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Abstract Background Vaccination rates are still suboptimal in cancer patients. Oncologists play a central role in recommending vaccines to their patients. Our goal was to investigate vaccine acceptance among cancer patients and understand the factors shaping their choices, thereby aiding physicians in better supporting their patients’ vaccination decisions. Methods We designed a prospective cross-sectional survey exploring vaccination status, attitudes, and reasons for hesitancy towards vaccinations against the main vaccine preventable diseases (VPDs) among patients undergoing active cancer treatment. The primary endpoint was to evaluate the proportion of vaccinated subjects in our cohort of cancer patients. The secondary endpoints were to assess the proportion of vaccinated subjects against different types of VPDs: flu, COVID-19, pneumococcal disease, Herpes Zoster (HZ). Results Between 12 February and 01 March 2024, a total of three hundred and seventeen patients with cancer were invited to respond to the survey, 309 of whom (97%) agreed to do it. Two hundred seventy-three patients (0.88, 95% confidence interval [CI] 0.84–0.91) had received at least one vaccination. Two hundred thirty-one patients (74.76%) reported that at their first oncology visit their oncologist recommended vaccinations, primarily anti-flu (92.21%) and anti-SARS-CoV-2 (83.55%) vaccinations, while less frequently the anti-pneumococcal (42.42%) and anti-HZ (37%) vaccines were recommended. On the univariate analysis, age over 75 years (p = 0.041), marital status (p = 0.003) and the oncologist’s vaccine recommendation during the first visit (p

Modern healthcare is experiencing a significant transformation, utilizing technology to improve patient outcomes and make processes more efficient. Breast cancer, being the most commonly diagnosed cancer in women globally, requires innovative approaches for effective management. Digital Therapeutics (DTx) and Clinical Decision Support Systems (CDSSs) have emerged as pivotal technologies, offering personalized, patient-centered care and optimizing clinical decision-making. This review provides a comprehensive analysis of the applications, benefits, and challenges of these digital tools in breast cancer treatment. We examine DTx tools’ ability to offer real-time symptom monitoring, treatment adherence, psychological support, and lifestyle modification guidance. Simultaneously, the role of CDSSs in providing personalized treatment recommendations, early detection, data analysis, and enhancing multidisciplinary collaborations is evaluated. The challenges of implementing these technologies, such as data privacy, interoperability, and accessibility are also discussed, along with potential solutions. By exploring the current research findings, the review underscores the significant impact of DTx and CDSSs on patient outcomes, treatment efficiency, and overall quality of life. This manuscript concludes with a forward-looking perspective, emphasizing the importance of collaborative efforts to overcome obstacles and unlock the full potential of digital innovations in breast cancer oncology. Our analysis suggests that adopting these digital tools can lead to more holistic, efficient, and patient-centric cancer care, marking a significant shift in the paradigm of breast cancer management.

Scientific research has often investigated the role of diet as a risk factor for cancer development. It is well known that cancer has a multifactorial origin in which several factors are involved: genetic predisposition, dietary factors, personal habits, and infectious and environmental factors. In this Commentary, the role of diet in cancer is discussed following the scientific evidence suggesting that excessive consumption of red meat and processed foods is correlated with a greater risk of contracting cancer. Nevertheless, public health strategies on nutrition in cancer prevention are struggling to take off. The decision to pursue a healthier diet, along with a healthier lifestyle, often comes when the cancer diagnosis is made and not before. On the other hand, scientific evidence demonstrates how nutritional support is increasingly important during oncological treatments. This paper highlights how far we are still from the global adoption of a healthy and sustainable food style from a health, economic, social and environmental perspective. Additionally, it highlights the ancient vision of the role of nutrition on cancer development in which diet is seen only as a possible risk factor, underestimating the protective role in terms of cancer prevention and the modulatory one once the oncological diagnosis has been made.

