Clinical utility of ctDNA by amplicon based next generation sequencing in first line non small cell lung cancer patients.

The assessment of ctDNA has emerged as a minimally invasive avenue for molecular diagnosis and real-time tracking of tumor progression in NSCLC. However, the evaluation of ctDNA by amplicon-based NGS has been not endorsed by all the healthcare systems and remains to be fully integrated into clinical routine practice. To compare tissue single-gene with plasma multiplexed testing, we retrospectively evaluated 120 plasma samples from 12 consecutive patients with advanced non-squamous NSCLC who were part of a prospective study enrolling treatment-naïve patients and in which tissue samples were evaluated using a single-gene testing approach. While the plasma ctDNA detection of EGFR and BRAF mutations had an acceptable level of concordance with the archival tissue (85%), discordance was seen in all the patients in whom ALK alterations were only detected in tissue samples. Among six responders and six non-responders, early ctDNA mutant allelic frequency (MAF) reduction seemed to predict radiologic responses and longer survival, whereas increasing MAF values with the emergence of co-mutations like BRAFV600E, KRASG12V or TP53M237I seemed to be an early indicator of molecular and radiologic progression. This report using an amplicon-based NGS assay on ctDNA underscores the real-life need for plasma and tissue genotyping as complementary tools in the diagnostic and therapeutic decision-making process.

Impact analysis of SARS-CoV-2 vaccination in patients treated with monoclonal antibodies: A monocentric experience.

BACKGROUND: Since the discovery of SARS-CoV-2, no treatment has been able to completely eradicate the virus. The study aimed to evaluate the virological and clinical impact of the vaccination in SARS-CoV-2 infected patients treated with monoclonal antibodies (mAbs). METHODS: This single-centre, observational, retrospective, real-life study was performed on SARS-CoV-2 symptomatic outpatients and inpatients treated with mAbs from March 2021 to November 2022 includes 726 patients. Each patient received available mAbs (bamlanivimab-etesevimab or casirivimab-indevimab or sotrovimab or tixagevimab-cilgavimab) according to the circulating virus strains. Age, comorbidities, vaccination status, death rates, duration of virological clearance, average length of stay, risk factors, and hospitalization or ICU admission were recorded. RESULTS: Of 726 patients with complete data analyzed (median age 64), 516 outpatients and 210 inpatients were included. Vaccination status was known for all participants: 74.4 % and 51.7 % were vaccinated against SARS-CoV-2 among inpatients and outpatients, respectively. A shorter duration of virological clearance was observed in the vaccinated group, with a median of 16 days (IQR 15-17), compared to 19 days (IQR 18-21) in the unvaccinated group [HR 1.21; p < 0.032]. Multivariate analysis of virological clearance also showed statistical significance with tixagevimab cilgavimab 300 mg/300 mg (HR 2.73, p value < 0.001). No significant difference was found in worsening [OR 1,29; p = 0.57] and mortality [OR 0.65; p = 0.81] rates between vaccinated and unvaccinated patients treated with mAbs. CONCLUSIONS: Key findings include a shorter duration of virological clearance in vaccinated outpatients but no significant differences in worsening or mortality rates between vaccinated and unvaccinated patients treated with mAbs. The study suggests a potential synergistic role of mAbs in accelerating virological clearance in vaccinated patients with mild to moderate COVID-19, with differing effects in hospitalized patients. Therefore, it is essential to implement health surveillance in high-risk patients with comorbidities in order to identify early any variants that might otherwise escape neutralizing antibodies.

Harnessing the potential of genomic characterization of mutational profiles to improve early diagnosis of lung cancer.

INTRODUCTION: Lung Cancer (LC) continues to be a leading cause of cancer-related mortality globally, largely due to the asymptomatic nature of its early stages and the limitations of current diagnostic methods such as Low-Dose Computed Tomography (LDCT), whose often result in late diagnosis, highlighting an urgent need for innovative, minimally invasive diagnostic techniques that can improve early detection rates. AREAS COVERED: This review delves into the potential of genomic characterization and mutational profiling to enhance early LC diagnosis, exploring the current state and limitations of traditional diagnostic approaches and the revolutionary role of Liquid Biopsies (LB), including cell-free DNA (cfDNA) analysis through fragmentomics and methylomics. New genomic technologies that allow for earlier detection of LC are scrutinized, alongside a detailed discussion on the literature that shaped our understanding in this field. EXPERT OPINION: Despite the promising advancements in genomic characterization techniques, several challenges remain, such as the heterogeneity of LC mutations, the high cost, and limited accessibility of Next-Generation Sequencing (NGS) technologies. Additionally, there is a critical need of standardized protocols for interpreting mutational data. Future research should focus on overcoming these barriers to integrate these novel diagnostic methods into standard clinical practice, potentially revolutionizing the management of LC patients.

Anesthesiologists ultrasound-guided regional anesthesia core curriculum: a Delphi consensus from Italian regional anesthesia experts.

INTRODUCTION: The need for a standardized core curriculum in regional anesthesia has become essential, particularly with the integration of ultrasound revolutionizing and exponentially increasing clinical practice and possibilities. In fact, numerous novel techniques, often overlapping, can confuse practitioners. This study aims to establish a core curriculum for upper limb, lower limb, paraspinal and fascial plane blocks for residency training, addressing potential educational gaps caused by the multitude of techniques, through a Delphi consensus process involving recognized Italian regional anesthesia experts. METHODS: A steering committee was formed in order to select a panel of experts in regional anesthesia. A three-round Delphi consensus was planned: two rounds of electronic voting and a final round of mixed electronic voting and round table discussion. The consensus was defined as ≥ 75% agreement for inclusion and lower than ≤ 25% agreement for exclusion from the core curriculum list. Techniques reaching the 50% threshold were included with low consensus. RESULTS: Twenty-nine techniques were selected to be included in the ultrasound-guided regional anesthesia core curriculum. Twenty-two were included with strong consensus: Upper limb: interscalene brachial plexus block, supraclavicular brachial plexus block, infraclavicular brachial plexus block, axillary brachial plexus block, intermediate cervical plexus block Lower limb: femoral nerve block, pericapsular nerve group block, adductor canal block, sciatic nerve block (transgluteal approach, infragluteal approach, and at the popliteal fossa), ankle block Paraspinal/fascial plane blocks: erector spinae plane block, deep serratus anterior plane block, superficial pectointercostal plane block, interpectoral plane block, pectoserratus plane block, rectus sheath block, ilioinguinal iliohypogastric nerves block, transversus abdominis plane block (with subcostal and midaxillary approaches) The remaining seven techniques were included with low consensus: superficial cervical plexus block, lumbar plexus block, fascia iliaca block (suprainguinal approach), anterior quadratus lumborum block, lateral quadratus lumborum block, paravertebral block, and serratus anterior plane block. CONCLUSIONS: This curriculum aims to standardize training and ensure that residents acquire the essential skills required for effective and safe practice regardless of the residents' subsequent specialization. By incorporating these techniques, educational programs can provide a structured and consistent approach to regional anesthesia, enhancing the quality of patient care and improving outcomes.

An overview of artemisinin-resistant malaria and associated Pfk13 gene mutations in Central Africa.

Malaria caused by Plasmodium falciparum is one of the deadliest and most common tropical infectious diseases. However, the emergence of artemisinin drug resistance associated with the parasite's Pfk13 gene, threatens the public health of individual countries as well as current efforts to reduce malaria burdens globally. It is of concern that artemisinin-resistant parasites may be selected or have already emerged in Africa. This narrative review aims to evaluate the published evidence concerning validated, candidate, and novel Pfk13 polymorphisms in ten Central African countries. Results show that four validated non-synonymous polymorphisms (M476I, R539T, P553L, and P574L), directly associated with a delayed therapy response, have been reported in the region. Also, two Pfk13 polymorphisms associated to artemisinin resistance but not validated (C469F and P527H) have been reported. Furthermore, several non-validated mutations have been observed in Central Africa, and one allele A578S, is commonly found in different countries, although additional molecular and biochemical studies are needed to investigate whether those mutations alter artemisinin effects. This information is discussed in the context of biochemical and genetic aspects of Pfk13, and related to the regional malaria epidemiology of Central African countries.

TTV and CMV viral load dynamics: Which emerges first during immunosuppression?

Novel biomarkers reflecting the degree of immunosuppression in transplant patients are required to ensure eventual personalized equilibrium between rejection and infection risks. With the above aim, Torque Teno Virus (TTV) viremia was precisely examined in a large cohort of transplanted immunocompromised patients (192 hematological and 60 solid organ transplant recipients) being monitored for Cytomegalovirus reactivation. TTV load was measured in 2612 plasma samples from 448 patients. The results revealed a significant increase in TTV viral load approximately 14 days following CMV reactivation/infection in solid organ transplant (SOT) patients. No recognizable difference in TTV load was noted among hematological patients during the entire timeframe analyzed. Furthermore, a temporal gap of approximately 30 days was noted between the viral load peaks reached by the two viruses, with Cytomegalovirus (CMV) preceding TTV. It was not possible to establish a correlation between CMV reactivation/infection and TTV viremia in hematological patients. On the other hand, the SOT patient cohort allowed us to analyze viral kinetics and draw intriguing conclusions. Taken together, the data suggest, to our knowledge for the first time, that CMV infection itself could potentially cause an increase in TTV load in the peripheral blood of patients undergoing immunosuppressive therapy.

Factors associated with the occurrence of maternal deaths in the West Region between 2020 - 2022: case control study.

WHO defines maternal mortality as any death of a woman occurring during pregnancy or within 42 days of its termination or after delivery. Our aim was to study the factors associated with the occurrence of maternal deaths in the West Region of Cameroon between 2020 and 2022. This was a case-control study. Cases consisted of maternal deaths that occurred during the study period. The controls for their part were made up of women who normally gave birth in the same health facilities from which the cases came and during the same period as the cases. The only exposure criterion being the status of death. The data useful for our investigation were collected respectively with the investigation sheets, audit reports and via interviews with the heads of the health facilities where the maternal deaths occurred with a view to considerably reducing information bias. Analysis were done with IBM-SPSS 25 and RStudio 2023.03.0. The West Region of Cameroon recorded 161 maternal deaths between 2020 and 2022. 67% of them were housewives. The most frequently identified causes were haemorrhage (ante-, per- and post-partum), followed far behind by complications and sepsis, with respective 42.2%, 12.4% and 10.6%. Slightly more than one child out of 10 had an abnormal presentation. Nearly 50% had a short labor (less than 10 hours), the partograph was used in 38% of the women, and the GATP practiced in 50.1% of them. Abnormal presentation of the fetus (aOR = 2.7 (95% CI: 1.4 - 5.1), p=0.002), failure to use the partograph (aOR = 4.4 (95% CI: 2 .6 - 7.4), p<0.001), the fact of not having an economic activity (aOR = 1.7 (95% CI: 1.0 - 2.7), p = 0.033), the fact of having taken less than 2 doses of VAT ( aOR = 2.8 (95% CI: 1.8 - 4.4), p<0.001) and the absence of practice of GATP (aOR = 1.6 (CI 95%: 1.0 - 2.6), p=0.040) were identified as factors that significantly favored the occurrence of maternal deaths. Several factors negatively influence the occurrence of maternal deaths in the West Region. Operational strategies such as continuous training of maternity ward staff, and the establishment of systematic maternal death audits and review meetings should be implemented to reduce and control these risk factors.

The Impact of potential 'confounders' on the diagnostic sensitivity of circulating free DNA in management of FIT+ patients: a pilot study.

Cell-free DNA (cfDNA) has long been established as a useful diagnostic and prognostic tool in a variety of clinical settings, ranging from infectious to cardiovascular and neoplastic diseases. However, non-neoplastic diseases can act as confounders impacting on the amount of cfDNA shed in bloodstream and on technical feasibility of tumour derived free circulating nucleic acids selecting patients with cancer. Here, we investigated the potential impact of other pathological processes in the clinical stratification of 637 FIT+ patients. A single and multiple logistic regression yielded similar results. Crude sensitivity was 75.9% versus adjusted sensitivity of 74.1%, relative risk 0.9761 (0.8516 to 1.1188), risk difference 0.0181 (-0.0835 to 0.1199) and OR 0.9079 (0.5264 to 1.5658). Potential confounding effect from other source of cfDNA plays a pivotal role in the clinical stratification of FIT+ patients.

The Long-Term Immunogenicity of mRNABNT162b Third Vaccine Dose in Solid Organ Transplant Recipients.

We investigated humoral and T-cell response to a SARS-CoV-2 mRNA vaccine in solid organ transplant recipients (SOT-Rs) and healthy donors (HDs) before (T0) and after two (T1) and twelve months (T2) since the third dose administration. SOT-Rs were stratified according to the transplanted organ and to the time elapsed since the transplant. In SOT-Rs, detectable levels of anti-S antibodies were observed in 44%, 81% and 88% at T0, T1 and T2, respectively. Conversely, anti-S antibody levels were detected in 100% of HD at all time points. Lower antibody titers were observed in SOT-Rs compared to HDs, even stratifying by transplanted organs and the time elapsed since transplant. Lower percentages of responding and polyfunctional T-cells were observed in SOT-Rs as well as in each subgroup of SOT-Rs compared to HDs. At both T0 and T1, in SOT-Rs, a predominance of one cytokine production shortly was observed. Conversely, at T2, a dynamic change in the T-cells subset distribution was observed, similar to what was observed in HDs. In SOT-Rs, the third dose increased the rate of seroconversion, although anti-S levels remained lower compared to HDs, and a qualitatively inferior T-cell response to vaccination was observed. Vaccine effectiveness in SOT-Rs is still suboptimal and might be improved by booster doses and prophylactic strategies.

PIK3CA testing in hormone receptor-positive/HER2-negative metastatic breast cancer: real-world data from Italian molecular pathology laboratories.

Introduction: PIK3CA gene mutations occur in approximately 40% of hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancers (MBCs), electing them to targeted therapy. Testing PIK3CA status is complex due to selection of biological specimen and testing method. Materials & methods: This work investigates real-life experience on PIK3CA testing in HR+/HER2- MBC. Clinical, technical and molecular data on PIK3CA testing were collected from two referral laboratories. Additionally, the results of a nationwide PIK3CA survey involving 116 institutions were assessed. Results: Overall, n = 35 MBCs were PIK3CA-mutated, with mutations mostly occurring in exons 9 (n = 19; 51.4%) and 20 (n = 15; 40.5%). The nationwide survey revealed significant variability across laboratories in terms of sampling methodology, technical assessment and clinical report signing healthcare figures for PIK3CA molecular testing in diagnostic routine practice. Conclusion: This study provides insights into the real-world routine of PIK3CA testing in HR+/HER2- MBC and highlights the need for standardization and networking in predictive pathology.

Molecular monitoring of viral infections in immunocompromised patients in a large university hospital in Italy: reflections after thirteen years of real-life activity.

PURPOSE: This study aimed to investigate the prevalence and viral reactivations of clinical interest in the immunocompromised patient with particular focus on hematologic and solid organ transplant recipients. METHODS: Molecular screening data of CMV, EBV, JCV and BKV from 2011 to 2023 were analyzed. This extensive time span allowed the access to more than 100,000 samples from over 20,000 patients treated at Policlinico Umberto I. It was possible to temporally investigate patient attendance patterns, average age distribution, seasonality of infections, and positivity rates of the analyzed viruses. RESULTS: Between 2019 and 2022 a significant reduction in organ transplants performed and in the positive molecular detection of EBV, JCV and BKV was observed. Additionally, there has been a noteworthy decrease in CMV reactivations, with a reduction of up to 50% starting in 2019. A remarkable reduction of 39% in the rate of CMV viral reactivation has been also achieved in SOT between 2016 and 2023. CONCLUSION: The years following 2019 were profoundly impacted by the COVID-19 pandemic era. This period resulted in a substantial reduction in healthcare services and hospital visits. Furthermore, the introduction of the drug Letermovir in Italy in 2019 demonstrated remarkable efficacy, evidenced by a reduction in CMV reactivations. Additionally, the adoption of a novel clinical approach centered on personalized therapy facilitated improved management of immunocompromised patients.

Cost saving in implementing ERAS protocol in emergency abdominal surgery.

INTRODUCTION: ERAS (Enhanced Recovery After Surgery) protocol is now proposed as the standard of care in elective major abdominal surgery. Implementation of the ERAS protocol in emergency setting has been proposed but his economic impact has not been investigated. Aim of this study was to evaluate the cost saving of implementing ERAS in abdominal emergency surgery in a single institution. METHODS: A group of 80 consecutive patients treated by ERAS protocol for gastrointestinal emergency surgery in 2021 was compared with an analogue group of 75 consecutive patients treated by the same surgery the year before implementation of ERAS protocol. Adhesion to postoperative items, length of stay, morbidity and mortality were recorded. Cost saving analysis was performed. RESULTS: 50% Adhesion to postoperative items was reached on day 2 in the ERAS group in mean. Laparoscopic approach was 40 vs 12% in ERAS and control group respectively (p ,002). Length of stay was shorter in ERAS group by 3 days (9 vs 12 days p ,002). Morbidity and mortality rate were similar in both groups. The ERAS group had a mean cost saving of 1022,78 € per patient. CONCLUSIONS: ERAS protocol implementation in the abdominal emergency setting is cost effective resulting in a significant shorter length of stay and cost saving per patient.

The role of liquid biopsy in epithelial ovarian cancer: State of the art.

The clinical implementation of liquid biopsy has dramatically modified the analytical paradigm for several solid tumors. To date, however, only circulating free DNA (cfDNA) has been approved in clinical practice to select targeted treatments for patients with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and breast cancer (BC). Interestingly, emerging liquid biopsy analytes in peripheral blood, including circulating tumor cells (CTC), miRNA, and extracellular vesicles (EVs), have been shown to play a crucial role in the clinical management of solid tumor patients. Here, we review how these blood-based biomarkers may positively impact early diagnosis, prognosis, and treatment response in ovarian cancer (OC) patients.

Non-Small Cell Lung Cancer Testing on Reference Specimens: An Italian Multicenter Experience.

INTRODUCTION: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. METHODS: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon 19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon 2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene 1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon 14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico II before shipment. Methodological and molecular data from reference specimens were annotated. RESULTS: Overall, a median DNA concentration of 3.3 ng/µL (range 0.1-10.0 ng/µL) and 13.4 ng/µL (range 2.0-45.8 ng/µL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7 ng/µL (range 0.2-11.9 ng/µL) and 9.3 ng/µL (range 0.5-18.0 ng/µL) were also detected. KRAS exon 2 p.G12C, EGFR exon 19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon 14 skipping mutation. CONCLUSIONS: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice.

The lack of head-to-head randomised trials and the consequences for patients and national health service: The case of non-small cell lung cancer.

INTRODUCTION: To introduce a drug to the market, it's not mandatory for it to be more effective and safer than the current treatment for the same condition. Consequently, head-to-head studies between the two best treatments for the same condition are not required, and this could result in a lack of information for patients, clinicians, and decision-makers. This study aims to evaluate the presence of head-to-head studies among the drugs used for the treatment of non-small cell lung cancer (NSCLC). METHODS: Taking into account the National Comprehensive Cancer Network (NCCN) guidelines updated to 2022, which list all available treatments for each NSCLC subtype, the search engine Pubmed and the platform clinicaltrials.gov were consulted to find all completed and ongoing head-to-head studies among various treatments for NSCLC. RESULTS: Among the anti-EGFR (epidermal growth factor receptor) drugs, 7 studies were found, with 6 completed and 5 registrational for drug commercialisation. No completed study to date has compared osimertinib and afatinib. For anti-ALK (anaplastic lymphoma kinase) drugs, 7 studies were found, with 5 completed. Alectinib, brigatinib, and lorlatinib have no completed comparison studies, but all were compared with crizotinib. Among various immunotherapy-based regimens, 5 studies were found, with only 1 completed. Therapeutic regimens based on pembrolizumab, atezolizumab, or the combination of nivolumab/ipilimumab have not been compared in studies published to date. CONCLUSION: There are few head-to-head studies comparing treatments for NSCLC; there are no such studies between the latest generation of drugs. Consequently, ambiguous areas exist due to the lack of comparative studies among the available evidence, preventing the clinician's choice of the most effective treatment and risking the patient receiving suboptimal therapy. Simultaneously, the price of the drug cannot be determined correctly, relying only on indirect evaluations from different trials. To dispel this uncertainty, it would be desirable to initiate a process that brings together the demands derived from clinical practice and clinical research to provide clinicians and patients with the best possible evidence.

Liquid biopsy: A promising tool for driving strategies and predicting failures in patients with classic Hodgkin lymphoma.

Classic Hodgkin lymphoma (cHL) consists of a heterogeneous group of haematological disorders that covers undifferentiated B cell neoplasms originating from germinal centre B cells. The HL molecular characterization still represents an ongoing challenge due to the low fraction of tumour Hodgkin and Reed-Sternberg cells mixed with a plethora of non-tumour haematological cells. In this scenario, next generation sequencing of liquid biopsy samples is emerging as a useful tool in HL patients' management. In this review, we aimed to overview the clinical and methodological topics regarding the implementation of molecular analysis in cHL, focusing on the role of liquid biopsy in diagnosis, follow-up, and response prediction.

Genomic profiling of tissue and blood predicts survival outcomes in patients with resected pleural mesothelioma.

PURPOSE: Pleural mesothelioma (PM) is an aggressive tumor still considered incurable, in part due to the lack of predictive biomarkers. Little is known about the clinical implications of molecular alterations in resectable PM tissues and blood. Here, we characterized genetic alterations to identify prognostic and predictive biomarkers in patients with resected PM. EXPERIMENTAL DESIGN: Targeted next-generation sequencing was performed in retrospective pleural tumor tissue and paired plasma samples from stage IB-IIIB resected PM. Association between prognosis and presence of specific mutations was validated in silico. RESULTS: Thirty PM tissues and paired blood samples from 12 patients were analyzed. High tissue tumor mutational burden (TMB) (>10 mutations/Mb), tissue median minor allele frequency (MAF) (>9 mutations/Mb), and blood TMB (>6 mutations/Mb), tissue KMT2C, PBRM1, PKHD1,EPHB1 and blood LIFR mutations correlated with longer disease-free survival and/or overall survival. High concordance (>80%) between tissue and blood was found for some mutations. CONCLUSIONS: Tissue TMB and MAF, blood TMB, and specific mutations correlated with outcomes in patients with resected PM and should be further studied to validate their role as prognostic biomarkers and potentially predictive factors for combinations with immune-checkpoint inhibitors. This suggest that molecular profiling could identify longer survivors in patients with resected PM.

Steroid use in measles: A retrospective cohort study during the 2017 outbreak in tertiary referral center, Rome and Latina, Italy.

INTRODUCTION: Since early January 2017, a new measles outbreak in Italy has been observed. The aim of the study was to compare features between adults and children measles cases and evaluate the effect of steroid treatment on the above parameters. METHODS: A retrospective multicenter, descriptive study was performed. We analyzed all patients admitted to the Department of Public Health and Infectious Diseases, Sapienza University, Rome and Latina, from January 2017 to December 2017 and discharged with diagnosis of measles. RESULTS: We identified 113 patients discharged with the diagnosis of measles infection cases of which 59 adults and 54 children (≤16 years). In adult population 32 patients (54 %) were males, with a median age of 30.5 years old and all unvaccinated (100 %). Keratoconjunctivitis 30 (50 %) was the most frequent complication. In pediatric population 27 (50 %) patients were males, with a median age of 3 years old. Information on measles vaccination status was available for only 21 (38.8 %) of cases. Keratoconjunctivitis 40 (74 %) was the most frequent complication. Analyzing the differences between adult and pediatric patients we found that children were significantly more likely to have keratoconjunctivitis and diarrhea as complications than adults in which the rate of thrombocytopenia and hepatitis was highest. Thirty-nine adult subjects (66 %) have been treated with systemic corticosteroids. CONCLUSIONS: Pediatric patients differ from adults in complications and liver involvement. Regarding steroids use, although there is no clear indication of steroid use during measles, there is no evidence of a worse outcome in our cases series.

Rollout of the 2022/2023 Seasonal Influenza Vaccination and Correlates of the Use of Enhanced Vaccines among Italian Adults.

In Italy, several types of seasonal influenza vaccines (SIVs) are available for older adults, but for the 2022/2023 season there were no guidelines on their specific use. This cross-sectional study assessed the frequency and determinants of the use of enhanced (adjuvanted and high-dose) SIVs in Italian older adults, as compared to standard-dose non-adjuvanted formulations. Of 1702 vaccines administered to a representative outpatient sample of adults aged ≥ 60 years and residing in Genoa, 69.5% were enhanced SIVs. Older age (adjusted odds ratio (aOR) for each 1-year increase 1.10; p < 0.001), and the presence of cardiovascular disease (aOR 1.40; p = 0.011) and diabetes (aOR 1.62; p = 0.005) were associated with the use of enhanced vaccines. Compared with the adjuvanted SIV, subjects immunized with the high-dose vaccine were older (aOR for each 1-year increase 1.05; p < 0.001) and had higher prevalence of respiratory diseases (aOR 1.85; p = 0.052). Moreover, usage of the enhanced SIVs was driven by the period of immunization campaign, place of vaccination and physician. Despite their superior immunogenicity and effectiveness, the adoption of enhanced SIVs in Italy is suboptimal, and should be increased. Enhanced formulations are mostly used in the oldest, and in subjects with some co-morbidities.