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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.
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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.
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Infecções por Citomegalovirus , Citomegalovirus , Infecções por Vírus de DNA , Hospedeiro Imunocomprometido , Torque teno virus , Carga Viral , Viremia , Humanos , Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/sangue , Masculino , Infecções por Vírus de DNA/virologia , Infecções por Vírus de DNA/sangue , Infecções por Vírus de DNA/imunologia , Pessoa de Meia-Idade , Feminino , Adulto , Terapia de Imunossupressão/efeitos adversos , Ativação Viral , Transplantados/estatística & dados numéricos , Idoso , Estudos de CoortesRESUMO
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.
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Antimaláricos , Artemisininas , Resistência a Medicamentos , Malária Falciparum , Mutação , Plasmodium falciparum , Proteínas de Protozoários , Humanos , África Central/epidemiologia , Antimaláricos/farmacologia , Artemisininas/farmacologia , Malária Falciparum/parasitologia , Malária Falciparum/epidemiologia , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/genética , Plasmodium falciparum/efeitos dos fármacos , Polimorfismo Genético , Proteínas de Protozoários/genéticaRESUMO
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.
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Mortalidade Materna , Humanos , Feminino , Camarões/epidemiologia , Estudos de Casos e Controles , Gravidez , Adulto , Mortalidade Materna/tendências , Fatores de Risco , Complicações na Gravidez/mortalidade , Complicações na Gravidez/epidemiologia , Morte Materna/estatística & dados numéricos , Adulto Jovem , Adolescente , Causas de MorteRESUMO
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.
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Biomarcadores Tumorais , Ácidos Nucleicos Livres , Humanos , Projetos Piloto , Feminino , Masculino , Pessoa de Meia-Idade , Ácidos Nucleicos Livres/sangue , Idoso , Biomarcadores Tumorais/sangue , Neoplasias/sangue , Neoplasias/diagnóstico , Prognóstico , Sensibilidade e Especificidade , Adulto , DNA Tumoral Circulante/sangueRESUMO
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.
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Hospitais Universitários , Hospedeiro Imunocomprometido , Humanos , Itália/epidemiologia , Hospitais Universitários/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Ativação Viral , Viroses/epidemiologia , Viroses/virologia , Idoso , Adulto , Vírus JC/genética , Vírus JC/isolamento & purificação , Vírus JC/imunologia , Vírus BK/genética , Vírus BK/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/tratamento farmacológico , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Prevalência , Transplante de Órgãos/efeitos adversos , Transplantados/estatística & dados numéricos , Citomegalovirus/genética , Citomegalovirus/imunologia , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologiaRESUMO
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.
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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.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/genética , Laboratórios , Patologia Molecular , Mutação/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/uso terapêutico , ItáliaRESUMO
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.
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Procedimentos Cirúrgicos do Sistema Digestório , Recuperação Pós-Cirúrgica Melhorada , Humanos , Redução de Custos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Eletivos/métodos , Tempo de InternaçãoRESUMO
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.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Carcinoma Epitelial do Ovário/diagnóstico , Biomarcadores Tumorais/genética , Biópsia Líquida , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologiaRESUMO
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.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicina Estatal , Neoplasias Pulmonares/tratamento farmacológico , Crizotinibe/uso terapêutico , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
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.
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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.
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Doença de Hodgkin , Linfoma de Células B , Humanos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/patologia , Células de Reed-Sternberg/patologia , Linfoma de Células B/patologia , Biópsia Líquida , BiópsiaRESUMO
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.
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Ceratoconjuntivite , Sarampo , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Surtos de Doenças/prevenção & controle , Itália/epidemiologia , Ceratoconjuntivite/epidemiologia , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacina contra Sarampo , Estudos Retrospectivos , Cidade de Roma/epidemiologia , Esteroides/efeitos adversos , Centros de Atenção Terciária , Vacinação , AdolescenteRESUMO
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.
