Enhancing the light yield of He:CF 4 based gaseous detector.

The CYGNO experiment aims to build a large ( O ( 10 ) m 3 ) directional detector for rare event searches, such as nuclear recoils (NRs) induced by dark matter (DM), such as weakly interactive massive particles (WIMPs). The detector concept comprises a time projection chamber (TPC), filled with a He:CF 4 60/40 scintillating gas mixture at room temperature and atmospheric pressure, equipped with an amplification stage made of a stack of three gas electron multipliers (GEMs) which are coupled to an optical readout. The latter consists in scientific CMOS (sCMOS) cameras and photomultipliers tubes (PMTs). The maximisation of the light yield of the amplification stage plays a major role in the determination of the energy threshold of the experiment. In this paper, we simulate the effect of the addition of a strong electric field below the last GEM plane on the GEM field structure and we experimentally test it by means of a 10 × 10 cm 2 readout area prototype. The experimental measurements analyse stacks of different GEMs and helium concentrations in the gas mixture combined with this extra electric field, studying their performances in terms of light yield, energy resolution and intrinsic diffusion. It is found that the use of this additional electric field permits large light yield increases without degrading intrinsic characteristics of the amplification stage with respect to the regular use of GEMs.

The Next Frontier for Colorectal Cancer Screening: Blood-Based Tests.

Colorectal cancer is associated with substantial morbidity and mortality worldwide. Detection of early colorectal cancer is possible through approved screening tests but overall adherence is quite low. Implementation of effective noninvasive options could increase screening uptake and prevent a significant number of deaths. Noninvasive early cancer detection can potentially be achieved using a liquid biopsy. In this issue of Cancer Research, Cao and colleagues report on a novel multidimensional fragmentomics assay, named FRAGTECT, for colorectal cancer detection in circulating cell-free DNA with promising results. See related article by Cao et al., p. 3286.

A Microbial Phenomics Approach to Determine Metabolic Signatures to Enhance Seabream Sparus aurata Traceability, Differentiating between Wild-Caught and Farmed.

BACKGROUND: The need for efficient and simplified techniques for seafood traceability is growing. This study proposes the Biolog EcoPlate assay as an innovative method for assessing wild and farmed Sparus aurata traceability, offering advantages over other molecular techniques in terms of technical simplicity. METHODS: The Biolog EcoPlate assay, known for its high-throughput capabilities in microbial ecology, was utilized to evaluate the functional diversity of microbial communities from various organs of S. aurata (seabream) from the Mediterranean area. Samples were taken from the anterior and posterior gut, cloaca swabs and gills to distinguish between farmed and wild-caught individuals. The analysis focused on color development in OmniLog Units for specific carbon sources at 48 h. RESULTS: Gills provided the most accurate clusterization of sample origin. The assay monitored the development of color for carbon sources such as α-cyclodextrin, D-cellobiose, glycogen, α-D-lactose, L-threonine and L-phenylalanine. A mock experiment using principal component analysis (PCA) successfully identified the origin of a blind sample. Shannon and Simpson indexes were used to statistically assess the diversity, reflecting the clusterization of different organ samples; Conclusions: The Biolog EcoPlate assay proves to be a quick, cost-effective method for discriminate S. aurata traceability (wild vs. farmed), demonstrating reliable reproducibility and effective differentiation between farmed and wild-caught seabream.

Mammography classification with multi-view deep learning techniques: Investigating graph and transformer-based architectures.