Abstract The expansion of the CRISPR-Cas toolbox is highly needed to accelerate the development of therapies for genetic diseases. Here, through the interrogation of a massively expanded repository of metagenome-assembled genomes, mostly from human microbiomes, we uncover a large variety (n = 17,173) of type II CRISPR-Cas loci. Among these we identify CoCas9, a strongly active and high-fidelity nuclease with reduced molecular size (1004 amino acids) isolated from an uncultivated Collinsella species. CoCas9 is efficiently co-delivered with its sgRNA through adeno associated viral (AAV) vectors, obtaining efficient in vivo editing in the mouse retina. With this study we uncover a collection of previously uncharacterized Cas9 nucleases, including CoCas9, which enriches the genome editing toolbox.

Objectives: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19. Methods: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs. Results: Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92). Conclusion: In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer.

Collagen VI is an essential component of the extracellular matrix (ECM) composed by α1, α2 and α3 chains and encoded by COL6A1, COL6A2 and COL6A3 genes. Dominant negative pathogenic variants in COL6A genes result in defects in collagen VI protein and are implicated in the pathogenesis of muscular diseases, including Ullrich congenital muscular dystrophy (UCMD). Here, we designed a CRISPR genome editing strategy to tackle a dominant heterozygous deletion c.824_838del in exon 9 of the COL6A1 gene, causing a lack of secreted collagen VI in a patient’s dermal fibroblasts. The evaluation of efficiency and specificity of gene editing in treating patient’s fibroblasts revealed the 32% efficiency of editing the mutated allele but negligible editing of the wild-type allele. CRISPR-treated UCMD skin fibroblasts rescued the secretion of collagen VI in the ECM, which restored the ultrastructure of the collagen VI microfibril network. By using normal melanocytes as surrogates of muscle cells, we found that collagen VI secreted by the corrected patient’s skin fibroblasts recovered the anchorage to the cell surface, pointing to a functional improvement of the protein properties. These results support the application of the CRISPR editing approach to knock out COL6A1 mutated alleles and rescue the UCMD phenotype in patient-derived fibroblasts.

Abstract Introduction The most studied anticancer restrictive diets include fasting, fasting‐mimicking diets (FMDs) and ketogenic diets (KDs). Besides the current lack of established clinical benefit and the significant risk of malnutrition and micronutrient deficiencies, dietary restrictions in cancer patients might have relevant psychological effects. Materials and Methods We reviewed the randomized and non‐randomized controlled clinical trials (CCTs) reporting data on the psychological impact of fasting, FMDs and KDs in cancer patients. We excluded trials on restrictive diets performed for weight reduction in obese or overweight patients, studies on dietary restrictions lasting less than 24 h, and studies on fasting related to cultural or religious beliefs. Results Three CCTs on fasting or FMDs and eight CCTs on KDs in cancer patients were included. In terms of diet‐related distress, emotional, social, and family well‐being, none of these studies showed a detrimental impact of fasting, FMDs and KDs. However, clinical trials specifically assessing the psychological aspects in the long term are lacking. Conclusions and Perspectives In the absence of a conclusive evidence on the clinical benefits of restrictive diets, which carry significant risks especially if unsupervised, further studies are needed to clarify their psychological impact in cancer patients. Multidisciplinary approaches including psychological evaluations should be used to ameliorate patient selection for clinical trials, identify early distress symptoms, and increase patient compliance to dietary recommendations.

Abstract The leafhopper genus Arboridia includes several species that feed on Vitis vinifera and cause leaf chlorosis. We report the first alien Arboridia infestation in Italy in 2021 in an Apulian vineyard. To confirm the taxonomic status of the species responsible for crop damage, and reconstruct its demographic history, we barcoded individuals from Apulia together with Arboridia spp. from Crete (Greece), A. adanae from Central Turkey and other specimens of the presumed sister species, A. dalmatina from Dalmatia (Croatia). Molecular phylogenies and barcoding gap analysis identified clades not associated with sampling locations. This result is incongruent with classical specimen assignment and is further supported by morphological analyses, which did not reveal significant differences among the populations. Therefore, we propose A. dalmatina as a junior synonym of A. adanae, which would become the only grapevine-related Arboridia species in the eastern Mediterranean. To further characterise A. adanae evolution, we performed a molecular clock analysis that suggested a radiation during the Pleistocene glaciations. Finally, to assess whether the Apulian individuals carried microorganisms of agricultural relevance, we sequenced their bacterial microbiota using 16S rRNA amplicon sequencing identifying three phytopathogens not generally associated with Arboridia activities as well as Wolbachia in one Apulian haplogroup. We discuss the agricultural implications of this infestation.

