Search for Leptonic Decays of Dark Photons at NA62.

The NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of 1.4×10^{17} protons on dump collected in 2021. No evidence for a dark photon signal is observed. The combined result for dark photon searches in lepton-antilepton final states is presented and a region of the parameter space is excluded at 90% confidence level, improving on previous experimental limits for dark photon mass values between 50 and 600 MeV/c^{2} and coupling values in the range 10^{-6} to 4×10^{-5}. An interpretation of the e^{+}e^{-} search result in terms of the emission and decay of an axionlike particle is also presented.

Navigating the transition: a multidisciplinary approach to inflammatory bowel disease in children.

PURPOSE: A multidisciplinary approach to Inflammatory Bowel Disease (IBD) has recently demonstrated a positive impact in pediatric patients, reducing dropout rates and facilitating the transition to adult care. Our study aims to evaluate how this approach influences disease activity, dropout rates, and transition. METHODS: We conducted a longitudinal observational study including all patients diagnosed with IBD during pediatric-adolescent age, with a minimum follow-up period of 12 months. For each patient, endpoints included therapeutic approach, need for surgery and transition features. RESULTS: We included 19 patients: 13 with Ulcerative Colitis (UC) and 6 with Crohn's disease (CD). Most patients required multiple lines of therapy, with over 50% in both groups receiving biological drugs. Compliance was good, with a single dropout in each group (10, 5%). The need for surgery was significantly higher in the CD group compared to the UC group (16% vs. 7.7%, p < 0.01). Mean age at transition was significantly higher in the UC group compared to the CD group (19.2 ± 0.7 years SD vs. 18.3 ± 0.6 years SD, p < 0.05). CONCLUSIONS: In our experience, the multidisciplinary approach to IBD in transition-age patients appears effective in achieving clinical remission, offering the potential to reduce therapeutic dropouts.

Lesson Learned with the Use of Iliac Branch Devices: Single Centre 10 Year Experience in 157 Consecutive Procedures.

OBJECTIVE/BACKGROUND: Absence of an adequate iliac seal rarely represents an absolute contraindication to endovascular abdominal aortic aneurysm repair. Iliac branch devices (IBD) are increasingly used in patients with extensive aorto-iliac aneurysmal disease, but few data are available on the long-term results of these procedures. METHODS: Between 2006 and 2016, 157 consecutive IBD procedures performed at a single centre were entered into a prospective database. Indications included unilateral or bilateral common iliac artery aneurysms combined or not with abdominal aortic aneurysms. Long-term results were reported according to the Kaplan-Meier method. RESULTS: During the study period 149 patients were treated with an iliac branched endograft. Isolated IBD was implanted in 17.8% of the cases; technical success rate was 97.5%. Peri-operative procedure failure occurred in seven patients, four during surgery and three within 30 days of the procedure. Presence of ipsilateral hypogastric aneurysm (p = .031; Exp [B] = 6.72) and intervention performed during the initial study period (p = .006; Exp [B] = 10.40) were predictive of early failure on multivariate analysis. After a mean follow-up of 44.2 months actuarial freedom from IBD related re-intervention was 97.4%, 95.6%, 94.0%, and 91.8% at 1, 3, 5, and 9 years, respectively. Hypogastric artery patency was 94.7%, 92.6%, and 90.4% at 1, 3, and 10 years, respectively. Presence of a hypogastric aneurysm was an independent predictor of target artery occlusion during follow-up on multivariate analysis (p = .007; Exp [B] = 5.93). CONCLUSION: Iliac branched endografting can now be performed with a high technical success rate; long-term freedom from re-intervention is comparable with patients treated with standard aortic endografting. IBD should be considered a first-option treatment in patients with adequate vascular anatomy unsuitable for standard endovascular aortic repair.

Arbitrary Palliation of Ruptured Abdominal Aortic Aneurysms in the Elderly is no Longer Warranted.

