HighlightsBiological sex differences are found in the nigrostriatal dopaminergic pathway.These may underpin the greater male susceptibility to develop Parkinson’s disease.Female gonadal factors (estradiol) provide resilience to dopamine loss.Male gonadal factors (testosterone/estradiol) fail to protect/worsen dopamine loss.Sex-specific hormone-based therapies hold promise for novel treatments.

Post-mortem and neuroimaging studies suggest that the serotonergic system, which originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease. This could contribute to the occurrence of non-motor symptoms and tremor, which are only partially explained by dopamine loss. However, the level of involvement of the serotonergic raphe nuclei in early Parkinson's disease is still debated. (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine and serotonin transporter availability. While (123)I-FP-CIT binds primarily to dopamine transporters in the striatum, its binding in the brainstem raphe nuclei reflects serotonin transporter availability. We interrogated baseline single photon emission computed tomography scans of subjects recruited by the Parkinson's Progression Markers Initiative to determine: (i) the integrity of the brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe serotonin transporter levels correlate with severity of tremor and symptoms of fatigue, depression, and sleep disturbance. Three hundred and forty-five patients with early drug-naïve Parkinson's disease, 185 healthy controls, and 56 subjects with possible Parkinson's disease without evidence of dopaminergic deficit were included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106 patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with Parkinson's disease had significantly lower serotonin transporter availability in the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with Parkinson's disease individually had reduced signals. Raphe serotonin transporter availability over the entire Parkinson's disease cohort were associated with rest tremor amplitude (β = -0.106, P < 0.05), rest tremor constancy (β = -0.109, P < 0.05), and index of rest tremor severity (β = -0.104, P < 0.05). The tremulous Parkinson's disease subgroup had significantly lower raphe serotonin transporter availability but less severe striatal dopaminergic deficits compared to akinetic-rigid patients with no resting tremor (P < 0.05). In tremulous patients, raphe serotonin transporter availability was also associated with rest tremor constancy (β = -0.380, P < 0.05) and index of rest tremor severity (β = -0.322, P < 0.05). There was no association between raphe serotonin transporter availability and fatigue, depression, excessive daytime sleepiness, or rapid eye movement sleep behaviour disorder in early Parkinson's disease. We conclude that the raphe nuclei are affected in a subgroup of early drug-naïve Parkinson's disease patients and that reduced raphe serotonin transporter availability is associated with the severity of resting tremor but not non-motor symptoms.

Rest tremor is one of the cardinal signs of Parkinson's disease. Kinetic and postural tremors may also occur. The coexistence of these three types of tremor at disease onset and their subsequent progression could have important clinical and therapeutic implications but remain to be fully elucidated. We aimed to: (i) evaluate prevalence and progression of these three types of tremor in early stages of the disease; and (ii) investigate longitudinally the relationship between dopaminergic and serotonergic terminal dysfunction, rest tremor severity and its response to dopaminergic therapy. The Parkinson's Progressive Markers Initiative database provided the baseline and 2-year follow-up clinical ratings and 123ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodophenyltropane (123I-FP-CIT) single photon emission computed tomography images for this study. 123I-FP-CIT measured putamen dopamine transporter and median raphe serotonin transporter availability. A raphe/putamen uptake ratio was calculated for each patient as an index of relative involvement of these structures. Clinical analysis of tremor was conducted on 378 patients: 87.8% presented with tremor at baseline; rest tremor occurred in 69.6% of patients at baseline; and 67.9% at follow-up. Postural and kinetic tremors occurred in about 50% of patients at both baseline and follow-up. Over 20% of patients presenting with tremor did not exhibit a rest component at baseline. The number of patients with isolated rest tremor was halved at follow-up. In tremor predominant patients, rest tremor severity was inversely correlated with raphe serotonin transporter availability both at baseline and follow-up (baseline: constancy P < 0.05, tremor index P < 0.05; follow-up: amplitude P < 0.05, constancy P < 0.05, tremor index P < 0.05). In the entire cohort, more severe tremor scores correlated with lower raphe/putamen uptake ratio values, indicative of more severe raphe dysfunction (baseline: constancy P < 0.01, tremor index P < 0.05; follow-up: amplitude P < 0.01, constancy P < 0.001, tremor index P < 0.001). The percentage of improvement in rest tremor amplitude after acute dopaminergic therapy was smaller in patients with lower raphe/putamen uptake ratio values (P < 0.01). Rest tremor is the most represented type of tremor in early Parkinson's disease. However, postural and kinetic tremor can affect approximately half of these patients and can occur in absence of resting tremor. As disease progresses, both raphe serotonergic dysfunction and putamen dopamine depletion could contribute to the occurrence of rest tremor. The former is linked to more severe tremor scores and poorer response to dopaminergic therapy. Non-dopaminergic treatments might be beneficial for patients whose tremor is associated with a raphe-predominant dysfunction.