Abstract Objective: Food advertising is an important determinant of unhealthy eating. However, analysing a large number of advertisements (ads) to distinguish between food and non-food content is a challenging task. This study aims to develop a machine learning-based method to automatically identify and classify food and non-food ad videos. Design: Methodological study to develop an algorithm model that prioritises both accuracy and efficiency in monitoring and classifying advertising videos. Setting: From a collection of Brazilian television (TV) ads data, we created a database and split it into three sub-databases (i.e. training, validation and test) by extracting frames from ads. Subsequently, the training database was classified using the EfficientNet neural network. The best models and data-balancing strategies were investigated using the validation database. Finally, the test database was used to apply the best model and strategy, and results were verified with field experts. Participants: The study used 2124 recorded Brazilian TV programming hours from 2018 to 2020. It included 703 food ads and over 20 000 non-food ads, following the protocol developed by the INFORMAS network for monitoring food marketing on TV. Results: The results showed that the EfficientNet neural network associated with the balanced batches strategy achieved an overall accuracy of 90·5 % on the test database, which represents a reduction of 99·9 % of the time spent on identifying and classifying ads. Conclusions: The method studied represents a promising approach for differentiating food and non-food-related video within monitoring food marketing, which has significant practical implications for researchers, public health policymakers, and regulatory bodies.

Gastric cancer (GC) is a complex disease with various etiologies. While Helicobacter pylori infection is still one of the leading risk factors for GC, increasing evidence suggests a link between GC and other infective agents such as Epstein Bar Virus (EBV). EBV-associated gastric cancer (EBVaGC) is now recognized as a distinct subgroup of GC, and the complex interactions between the virus and gastric mucosa may influence its development. A recent integrative analysis of the genome and proteome of GC tissues by The Cancer Genome Atlas project has identified EBVaGC as a specific subtype characterized by PIK3CA and ARID1A mutations, extensive DNA hyper-methylation, and activation of immune signaling pathways. These molecular characteristics are markers of the unique molecular profile of this subset of GC and are potential targets for therapy. This review aims to provide an overview of the current knowledge on EBVaGC. It will focus on the epidemiology, clinic-pathological features, and genetic characteristics of EBVaGC. Additionally, it will discuss recent data indicating the potential use of EBV infection as a predictive biomarker of response to chemotherapy and immune checkpoint inhibitors. The review also delves into potential therapeutic approaches for EBVaGC, including targeted therapies and adoptive immunotherapy, highlighting the promising potential of EBV as a therapeutic target.

Abstract Introduction The gut microbiota (GM) can influence the pathogenesis of immune‐mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. Methods In this retrospective single‐center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). Results Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty‐three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11–56.10, p

Gastric cancer patients undergoing surgical procedures, such as total or subtotal gastrectomy, often encounter a range of challenging symptoms during postoperative rehabilitation. Indeed, surgery alters patients' gastrointestinal anatomy and physiological functions, affecting nutrient absorption and giving rise to gastrointestinal symptoms. Common symptoms include dumping syndrome, diarrhea, gastroesophageal reflux as well as nausea and early satiety. Moreover, the severity of these symptoms can lead to additional psychological distress and negatively impact oral food intake. Disturbances in symptoms and systemic inflammation, related to cancer and surgery along with emotional distress, can progressively contribute to wasting, ultimately resulting in weight loss. Following gastrectomy, most patients experience insufficient protein and calorie intake, leading to continued weight loss over an extended period. Malnutrition stands as a risk factor for postoperative complications and a poor prognosis. Therefore, to prevent this and ensure a swift recovery after surgery, individualized nutritional interventions led by dietary counseling should be consistently carried out. This should be done both during the postoperative hospitalization period (aimed at gradually increasing oral feeding intake) and in the subsequent phase at home (by providing nutritional advice to fully meet nutritional requirements and regain an adequate diet). Understanding the issues that affect patients' nutritional status after gastric cancer surgery is a critical aspect of rehabilitation programs, which are designed to enhance clinical outcomes and optimize quality of life.