The potential and promise of deep learning systems to provide an independent assessment and relieve radiologists' burden in screening mammography have been recognized in several studies. However, the low cancer prevalence, the need to process high-resolution images, and the need to combine information from multiple views and scales still pose technical challenges. Multi-view architectures that combine information from the four mammographic views to produce an exam-level classification score are a promising approach to the automated processing of screening mammography. However, training such architectures from exam-level labels, without relying on pixel-level supervision, requires very large datasets and may result in suboptimal accuracy. Emerging architectures such as Visual Transformers (ViT) and graph-based architectures can potentially integrate ipsi-lateral and contra-lateral breast views better than traditional convolutional neural networks, thanks to their stronger ability of modeling long-range dependencies. In this paper, we extensively evaluate novel transformer-based and graph-based architectures against state-of-the-art multi-view convolutional neural networks, trained in a weakly-supervised setting on a middle-scale dataset, both in terms of performance and interpretability. Extensive experiments on the CSAW dataset suggest that, while transformer-based architecture outperform other architectures, different inductive biases lead to complementary strengths and weaknesses, as each architecture is sensitive to different signs and mammographic features. Hence, an ensemble of different architectures should be preferred over a winner-takes-all approach to achieve more accurate and robust results. Overall, the findings highlight the potential of a wide range of multi-view architectures for breast cancer classification, even in datasets of relatively modest size, although the detection of small lesions remains challenging without pixel-wise supervision or ad-hoc networks.

First line therapy in stage IV BRAF mutated colorectal cancer.

Introduction: The molecular profile of colorectal cancer (CRC) plays a crucial role in understanding patient prognosis and treatment response. Within CRC, a distinct subgroup can be identified by the presence of the BRAF V600E mutation. This specific mutation, classified as Class I of BRAF mutations, is known to be associated with a poor prognosis and resistance to standard therapy. To determine the most effective treatment approach for this specific subgroup of CRC, we conducted a network meta-analysis (NMA) to compare various pharmacological interventions and evaluate their relative effectiveness in BRAF-mutated CRCs. Materials and methods: On July 31, 2023, we conducted a systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Embase. The inclusion criteria were as follows: 1) reporting of outcomes in patients with BRAF-mutated CRC who underwent first-line chemotherapy; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. The data were combined using HRs for overall and progression-free survival (OS and PFS) using random-effects models. NMA was performed under the Bayesian framework, utilizing the GeMTC package. The relative rankings of the treatments were determined using SUCRA scores. Results: A total of 16 studies were included. When compared to standard chemotherapy (CT) doublets (such as FOLFOX or FOLFIRI), none of the comparison arms demonstrated a gain in OS. CT doublet + bevacizumab did not show significant superiority over either CT doublet alone or 5FU/capecitabine + bevacizumab. FOLFOXIRI and FOLFOXIRI + bevacizumab did not show superiority over any other treatment schedule that was compared. CT doublets + bevacizumab had the highest SUCRA score (0.87), followed by single-agent fluoropyrimidines + bevacizumab (0.61), and FOLFOXIRI (0.56). Regarding PFS, no regimen was found to be superior to the combination of CT doublet plus bevacizumab. However, FOLFOXIRI + bevacizumab + atezolizumab showed a tendency towards better results (HR = 0.26, 95 % CI 0.05-1.1). Conclusions: Our review suggests that a CT doublet with bevacizumab is the most favorable option for OS. However, a reasonable alternative could be a triplet CT without bevacizumab.

Ultrasound Imaging in Knee Osteoarthritis: Current Role, Recent Advancements, and Future Perspectives.

While conventional radiography and MRI have a well-established role in the assessment of patients with knee osteoarthritis, ultrasound is considered a complementary and additional tool. Moreover, the actual usefulness of ultrasound is still a matter of debate in knee osteoarthritis assessment. Despite that, ultrasound offers several advantages and interesting aspects for both current clinical practice and future perspectives. Ultrasound is potentially a helpful tool in the detection of anomalies such as cartilage degradation, osteophytes, and synovitis in cases of knee osteoarthritis. Furthermore, local diagnostic and minimally invasive therapeutic operations pertaining to knee osteoarthritis can be safely guided by real-time ultrasound imaging. We are constantly observing a growing knowledge and awareness among radiologists and other physicians, concerning ultrasound imaging. Ultrasound studies can be extremely useful to track the response to various therapies. For this specific aim, tele-ultrasonography may constitute an easy tool aiding precise and repeated follow-up controls. Moreover, raw radio-frequency data from US backscattering signals contain more information than B-mode imaging. This paves the way for quantitative in-depth analyses of cartilage, bone, and other articular structures. Overall, ultrasound technologies and their rapid evolution have the potential to make a difference at both the research and clinical levels. This narrative review article describes the potential of such technologies and their possible future implications.

