Search

Background: There is ongoing discussion around the optimal course of treatment for metastatic colorectal cancer (mCRC) following the second line. Trifluridine/tipiracil (T) and regorafenib (R) have been the mainstay of therapy in this situation, as they both increased overall survival (OS) in comparison to a placebo. Despite the paucity of evidence, therapy rechallenge is also recognized as an option for practical use. In the third-line scenario of mCRC, we planned to investigate the survival outcomes using (T) and (R), both with and without prior rechallenge treatment. Materials and methods: Between 2012 and 2023, we examined the medical records of 1156 patients with refractory mCRC who were enrolled in the multicenter retrospective ReTrITA study. We then separated the patients into two cohorts based on the rechallenge therapy that was given before regorafenib and/or trifluridine/tipiracil at 17 Italian centres. Results: A total of 981 patients underwent T and/or R therapy, while 175 patients had therapy rechallenge before T and/or R. The median overall survival (mOS) for patients treated with T/R and R/T sequences in the rechallenge therapy cohort was 14.5 months and 17.6 months, respectively (p = 0.1955). A statistically significant survival benefit was observed in patients who received monotheraphy with R (mOS: 6 months) compared to the T group (mOS: 4.2 months) (p = 0.0332). In the same cohort, a median progression-free survival (mPFS) benefit was demonstrated in favour of the R/T group (11.3 months) vs. 9 months of the reverse sequence (p = 0.4004). In the no-rechallenge cohort, the mOS was statistically longer in the R/T sequence than in the T/R sequence (16.2 months vs. 12.3 months, respectively; p = 0.0014). In terms of the mPFS, we saw the same significant result for the adoption of R/T treatment (11.5 months vs. 8.4 months, respectively; p < 0.0001). The two monotherapy groups did not reveal any significant differences. Conclusions: This study suggests that rechallenge therapy may improve survival rates in the third-line treatment of mCRC, particularly if it is administered before sequential R/T treatment. This could allow for the extension of mCRC treatment choices until prospective studies are finished or randomised trials are performed.

Technological progress is increasing rapidly, and keeping up is particularly challenging for older adults. Thus, adapting technological innovations to human needs has become urgent. The first step toward this aim is to understand how people conceptualize technology. Here, we asked 54 younger and 54 older adults to perform a Go/No-Go, a rating, and a feature generation task to investigate the processing and representation of Technological concepts (e.g., “Internet”) compared to Abstract (e.g., “logic”) and Concrete concepts (e.g., “bottle”). Younger adults showed an elaboration advantage for Technological upon Abstract and Concrete concepts. Technological concepts exhibited a hybrid character, but in older adults, they had a more abstract characterization. Finally, the semantic knowledge associated with Technology was differently organized in content across generations and less structurally robust in older adults. Overall, our results highlight how concepts flexibly change across life and can help societal policies to increase awareness in technology-use across generations.

Peritoneal metastases (PM) are the spread of tumor forms into the peritoneum as metastases from another organ. PM is a frequent condition in metastatic gastrointestinal cancer (colorectal, gastric, pancreatic, appendiceal, and cholangiocarcinoma); their presence confers a poor prognosis, reducing patient survival. The standard treatment consists of systemic chemotherapy according to current guidelines. In recent years, scientific evidence has shown how combined cytoreductive surgery (CRS) techniques followed by hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival in this patient population. Despite the results still obtained, using this combined technique is still under discussion. This review aims to highlight the benefits and limitations of this combined procedure, which is already widely used to treat peritoneal metastases in gynecological tumors.

There are growing demands to proactively support students with disabilities in postsecondary education. This article examines a mixed-methods study with accessibility consultants and other faculty in a community college pilot program focussed on redesigning courses to increase inclusiveness. Findings highlight the successful and well-received role of the accessibility consultants collaborating in redesign triads. Challenges experienced by accessibility consultants are also discussed, for example, around time allocation for this type of work along with their daily support of students. Recommendations for accessibility consultants involvement in expanding inclusive course redesigns are made, such as, including them more in the process of curriculum design and ensuring appropriate time for their participation.

