A recent article highlighted the hepatic benefits of intermittent fasting, particularly during Ramadan. However, the rising use of glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (RAs) is altering public behavior, leading to decreased interest in diet and exercise. With a focus on hepatic health, we analyzed global search trends using Google Trends™ data from January 1, 2022 to December 31, 2024, focusing on the keywords "fasting", "intermittent fasting", "diet", "nutrition", "liver", Semaglutide ("Ozempic"™, the most widely known GLP-1 RA) and Tirzepatide ("Mounjaro"™, a newer dual GLP-1 and GIP RA). Search interest for "intermittent fasting" and "diet" showed a significant decline over time (Spearman's rho: -0.582 and -0.605, respectively, both P < 0.001), while interest in "fasting" and "nutrition" remained stable. Search interest for Semaglutide, Tirzepatide, "fasting and liver", "diet and liver" and Semaglutide and "liver" increased (Spearman's rho: +0.914, +0.936, +0.369, +0.297 and +0.808, respectively, all P < 0.001). These findings suggest a trend of shifting away from traditional dieting toward broader health concerns, likely influenced by the increasing use of GLP-1/GIP RAs.

A carotid web (CaW) is a non-atheromatous, shelf-like intraluminal projection, commonly affecting the internal carotid artery. It can be associated with embolic stroke, particularly in younger patients without traditional stroke risk factors. The natural history of CaW is not well-established. Several studies have reported on outcomes after interventional and medical therapy with variable results. To synthesize the literature and report the clinical characteristics and management outcomes of patients with CaWs. A systematic literature review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. 33 studies comprising 737 patients (mean age 50.2 years, female 59.4%, African American 65%) with 835 CaWs were included. The majority of the CaWs were symptomatic (72.9%) with a mean National Institutes of Health Stroke Scale (NIHSS) admission score of 7.5. Atherosclerotic plaques and intramural thrombi were each present in 33% of patients. The classic atherosclerotic and stroke risk factors were prevalent as follows: hypertension 37.8%, diabetes 14.6%, smoking 21.7%, dyslipidemia 16.7%. In total, treatment outcomes were available for 376 patients with 448 symptomatic CaWs (227 medical, 221 interventional). Medical therapy consisted of antiplatelet or anticoagulation medications, while interventional treatment included carotid artery stenting (CAS), carotid endarterectomy (CEA), and internal carotid artery resection and primary anastomosis (ICRA). The interventional group was associated with a significantly lower risk of recurrent ischemic events compared with the medical group (interventional 0%, medical 36.1%; OR 14.18, 95% CI 3.17 to 63.46, P=0.001) over a mean follow-up of 21.2 months. The odds ratio of cerebral ischemic event recurrence was correlated with the need for thrombectomy at the first event and history of dyslipidemia. Most CaWs were found during stroke work-up. Prevention of secondary ischemic events was superior in the interventional management group (CAS, CEA, ICRA) compared with the medical management group.

This phase 2a study evaluated pharmacokinetics and safety of ceftazidime-avibactam (CAZ/AVI; combination dosed as fixed 4:1 ratio) in neonates and young infants with suspected/confirmed infections due to Gram-negative pathogens requiring intravenous antibiotics. Hospitalized neonates and infants (gestational age ≥ 26 weeks to < 3 months), enrolled sequentially into 3 age cohorts, received CAZ/AVI single dose (Part A) or multiple dose every 8h (Part B) by 2-h intravenous infusions. Infants > 28 days (Cohort 1) received CAZ/AVI 37.5mg/kg/dose (CAZ 30mg/kg and AVI 7.5mg/kg). Full-term neonates ≤ 28 days (Cohort 2) and preterm neonates ≤ 28 days (Cohort 3) received 25mg/kg/dose (CAZ 20mg/kg and AVI 5mg/kg). Pharmacokinetics, safety, and clinical and microbiological outcomes (Part B only) were assessed descriptively. Forty-six patients received CAZ/AVI, 25 in Part A and 21 in Part B. Sepsis (39.1%) and urinary tract infection (15.2%) were the predominant diagnoses. Observed drug plasma-concentration time profiles were generally similar across cohorts. Overall, 23 patients (50%) had ≥ 1 adverse event (AE), 8 patients (17.4%) had ≥ 1 serious AE (SAE), and 2 patients (4.3%) died; no SAE or death was treatment related. In Part B, ≥ 80% of patients had favorable clinical and microbiological responses. Plasma exposures after single and multiple CAZ/AVI doses in neonates and young infants < 3 months old (37.5 [30/7.5] mg/kg/dose for > 28 days; 25 [20/5] mg/kg/dose for ≤ 28 days) were similar to approved doses for older children. The safety profile of CAZ/AVI was as expected based on previous observations. Study funded by Pfizer. Trial registration: NCT04126031.