Malnutrition is associated with higher rates of surgical complications, increased anticancer treatment toxicities, longer hospital stays, higher healthcare costs, poorer patient quality of life, and lower survival rates. Nutritional support has been shown to improve all of these outcomes. However, the nutritional care of cancer patients is still suboptimal and several issues remain unresolved. Although the effectiveness of nutritional support depends on the timeliness of intervention, assessment of nutritional status is often delayed and perceived as unimportant. When diagnoses of malnutrition are made, they are rarely recorded in medical records. Hospitals lack medical staff dedicated to clinical nutrition, making it difficult to integrate nutritional care into the multidisciplinary management of cancer patients. Outside the hospital, nutritional support is hampered by heterogeneous reimbursement policies and a lack of adequate community nutrition services. In addition, an increasing number of patients are turning to potentially harmful “anti-cancer” diets as trust in medicine declines. Adopting mandatory nutrition screening, monitoring quality of care metrics, providing nutrition education to care providers, and implementing telehealth systems are some of the most urgent interventions that need to be established in the future.

Abstract This is a report on some of the research activities currently ongoing in Italy as outlined at the “Viruses and solid tumors” meeting jointly organized by the Oncology Sections of IRCCS Policlinico “San Matteo” (Pavia) and IRCCS National Cancer Institute (Aviano), held in Pavia, Italy, on October 2011. Experts from the various disciplines involved in the study of the complex relationships between solid tumors and viruses met to discuss recent developments in the field and to report their personal contributions to the specified topics. Secondary end point was to establish a multidisciplinary work group specifically devoted to solid tumors and infectious agents, aimed to identify areas of common interest, promoting and establishing collaborative projects and programs, and to coordinate clinical and research activities. The group, which will be named IVOG (Italian Viral Oncology Group), will operate under the patronage of the various scientific societies of interest.

Abstract Colorectal carcinoma (CRC) represents the fourth most common cancer worldwide and is the third most common cause of malignancy-associated mortality. Distant metastases to the liver and lungs are the main drivers of CRC-dependent death. Pro-oxidant therapies, which halt disease progression by exacerbating oxidative stress, represent an antitumour strategy that is currently exploited by chemotherapy and ionizing radiation. A more selective strategy to therapeutically exploit reactive oxygen species (ROS) signaling would consist in targeting a redox sensor that is up-regulated in metastatic cells and is tightly coupled to the stimulation of cancer cell death programs. The non-selective cation channel, Transient Receptor Potential Ankyrin 1 (TRPA1), serves as a sensor of the cellular redox state, being activated to promote extracellular Ca2+ entry by an increase in oxidative stress. Recent work demonstrated that TRPA1 channel protein is up-regulated in several cancer types and that TRPA1-mediated Ca2+ signals can either engage an antiapoptotic pro-survival signaling pathway or to promote mitochondrial Ca2+ dysfunction and apoptosis. Herein, we sought to assess for the first time the outcome of TRPA1 activation by ROS on primary cultures of metastatic colorectal carcinoma (mCRC cells). We found that TRPA1 channel protein is up-regulated and mediates enhanced hydrogen peroxide (H2O2)-induced Ca2+ entry in mCRC cells as compared to non-neoplastic control cells. The lipid peroxidation product 4-hydroxynonenal (4-HNE) is the main ROS responsible for TRPA1 activation upon mCRC cell exposure to oxidative stress. TRPA1-mediated Ca2+ entry in response to H2O2 and 4-HNE results in mitochondrial Ca2+ overload, followed by mitochondrial depolarization and caspase-3/7 activation. Therefore, targeting TRPA1 could represent an alternative strategy to eradicate metastatic CRC by enhancing its sensitivity to oxidative stress.