BackgroundRheumatological toxicity associated with immunotherapy, particularly Sjögren’s syndrome (SjS), has been observed with variable incidence in patients treated with immune checkpoint inhibitors (ICIs). Although SjS is a well-known autoimmune disease, its occurrence as an immune-related adverse event (irAE) during cancer treatment is less well understood. Current literature documents a range of incidence rates and clinical manifestations of SjS in patients undergoing ICI therapy, highlighting the need for early diagnosis and multidisciplinary management.Case presentationA 40-year-old woman underwent mammography, which revealed a 43 mm mass in the left breast. Core biopsy confirmed grade 3 infiltrating triple negative ductal carcinoma with high MIB-1. She received neoadjuvant chemotherapy, followed by surgery and radiotherapy. A CT scan in September 2022 showed lung nodules and lymph node involvement. A lung biopsy confirmed breast cancer metastasis. She started treatment with atezolizumab and nab-paclitaxel with evidence of a partial response. Nab-paclitaxel was discontinued due to side effects and atezolizumab was continued as maintenance therapy. After four cycles, the patient developed symptoms consistent with Sjögren’s syndrome (SjS), which were confirmed by diagnostic tests. Treatment with prednisone, pilocarpine and hydroxychloroquine was initiated alongside ongoing immunotherapy. The patient continues to receive atezolizumab with stable disease and good quality of life.ConclusionThis case highlights the importance of recognizing SjS as a potential irAE in patients treated with ICIs, particularly those with TNBC. Multidisciplinary collaboration is essential for the prompt diagnosis and effective management of SjS to maintain both cancer control and patient quality of life. Given the recent emergence of these events and the lack of specific guidelines, our case report may provide valuable insights into the management of a little-known adverse event and pave the way for further real-world data collection on the management of these rare but significant toxicities that impact on patient quality of life. Further research is needed to optimize treatment protocols and outcomes for patients experiencing rheumatological irAEs during cancer immunotherapy.

Immunotherapy is increasingly used in advanced non-small-cell lung cancer (NSCLC), offering a significant anti-tumor response, as well as causing rising immune-related adverse effects. The incidence of immune checkpoint inhibitor-induced myocarditis–myositis–myasthenia gravis is increasing and particularly concerning due to its high mortality rate. Prompt recognition, diagnosis, and management are crucial. A 40-year-old patient, diagnosed with stage IV non-oncogene addicted lung adenocarcinoma, with nivolumab–ipilimumab–chemotherapy as first-line treatment, developed a rare myocarditis–myositis–myasthenia gravis overlap syndrome. Following the treatment, the patient presented with flu-like symptoms and chest pain and subsequently transferred to the cardiac intensive care unit. The physical examination revealed a visual acuity deficit, diplopia, ophthalmoparesis, ptosis, mydriasis, dysphagia, dyspnea, headache, nausea, dry mouth, asthenia, myalgia, and muscle weakness. Imaging and laboratory tests confirmed the triad, showing an elevation of hs-cTnI and CK and positive results for anti-SAE1 and anti-PL-7 Abs. ECG revealed ST segment elevation and RBBB. The echo showed hyperechogenicity of the inferolateral wall, pericardial detachment, and thickening. The cardiac MRI demonstrated hypokinesia, edema, subepicardial LGE, and pericardial effusion. Muscle biopsy revealed muscle fiber necrosis and regeneration with B and T lymphocytic endomysial inflammatory infiltrate and expression of MHC-I. Treatment with oral prednisone, pyridostigmine, and IV Igs was started due to poor clinical response followed by methylprednisolone. Despite stopping immunotherapy, the patient continued to benefit from it, as highlighted on subsequent re-evaluation CT scans by partial disease response, and as the patient was in complete remission, we decided to resume chemotherapy by omitting immunotherapy. At the radiological control following the four cycles of double CHT and during CHT maintenance, there was a further reduction of the disease. This report aims to raise awareness among physicians about these serious side effects. A multidisciplinary approach led to clinical improvement and early intervention, optimizing patient outcomes.