OBJECTIVE/BACKGROUND: A consistent number of elderly patients with ruptured abdominal aortic aneurysms (rAAAs) are deemed unfit for repair and excluded from any treatment. The objective of this study was to examine the impact on survival of endovascular repair and open surgery with restricted turndown in acute AAA repair. METHODS: A prospective database for patients treated for rAAA was established. None of the patients admitted alive with rAAA were denied treatment. Multivariate regression models, the predictive risk assessment Glasgow Aneurysm Score (GAS), and subgroup analyses in older patients were applied to identify indicators of excessive 30 day mortality risk that could affect the decision for turndown. RESULTS: From 2006 to 2015, 113 consecutive patients (93 males; mean age 77.2 years) with rAAAs were treated (69 open surgery; 44 EVAR). Overall peri-operative (30 day) mortality was 38.9% (44/113): 40.6% (28/69), and 36.4% (16/44) after open surgery and EVAR, respectively (p = .70). Multivariate logistic regression identified old age as an indicator of increased peri-operative mortality (odd ratio [OR] 1.2, 95% confidence interval [CI] 1.1-1.3; p = .001), as well as free aneurysm rupture (OR 5.0, 95% CI 1.3-19.9; p = .02). GAS was higher in patients who died (97.75 vs. 86.62), but the score failed to identify increased peri-operative mortality risk in adjusted analyses (OR 1.0; p = .06). Almost two thirds of the patients (n = 71) were older than 75 at the time of aneurysm rupture (48.6% octogenarians) and EVAR was more commonly applied than open surgery (86.4% vs. 47.8%; p < .0001). Peri-operative mortality in > 75 year old patients was 46.5% compared with 26.2% in younger patients (p = .05), with rates increased after open surgery (54.5% vs. 27.8%, p = .03) but not after EVAR (39.5% vs. 16.7%; p = .39). According to Kaplan-Meier estimates, mean survival was 39.7 ± 4.8 months. Patients older than 75 years of age survived for a mean of 23.0 ± 4.47 months after rupture. CONCLUSION: In this study aggressive treatment with a very restricted or no turndown strategy for any rAAA, also applied to older patients, allowed for an additional mean 40 months of survival after aneurysm rupture. In the contemporary endovascular era the decision to deny repair arbitrarily to older patients with rAAAs must be revisited.

Diabetes and abdominal aortic aneurysms.

Epidemiologic evidence suggests that patients with diabetes may have a lower incidence of abdominal aortic aneurysm (AAA); however, the link between diabetes and AAA development and expansion is unclear. The aim of this review is to analyze updated evidence to better understand the impact of diabetes on prevalence, incidence, clinical outcome, and expansion rate of AAA. A systematic review of literature published in the last 20 years using the PubMed and Cochrane databases was undertaken. Studies reporting appropriate data were identified and a meta-analysis performed using the generic inverse variance method. Sixty-four studies were identified. Methodological quality was "fair" in 16 and "good" in 44 studies according to a formal assessment checklist (Newcastle-Ottawa). In 17 large population prevalence studies there was a significant inverse association between diabetes and AAA: pooled odds ratio (OR) 0.80; 95% confidence intervals (CI) 0.70-0.90 (p = .0009). An inverse association was also confirmed by pooled analysis of data from smaller prevalence studies on selected populations (OR 0.59; 95% CI 0.35-0.99; p = .05), while no significant results were provided by case-control studies. A significant lower pooled incidence of new AAA in diabetics was found over six prospective studies: OR 0.54; 95% CI 0.31-0.91; p = .03. Diabetic patients showed increased operative (30-day/in-hospital) mortality after AAA repair: pooled OR 1.26; 95% CI 1.10-1.44; p = .0008. The increased operative risk was more evident in studies with 30-day assessment. In the long-term, diabetics showed lower survival rates at 2-5 years, while there was general evidence of lower growth rates of small AAA in patients with diabetes compared to non-diabetics. There is currently evidence to support an inverse relationship between diabetes and AAA development and enlargement, even though fair methodological quality or unclear risk of bias in many available studies decreases the strength of the finding. At the same time, operative and long-term survival is lower in diabetic patients, suggesting increased cardiovascular burden. The higher mortality in diabetics raises the question as to whether AAA repair should be individualized in selected diabetic populations at higher AAA rupture risk.

A 1-year follow-up study on checkpoint inhibitor-induced colitis: results from a European consortium.

