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

Deep brain stimulation imposes complex informational lesions.

Deep brain stimulation (DBS) therapy has become an essential tool for treating a range of brain disorders. In the resting state, DBS is known to regularize spike activity in and downstream of the stimulated brain target, which in turn has been hypothesized to create informational lesions. Here, we specifically test this hypothesis using repetitive joint articulations in two non-human Primates while recording single-unit activity in the sensorimotor globus pallidus and motor thalamus before, during, and after DBS in the globus pallidus (GP) GP-DBS resulted in: (1) stimulus-entrained firing patterns in globus pallidus, (2) a monophasic stimulus-entrained firing pattern in motor thalamus, and (3) a complete or partial loss of responsiveness to joint position, velocity, or acceleration in globus pallidus (75%, 12/16 cells) and in the pallidal receiving area of motor thalamus (ventralis lateralis pars oralis, VLo) (38%, 21/55 cells). Despite loss of kinematic tuning, cells in the globus pallidus (63%, 10/16 cells) and VLo (84%, 46/55 cells) still responded to one or more aspects of joint movement during GP-DBS. Further, modulated kinematic tuning did not always necessitate modulation in firing patterns (2/12 cells in globus pallidus; 13/23 cells in VLo), and regularized firing patterns did not always correspond to altered responses to joint articulation (3/4 cells in globus pallidus, 11/33 cells in VLo). In this context, DBS therapy appears to function as an amalgam of network modulating and network lesioning therapies

Effect of GP-DBS on kinematic tuning of VLo spike activity.

<p>A: Two examples of responses to joint movement during therapeutic DBS. B: Population analysis of cells that did and did not maintain tuning to joint movement during therapeutic DBS. C: (left) Proportion of the recorded population with partial or complete loss of tuning during therapeutic DBS whose PSTH was also modulated (grey hash) or unchanged (white hash); (right) Proportion that maintained tuning during therapeutic DBS and whose PSTH was modulated (grey) or unchanged (white) by therapeutic DBS.</p

Cellular responses in globus pallidus to GP-DBS during joint movement.

<p>A: Example of firing rate in two pallidal cells before, during (grey bar), and after DBS. Periods of joint articulation used for analysis are denoted by white bars. B: Population average firing rate change during therapeutic and sub-therapeutic DBS. Error bars indicate +/- 1 SEM (n=16 therapeutic DBS, n=10 sub-therapeutic DBS). C: Proportion of recorded cells with statistically significant changes in firing rate during therapeutic DBS. D: Corresponding PSTHs to the example pallidal neurons shown in part A, before (light grey), during (black) and after DBS (dark grey). E: Population average change in firing pattern during therapeutic (dark grey) and subtherapeutic (light grey - dashed) DBS. Filled areas indicate +/- 1 SEM. F: Proportion of recorded cells with statistically significant changes in their PSTHs during therapeutic DBS.</p

Experimental design used to investigate the effects of GP-DBS on encoding of joint kinematics through the pallidofugal pathway.

<p>A: Microelectrode recordings were performed in regions of the globus pallidus and thalamus with spike activity that was responsive to passive joint movement. B: Results of experimenter-blinded muscle rigidity scoring for both monkeys at three DBS settings. C and D: Co-registration of pre-operative MRI and post-electrode implantation CT showing DBS electrode location for monkey R (C) and K (D). E and F: Localization of recorded cells obtained from stereotactic navigation software and overlaid on corresponding atlas plates for monkey R (top) and K (bottom) for both the pallidum (E) and the thalamus (F). G: A generalized linear model (GLM) accounting for position, velocity, and acceleration of the joint movement was applied to determine the correlation between kinematics of the joint movement (top row) and spike activity (2^nd row: spike raster, 3^rd row: corresponding rate histogram). Bottom row shows the GLM prediction of firing rate.</p

Neuronal encoding of joint movement during subtherapeutic and therapeutic DBS in globus pallidus.

<p>Shown is an example of the response of a cell to shoulder flexion/extension before, during and after subtherapeutic DBS (left) and therapeutic DBS (right) (top: motion capture data of the joint movement; middle: corresponding raster plots triggered to the beginning of each movement cycle; bottom: PETHs showing responses before, during, and after DBS).</p

Evolution of deep brain stimulation: Human electrometer and smart devices supporting the next generation of therapy

Deep brain stimulation (DBS) provides therapeutic benefit for several neuropathologies, including Parkinson disease (PD), epilepsy, chronic pain, and depression. Despite well-established clinical efficacy, the mechanism of DBS remains poorly understood. In this review, we begin by summarizing the current understanding of the DBS mechanism. Using this knowledge as a framework, we then explore a specific hypothesis regarding DBS of the subthalamic nucleus (STN) for the treatment of PD. This hypothesis states that therapeutic benefit is provided, at least in part, by activation of surviving nigrostriatal dopaminergic neurons, subsequent striatal dopamine release, and resumption of striatal target cell control by dopamine. While highly controversial, we present preliminary data that are consistent with specific predications testing this hypothesis. We additionally propose that developing new technologies (e.g., human electrometer and closed-loop smart devices) for monitoring dopaminergic neurotransmission during STN DBS will further advance this treatment approach. © 2009 International Neuromodulation Society