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Francesca Battaglin,1 Alberto Puccini,2 Selma Ahcene Djaballah,3 Heinz-Josef Lenz11Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; 2Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 3Medical Oncology Unit 1, Clinical and Experimental Oncology Department, Veneto Institute of Oncology IOV - IRCCS, Padua 35128, ItalyAbstract: Panitumumab is a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR). It is currently approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC) in combination with chemotherapy in first- and second-line and as monotherapy in chemorefractory patients. This review will provide an overview of main efficacy data on panitumumab from its early development up to latest evidences, including novel perspectives on predictive biomarkers of anti-EGFRs efficacy and mechanisms of secondary resistance. Quality of life (QoL) related issues and panitumumab safety profile will be addressed as well.Keywords: panitumumab, colorectal cancer, EGFR, RAS, biomarker, quality of life

AbstractLocally advanced head and neck squamous cell carcinoma (LA-HNSCC) is characterized by high rate of recurrence, resulting in a poor survival. Standard treatments are associated with significant toxicities that impact the patient’s quality of life, highlighting the urgent need for novel therapies to improve patient outcomes. On this regard, noble metal nanoparticles (NPs) are emerging as promising agents as both drug carriers and radiosensitizers. On the other hand, co-treatments based on NPs are still at the preclinical stage because of the associated metal-persistence.In this bioconvergence study, we introduce a novel strategy to exploit tumour chorioallantoic membrane models (CAMs) in radio-investigations within clinical equipment and evaluate the performance of non-persistent nanoarchitectures (NAs) in combination with radiotherapy with respect to the standard concurrent chemoradiotherapy for the treatment of HPV-negative HNSCCs. A comparable effect has been observed between the tested approaches, suggesting NAs as a potential platinum-free agent in concurrent chemoradiotherapy for HNSCCs. On a broader basis, our bioconvergence approach provides an advance for the translation of Pt-free radiosensitizer to the clinical practice, positively shifting the therapeutic vs. side effects equilibrium for the management of HNSCCs.

Background: Patients with metastatic colorectal cancer (mCRC) carrying a deficit in the mismatch repair system/microsatellite instability (dMMR/MSI) show great responses to immune checkpoint inhibitors. However, 30% of patients with dMMR/MSI are primarily immunoresistant, and another 30% develop secondary resistance. Thus several combinations such as anti-programmed cell death protein 1 (anti-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) are being pursued. The combination of radiotherapy and immunotherapy is another avenue of research that can increase the release of neoantigens resulting in the abscopal effect. This phenomenon has demonstrated promising potential activity in colon cancer preclinical studies; nevertheless, clinical results are limited to just a few case series. Patients and methods: We conducted a prospective interventional single-institution study to assess the feasibility, safety, and disease control rate of the combination of pembrolizumab and stereotactic ablative radiotherapy (SABR) in a cohort of 14 consecutive patients with dMMR/MSI mCRC. Results: Among the 14 patients enrolled, 11 received SABR in combination with pembrolizumab as the first to the fourth line. The disease control rate was 50% in the intention-to-treat population, with six patients still maintaining the response after >15 months. Any-grade treatment-related adverse events occurred in 50% of patients, with grade 3 (G3) events in three patients; no treatment-related death occurred. Conclusions: Our findings convey no signal of enhanced systemic efficacy compared with historical data on pembrolizumab alone even if the local control rate is high. To our knowledge, this represents the largest study conducted in this population; further studies could extend the knowledge on the toxicity profile of this combination.

Parathyroid lipoadenoma is an uncommon type of parathyroid adenoma and a rare cause of primary hyperparathyroidism (PHPT). The rarity of this entity, the difficult detection on imaging and the resemblance with normal parathyroid tissue microscopically makes its diagnosis difficult. We reported the case of an asymptomatic 48-year-old male treated for amiodarone-induced thyrotoxicosis and incidental sporadic PHPT, that supplements and supports the rare literature data concerning the knowledge, diagnosis, and treatment of parathyroid lipoadenoma.