BACKGROUND: Data regarding the clinical outcome of patients with immune checkpoint inhibitor (ICI)-induced colitis are scant. We aimed to describe the 12-month clinical outcome of patients with ICI-induced colitis. MATERIALS AND METHODS: This was a retrospective, European, multicentre study. Endoscopy/histology-proven ICI-induced colitis patients were enrolled. The 12-month clinical remission rate, defined as a Common Terminology Criteria for Adverse Events diarrhoea grade of 0-1, and the correlates of 12-month remission were assessed. RESULTS: Ninety-six patients [male:female ratio 1.5:1; median age 65 years, interquartile range (IQR) 55.5-71.5 years] were included. Lung cancer (41, 42.7%) and melanoma (30, 31.2%) were the most common cancers. ICI-related gastrointestinal symptoms occurred at a median time of 4 months (IQR 2-7 months). An inflammatory bowel disease (IBD)-like pattern was present in 74 patients (77.1%) [35 (47.3%) ulcerative colitis (UC)-like, 11 (14.9%) Crohn's disease (CD)-like, 28 (37.8%) IBD-like unclassified], while microscopic colitis was present in 19 patients (19.8%). As a first line, systemic steroids were the most prescribed drugs (65, 67.7%). The 12-month clinical remission rate was 47.7 per 100 person-years [95% confidence interval (CI) 33.5-67.8). ICI was discontinued due to colitis in 66 patients (79.5%). A CD-like pattern was associated with remission failure (hazard ratio 3.84, 95% CI 1.16-12.69). Having histopathological signs of microscopic colitis (P = 0.049) and microscopic versus UC-/CD-like colitis (P = 0.014) were associated with a better outcome. Discontinuing the ICI was not related to the 12-month remission (P = 0.483). Four patients (3.1%) died from ICI-induced colitis. CONCLUSIONS: Patients with IBD-like colitis may need an early and more aggressive treatment. Future studies should focus on how to improve long-term clinical outcomes.

High-on-treatment platelet reactivity predicts adverse outcome after carotid artery stenting: A prospective study.

BACKGROUND AND PURPOSE: High-on-treatment platelet reactivity (HTPR) has been established as a predictor of major adverse cardiovascular events (MACE) in patients undergoing percutaneous coronary interventions on dual antiplatelet therapy (DAPT), but no data are available on its predictive value in patients on DAPT after carotid artery stenting (CAS). We aimed to evaluate the possible association between HTPR in patients on aspirin plus clopidogrel therapy after CAS and subsequent MACE. METHODS: All consecutive patients treated with CAS in a single institution were enrolled in a prospective clinical study. HTPR was evaluated with 5 different laboratory assays carried out just before CAS. MACE incidence (cerebral ischemia, myocardial infarction, stent thrombosis, acute limb ischemia and vascular death) was evaluated at 30 days and thereafter at yearly visits. RESULTS: A total of 300 patients were enrolled in the study, and eight were then excluded because blood samples resulted unsuitable for the laboratory testing or CAS aborted for technical problems. Median follow-up was 5.8 years and during this period 47 MACE occurred. HTPR detected by multiplate electronic aggregometry (MEA) and the VASP phosphorylation assay (VASP) were associated with a significantly enhanced risk of MACE (p = 0.048 and p = 0.038, respectively). However, HTPR to three tests (HTPR3) was more strongly predictive of increased risk of a vascular event at follow up (p = 0.005) at bivariate analysis and also at Cox regression multivariate analysis (p = 0.002). CONCLUSIONS: HTPR to three different assays (mainly to VASP + PFA P2Y+ VerifyNow) in patients on DAPT after CAS has predictive value for subsequent MACE. Prospective studies to assess whether platelet function testing-guided antiplatelet therapy is superior to standard DAPT in patient undergoing CAS should be considered.

No benefit from carotid intervention in fatal stroke prevention for >80-year-old patients.

