Peripheral arterial disease (PAD) is a prevalent medical condition associated with high mortality and morbidity rates. Despite the high clinical burden, sex-based differences among PAD patients are ...not well defined yet, in contrast to other atherosclerotic diseases. This study aimed to describe sex-based differences in clinical characteristics and outcomes among hospitalized patients affected by PAD. This was a retrospective study evaluating all patients with a diagnosis of PAD admitted to the Emergency Department from 1 December 2013 to 31 December 2021. The primary endpoint of the study was the difference between male and female PAD patients in cumulative occurrence of Major Adverse Cardiovascular Events (MACEs) and Major Adverse Limb Events. A total of 1640 patients were enrolled. Among them, 1103 (67.3%) were males while females were significantly older (median age of 75 years vs. 71 years;
=< 0.001). Females underwent more angioplasty treatments for revascularization than men (29.8% vs. 25.6%;
= 0.04); males were treated with more amputations (19.9% vs. 15.3%;
= 0.012). A trend toward more MALEs and MACEs reported in the male group did not reach statistical significance (OR 1.27 0.99-1.64;
= 0.059) (OR 0.75 0.50-1.11;
= 0.153). However, despite lower extremity PAD severity seeming similar between the two sexes, among these patients males had a higher probability of undergoing lower limb amputations, of cardiovascular death and of myocardial infarction. Among hospitalized patients affected by PAD, even if there was not a sex-based significant difference in the incidence of MALEs and MACEs, adverse clinical outcomes were more common in males.
This study aims to evaluate the prognostic role of serum PCT in older patients with suspect sepsis or infective diagnosis in the Emergency Department (ED) with a particular focus on the clinical ...consequences and characteristics due to frailty status.
This is a observational retrospective study conducted in the ED of a teaching hospital. We identified all consecutive patients aged ≥ 80 years admitted to the ED and subsequently hospitalized for clinical suspicion of infection. Inclusion criteria were: age ≥ 80 years and clinical suspicion of infection; availability of a PCT determination obtained < 24 h since ED access; and Clinical Frailty Scale (CFS) determination. Study endpoints were the diagnostic accuracy of PCT for all-cause in-hospital death, infective diagnosis at discharge, and bloodstream infection. Diagnostic accuracy was calculated via ROC analysis and compared in the patients with severe frailty, measured by CFS > 6, and patients with low or moderate frailty (CFS 1-6). A multivariate analysis was performed to calculate the adjusted odds of raised PCT values for the study endpoints.
In total, 1459 adults ≥ 80 years with a clinical suspicion of infection were included in the study cohort. The median age of the sample was 85 years (82-89), with 718 (49.2%) males. The multivariate models revealed that, after adjusting for significant covariates, the PCT values at ED admission were significantly associated with higher odds of infective diagnosis only in the fit/moderately frail group (Odds Ratio 95% CI 1.04 1.01-1.08,
0.009) and not in very frail patients (Odds Ratio 95% CI 1.02 0.99-1.06,
0.130). Similarly, PCT values were significantly associated with higher odds of in-hospital death in the fit/moderately frail group (Odds Ratio 95% CI 1.01 1.00-1.02,
0.047), but not in the very frail ones (Odds Ratio 95% CI 1.00 0.98-1.02,
0.948). Conversely, the PCT values were confirmed to be a good independent predictor of bloodstream infection in both the fit/moderately frail group (Odds Ratio 95% CI 1.06 1.04-1.08,
< 0.001) and the very frail group (Odds Ratio 95% CI 1.05 1.03-1.07,
< 0.001).
The PCT values at ED admission do not predict infective diagnosis, nor are associated with higher odds of in-hospital death. Still, in frail older adults, the PCT values in ED could be a useful predictor of bloodstream infection.
Background
Ursodeoxycholic acid (UDCA) has been recently proposed as a modulator of angiotensin‐converting enzyme 2 (ACE2) receptor expression, with potential effects on COVID‐19.
Aim and Study ...Design
We retrospectively evaluated the clinical course and outcome of subjects taking UDCA admitted to the hospital for COVID‐19 compared with matched infected subjects. Differences regarding the severity and outcome of the disease between treated and non‐treated subjects were assessed. The Kaplan–Meier survival analysis and log‐rank test were used to evaluate the effect of UDCA on all‐cause intra‐hospital mortality.