Abstract Background Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. Methods Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. Results The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. Conclusions Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

Myriophyllum aquaticum (Vell.) Verdc., an invasive aquatic plant from South America, is to date worldwide distributed. In Tuscany M. aquaticum has colonized much of the surface water network of reclamation channels, forcing the reclamation authority to its removal, with the production of a huge amount of wet biomass to be disposed as a biological waste. In the present study the hydrothermal carbonization (HTC) process was proposed and investigated as a path for the valorisation of this waste biomass. Performed in aqueous conditions at moderate temperatures, HTC does not require energy-intensive pre-drying steps, making HTC applicable to biomass feedstocks with high moisture contents. HTC leads to a carbonaceous solid product, referred to as hydrochar, with different potential applications, such as solid biofuel, or soil-improving material. An experimental investigation was carried out performing HTC tests in a laboratory-scale reactor. The joint effect of operating parameters (temperature, residence time and solid load) on process yields and hydrochar properties was investigated by Design of Experiments – Response Surface Methodology (DoE-RSM), a statistical and mathematical approach for process analysis, prediction, and optimization. The results obtained demonstrated the feasibility of HTC for M. aquaticum, suggesting HTC as a promising treatment path. Beyond the use as biofuel, the suitability of the hydrochar produced from M. aquaticum as organic growth medium for vegetable seedlings in horticulture and gardening or soil amendment was evaluated. Potential phytotoxic effects of M. aquaticum hydrochar were evaluated through bioassays using cress seeds (Lepidium sativum L.) as a model species.

Hydrothermal Carbonization (HTC) represents a promising green technology for converting various biomass feedstocks into valuable hydrochar and liquid products. In this study, the HTC process of Myriophyllum aquaticum Verd., highly diffused in Tuscany (Italy), was investigated varying the process temperatures and the holding times. Indeed, it is one of the world's most troublesome invasive aquatic weeds, impacting not only the quality of water but also contributing to habitat deterioration; therefore, several management practices are required to address the problem. This research focused on obtaining preliminary experimental data to be further implemented in a lumped kinetic model to elucidate the reaction pathways leading to the formation of primary hydrochar and liquid compounds responsible for secondary hydrochar production. To figure out the HTC liquid phase composition and the organic compounds responsible for secondary hydrochar formation, the High-Performance Liquid Chromatography (HPLC) analytical technique was employed. This technique allowed to identify and quantify some of key chemical components present in the HTC liquid phase, i.e., sugars and furans. Moreover, the future integration of a lumped kinetic model and advanced analytical techniques not only will enhance the understanding of the Myriophyllum aquaticum HTC process but will also provide valuable insights into the optimization of HTC conditions for biomass conversion and resource recovery.

Caterina Fieschi (1447-1510) était une aristocrate de Gênes, souhaitant s’engager dans la vie religieuse mais forcée au mariage par sa famille. Après avoir eu une vision mystique, elle consacra toute son existence aux miséreux et aux malades, impliquant même son mari dans sa pratique de rigueur morale. Il choisira en effet de la soutenir dans ses activités caritatives et d’assistanat à l’hôpital de Pammatone (dont elle prendra la gestion), à l’Hôpital degli Incurabili et à la Léproserie de San Lazzaro.

Berries represent healthy dietary options and contain bioactive compounds associated with a decreased risk of diseases. Despite representing healthy food choices, these products can be contaminated by pathogenic microorganisms, including parasites. Among foodborne parasites, Giardia duodenalis, Cryptosporidium parvum, Cyclospora cayetanensis, Toxoplasma gondii, and Echinococcus multilocularis are of significant public health importance and have been recently detected in fresh berries in Europe, including Italy. Berries can be purchased fresh or frozen, and it is worrying that even frozen berries could represent a risk for the consumer. In fact, several parasites can resist freezing temperatures and have been responsible for outbreaks of infection. The aim of this study was to investigate the presence of G. duodenalis, C. parvum, C. cayetanensis, T. gondii, and E. multilocularis in frozen berries with simplex and multiplex real-time PCR protocols. A total of 108 packages of mixed frozen berries were bought from supermarkets located in a south-eastern region of Italy. The samples were tested using two simplex real-time PCR protocols targeting C. parvum and G. duodenalis, respectively, and a multiplex real-time PCR targeting C. cayetanensis, T. gondii, and E. multilocularis. None of the investigated parasites were detected in the frozen berry samples tested. This research topic is still unexplored and of great current interest. These results represent a first attempt to investigate parasitic contamination of frozen berries sold on the Italian market, but further large-scale surveys are required.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.

FLASH-radiotherapy delivers a radiation beam a thousand times faster compared to conventional radiotherapy, reducing radiation damage in healthy tissues with an equivalent tumor response. Although not completely understood, this radiobiological phenomenon has been proved in several animal models with a spectrum of all kinds of particles currently used in contemporary radiotherapy, especially electrons. However, all the research teams have performed FLASH preclinical studies using industrial linear accelerator or LINAC commonly employed in conventional radiotherapy and modified for the delivery of ultra-high-dose-rate (UHDRs). Unfortunately, the delivering and measuring of UHDR beams have been proved not to be completely reliable with such devices. Concerns arise regarding the accuracy of beam monitoring and dosimetry systems. Additionally, this LINAC totally lacks an integrated and dedicated Treatment Planning System (TPS) able to evaluate the internal dose distribution in the case of in vivo experiments. Finally, these devices cannot modify dose-time parameters of the beam relevant to the flash effect, such as average dose rate; dose per pulse; and instantaneous dose rate. This aspect also precludes the exploration of the quantitative relationship with biological phenomena. The dependence on these parameters need to be further investigated. A promising advancement is represented by a new generation of electron LINAC that has successfully overcome some of these technological challenges. In this review, we aim to provide a comprehensive summary of the existing literature on in vivo experiments using electron FLASH radiotherapy and explore the promising clinical perspectives associated with this technology.

Background: International guidelines recommend universal screening for Lynch syndrome (LS) through somatic DNA mismatch repair deficiency (dMMR) testing in all colorectal cancers (CRCs). However, LS remains largely underdiagnosed. Mainstreaming LS diagnosis through oncologist-driven genetic testing could increase detection rates, thus extending the benefits of precision prevention to patients with LS and their families. We aim to evaluate the feasibility of the mainstreaming diagnostic algorithm for LS. Patients and methods: ItaLynch is an ongoing, prospective, observational, multicenter, multidisciplinary, Italian study in patients with dMMR CRC. Being descriptive in nature, it does not attempt to test any specific, a priori, hypothesis. Patients with dMMR CRC are selected by universal screening by immunohistochemistry (IHC). In MLH1-deficient patients, reflex testing for BRAFV600E and, when appropriate, for MLH1 promoter hypermethylation is carried out. For all dMMR CRC, a ‘Lynch Alert’ is added to the pathology report: positive when a patient is at high risk for LS, due to reflex testing results or to loss of non-MLH1 proteins. Conversely, a ‘Lynch Alert’ is negative when the patient is likely to be a nonhereditary case (i.e. MLH1 loss and BRAFV600E or MLH1 promoter hypermethylation). In patients with a positive ‘Lynch Alert’, after providing a brief explanation about the risks and benefits of genetic testing, the oncologist asks patients for their consent to mainstream genetic testing. Thus a blood sample is drawn for constitutional variants of the MMR genes. Carriers of a germline variant are then referred to post-test genetic counseling. Referral to clinical genetic services is also advised for patients with clinical suspect criteria.

Background and purposeBrain cavernous angiomas with symptomatic hemorrhage (CASH) have a high risk of neurological disability from recurrent bleeding. Systematic assessment of baseline features and multisite validation of novel magnetic resonance imaging biomarkers are needed to optimize clinical trial design aimed at novel pharmacotherapies in CASH.MethodsThis prospective, multicenter, observational cohort study included adults with unresected, adjudicated brain CASH within the prior year. Six US sites screened and enrolled patients starting August 2018. Baseline demographics, clinical and imaging features, functional status (modified Rankin Scale and National Institutes of Health Stroke Scale), and patient quality of life outcomes (Patient-Reported Outcomes Measurement Information System-29 and EuroQol-5D) were summarized using descriptive statistics. Patient-Reported Outcomes Measurement Information System-29 scores were standardized against a reference population (mean 50, SD 10), and one-sample t test was performed for each domain. A subgroup underwent harmonized magnetic resonance imaging assessment of lesional iron content with quantitative susceptibility mapping and vascular permeability with dynamic contrast-enhanced quantitative perfusion.ResultsAs of May 2020, 849 patients were screened and 110 CASH cases enrolled (13% prevalence of trial eligible cases). The average age at consent was 46±16 years, 53% were female, 41% were familial, and 43% were brainstem lesions. At enrollment, ≥90% of the cohort had independent functional outcome (modified Rankin Scale score ≤2 and National Institutes of Health Stroke Scale score 30% of patients (EuroQol-5D). Patients had significantly worse Patient-Reported Outcomes Measurement Information System-29 scores for anxiety (P=0.007), but better depression (P=0.002) and social satisfaction scores (P=0.012) compared with the general reference population. Mean baseline quantitative susceptibility mapping and permeability of CASH lesion were 0.45±0.17 ppm and 0.39±0.31 mL/100 g per minute, respectively, which were similar to historical CASH cases and consistent across sites.ConclusionsThese baseline features will aid investigators in patient stratification and determining the most appropriate outcome measures for clinical trials of emerging pharmacotherapies in CASH.

The major challenge in the current context of the rising world energy demand is to limit the global temperature increase for mitigating climate change. This goal requires a large reduction of CO2 emissions, mainly produced by power generation and industrial processes using fossil fuels. In this study, a novel methodology for K2CO3-doped Li4SiO4 sorbents production for CO2 capture at high temperatures was adopted based on the Design of Experiments (DoE). This innovative approach systematically tested different synthesis (temperature and K2CO3 content) and adsorption conditions (sorption temperature and CO2 concentration), allowing for the assessment of individual and interactive effects of process parameters. The Response Surface Methodology (RSM) was employed to obtain non-linear predictive models of CO2 uptake and Li4SiO4 conversion. The results of RSM analysis evidenced a maximum adsorption capacity of 196.4 mg/g for a sorbent produced at 600 °C and with 36.9 wt% of K2CO3, tested at 500 °C and 4 vol% of CO2. Whereas at 50 vol% of CO2, the best uptake of 295.6 mg/g was obtained with a sorbent synthesized at 600 °C, containing less K2CO3 (17.1 wt%) and tested at a higher temperature (662 °C). These findings demonstrate that K2CO3-doped Li4SiO4 sorbents can be tailored to maximize CO2 capture under various operating conditions, making them suitable for use in industrial processes.

Introducción. La baja agudeza es un problema de salud pública en el mundo, que aumenta año tras año, relacionada con factores comportamentales poco saludables como el sedentarismo. La baja agudeza afecta especialmente a escolares, en quienes la visión representa uno de los sistemas más importantes para su desarrollo, tanto para el aprendizaje como para las relaciones sociales. El objetivo es establecer asociación entre baja agudeza visual y características sociodemográficas y comportamentales en una población escolar de la ciudad de Bucaramanga, Colombia. Metodología. Estudio observacional de corte transversal basado en datos recolectados de encuestas a estudiantes de una institución educativa de Bucaramanga entre los años 2006 y 2017, sobre las cuales se realizó un análisis bivariado entre características sociodemográficas y comportamentales con baja agudeza visual. Resultados. La prevalencia de baja agudeza visual fue de 33.57%, con mayor prevalencia de baja agudeza visual en mujeres y aquellos con mayor índice de masa corporal. La agudeza visual baja no tuvo asociación estadísticamente significativa con las otras variables estudiadas. Discusión. Las mujeres tienen una mayor prevalencia de baja agudeza visual. Parece existir una relación entre la actividad física y la agudeza visual. Conclusiones. Las diferencias encontradas según el sexo pueden deberse a patrones comportamentales diferentes entre hombres y mujeres, como la actividad física y el sedentarismo. Hacen falta estudios que evalúen la causalidad de la asociación entre los problemas de agudeza visual y los hábitos de vida poco saludables. Introduction. Low visual acuity is a public health problem worldwide, which is increasing year by year, and it is associated with unhealthy behavioral factors such as sedentary lifestyle. Low visual acuity particularly affects schoolchildren, whom eyesight is one of the most important abilities for their development, both in terms of learning and social interactions. The objective of this study is to establish an association between low visual acuity, sociodemographic, and behavioral characteristics of a student population in Bucaramanga, Colombia. Methodology. This was a cross-sectional observational study based on data collected from surveys of students within an educational institution sited in Bucaramanga between 2006 and 2017. A bivariate analysis was conducted between sociodemographic and behavioral characteristics and low visual acuity. Results. The prevalence of low visual acuity was 33.57%, with a higher prevalence of low visual acuity in women and those with a higher body mass index. However, low visual acuity didn’t have a statistically significant association with the other variables studied. Discussion. Women have a higher prevalence of low visual acuity. There appears to be an association between physical activity and visual acuity. Conclusions. The encountered differences according to sex may be due to different behavioral patterns between males and females, such as physical activity and sedentary lifestyle. Further studies are needed to assess the causality of the association. Introdução. A baixa acuidade é um problema de saúde pública no mundo, que aumenta a cada ano, relacionada a fatores comportamentais pouco saudáveis, como o sedentarismo. A baixa acuidade atinge especialmente as crianças em idade escolar, para as quais a visão representa um dos sistemas mais importantes para o seu desenvolvimento, tanto para a aprendizagem quanto para as relações sociais. O objetivo é estabelecer uma associação entre baixa acuidade visual e características sociodemográficas e comportamentais em uma população escolar na cidade de Bucaramanga, Colômbia. Metodologia. Estudo observacional transversal baseado em dados coletados em pesquisas com estudantes de uma instituição de ensino de Bucaramanga entre 2006 e 2017, nos quais foi realizada uma análise bivariada entre características sociodemográficas e comportamentais com baixa acuidade visual. Resultados. A prevalência de baixa acuidade visual foi de 33.57%, com maior prevalência de baixa acuidade visual em mulheres e naqueles com maior índice de massa corporal. A baixa acuidade visual não teve associação estatisticamente significativa com as demais variáveis estudadas. Discussão. As mulheres apresentam maior prevalência de baixa acuidade visual. Parece haver uma relação entre atividade física e acuidade visual. Conclusões. As diferenças encontradas segundo o sexo podem ser decorrentes de diferentes padrões comportamentais entre homens e mulheres, como atividade física e sedentarismo. Estudos são necessários para avaliar a causalidade da associação entre problemas de acuidade visual e hábitos de vida pouco saudáveis.

Objectives: To identify the impact of birth weight on the development of metalinguistic skills and performance in reading, writing, and arithmetic in students aged 6 to 10 years, enrolled from the 1st to the 4th grade of Elementary School in public schools of the metropolitan region of São Paulo. Methods: The concurrent cohort included 315 students. Birth weight was the exposure variable, and the outcomes were performance in receptive and expressive language, oral metalinguistic skills, and performance in writing, arithmetic, and reading. The tools employed were the Test of Language Competence (TLC) and the School Performance Test (SPT). Students were grouped into quartiles by birth weight for data analysis (P1: < 2170 g, P2: from 2171 g to 2450 g, P3: from 2451 g to 3150 g, and P4: > 3150 g). Results: The authors observed a tendency for the lower performance of the two groups with lower birth weights in listening comprehension and oral expression. The lower-weight group tended to perform poorly compared to the other groups vis-à-vis reading. In the global result of the SPT, worse performance was observed in the students in the first quartile compared to the others (p = 0.019). The multivariate analysis revealed no association between birth weight and results in the tests applied after adjusting for maternal schooling. Conclusions: Birth weight can interfere with oral and written language development. However, the determination of these processes occurs in the face of complex interaction that includes sociodemographic factors, especially family support and maternal schooling.

Abstract Polybromo-1 (PBRM1) loss of function mutations are present in a fraction of biliary tract cancers (BTCs). PBRM1, a subunit of the PBAF chromatin-remodeling complex, is involved in DNA damage repair. Herein, we aimed to decipher the molecular landscape of PBRM1 mutated (mut) BTCs and to define potential translational aspects. Totally, 1848 BTC samples were analyzed using next-generation DNA-sequencing and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). siRNA-mediated knockdown of PBRM1 was performed in the BTC cell line EGI1 to assess the therapeutic vulnerabilities of ATR and PARP inhibitors in vitro. PBRM1 mutations were identified in 8.1% (n = 150) of BTCs and were more prevalent in intrahepatic BTCs (9.9%) compared to gallbladder cancers (6.0%) or extrahepatic BTCs (4.5%). Higher rates of co-mutations in chromatin-remodeling genes (e.g., ARID1A 31% vs. 16%) and DNA damage repair genes (e.g., ATRX 4.4% vs. 0.3%) were detected in PBRM1-mutated (mut) vs. PBRM1-wildtype (wt) BTCs. No difference in real-world overall survival was observed between PBRM1-mut and PBRM1-wt patients (HR 1.043, 95% CI 0.821–1.325, p = 0.731). In vitro, experiments suggested that PARP ± ATR inhibitors induce synthetic lethality in the PBRM1 knockdown BTC model. Our findings served as the scientific rationale for PARP inhibition in a heavily pretreated PBRM1-mut BTC patient, which induced disease control. This study represents the largest and most extensive molecular profiling study of PBRM1-mut BTCs, which in vitro sensitizes to DNA damage repair inhibiting compounds. Our findings might serve as a rationale for future testing of PARP/ATR inhibitors in PBRM1-mut BTCs.

To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients’ characteristics and median treatment duration of biologics approved for IMIDs between RCTs’ and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8–1.9) compared to RCTs (F/M ratio: 0.5–0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4–100 vs. 6–167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.