Ingestion of chitosan-starch blends: Effect on the survival of supralittoral amphipods.

Sandy beach ecosystems are particularly affected by plastic pollution. Supralittoral amphipods are important components of the food web in sandy beaches and their ability to ingest microplastics and bioplastics has been assessed. Chitosan, a polysaccharide obtained by deacetylation of chitin, the second most abundant polymer in the world, represents an interesting component to produce novel bioplastics in combination with other biopolymers like starch. Here, the possibility of ingesting chitosan-starch blends and the possible effects on the amphipod Talitrus saltator were investigated. Groups of adult individuals were fed with sheets containing mixtures of chitosan and starch in different percentages for 7 and 14 days. The results showed that chitosan ingestion is dependent on the percentage of starch present in the mixture. Moreover, FTIR analyses of both sheets and faecal pellets after consumption show that chitosan is not digested. Furthermore, the survival rate of amphipods fed with a mixture of chitosan and starch decreases after one week compared to the control groups (100 % starch and paper), and drops drastically to 0 % after two weeks the experiment began. In addition, consumption of 100 % chitosan is negligible. Therefore, the results of the experimental observations evidenced that chitosan is avoided as food resource and its consumption significantly affects the survival capacity of T. saltator. It is emphasized that the release of mixtures of chitosan and starch into the marine environment appears to be dangerous for littoral amphipods.

Double agents in immunotherapy: Unmasking the role of antibody drug conjugates in immune checkpoint targeting.

Antibody-drug conjugates (ADCs) have high specificity with lesser off-target effects, thus providing improved efficacy over traditional chemotherapies. A total of 14 ADCs have been approved for use against cancer by the US Food and Drug Administration (FDA), with more than 100 ADCs currently in clinical trials. Of particular interest ADCs targeting immune antigens PD-L1, B7-H3, B7-H4 and integrins. Specifically, we describe ADCs in development along with the gene and protein expression of these immune checkpoints across a wide range of cancer types let url = window.clickTag || window.clickTag1 || window.clickTag2 || window.clickTag3 || window.clickTag4 || window.bsClickTAG || window.bsClickTAG1 || window.bsClickTAG2 || window.url || ''; if(typeof url == 'string'){ document.body.dataset['perxceptAdRedirectUrl'] = url;}.

The Discrepancy Between Visual Acuity Decline and Foveal Involvement in Geographic Atrophy.

PURPOSE: To investigate the discrepancy between visual acuity (VA) decline and foveal involvement in geographic atrophy (GA) secondary to nonexudative age-related macular degeneration (AMD), and to explore how early retinal changes impact the progression of visual impairment. DESIGN: Retrospective, longitudinal cohort study. SUBJECTS: This study evaluated 80 eyes from 60 patients (mean age, 74.2 ± 10 years) with progressing non-neovascular AMD. METHODS: Blue-light fundus autofluorescence (FAF) and spectral-domain OCT (SD-OCT) were utilized to monitor GA progression and the onset of foveal involvement. The study analyzed VA changes over an average follow-up of 60 ± 26.4 months, encompassing 785 observations. Mixed-effects models with natural splines assessed the effects of demographic and ocular characteristics on baseline VA and its rate of decline. Survival analyses compared the timing of anatomic changes with the most rapid functional declines, indicated by the highest first derivative of VA trajectories. Discrepancies between visual and anatomic changes were explored using generalized linear mixed-effects models. MAIN OUTCOME MEASURES: Monthly VA changes, onset and impact of foveal involvement, and factors influencing baseline VA and rate of decline. RESULTS: Visual acuity declined consistently by an average of 0.010 logarithm of the minimum angle of resolution (LogMAR) per month (standard error [SE], 0.0003; P < 0.001). The onset of foveal involvement significantly exacerbated this decline, adding an average loss of 0.15 LogMAR (SE, 0.02; P < 0.001). Stabilization of VA typically occurred around 41 months post-foveal involvement. Significant factors associated with worse baseline VA were older age, female gender, unifocal GA morphology, and drusen-associated forms of GA (P < 0.05). The most rapid declines in VA typically occurred about 9 months (interquartile range, 0-27 months) before detectable subfoveal changes. The reticular FAF pattern (27/46 [59%] vs. 2/13 [15%], P = 0.02) and smaller baseline GA lesions (P = 0.01) were associated with faster deterioration preceding visible foveal damage. CONCLUSIONS: This study demonstrates that significant VA loss in GA can precede detectable foveal involvement, suggesting a window for early interventions to slow the progression of visual impairment. Identifying specific GA characteristics and FAF patterns as predictors of rapid VA decline supports the need for personalized treatment strategies to optimize outcomes for patients with nonexudative AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Arthroscopic device with bendable tip for the controlled extrusion of hydrogels on cartilage defects.