BACKGROUND: Invasive management of patients ≥80 years of age with carotid stenosis may be questionable. The higher likelihood of stroke needs to be balanced with the increased perioperative risk and the reduced life expectancy of this ageing population. The purpose of this study was to evaluate the clinical relevance of carotid stenosis revascularisation in octogenarians. METHODS: All patients ≥80 years of age who received carotid revascularisation in 2001-2010 were reviewed for perioperative and 5-year outcomes. The experience was comprehensive of carotid endarterectomy (CEA) and carotid stenting (CAS) performed during the training frame when age was not a contraindication for this procedure. Mortality rates were compared to those of octogenarians of the same geographical territory according to all-cause and stroke-related mortality national statistics datasets. RESULTS: A total of 348 procedures performed in ≥80-year-old patients (272 males) were reviewed: 162 (46.6%) were by CAS and 169 (48.6%) were for symptomatic disease. Perioperative stroke/death rate was 5.5% and was non-significantly higher for symptomatic disease (7.1% vs. 3.9% asymptomatic; p = 0.24), after CAS (6.2% vs. 4.8% CEA; p = 0.64) and in females (6.6% vs. 5.1% males; p = 0.57). At median follow-up of 36.18 months, 95 deaths and 21 new ischaemic strokes (12 fatal) occurred with 5-year Kaplan-Meier freedom from stroke of 84.8% (78.7%, symptomatic vs. 90.3% asymptomatic; p = 0.003). According to national datasets, in 80-85-year-old resident population 5-year mortality was 29.9% (23.4% females, 40.6% males) and ischaemic stroke-related mortality was 14.9% (16.8% females, 13.0% males). Corresponding figures from treated population showed a 5-year mortality of 49.4%, higher in males (39.5% females, 52.5% males) and ischaemic stroke-related mortality of 20.2%, higher in females (40.0% females, 15.6% males). Comparing data from the study population with residents' figures, ischaemic stroke-related mortality hazard was significantly higher in the study females: odds ratio (OR) 3.2, 95% confidence interval (CI) 1.16-9.17; p = 0.029 (for males: OR 0.97, 95%CI 0.89-1.10; p = 0.99). CONCLUSIONS: Despite perioperative stroke/death risks being lower compared with CAS, the benefit of surgical carotid revascularisation in old patients remains controversial due to limited life expectancy and high fatality of stroke in this ageing population. Invasive treatment of carotid stenosis may not be warranted in most patients ≥80 years of age with carotid stenosis, especially when female and asymptomatic.

Functional ability in patients with critical limb ischaemia is unaffected by successful revascularisation.

OBJECTIVE: Patient- and society-oriented measures of outcome have a critical role in determining the effectiveness of any treatment in patients with critical limb ischaemia (CLI). In particular, the impact of an intervention on patient's dependency and functional performance is relevant but is largely unknown. The aim of the study was to investigate whether the limitations encountered in the activities of daily living (ADLs) measured with the Katz Index (KI) in patients with CLI were changed by the treatment. METHODS: During the period 2006-2008, 248 consecutive patients undergoing repair for CLI were investigated with an ADL questionnaire for assessing KI before and after a mean of 16.19 months from treatment. Changes in KI were stratified by type of treatment and outcome. RESULTS: There were 165 males and 83 females, mean age 73.3 ± 8.3 years; 125 patients showed tissue loss and 123 rest pain alone, 98 received surgical bypass and 150 endovascular repair. Pre-operative KI mean was 10.42. At the post-operative assessment, there was significant worsening in patients' functional outcome (mean KI decreased to 9.78) despite relief of pain (81.5%), tissue healing (72%), good vessel patency (83.8%) and low amputation rate (9.7%). Deterioration of KI was not significantly higher in patients undergoing endovascular repair. Patients receiving major amputation started with worse pre-operative functional score (KI mean 9.42) and did further deteriorate (KI mean 7.71) after demolition surgery. However, patients who received successful revascularisation showed deterioration in the dependence index. CONCLUSIONS: Successful vascular treatment is not associated with improved functional ability in patients with CLI, especially when already highly dependent in their activities. Large nationwide preventive and educational programmes should be implemented to prevent irreversible and severe health deterioration in populations with CLI.

Vigilance on use of drugs, herbal products, and food supplements during pregnancy: focus on fosfomycin.

