Facilitatory quadripulse stimulation (QPS) was applied to the primary motor cortex in 18 acute relapsing and 18 stable MS patients, as well as 18 HCs. The degree of synaptic plasticity was measured by the change in motor evoked potential amplitude following QPS. Symptom recovery was assessed three months after relapse. RESULTS Synaptic plasticity was induced in all groups. The degree of induced plasticity did not differ between acute relapsing patients, HCs, and stable MS patients. Plasticity was significantly higher in relapsing patients with motor disability compared to relapsing patients without motor disability. In most patients (n = 9, 50%) symptoms had at least partially recovered three months after the relapse, impeding meaningful analysis of the functional relevance of baseline synaptic plasticity. CONCLUSIONS QPS-induced synaptic plasticity is retained during acute MS relapses. Subgroup analyses suggest that stabilizing metaplastic mechanisms may be more important to prevent motor disability but its functional relevance needs to be verified in larger, longitudinal studies. SIGNIFICANCE New insights into synaptic plasticity during MS relapses are provided