Advanced tools for the in situ treatment of articular cartilage lesions are attracting a growing interest in both surgery and bioengineering communities. The interest is particularly high concerning the delivery of cell-laden hydrogels. The tools currently available in the state-of-the-art hardly find an effective compromise between treatment accuracy and invasiveness. This paper presents a novel arthroscopic device provided with a bendable tip for the controlled extrusion of cell-laden hydrogels. The device consists of a handheld extruder and a supply unit that allows the extrusion of hydrogels. The extruder is equipped with a disposable, bendable nitinol tip (diameter: 4 mm, length: 92 mm, maximum bending angle: 90°) that guarantees access to hard-to-reach areas of the joint, which are difficult to get to, with conventional arthroscopic instruments. The tip accommodates a biocompatible polymer tube that is directly connected to the cartridge containing the hydrogel, whose plunger is actuated by a volumetric or pneumatic supply unit (both tested, in this study). Three different chondrocyte-laden hydrogels (RGD-modified Vitrogel®, methacrylated gellan gum, and an alginate-gelatine blend) were considered. First, the performance of the device in terms of resolution in hydrogel delivery was assessed, finding values in the range between 4 and 102 µL, with better performance found for the pneumatic supply unit and no significant differences between straight tip and bent tip conditions. Finite element simulations suggested that the shear stresses and pressure levels generated during the extrusion process were compatible with a safe deposition of the hydrogels. Biological analyses confirmed a high chondrocyte viability over a 7-day period after the extrusion of the three cell-laden hydrogel types, with no differences between the two supply units. The arthroscopic device was finally tested ex vivo by nine orthopedic surgeons on human cadaver knees. The device allowed surgeons to easily deliver hydrogels even in hard-to-reach cartilage areas. The outcomes of a questionnaire completed by the surgeons demonstrated a high usability of the device, with an overall preference for the pneumatic supply unit. Our findings provide evidence supporting the future arthroscopic device translation in pre-clinical and clinical scenarios, dealing with osteoarticular treatments.

Preoperative right ventricular strain as an early predictor of perioperative cardiac failure in patients undergoing mitral surgery: An exploratory study.

Objectives: This study's primary purpose was to demonstrate the correlation of preoperative right ventricular free-wall longitudinal strain (RVFWLS) and pre-/postsurgical variation in strain (delta strain) with the clinical and echocardiographic diagnosis of right ventricular dysfunction. Its secondary purpose was to determine the correlation of RVFWLS and delta strain with length of stay (LOS) in the intensive care unit (ICU), ventilation days, trend of natriuretic peptide test. (NT-proBNP) and lactate in the first 48 h, incidence of acute renal failure, and 28-day mortality. Design: Prospective observational study. Setting: Cardio-thoracic and Vascular Anaesthesia Department and ICU of the University Hospital Integrated Trust of Verona. Participants: Patients scheduled for mitral surgery. Interventions: None. Measurements and Main Results: All clinical and transoesophageal echocardiographic (TEE) parameters were collected at baseline, before surgery (T1) and at admission in the ICU postsurgery (T2). During the postoperative period, the clinical and echocardiographic diagnoses of right, left, or biventricular dysfunction were evaluated. TEE parameters were evaluated by a cardiologist offline. The patients were divided into two subgroups according to the development of any type of ventricular dysfunction. No statistically significant differences emerged between the two groups. According to a logistic regression model, a T1-RVFWLS value of -15% appeared to predict biventricular dysfunction (sensitivity: 100%; specificity: 91.3%). No correlation between T1- or T2-RVFWLS and creatinine, hours of ventilation or ICU LOS was found. Conclusions: Our study introduces a new parameter that could be used in perioperative evaluations to identify patients at risk of postoperative biventricular dysfunction.