α -1 antitrypsin (A1AT) is a 52 kDa acute-phase glycoprotein belonging to the serine protease inhibitor superfamily (SERPIN). It is primarily synthesized by hepatocytes and to a lesser extent by monocytes, macrophages, intestinal epithelial cells, and bronchial epithelial cells. A1AT is encoded by SERPINA1 locus, also known as PI locus, highly polymorphic with at least 100 allelic variants described and responsible for different A1AT serum levels and function. A1AT inhibits a variety of serine proteinases, but its main target is represented by Neutrophil Elastase (NE). However, recent attention has been directed towards its immune-regulatory and homeostatic activities. A1AT exerts immune-regulatory effects on different cell types involved in innate and adaptive immunity. Additionally, it plays a role in metal and lipid metabolism, contributing to homeostasis. An adequate comprehension of these mechanisms could support the use of A1AT augmentation therapy in many disorders characterized by a chronic immune response. The aim of this review is to provide an up-to-date understanding of the molecular mechanisms and regulatory pathways responsible for immune-regulatory and homeostatic activities of A1AT. This knowledge aims to support the use of A1AT in therapeutic applications. Furthermore, the review summarizes the current state of knowledge regarding the application of A1AT in clinical and laboratory settings human and animal models.

Using the framework of an investigation of the stimuli-responsive behavior of peptide assembly on a solid surface, this study on the behavior of a chemisorbed peptide on a gold surface was performed. The studied peptide is a dimeric form of the antimicrobial peptide Trichogin GAIV, which was also modified by substituting the glycine with lysine residues, while the N-terminus octanoyl group was replaced by a lipoic one that was able to bind to the gold surface. In this way, a chemically linked peptide assembly that is pH-responsive was obtained because of the protonation/deprotonation of the sidechains of the Lys residues. Information about the effect of protonation/deprotonation equilibria switching the pH from acid (pH = 3) to basic (pH = 11) conditions was obtained macroscopically by performing Quartz crystal microbalance with dissipation monitoring (QCM-D), Surface Plasmon Resonance (SPR), Nanoplasmonic Sensing (NPS), and FTIR techniques. Using molecular dynamics (MD) simulations, it is possible to explain, at the molecular level, our main experimental results: (1) pH changes induce a squeezing behavior in the system, consisting in thickness and mass variations in the peptide layer, which are mainly due to the pH-driven hydrophilic/hydrophobic character of the lysine residues, and (2) the observed hysteresis is due to small conformational rearrangements from helix to beta sheets occurring mainly on the first half of the peptide, closer to the surface, while the second half remains almost unaffected. The latter result, together with the evidence that the layer thickness is not simply double the assembly of the monomeric analog, indicates that the dimeric peptide does not behave as a double monomer, but assumes very peculiar features.

Mycotoxins, specifically aflatoxin B1 (AFB1), ochratoxin A (OTA), trichothecenes (TCNs), and patulin, are a group of secondary metabolites that can contaminate food, leading to severe health implications for humans. Their detection and analysis within forensic toxicology are crucial, particularly as they can be implicated in cases of poisoning, foodborne illnesses, or lethal chronic exposure. However, little is known about the application that mycotoxins could have in forensic investigations and especially about the possibility of extracting and quantifying these molecules on tissues or post-mortem fluids collected at autopsy. We propose a review of the scientific literature on autopsy case studies in which the presence of mycotoxins on cadavers in cases of acute and chronic exposure has been investigated and identified. This review demonstrates how the analysis of mycotoxins on cadavers could be fundamental in the study of mushroom poisonings or even in the investigation of the chronic effects of mycotoxins on the human organism, by virtue of the known carcinogenic and mutagenic effects of many of them. This paper aims to explore the multifaceted role of mycotoxins within forensic sciences, focusing on their detection methods, implications in criminal contexts, and their potential as forensic evidence, thereby underscoring the critical importance they could assume in post-mortem toxicology, public health prevention, and forensic investigations.