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Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Estudos Retrospectivos , Biomarcadores Tumorais/genética , Mutação , Mesotelioma/genética , Mesotelioma/cirurgia , Neoplasias Pleurais/genética , Neoplasias Pleurais/cirurgia , GenômicaRESUMO
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.
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Activating mutations of the estrogen receptor alpha gene (ESR1) are common mechanisms of endocrine therapy (ET) resistance in hormone receptor-positive (HR + )/Human Epidermal Growth Factor Receptor 2 (HER2)-negative metastatic breast cancer (MBC). Recent clinical findings emphasize that both old and new generations of selective ER degraders (SERDs) demonstrate enhanced clinical effectiveness in patients with MBC who have detectable ESR1 mutations via liquid biopsy. This stands in contrast to individuals with MBC carrying these mutations and undergoing conventional endocrine monotherapies like aromatase inhibitors (AIs). Liquid biopsy, particularly the analysis of circulating tumor DNA (ctDNA), has emerged as a promising, minimally invasive alternative to conventional tissue-based testing for identifying ESR1 mutations. Within the context of the PADA-1 and EMERALD trials, distinct molecular methodologies and assays, specifically digital droplet PCR (ddPCR) and next-generation sequencing (NGS), have been employed to evaluate the mutational status of ESR1 within ctDNA. This manuscript critically examines the advantages and indications of various ctDNA testing methods on liquid biopsy for HR+/HER2-negative MBC. Specifically, we delve into the capabilities of ddPCR and NGS in identifying ESR1 mutations. Each methodology boasts unique strengths and limitations: ddPCR excels in its analytical sensitivity for pinpointing hotspot mutations, while NGS offers comprehensive coverage of the spectrum of ESR1 mutations. The significance of meticulous sample handling and timely analysis is emphasized, acknowledging the transient nature of cfDNA. Furthermore, we underscore the importance of detecting sub-clonal ESR1 mutations, as these variants can exert a pivotal influence on predicting both endocrine therapy resistance and responsiveness to SERDs. In essence, this work discusses the role of ctDNA analysis for detecting ESR1 mutations and their implications in tailoring effective therapeutic strategies for HR+/HER2- MBC.
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Neoplasias da Mama , DNA Tumoral Circulante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Mutação , Receptores de Estrogênio/metabolismo , DNA Tumoral Circulante/genéticaRESUMO
INTRODUCTION: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. METHODS: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. RESULTS: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. CONCLUSIONS: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51.
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Nematodes of the genus Anisakis (Rhabditida, Anisakidae) are zoonotic fish-borne parasites and cause anisakiasis, a disease with mild to severe acute or chronic gastrointestinal and allergic symptoms and signs. Anisakiasis can potentially lead to misdiagnosis or delay in diagnosis, and it has been suggested as a risk factor for gastrointestinal tumors. Here, we describe a case report of a 25-year-old woman who presented with gastrointestinal (abdominal pain, nausea, diarrhea) and allergic (diffuse skin rash) symptoms and reported ingestion of raw fish contaminated by worms. Gastro and colon endoscopy allowed the visualization and removal of nematodes and collection of bioptic tissue from ulcers and polyps. The removed nematodes were molecularly identified as Anisakis pegreffii. The patient was treated with chlorphenamine maleate, betamethasone, omeprazole, paracetamol, albendazole. We conclude that an upper endoscopy matched with a colonoscopy and molecular characterization of the pathogen yields the most reliable diagnosis and treatment for human anisakiasis, enabling the complete removal of the larvae and preventing chronic inflammation and damage.
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In recent years, there has been a considerable increase in the number of image-guided interventional procedures performed for the management of acute and chronic pain. Concomitantly, there has also been an increase in the complication rate related to these procedures. The aim of this narrative review is to summarize the primary complications associated with commonly performed image-guided (fluoroscopic- or ultrasound-guided) interventional procedures. We conclude that although complications from interventional pain procedures can be mitigated to a certain degree, they cannot be eliminated altogether. In order to avoid adverse events, patient safety should be given considerable attention and physicians should be constantly aware of the possibility of developing complications.