Facing an un-met need in lung cancer screening: The never smokers.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide and the second most common cancer in both men and women. In addition to smoking, other risk factors, such as environmental tobacco smoke, air pollution, biomass combustion, radon gas, occupational exposure, lung disease, family history of cancer, geographic variability, and genetic factors, play an essential role in developing LC. Current screening guidelines and eligibility criteria have limited efficacy in identifying LC cases (50 %), as most screening programs primarily target subjects with a smoking history as the leading risk factor. Implementing LC screening programs in people who have never smoked (PNS) can significantly impact cancer-specific survival and early disease detection. However, the available evidence regarding the feasibility and effectiveness of such programs is limited. Therefore, further research on LC screening in PNS is warranted to determine the necessary techniques for accurately identifying individuals who should be included in screening programs.

Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Early initiation of combined therapy in severely immunocompromised patients with COVID-19: a retrospective cohort study.

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1-3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6-17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413-575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138-401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature.

Antibiotic Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections in View of the Newly Developed ß-Lactams: A Narrative Review of the Existing Evidence.

It is estimated that antimicrobial resistance (AMR) is responsible for nearly 5 million human deaths worldwide each year and will reach 10 million by 2050. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. Among the antibiotics under consideration, Sulbactam/durlobactam seems to be the best candidate to replace current back-bone agents. Cefiderocol could play a pivotal role within combination therapy regimens. Due to toxicity and the pharmacokinetics/pharmacodynamics (PK/PD) limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the efficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and "old" drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with improved lung activity, as well as on the iv rifabutin formulation. In this narrative review, we focused the antibiotic treatment of CRAB infections in view of newly developed ß-lactam agents (NBLs).

Usability Assessment of Technologies for Remote Monitoring of Knee Osteoarthritis.

Goal: To evaluate the usability of different technologies designed for a remote assessment of knee osteoarthritis. Methods: We recruited eleven patients affected by mild or moderate knee osteoarthritis, eleven caregivers, and eleven clinicians to assess the following technologies: a wristband for monitoring physical activity, an examination chair for measuring leg extension, a thermal camera for acquiring skin thermographic data, a force balance for measuring center of pressure, an ultrasound imaging system for remote echographic acquisition, a mobile app, and a clinical portal software. Specific questionnaires scoring usability were filled out by patients, caregivers and clinicians. Results: The questionnaires highlighted a good level of usability and user-friendliness for all the technologies, obtaining an average score of 8.7 provided by the patients, 8.8 by the caregivers, and 8.5 by the clinicians, on a scale ranging from 0 to 10. Such average scores were calculated by putting together the scores obtained for the single technologies under evaluation and averaging them. Conclusions: This study demonstrates a high level of acceptability for the tested portable technologies designed for a potentially remote and frequent assessment of knee osteoarthritis.

