Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease.
Optimistic bias (OB) is seen when individuals underestimate their probability of experiencing negative life events and overestimate their probability of experiencing positive life events. A reduced OB has been linked with increased depression symptoms . However, given the relevance of this information to mood and anxiety disorders, little is currently known regarding the neurobiology of OB. In the current study, we examine the neural basis of OB in healthy individuals (n=33) during probability estimation of future positive and negative events occurring to themselves relative to other, comparable individuals. In line with previous work, subjects showed significant OB; they considered themselves significantly more likely to experience future positive and significantly less likely to experience future negative events relative to comparable others. Positive, relative to negative events, un-modulated by subjects’ probability estimates, were associated with significantly greater activity within ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Moreover, responses within both regions to positive events negatively related to the healthy subjects’ self reports of depression symptoms. However, there was no significant modulation of activity in either region by the subject’s OB, objectified as the level to which they thought the event was more likely [positive events] or less likely [negative events] to occur to them relative to comparable others. In contrast, activity within rostral anterior cingulate cortex (rACC) was positively modulated by OB for positive events and activity within anterior insula and dorsomedial prefrontal cortex (dmPFC) was negatively modulated by OB for negative events. However, there was no significant relationship between responsiveness within these regions and self reports of depression symptoms. The data are discussed with reference to current models of vmPFC, rACC and anterior insula functioning.
Objective Deficits in reinforcement-based decision-making have been reported in Generalized Anxiety Disorder. However, the pathophysiology of these deficits is largely unknown, extant studies have mainly examined youth and the integrity of core functional processes underpinning decision-making remain undetermined. In particular, it is unclear whether the representation of reinforcement prediction error (PE: the difference between received and expected reinforcement) is disrupted in Generalized Anxiety Disorder. The current study addresses these issues in adults with the disorder. Methods Forty-six un-medicated individuals with Generalized Anxiety Disorder and 32 healthy controls group-matched on IQ, gender and age, completed a passive avoidance task while undergoing functional MRI. Results Behaviorally, individuals with Generalized Anxiety Disorder showed impaired reinforcement-based decision-making. Imaging results revealed that during feedback, individuals with Generalized Anxiety Disorder relative to healthy controls showed a reduced correlation between PE and activity within ventromedial prefrontal cortex, ventral striatum and other structures implicated in decision-making. In addition, individuals with Generalized Anxiety Disorder relative to healthy participants showed a reduced correlation between punishment, but not reward, PEs and activity within bilateral lentiform nucleus/putamen. Conclusions This is the first study to identify computational impairments during decision-making in Generalized Anxiety Disorder. PE signaling is significantly disrupted in individuals with the disorder and may underpin the decision-making deficits observed in patients with GAD.
SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality ). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
Summary How animals coordinate gene expression in response to starvation is an outstanding problem closely linked to aging, obesity, and cancer [1–5]. Newly hatched Caenorhabditis elegans respond to food deprivation by halting development and promoting long-term survival (L1 diapause), thereby providing an excellent model to study starvation response [2, 6, 7]. Through a genetic search, we have discovered that the tumor suppressor Rb critically promotes survival during L1 diapause and likely does so by regulating the expression of genes in both insulin-IGF-1 signaling (IIS)-dependent and -independent pathways mainly in neurons and the intestine. Global gene expression analyses suggested that Rb maintains the “starvation-induced transcriptome” and represses the “re-feeding induced transcriptome”, including the repression of many pathogen/toxin/oxidative stress-inducible and metabolic genes, as well as the activation of many other stress-resistant genes, mitochondrial respiratory chain genes, and potential IIS receptor antagonists. Notably, the majority of genes dysregulated in starved L1 Rb(−) animals were not found to be dysregulated in fed conditions. Together, these findings identify Rb as a critical regulator of the starvation response and suggest a link between functions of tumor suppressors and starvation survival. These results may provide mechanistic insights into why cancer cells are often hypersensitive to starvation treatment.
Background Generalized Anxiety Disorder (GAD) and Social Anxiety Disorder (SAD) are comorbid and associated with similar neural disruptions during emotion regulation (Blair et al., 2012). In contrast, the lack of optimism examined here may occur specifically in GAD and could prove an important biomarker for that disorder. Methods Un-medicated individuals with GAD (n=18) and age, IQ and gender-matched SAD (n=18) and healthy (n=18) comparison individuals were scanned while contemplating likelihoods of high and low impact negative (e.g., having heart attack; getting heartburn) or positive (e.g., winning the lottery; getting a hug) events occurring to themselves in the future. Results In line with previous work, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others. This was also seen in SAD. However, GAD patients showed no OB for positive events and at the neural level showed significantly reduced modulation relative to the two other groups of regions including medial prefrontal cortex (mPFC) and caudate to these events. The GAD group further differed from the other groups by showing increased neural responses to low impact events in regions including rostral mPFC. Conclusions The form of neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events that occurs in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents an important biomarker for GAD.
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