Investigating how people represent the natural environment and abstract it into geographical (e.g., mountain) and geopolitical (e.g., city) categories is pivotal to comprehending how they move and interact with the places they inhabit. Yet, the conceptualization of geographical and geopolitical domains has received scant attention so far. To deal with that, we reviewed 50 articles tackling this topic. Most studies have focused on assessing the universality of these concepts—especially geographical ones—mainly using free-listing and ethnophysiographic methods. Current perspectives tend to favor a non-universalistic characterization of these kinds of concepts, emphasizing their high cross-linguistic and cross-cultural variability, especially when compared to other semantic domains. Since geographical and geopolitical features are not pre-segmented by nature, the role of categories imposed by humans is crucial for these concepts. Significantly, their variability does not only depend on “cross” differences: evidence suggests that the cognitive demand requested by the task, idiosyncratic characteristics of individuals such as expertise level, and the typology of inhabited environments are further factors impacting the conceptual flexibility of these domains. Exploring the factors influencing our understanding of geographical and geopolitical categories can provide valuable insights for instructing effective communication policies to enhance sustainable development and address ecological emergencies, taking into consideration diverse cultural backgrounds within different populations.

Down’s syndrome (DS), or Trisomy 21, represents the most common chromosomal abnormality in live births, characterized by an extra chromosome 21. Children affected by Down’s syndrome are more susceptible to the development of obesity and of becoming overweight compared with other children. Furthermore, they seem to present a more unfavorable lipid profile than the non-DS obese pediatric population. Diet and physical activity are closely related to the development of overweight and obesity, and they can be assessed using questionnaires such as the Mediterranean Diet Quality Index in children and adolescents (KIDMED) and the Godin–Shephard Leisure-Time Physical Activity Questionnaire. This review aims to undertake a comprehensive analysis of the intricate interplay between diet and physical activity in children affected by Down’s syndrome. Specifically, it seeks to deepen understanding regarding the question of how diet and exercise can influence and prevent the development of overweight and obesity in that special pediatric population.

A penetrating thoracic aorta injury (PTAI) is a life-threatening condition with significant morbidity and mortality, often resulting from several traumatic mechanisms. Among these, gunshot wounds leading to aortic injury are exceedingly rare and pose unique challenges in terms of diagnosis, management, and surgical intervention. We present a case of a 47-year-old male victim of a gunshot wound resulting in penetrating chest trauma and a descending thoracic aorta injury. This report outlines the sequential management involving thoracic endovascular aortic repair (TEVAR), followed by surgical intervention for hematoma drainage and foreign body removal, highlighting the interdisciplinary approach required in managing complex cardiothoracic injuries.

PurposeThe coronavirus pandemic (COVID-19) significantly impacted the global economy and health. Italy was one of the first and most affected countries. The objective of our study was to assess the impact of the pandemic and the vaccination campaign on the radiological examinations performed in a radiology department of a tertiary center in Southern Italy.Materials and methodsWe analyzed weekly and retrospectively electronic medical records of case volumes performed at the Radiology Department of “Mater Domini” University Hospital of Catanzaro from March 2020 to March 2022, comparing them with the volumes in the same period of the year 2019. We considered the origin of patients (outpatient, inpatient) and the type of examinations carried out (x-ray, mammography, CT, MRI, and ultrasound). A non-parametric test (Wilcoxon Signed Rank test) was applied to evaluate the average volumes.ResultsTotal flows in the pandemic period from COVID-19 were lower than in the same pre-pandemic period with values of 552 (120) vs. 427 (149) median (IQR) (p