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To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes.MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20e5/1/21.RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001).CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use

WHAT THIS PAPER ADDSThis systematic review and meta-analysis summarises the evidence for endoanchor use in EVAR and TEVAR to treat type Ia endoleak (TIaE) and graft migration. Endoanchor fixation in EVAR is technically feasible with at least comparable early outcomes to the latest generation of stent grafts in treating TIaE and graft migration. Evidence for endostapling in TEVAR is sparse, and results show lower technical success, higher peri-operative mortality, and potential serious adverse events. The current evidence is limited by short term data and a lack of case controlled trials. Further robust studies are required before endoanchor use can be recommended in routine clinical practice.Objective: Endoanchor fixation might be a potential adjunct for the prevention and treatment of type Ia endoleak (TIaE) and graft migration in thoracic or abdominal endovascular aortic aneurysm repairs (TEVAR or EVAR). This review aimed to explore the safety and effectiveness of endoanchor fixation in TEVAR and EVAR. Methods: A systematic review and random effects meta-analysis was conducted. Data sources were PubMed/ MEDLINE, Embase, and the Cochrane Library. Results: Seven EVAR and three TEVAR studies using the Heli-FXÔ EndoAnchorÔ system were included in the meta-analysis. A total of 455 EVAR patients underwent primary endoanchor fixation. Technical success was 98.4% (95% CI 95.7e99.8%). The rate of TIaE and graft migration was 3.5% (95% CI 1.7e5.9%) and 2.0% (95% CI 0.12e6.0%), respectively, after 15.4 months (95% CI 1.76e29.0) follow up. A total of 107 EVAR patients underwent secondary fixation with a technical success of 91.8% (95% CI 86.1e96.2%). Rates of TIaE and graft migration were 22.6% (95% CI 9.1e40.0%) and 0% after a mean 10.7 month (95% CI 7.8e13.6) follow up. Adverse events included three endoanchor fractures, three dislocated endoanchors, one entrapped endoanchor, and one common iliac artery dissection. All cause 30 day EVAR mortality was 0.82% (95% CI 0.20e1.85%). Sixty-six TEVAR patients underwent endoanchor fixation with a mean 9.8 month (95% CI 8.1e 11.5) follow up. Technical success was 90.3% (95% CI 72.1e99.4%). The rates of TIaE and migration were 8.7% (95% CI 1.0e18.9%) and 0%, respectively. Adverse events included two misdeployed endoanchors with one fatal aortic dissection. All cause 30 day TEVAR mortality was 11.9% (95% CI 5.4e20.6%). Conclusion:Endoanchor fixation in EVAR is technically feasible and safe, with at least comparable early outcomes to the latest generation of stent grafts. Endostapling in TEVAR is associated with lower technical success, higher peri-operative mortality, and potential serious adverse events. Current evidence lacks long term follow up and case controlled trials to recommend endoanchor use in routine practice.

Background: Repair of ruptured infrarenal abdominal aortic aneurysms (rAAA) has shifted from open surgical (OAR) to endovascular (EVAR) over the last decade. However, the long term impact of EVAR vs. OAR for rAAA has not been well described.Methods: Prospectively collected registry data (Vascular Quality Initiative [VQI]) were analysed retrospectively to identify patients who underwent EVAR or OAR for rAAA (2004e2018). The primary outcome was death (in hospital and overall post-discharge). Inverse probability weighting (IPW) was used to adjust for treatment selection. Poisson regression assessed the number of one year post-discharge re-interventions.Results: In total, 4257 patients receiving EVAR (n = 2389 [56%]) or OAR (n = 1868 [44%]) for rAAA were identified. Patients were predominantly male (n = 3310 [77.8%]) with a mean 6 standard deviation age of 72.7 6 9.6 years; most (n = 2449 [59.4%]) presented with haemodynamic instability. Use of EVAR for rAAA increased from 7.8% in 2004 to 67.2% in 2018. After IPW, OAR was associated with a higher odds of in hospital mortality (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.54e2.01; p < .001), which was confirmed after multivariable logistic regression (OR 2.08, 95% CI 1.76e2.45; p < .001). Multivariable Cox proportional hazards showed that OAR was also associated with increased overall postdischarge mortality among all patients (hazard ratio 1.36, 95% CI 1.23e1.51; p < .001). Within weighted treatment groups, five year survival was significantly different (55% for EVAR vs. 46% for OAR; p < .001). OAR showed a significantly higher risk of one year post-discharge re-interventions (incidence rate ratio 2.10, 95% CI 1.52e2.89; p < .001).Conclusion: Within the VQI, EVAR for rAAA repair has been increasingly adopted with favourable short term outcomes in terms of morbidity and mortality, as compared with OAR. Unlike elective AAA repair, survival rates between EVAR and OAR do not converge in long term follow up for patients who survived the index hospitalisation.

Results: 139 patients (33 men, 106 women, mean age 57.4 years) were analyzed. 77 (55.4%) patients had ports placed with LE; 62 (44.6%) with L. 3 ports (2.2%) were removed because of hematoma and/or infection. No significant difference in mean procedure time between the two groups (23.6 (SD 6.4) LE vs 25.1 (SD 10.4) L, P ¼ 0.30) was observed. Among operators utilizing sharp dissection techniques, significant differences in mean procedure time were observed (19.2 (SD 4.3) LE vs 25.4 (SD 8.5) L, P ¼ 0.02). No significant differences were observed in those operators utilizing blunt dissection techniques (24.5 (SD 6.4) LE vs 25.0 (SD 10.8) L, P ¼ 0.74). Conclusions: No significant differences in procedural time or procedural complications were observed in patients receiving LE compared to L. Operators utilizing sharp dissection techniques may benefit from the use of LE for local anesthesia.