AbstractThe Salmo trutta species complex includes threatened or intensively managed taxa. Domestic-Atlantic strains are widely farmed and massively introduced into the wild to support fisheries, although such practices seriously threaten native populations of Mediterranean brown trout through anthropogenic hybridization. Characterizing the distribution and genetic composition of wild populations across river catchments is crucial to identify conservation priorities and define appropriate management strategies. Here, we genotyped 586 brown trout at the diagnostic nuclear LDH-C1 gene and the mitochondrial D-loop fragment, to assess the conservation status of 33 sites in a protected area spanning river catchments from both the Adriatic and Tyrrhenian slopes in the northern Apennines (Italy). The results indicated a critical situation of widespread domestic-Atlantic introgression. Further analyses at 15 microsatellite loci on 159 individuals from 12 natural sites (along with 113 references from hatcheries) revealed similarity to hatchery stocks, higher genetic diversity and bottleneck signals in introgressed/exotic populations, consistently with relatively recent introductions of domestic-Atlantic individuals into wild sites. Conversely, the only native sites from a single river catchment on the Adriatic slope showed genetic distinctiveness, reduced diversity and demographic stability. We also found genetic evidence of a human-mediated introduction of allochthonous Mediterranean trout in a single wild site, as well as of a putative between-slopes translocation. We provide further insight into the occurrence and consequences of human manipulations on wild Mediterranean brown trout populations, contextually offering a reliable baseline for an ongoing conservation project aiming at preserving native populations of this endangered taxon.

Breast cancer is the most common malignancy in the female sex; although recent therapies have significantly changed the natural history of this cancer, it remains a significant challenge. In the past decade, evidence has been put forward that some oncogenic viruses may play a role in the development of sporadic breast cancer; however, data are scattered and mostly reported as sparse case series or small case–control studies. In this review, we organize and report current evidence regarding the role of high-risk human papillomavirus, mouse mammary tumor virus, Epstein–Barr virus, cytomegalovirus, bovine leukemia virus, human polyomavirus 2, and Merkel cell polyomavirus in the pathogenesis of breast cancer.

ABSTRACTHerpes zoster (HZ) is caused by the reactivation of latent varicella zoster virus (VZV). Severe immunocompromising conditions, such as solid tumors, have been largely associated with an increased risk for HZ due to waning VZV-specific cellular immunity. With the approval of the adjuvanted glycoprotein E (gE)-based recombinant vaccine (RZV; Shingrix™, GSK) also in immunocompromised subjects, HZ is considered a vaccine-preventable disease changing perspectives in immunocompromised subjects. To date, no clinical trial has evaluated the immunogenicity in the patients with cancer undergoing immunotherapy. In this study, we describe the humoral and cell-mediated immune responses in 38 cancer patients treated with immune checkpoint inhibitors (ICIs) and receiving RZV. We used samples collected at baseline (T0), 3 weeks (T2), and 6 months (T3) after the complete RV vaccination schedule. Our data showed that a significant proportion (40,5%) of RZV recipients mounted a stronger humoral and cell-mediated immune response at 3 weeks (T2) after complete RZV vaccination schedule. Interestingly, both humoral and cell-mediated immune responses were mostly stable over 6 months (T3). Interestingly, the overall IFNγ-producing lymphocytes was mainly associated with CD4 T cell response (p = .0012). In conclusion, data from our pilot study suggest a strong and long-lasting immunogenicity of RZV in ICI-treated patients. Prospective analyses at 1 year after vaccination will be performed in order to evaluate the long-term persistence of humoral and cell-mediated response against RZV.