PURPOSE: Urinary tract infection (UTI) is defined as a common bacterial infection that can lead to significant morbidity such as stricture, fistula, abscess formation, bacteremia, sepsis, pyelonephritis, and kidney dysfunction with a mortality rates reported of 1% in men and 3% in women because of development of pyelonephritis. UTIs are more common in women and the 33% of them require antimicrobials treatment for at least one episode by the age of 24 years. UTIs are the most common infections observed during pregnancy and up to 30% of mothers with not treated asymptomatic bacteriuria may develop acute pyelonephritis which consequently can be associated to adverse maternal and fetal outcomes. All bacteriuria in pregnancy should be treated with antimicrobial treatments being safe for both the mother and the fetus. Approximately one every four women receives prescription of antibiotic treatment during pregnancy, nearly 80% of all the prescription medications during gestation. The use of fosfomycin to treat cystitis in pregnancy generally considered safe and effective. Even though use on antibiotics for urinary tract infections is considered generally safe for the fetus and mothers, this opinion is not based on specific studies monitoring the relationship of among urinary infections, consumption of antibiotics, and pregnancy outcomes. MATERIALS AND METHODS: On this basis we decided to analyze data from the database of our multicenter study PHYTOVIGGEST, reporting data from 5362 pregnancies, focusing on use of fosfomycin. Principal outcomes of pregnancy in women treated with fosfomycin were taken into consideration. RESULTS: Women who have been treated with urinary antibiotics during the pregnancy were 183. With respect to the total number of pregnancies of our sample, these women represented the percentage of 3.49% (187/5362). Analysis of different outcomes of pregnancy such as gestational age, neonatal weight, and neonatal Apgar index did not show any significant difference. At the same time, analysis of data of pregnancy complicancies (such as urgent cesarean delivery, use of general anesthesia, need to induce labor) did not show any difference in women taking fosfomycin during pregnancy and those not taking it. CONCLUSIONS: Our data, based on a large number of pregnancies, confirm the safety use of fosfomycin use in pregnancy.

Homocysteine-lowering therapy and carotid intima-media thickness in renal transplant recipients.

The aim of this study was to document, in hyperhomocysteinemic renal transplant recipients, the effect of vitamin supplementation on carotid intima-media thickness (cIMT). Fifty-six hyperhomocysteinemic stable renal transplant recipients were randomly assigned to either vitamin supplementation (group A) or placebo treatment (group B). All patients underwent high-resolution B mode ultrasound to measure IMT of common carotid arteries before and after 6 months of vitamin supplementation. In group A, cIMT significantly decreased after treatment, whereas no significant changes were observed in group B. In conclusion, our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on an early sign of atherosclerosis in a group of renal transplant recipients.

Plaque debulking for femoro-popliteal occlusions: techniques and results.

Although currently there is a trend of using percutaneous transluminal angioplasty (PTA) and stenting for the treatment of long occlusions of superficial femoral artery, many studies reported comparable results in terms of mid- and long-term patency between PTA and stenting and plaque debulking techniques such as remote endarterectomy, directional atherectomy catheter atherectomy and laser guided atherectomy. A successful debulking procedure is strongly associated with patients comorbidities, length of lesions and clinical presentation. In the last decade many new devices have been proposed to improve debulking results. Despite encouraging data about technical feasibility and limb salvage rate, debulking is still associated with a low rate of long-term primary and secondary patency. However, randomized clinical trials are expected and can hopefully provide conclusions on the effective durability of these procedures.

Muscle fibre conduction velocity and cardiorespiratory response during incremental cycling exercise in young and older individuals with different training status.

We investigated the effect of ageing and training on muscle fibre conduction velocity (MFCV) and cardiorespiratory response during incremental cycling exercise. Eight young (YT; 24+/-5 yrs) and eight older (OT; 64+/-3 yrs) cyclists, together with eight young (YU; 27+/-4 yrs) and eight older (OU; 63+/-2 yrs) untrained individuals underwent to an incremental maximal test on a cycle ergometer. Ventilatory threshold (VT), respiratory compensation point (RCP) and maximal oxygen uptake (VO(2)max) were identified and MFCV recorded from the vastus lateralis muscle using surface electromyography with linear arrays electrodes. In YT MFCV increased with the exercise intensity, reaching a peak of 4.99+/-1.02 [m/s] at VT. Thereafter, and up to VO(2)max, MFCV declined. In YU MFCV showed a similar trend although the peak [4.55+/-0.53m/s] was observed, at 75% of VO(2)max an intensity higher than VT (66% of VO(2)max). In both YT and YU MFCV did not decline until RPC, which occurred at 78% VO(2)max in YU and at 92% VO(2)max (P<0.01) in YT. Differently from young individuals, MFCV in older subjects did not increase with exercise intensity. Moreover, maximal MFCV in OU was significantly lower [3.53+/-0.40 m/s;] than that of YT (P<0.005) and YU (P<0.05). The present study shows that, especially in young individuals, MFCV reflects cardiorespiratory response during incremental dynamic cyclic exercise and hence can be used to investigate motor unit recruitment strategies.