Obstructive sleep apnoea (OSA) can occur in both rapid eye movement (REM) and non-REM sleep or be limited to REM sleep, when the upper airway is most prone to collapse due to REM sleep atonia. Respiratory events are usually longer and more desaturating in REM than in NREM sleep. The prevalence of REM OSA is higher in women than in men and REM OSA usually occurs in the context of mild–moderate OSA based on the apnoea–hypopnoea index calculated for the entire sleep study. Studies have highlighted some detrimental consequences of REM OSA; for example, its frequent association with systemic hypertension and a degree of excessive daytime sleepiness similar to that found in nonsleep-stage-dependent OSA. Moreover, REM OSA could increase cardiometabolic risk. Continuous positive airway pressure (CPAP) treatment aimed at preventing REM OSA should be longer than the 4 h usually considered as good compliance, since REM sleep occurs mostly during the second half of the night. Unfortunately, patients with REM OSA show poor adherence to CPAP. Alternative non-CPAP treatments might be a good choice for REM OSA, but data are lacking. This review summarises the available data on REM OSA and critically examines the weaknesses and strengths of existing literature.

Background: Patients with refractory mCRC rarely undergo third-line or subsequent treatment. This strategy could negatively impact their survival. In this setting, regorafenib (R) and trifluridine/tipiracil (T) are two key new treatment options with statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control with different tolerance profiles. This study aimed to retrospectively evaluate the efficacy and safety profiles of these agents in real-world practice. Materials and Methods: In 2012–2022, 866 patients diagnosed with mCRC who received sequential R and T (T/R, n = 146; R/T, n = 116]) or T (n = 325]) or R (n = 279) only were retrospectively recruited from 13 Italian cancer institutes. Results: The median OS is significantly longer in the R/T group (15.9 months) than in the T/R group (13.9 months) (p = 0.0194). The R/T sequence had a statistically significant advantage in the mPFS, which was 8.8 months with T/R vs. 11.2 months with R/T (p = 0.0005). We did not find significant differences in outcomes between groups receiving T or R only. A total of 582 grade 3/4 toxicities were recorded. The frequency of grade 3/4 hand-foot skin reactions was higher in the R/T sequence compared to the reverse sequence (37.3% vs. 7.4%) (p = 0.01), while grade 3/4 neutropenia was slightly lower in the R/T group than in the T/R group (66.2% vs. 78.2%) (p = 0.13). Toxicities in the non-sequential groups were similar and in line with previous studies. Conclusions: The R/T sequence resulted in a significantly longer OS and PFS and improved disease control compared with the reverse sequence. R and T given not sequentially have similar impacts on survival. More data are needed to define the best sequence and to explore the efficacy of sequential (T/R or R/T) treatment combined with molecular-targeted drugs.

BackgroundEvaluating oscillometry parameters separately for the inspiratory and expiratory breath phases and their within-breath differences can help to identify exercise-induced bronchoconstriction (EIB) in pediatric outpatients disclosing exercise-induced symptoms (EIS).AimsTo assess the response in impedance parameters following an exercise challenge in patients reporting EIS.MethodsSixty-eight patients reporting EIS (34 asthmatics and 34 suspected of asthma, age mean = 10.8 years, range = 6.0–16.0) underwent an incremental treadmill exercise test. Spirometry was performed at baseline and 1, 5-, 10-, 15-, and 20-min post exercise. Oscillometry was performed at baseline and at 3- and 18-min post exercise. Bronchodilator response to 200 µg albuterol was then assessed. EIB was defined as a forced expiratory volume in 1 s (FEV1) fall ≥10% from baseline. Expiratory and inspiratory resistance (Rrs) and reactance (Xrs), their z-score (Ducharme et al. 2022), and their mean within-breath differences (ΔRrs = Rrsexp-Rrsinsp, ΔXrs = Xrsexp-Xrsinsp) were calculated. Receiver operating characteristic (ROC) curves and their areas (AUCs) were used to evaluate impedance parameters’ performances in classifying EIB.ResultsAsthmatic patients developed EIB more frequently than those suspected of asthma [18/34 (52.9%) vs. 2/34 (5.9%), p