BackgroundBalance impairments are common in people with multiple sclerosis (MS), with reduced ability to maintain position and delayed responses to postural adjustments. Pilates is a popular alternative method for balance training that may reduce the rapid worsening of symptoms and the increased risk of secondary conditions (eg, depression) that are frequently associated with physical inactivity. ObjectiveIn this paper, we aimed to describe the design, development, and usability testing of MS Fitness Intervention Training (MS-FIT), a Kinect-based tool implementing Pilates exercises customized for MS. MethodsMS-FIT has been developed using a user-centered design approach (design, prototype, user feedback, and analysis) to gain the target user’s perspective. A team composed of 1 physical therapist, 2 game programmers, and 1 game designer developed the first version of MS-FIT that integrated the knowledge and experience of the team with MS literature findings related to Pilates exercises and balance interventions based on exergames. MS-FIT, developed by using the Unity 3D (Unity Technologies) game engine software with Kinect Sensor V2 for Windows, implements exercises for breathing, posture, and balance. Feedback from an Italian panel of experts in MS rehabilitation (neurologists, physiatrists, physical therapists, 1 statistician, and 1 bioengineer) and people with MS was collected to customize the tool for use in MS. The context of MS-FIT is traveling around the world to visit some of the most important cities to learn the aspects of their culture through pictures and stories. At each stay of the travel, the avatar of a Pilates teacher shows the user the exercises to be performed. Overall, 9 people with MS (n=4, 44% women; mean age 42.89, SD 11.97 years; mean disease duration 10.19, SD 9.18 years; Expanded Disability Status Scale score 3.17, SD 0.75) were involved in 3 outpatient user test sessions of 30 minutes; MS-FIT’s usability was assessed through an ad hoc questionnaire (maximum value=5; higher the score, higher the usability) evaluating easiness to use, playability, enjoyment, satisfaction, and acceptance. ResultsA user-centered design approach was used to develop an accessible and challenging tool for balance training. All people with MS (9/9, 100%) completed the user test sessions and answered the ad hoc questionnaire. The average score on each item ranged from 3.78 (SD 0.67) to 4.33 (SD 1.00), which indicated a high usability level. The feedback and suggestions provided by 64% (9/14) of people with MS and 36% (5/14) of therapists involved in the user test were implemented to refine the first prototype to release MS-FIT 2.0. ConclusionsThe participants reported that MS-FIT was a usable tool. It is a promising system for enhancing the motivation and engagement of people with MS in performing exercise with the aim of improving their physical status.

ABSTRACT: Objectives: World Health Organization recommends a 7-drug 9–11-month rifampicin-resistant tuberculosis (RR-TB) short treatment regimen (STR). To reduce the pill burden, we assessed the safety and effectiveness of a 5-drug 9–11-month modified STR (mSTR). Methods: Prospective cohort study of an all-oral mSTR (comprising bedaquiline, levofloxacin, linezolid [LZD], clofazimine, and/or pyrazinamide) for patients with RR-TB without confirmed fluoroquinolone resistance, enrolled in Vietnam between 2020-2021. Results: A total of 108 patients were enrolled in this study. Overall, 63 of 74 (85%) achieved culture conversion at 2 months. Of 106 evaluated, 95 (90%) were successfully treated, six (6%) were lost-to-follow-up, one (1%) died, and four (4%) had treatment failure, including three with permanent regimen change owing to adverse events (AE) and one with culture reversion. Of 108, 32 (30%) patients encountered at least one AE. Of 45 AEs recorded, 13 (29%) were serious (hospitalization, life threatening, or death). The median time to AE was 3 months (IQR: 2-5). A total of 26 AEs led to regimen adaptation: either dose reduction (N = 1), drug temporary interruption (N = 19), or drug permanent discontinuation (N = 6, 4 attributed to LZD). Conclusion: The high treatment success of 5-drug mSTR might replace the 7-drug regimen in routine care. AEs were frequent, but manageable in most patients. Active AEs monitoring is essential, particularly when using LZD throughout.