Persistence of SARS-CoV-2 infection and viral intra- and inter-host evolution in COVID-19 hospitalized patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) persistence in COVID-19 patients could play a key role in the emergence of variants of concern. The rapid intra-host evolution of SARS-CoV-2 may result in an increased transmissibility, immune and therapeutic escape which could be a direct consequence of COVID-19 epidemic currents. In this context, a longitudinal retrospective study on eight consecutive COVID-19 patients with persistent SARS-CoV-2 infection, from January 2022 to March 2023, was conducted. To characterize the intra- and inter-host viral evolution, whole genome sequencing and phylogenetic analysis were performed on nasopharyngeal samples collected at different time points. Phylogenetic reconstruction revealed an accelerated SARS-CoV-2 intra-host evolution and emergence of antigenically divergent variants. The Bayesian inference and principal coordinate analysis analysis showed a host-based genomic structuring among antigenically divergent variants, that might reflect the positive effect of containment practices, within the critical hospital area. All longitudinal antigenically divergent isolates shared a wide range of amino acidic (aa) changes, particularly in the Spike (S) glycoprotein, that increased viral transmissibility (K417N, S477N, N501Y and Q498R), enhanced infectivity (R346T, S373P, R408S, T478K, Q498R, Y505H, D614G, H655Y, N679K and P681H), caused host immune escape (S371L, S375F, T376A, K417N, and K444T/R) and displayed partial or complete resistance to treatments (G339D, R346K/T, S371F/L, S375F, T376A, D405N, N440K, G446S, N460K, E484A, F486V, Q493R, G496S and Q498R). These results suggest that multiple novel variants which emerge in the patient during persistent infection, might spread to another individual and continue to evolve. A pro-active genomic surveillance of persistent SARS-CoV-2 infected patients is recommended to identify genetically divergent lineages before their diffusion.

Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: A multi-centre clinical experience.

BACKGROUND: Severe infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been reported increasingly over the past few years. Many in-vivo and in-vitro studies have suggested a possible role of intravenous fosfomycin for the treatment of CRAB infections. METHODS: This multi-centre, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively to four hospitals in Italy from December 2017 to December 2022. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. RESULTS: One hundred and two patients with severe infections caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled in this study. Ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteraemia in 22% of patients, and central-venous-catheter-related infection in 16% of patients. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48) or ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia and a colistin-containing regimen were independently associated with 30-day mortality, whereas adequate source control of infection, early 24-h active in-vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteraemia were independently associated with clinical failure. Conversely, adequate source control of infection, a cefiderocol-containing regimen, and early 24-h active in-vitro therapy were associated with clinical success. CONCLUSIONS: Different antibiotic regimens containing fosfomycin in combination can be used for treatment of severe infections caused by CRAB.

Incidence and Prevalence of Dementia: A 2015-2020 Population-Based Study in the Campania Region of Italy.

OBJECTIVE: The aims of this study were to provide population-based estimates of prevalence and incidence of any dementia and Alzheimer's dementia (AD) in the Campania region (South Italy) and to validate towards a clinical registry. METHODS: This was a population-based study, using routinely collected healthcare data of individuals living in the Campania region (South Italy) from 2015 to 2020. We included individuals aged ≥65 years alive at the prevalence day (January 1, 2021) who had at least one administrative record for dementia and/or AD from 2015 to 2020. Age-and sex-standardised prevalence rates were calculated using direct standardisation method (European population in 2020 as the reference population). To estimate the incidence, we tested three possible algorithms, which differed for the duration of the time interval between study baseline (January 1, 2015) and index date (first record for dementia and/or AD in administrative databases). We employed a clinical database for the validation of our algorithms towards neuropsychological test results. RESULTS: Among individuals aged over 65 years, 80,392 had dementia, of which 35,748 had AD. The age- and sex-standardised prevalence rates per 1,000 individuals for any dementia and AD were 77.64 (95% confidence interval [CI] = 77.57; 77.68) and 34.05 (95% CI = 34.01; 34.09), respectively. There were 82.10 incident cases of any dementia per 100,000 per year (0.79 sensitivity and 0.62 specificity) and 59.89 incident cases of AD per 100,000 per year (0.80 sensitivity and 0.59 specificity). The capture-recapture method showed a very low number of undetected cases (1.7% for any dementia and 3.0% for AD). Our algorithms showed acceptable performance with the area under the curve ranging from 0.59 to 0.72 and a double likelihood ratio of correctly identifying individuals above and below mini-mental status examination (MMSE) standard cut-offs (24 and 26). CONCLUSIONS: Prevalence and incidence of any dementia and AD in the Campania region (South Italy) from 2015 to 2020 are in line with previous estimates from other countries. Our algorithm, integrating administrative and clinical data, holds potential for assessing dementia's epidemiological burden, identifying risk factors, planning healthcare access, and developing prevention strategies.