Results
Among 6444 subjects with confirmed COVID‐19 admitted to the emergency department (ED) from 1 March 2020 to 31 December 2022, 109 subjects were taking UDCA. After matching 629 subjects were included in the study: 521 in the no UDCA group and 108 in the UDCA group. In our matched cohort, 144 subjects (22.9%) died, 118 (22.6%) in the no‐UDCA group and 26 (24.1%) in the UDCA group. The Kaplan–Meier analysis showed no significant difference in survival between groups. In univariate regression analysis, the presence of pneumonia, National Early Warning Score (NEWS) score, and Charlson Comorbidity Index (CCI) were significant independent predictors of death. At multivariate Cox regression analysis, age, NEWS, pneumonia and CCI index were confirmed significant independent predictors of death. UDCA treatment was not a predictor of survival both in univariate and multivariate regressions.
Conclusions
UDCA treatment does not appear to have significant effects on the outcome of COVID‐19. Specially designed prospective studies are needed to evaluate efficacy in preventing infection and severe disease.
This study aims to analyze the clinical characteristics, demographic features, and injury circumstances of patients admitted to the Emergency Department (ED) at Fondazione Policlinico Universitario ...A. Gemelli (IRCCS) in Rome, Italy, due to bicycle accidents.
Data on clinical characteristics, accident timing, injury circumstances, and helmet use were collected for ED patients involved in bicycle accidents from January 2019 to December 2022. Subsequently, Abbreviated Injury Scale codes of all diagnoses were recorded and the Injury Severity Score was calculated.
Over the study period, 763 patients were admitted to the ED following bicycle accidents, with a 0.3 % fatality rate and a 30.4 % frequency of multitrauma. Multivariate analysis revealed that collisions with other vehicles increased trauma severity and the risk of ICU admission. Conversely, helmet use was associated with reduced severity of head trauma and a lower likelihood of ICU admission. Notably, toxicological investigations were not conducted for any ED-admitted patients.
Although a low mortality rate and a low incidence of multi-trauma have been shown in comparison to other nations, it is necessary to adopt prevention strategies like safety devices, more cycle paths, and better infrastructures on the one hand, and stricter laws on the other. It is essential to require toxicological testing in Italy for all accidents involving this means of transport, and to make helmet use compulsory for all ages.
Background:
Regorafenib (REG) is an oral multikinase inhibitor used in colorectal cancer, gastrointestinal stromal tumour and hepatocellular carcinoma. Several adverse events (AEs) are commonly ...reported during REG administration, and strategies for managing AEs in everyday clinical practice include supportive care, dose modifications and, when necessary, treatment withdrawal. We performed a systematic review and meta-analysis to assess the schedule treatment modifications of REG associated with AEs across randomized controlled clinical trials (RCTs).
Methods:
Eligible studies included RCTs assessing standard dose REG versus placebo. Outcomes of interest included: AE-related permanent discontinuation, dose interruptions and dose reductions.
Results:
We retrieved all the relevant RCTs through PubMed/Med, Cochrane library and EMBASE: 7 eligible studies involving a total of 2099 patients (Regorafenib: 1362; placebo: 737) were included in our analysis. The use of REG was associated with higher incidence and risk of all outcomes of interest when compared with placebo. The incidences of permanent discontinuation, dose interruptions and dose reductions in patients receiving REG were 9.7%, 57.2% and 47%, respectively, versus 3.3%, 16.7% and 7.7% of placebo group; compared with placebo, the summary relative risks (RRs) of permanent discontinuation, dose interruptions and dose reductions in REG arm were 2.80 (95% CI 1.85–4.22), 3.21 (95% CI 2.59–3.99) and 6.02 (95% CI 3.28–11.03), respectively.
Conclusions:
Treatment with REG at the standard dose of 160 mg is associated with a significant increase in AE-related permanent discontinuation, dose interruptions and dose reductions. Prompt identification and management of AEs seem mandatory to obtain maximal benefit from REG treatment. In the current landscape, dose personalization of REG may have the potential to improve quality of life, minimize treatment discontinuation and maximize patient outcomes.
Since the introduction of cisplatin in cancer therapy, metal complexes and organometallic compounds have been gaining growing importance in oncology.
The impressive clinical effectiveness of ...cisplatin is limited by significant side effects and the emergence of drug resistance. Thus, novel classic and unconventional Pt
II and Pt
IV complexes have been introduced in therapy or are presently in advanced clinical trials.
Moreover, innovative non-platinum metal-based antitumor agents, whose activity does not rely on direct DNA damage and may involve proteins and enzymes, have been developed.
Gold and tin derivatives are enjoying an increasing interest and appear very promising as potential drug candidates.
Asbestos causes malignant transformation of primary human mesothelial cells (HM), leading to mesothelioma. The mechanisms of asbestos carcinogenesis remain enigmatic, as exposure to asbestos induces ...HM death. However, some asbestos-exposed HM escape cell death, accumulate DNA damage, and may become transformed. We previously demonstrated that, upon asbestos exposure, HM and reactive macrophages releases the high mobility group box 1 (HMGB1) protein that becomes detectable in the tissues near asbestos deposits where HMGB1 triggers chronic inflammation. HMGB1 is also detectable in the sera of asbestos-exposed individuals and mice. Searching for additional biomarkers, we found higher levels of the autophagy marker ATG5 in sera from asbestos-exposed individuals compared to unexposed controls. As we investigated the mechanisms underlying this finding, we discovered that the release of HMGB1 upon asbestos exposure promoted autophagy, allowing a higher fraction of HM to survive asbestos exposure. HMGB1 silencing inhibited autophagy and increased asbestos-induced HM death, thereby decreasing asbestos-induced HM transformation. We demonstrate that autophagy was induced by the cytoplasmic and extracellular fractions of HMGB1 via the engagement of the RAGE receptor and Beclin 1 pathway, while nuclear HMGB1 did not participate in this process. We validated our findings in a novel unique mesothelial conditional HMGB1-knockout (HMGB1-cKO) mouse model. Compared to HMGB1 wild-type mice, mesothelial cells from HMGB1-cKO mice showed significantly reduced autophagy and increased cell death. Autophagy inhibitors chloroquine and desmethylclomipramine increased cell death and reduced asbestos-driven foci formation. In summary, HMGB1 released upon asbestos exposure induces autophagy, promoting HM survival and malignant transformation.
Abstract Pharmacokinetic studies of daptomycin in septic patients indicate that pharmacokinetic parameters may be altered. The purpose of this clinical investigation is to determine the ...pharmacokinetics of daptomycin in a population of hospitalized patients with clinically significant gram-positive infections and receiving daptomycin. Daptomycin was measured using an isocratic HPLC technique. Thirty-five patients suffering from gram-positive severe infections and receiving daptomycin were included in the study. Patients were divided into two groups, depending on the dose of daptomycin received: group A, including 24 patients receiving 6 mg/kg/day daptomycin and group B, 11 patients receiving 8 mg/kg/day. Patients receiving a daptomycin dosage of 8 mg/kg/day had significantly higher values of mean Cmax and AUC0–24 . Each group was further divided into three subgroups, according to the creatinine clearance (CrCl) values: (1) patients with a CrCl >80 ml/min, (2) patients with CrCl ranging between 80 and 40 ml/min, and (3) patients with CrCl <40 ml/min. Compared to patients with normal renal function, those with CrCl <40 ml/min had higher mean values of minimum concentration ( Cmin ) ( p < 0.001), AUC0–24 ( p = 0.03), and prolonged plasma half-time ( p < 0.001). These differences were present both in patients receiving 6 and those with 8 mg/kg/day. However, in each of the three subgroups with different degrees of renal function a marked variability of pharmacokinetics parameters was observed. The factors associated with increased mortality were an infection acquired in the ICU, hypoalbuminemia, and AUC/MIC <666. The marked variability that characterizes daptomycin pharmacokinetics in these patients suggest the monitoring of the main pharmacokinetic parameters in this clinical setting.
Hemorrhoidal disease (HD) is defined as the symptomatic enlargement and/or distal displacement of anal cushions and is one of the most common proctological diseases. Sclerotherapy (ST) with 3% ...polidocanol foam induces an inflammatory reaction with sclerosis of the submucosal tissue and consequent suspension of the hemorrhoidal tissue. The aim of this study was to evaluate the short-term effectiveness and safety of ST with 3% polidocanol foam for the treatment of symptomatic second- and third-degree HD.
A total of 66 patients with symptomatic second- and third-degree HD underwent a single ST session between March 2017 and July 2018. A visual analog scale score was used to assess post-operative pain and patient satisfaction. The symptoms severity and anal continence were investigated through the Hemorrhoid Severity Score (HSS) and Vaizey score, respectively, at baseline, at 4 weeks and after 1 year.
Fifty-seven out of 66 patients were male (86.3%), and the mean age was 52 (29-75; SD ± 12) years. The mean operative time was 4.5 (2-6; SD ± 1.23) minutes. No intraoperative complications and no drug-related side effects occurred. The overall success rate was 78.8% (52/66 patients) after a single ST session and 86% after two ST sessions (57/66 patients). The mean treatment effect, obtained comparing preoperative and 12 months symptom scores in each patient, showed a median change of 8 (p < 0.001). All patients resumed their normal daily activities the day after the procedures.
ST with 3% polidocanol foam is a safe, cost-effective and repeatable conservative treatment.
PDF