Abstract Background Nutritional support, including nutritional counseling and oral nutritional supplements (ONS), has been recommended as a first-line strategy in patients with non-small cell lung cancer (NSCLC). Evidence on the efficacy of immunonutrition during immunotherapy in these patients is positive, but still limited some secondary endpoints, such as treatment toxicity and tolerance. We hypothesize that early systematic provision of ONS with a high-protein-high calorie mixture containing immunonutrients (Impact®) in addition to nutritional counseling, compared to nutritional counseling alone, is beneficial to patients with NSCLC receiving immunotherapy with or without chemotherapy. We designed the present study to evaluate the efficacy of early systematic provision of ONS enriched with immunonutrients compared to nutritional counseling alone, in patients with NSCLC undergoing immunotherapy. Study endpoints were: treatment response (primary endpoint: progression-free survival), treatment tolerance and toxicity, body weight, body composition, protein-calorie intake, quality of life, fatigue, muscle strength and immunological profile. Methods This is a pragmatic, multicentre, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial (N = 180). Discussion The improvement of efficacy of nutritional support in oncology still deserves many efforts. Immunonutrition represents a promising approach also in patients with NSCLC, but evidence on its efficacy on clinical outcomes during immunotherapy is still inconclusive. The present pilot study, which guarantees early high-quality nutritional care (assessment and treatment) to all patients in agreement with current guidelines and recommendations, could represent one of the first proofs of efficacy of early oral immunonutrition in patients with cancer undergoing immunotherapy. Further large randomized trials addressing the improvement of supportive care could be hypothesized, accordingly. Trial registration This study is registered on ClinicalTrials.gov Identifier: NCT05384873.

Background Malnutrition is a frequent problem in oncology and is associated with reduced response to cancer treatments, increased drug-related toxicity, higher rates of clinical complications, reduced quality of life (QoL) and worse prognosis. Guidelines on clinical nutrition in oncology emphasise the usefulness of early assessment of nutritional status for a prompt identification of malnutrition and the implementation of effective interventions, but no real-world clinical data are available on the adequate management of nutritional support in patients with cancer in Italy.Methods and analysis This is an observational, longitudinal, multicentre registry of patients with a new diagnosis of cancer or metastatic disease, candidates for active treatment. They will be identified in at least 15 Italian oncological centres, members of the Alliance Against Cancer Working Group ‘Survivorship Care and Nutritional Support’. At least 1500 patients with cancer are expected to be enrolled each year. Detailed clinical and nutritional data will be collected by oncologists and clinical nutritionists during the visits foreseen in the clinical practice, through an ad hoc developed digital platform (e-Nutracare). The effects of malnutrition and nutritional support—at diagnosis and during follow-up—on overall survival and progression-free survival, as well as on patients’ symptoms and QoL, will be investigated.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Fondazione IRCCS Policlinico San Matteo, Pavia, Italy and from the Ethics Committees of all other participating centres. An informed consent will be obtained from each patient enrolled in the study. Study findings will be disseminated through peer-reviewed journals, conferences and patients with cancer or professional associations. The registry will allow a better monitoring of the nutritional status of patients with cancer, promoting adequate and sustainable nutritional support, with the ultimate goal of improving the care and prognosis of these patients.

Avian influenza viruses (AIVs), which circulate endemically in wild aquatic birds, pose a significant threat to poultry and raise concerns for their zoonotic potential. From August 2021 to April 2022, a multi-site cross-sectional study involving active AIV epidemiological monitoring was conducted in wetlands of the Emilia-Romagna region, northern Italy, adjacent to densely populated poultry areas. A total of 129 cloacal swab samples (CSs) and 407 avian faecal droppings samples (FDs) were collected, with 7 CSs (5.4%) and 4 FDs (1%) testing positive for the AIV matrix gene through rRT-PCR. A COI-barcoding protocol was applied to recognize the species of origin of AIV-positive FDs. Multiple low-pathogenic AIV subtypes were identified, and five of these were isolated, including an H5N3, an H1N1, and three H9N2 in wild ducks. Following whole-genome sequencing, phylogenetic analyses of the hereby obtained strains showed close genetic relationships with AIVs detected in countries along the Black Sea/Mediterranean migratory flyway. Notably, none of the analyzed gene segments were genetically related to HPAI H5N1 viruses of clade 2.3.4.4b isolated from Italian poultry during the concurrent 2021–2022 epidemic. Overall, the detected AIV genetic diversity emphasizes the necessity for ongoing monitoring in wild hosts using diverse sampling strategies and whole-genome sequencing.