Invasive meningococcal disease (IMD) remains a major public health challenge due to its rapid progression, which may lead to severe sequelae or death in children and adolescents. Published data on IMD sequelae are limited in Greece and many EU countries. In the present study, patients under 16 years of age with IMD were retrospectively identified from the files of the Hellenic National Meningitis Reference Laboratory (HNML) from 2010-2020, and their medical records were tracked from the corresponding hospitals. Demographic, clinical, and microbiological data were recorded for each case. A total of 161 patients younger than 16 years of age admitted to nine hospitals across the country were identified. Of those, 91 (56.5%) records were found. The patients' median age was 36 months (range 22 days to 16 years old); 37.4% presented with meningitis, 36.2% with both septicemia and meningitis, and 26.4% only with septicemia. The mortality rate was 5.5% and was significantly associated with septicemia, abnormal platelet count at presentation, ICU admission, and coagulation disorders, while sequelae were detected in 16.9% of patients upon discharge. Neisseria meningitidis serogroup B (MenB) was the most predominant (77%); of these, 269 cc was identified (36.8%). This is the first study on unfavorable sequelae and mortality due to IMD performed in Greece.

The use of antiplatelet agents is essential in percutaneous coronary interventions, both periprocedurally and in the post-interventional period. Procedural antiplatelet therapy, aiming to limit ischemic complications, is mostly administered with oral agents, including aspirin and P2Y12 inhibitors. However, there are several limitations in the use of oral P2Y12 inhibitors, including their difficult administration in patients presenting with cardiogenic shock and their relatively slower onset of action, leaving a significant period of the procedure with a suboptimal antiplatelet effect. These pitfalls could be avoided with the use of cangrelor, the only available intravenous P2Y12 inhibitor, which has a rapid onset and offset antiplatelet effect, as well as a favorable pharmacological profile. The use of cangrelor has been increasing in recent years, with several studies aiming to determine what the optimal patient phenotype to receive such treatment ultimately is and how its use could be adjunctive to oral P2Y12 inhibitors. Therefore, the aim of this review is to provide an overview of the pharmacological profile of cangrelor and an update regarding the clinical evidence supporting its use, as well as to discuss the optimal patient phenotype, related clinical algorithms, and future implications for larger implementation of this agent into everyday clinical practice.

BackgroundTo our knowledge, limited information is available about the differences in the characteristics of rheumatoid factor (RF)-negative polyarticular juvenile idiopathic arthritis (JIA) throughout the world. This study was aimed to compare the demographic and clinical features of patients with RF-negative polyarthritis across the world.MethodsPatients were part of a multinational sample included in a study aimed to investigate the prevalence of disease categories, treatment regimens, and disease status in patients from different geographical areas (EPOCA Study). All patients underwent a retrospective assessment, based on the review of clinical chart, and a cross-sectional evaluation, which included assessment of physician- and parent-reported outcomes and collection of ongoing medications.ResultsAmong the 9081 patients enrolled in the EPOCA study, 2141 patients (23.6%) with RF-negative polyarthritis were included in the present analysis. The prevalence of RF-negative polyarthritis was highest in North America and lowest in Southeast Asia (12.7%). The age at disease onset was lower in Northern and Southern Europe, where the highest prevalence of uveitis was found. Uveitis was rare in Southeast Asia, Africa & Middle East and Latin America. Patients from Eastern Europe, Latin America and Africa and Middle East presented with the highest prevalence of active joints at the visit. The combination of early onset, ANA positivity, and uveitis was observed mainly in Southern Europe (39%).ConclusionsOur results confirm the wide heterogeneity of the clinical presentation and outcome of children with RF-negative polyarticular JIA throughout the world. In particular, relevant differences in the onset age were observed across geographic areas. The group of children with early onset polyarthritis, ANA positivity, and risk of uveitis is remarkably frequent in Southern Europe.

Haemophilia A and B is a disease consistently associated with reduced bone mineral density, both in adults and children. However, whether haemophilia also increases fracture risk has not yet been proven. This systematic review and meta-analysis aimed to synthesize and analyse studies evaluating the association between haemophilia and fracture risk. Comprehensive research was conducted in three electronic databases (PubMed, CENTRAL, and Scopus) up to 30 June 2024. Data were expressed as relative risk (RR) with 95% confidence intervals (CI). The I2 index was employed to evaluate heterogeneity. Fourteen studies were included in the qualitative and four in the quantitative analysis (participants: 13,221, publication years: 2007-2022). Regarding design, five studies were retrospective cohorts, two were case-control, and seven were cross-sectional. Fracture prevalence in people with haemophilia (PWH) was 5.7%, ranging from 1.4% to 27.7% (data from 14 studies), compared with 0.9% in the control group, ranging from 0% to 5.1% (data from 3 studies). In comparison with healthy men, PWH demonstrated increased fracture risk (RR 4.56, 95% CI 1.28-16.25, p = 0.019, I2 90.74%). However, there was insufficient data to categorize fractures according to their location and to compare fracture incidence between patients receiving prophylaxis and those on-demand treatment, as well as according to the type or severity of haemophilia. This is the first meta-analysis showing a more than 4-fold increased fracture risk in PWH compared with the general population.