The disinfection of deteriogenic microorganisms and the removal of induced chromatic alterations in artworks are still open challenges in the field of conservation. For this purpose, a new alcoholic hydrogel was tested to remove an extensive fungal attack from a multimaterial collage by the artist Alessandro Kokocinski and to mitigate chromatic changes caused by the contamination of its poster paper and plywood support layers. A Gellan gum-based hydrogel was used, which was modified by adding a high concentration of alcohol (66.7% ethanol), to give the system an effective disinfecting agent in addition to the detergent capacity of the gel for water-sensitive works of art. It was successfully tested on samples mimicking the complex stratigraphy of the artwork under study. To create replica mock-ups, the artwork materials and stratigraphy were investigated through diagnostic and laboratory techniques such as multispectral imaging, X-ray fluorescence spectroscopy, Fourier transform infrared spectroscopy, and pyrolysis coupled with gas-chromatography-mass spectrometry. The treatment was shown to have a disinfecting effect on the test samples and did not alter their structure, allowing us to apply the method to the artwork. Here, the hydrogel successfully removed and inhibited fungal proliferation in addition to mitigating the color changes caused by fungi.

Abstract In this review we discuss the role of intraocular surgery preoperative prophylaxis. The correct choice of antimicrobial drug is variable in each surgical setting, according to the available strengths of evidence, the anatomical district involved, and the type of procedure. In the ophthalmic surgical field, there has been a progressive shift from antibiotic formulations, which are known to cause antibiotic resistance, to a new class of antiseptic compounds, which proved to be effective not only against bacteria, but also against fungi, protozoa, and viruses. Among these, povidone–iodine (PVI) is a water-soluble polymer that can form a complex with iodine, and the perioperative application of PVI 5–10% eye drop for 3 min is the gold standard for infection prophylaxis. A new formulation of 0.6% PVI eye drop is a new option for infection prophylaxis in the days before surgery. Chlorhexidine is a biguanide compound, which is a valid alternative with a good safety and efficacy profile and is the antiseptic of choice in patients with iodine allergy. New compounds that are currently being studied include polyhexamethylene biguanide (PHMB), picloxydine, ozone, hypochlorous acid (HOCl), and Biosecur. PHMB is a biguanide polymer that was found to be more effective than PVI in in vitro studies for reducing microorganisms and extending the duration of antisepsis, but to date, there are no formulations available on the market for preoperative ocular surgery in which it is present as main ingredient. Ozone is a molecule with oxidizing effect, which showed interesting preliminary results but is not effective against virus, Staphylococcus aureus and Candida albicans. HOCl has a natural bactericidal propriety but its applicability to prophylaxis of ocular infection in the setting of ocular surgery is not established. Biosecur is a non-toxic organic alcohol-free compound that exhibited bactericidal and fungicidal effect versus all common microorganisms and is currently available as an ocular spray.

In this work, the effect of X-ray irradiation as a disinfection treatment in original ancient parchment samples, belonging to a discarded book cover of a 16th-century archival register, has been evaluated. Specifically, the bacterial and fungal species isolated from the book cover have been characterized and then irradiated with increasing doses of X-rays with the aim to evaluate the effectiveness of the antimicrobial protocol on the isolated microorganisms. The deterioration effects induced by the X-ray treatment as well as the natural aging on the collagen matrix of the parchment sample have been tested by employing several techniques, namely, Light Transmission Analysis, Fiber Optic Reflectance Spectroscopy, Attenuated Total Reflectance-Fourier Transformed Infrared spectroscopy, UV Resonant Raman spectroscopy and Atomic Force Microscopy. The results reveal that the irradiation treatment applied to our ancient parchment samples deteriorated by biological attack and other naturally occurring phenomena, possibly associated with inappropriate conservation conditions, does not seem to induce further damage factors even when large doses of irradiation are employed. The X-rays-based disinfection treatment effects are limited on the collagen support and this confirms the potential of this method in mass disinfection of library and archival materials.