Abstract Background Hao-Fountain syndrome is a neurodevelopmental disorder characterized by global developmental delay, variably impaired intellectual development with significant speech delay and, in some males patients, it has been reported an association with hypogonadism. At present less than 50 cases are reported in literature. Case presentation We report a case of this rare syndrome in a young female with isolated tubal torsion; our patients had different hospitalizations without treatment but during the last episode we decide to perform an abdominal surgical explortion. This is the first case in Literature with a new USP7 mutation. Conclusions This case opens new perspective in this rare syndrome and a review approach to isolated tubal torsion. These symptoms should be always well checked.

Gastric cancer is the sixth most common malignancy in the world. However, its mortality has been decreasing in the last years thanks to improvement in diagnostics and therapeutics. Nevertheless, the high rate of malnutrition in patients with gastric cancer still has a major impact on the overall survival and quality of life of patients. The narrative review presents the most recent data on nutritional support in the resectable stages of gastric cancer, with a particular focus on perioperative strategies, and discusses malnutrition in gastric cancer, nutritional support before and after surgery, and the relationship between nutritional support and chemotherapy. Despite the predominantly methodological limitations related to the difficulty of performing randomized controlled trials on nutritional support in cancer patients, this review highlights important points. Nutritional counselling is essential starting from diagnosis. In limited or locally advanced forms (about 40% of cases), the therapeutic cornerstone is represented by gastric surgery. In most of these cases, perioperative chemotherapy is also indicated. Of note, nutritional support varies before and after surgery. In the preoperative period, the goal is to prepare the body for surgery, with available evidence recommending the prescription of immunonutrition (both oral and artificial, as appropriate). In the postoperative period, on the other hand, the objective is to facilitate recovery and adaptation to the new anatomy; an early and combined strategy (oral and enteral) seems to be the most suitable to pursue this. Unfortunately, rigorous data on the relationship between nutritional support and chemotherapy treatments used in resectable gastric cancer are not available. In the absence of strong scientific evidence, it may be useful to adopt a personalized multidisciplinary strategy for each patient wherein the chemotherapy programme is modulated based on nutritional status.

Cas9 proteins require a target-adjacent sequence, the PAM, in order to cleave DNA. Here the authors develop a pipeline to accurately predict PAM sequences in order to facilitate the identification of Cas9s targeting specific sequences, including mutations.

Tumour markers have no established role in the monitoring of the course of metastatic breast cancer during antineoplastic therapy, yet cancer antigen 15.3 (CA15.3) and carcinoembryonic antigen (CEA) are commonly used in clinical practice to aid in the early detection of progression of disease (PD). In our multicentre, prospective, real-life study, we enrolled 142 consecutive patients with advanced breast cancer receiving endocrine therapy in combination with a CDK4/6 inhibitor from January 2017 to October 2020; 75 patients had PD at the time of database closure. We measured serum marker concentrations at regular 4-month intervals together with radiological tumour response assessments and in cases of clinical suspicion of PD. Appropriate descriptive and inferential statistical methods were used to analyse serum marker level trends amongst prespecified subgroups and at specific time points (baseline, best radiologically documented tumour response and first detection of PD) in the subpopulation of patients with PD at the time of database closure. Notably, the median time from treatment initiation to best tumour response was 4.4 months. We evaluated the presence of an association between baseline CA15.3 and CEA levels and prespecified clinical characteristics but found no clinically meaningful correlation. We assessed marker level variations at the time of best radiologically documented disease response and PD: in the subgroup of patients who responded to treatment before progressing, we detected a statistically significant correlation with tumour marker variation between the time of best response and progression; this finding was not confirmed in the subgroup of patients that did not benefit from treatment. In conclusion, serum tumour marker flares can be useful in the early diagnosis of PD but should not be used as the sole factor prompting a change in treatment strategy without radiological confirmation. This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special_issues/tackling-clinical-complexity-in-breast-cancer/

BackgroundRefractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease.Patients and MethodsBetween 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 107 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters.ResultsAll patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (