Indici elettrocardiografici in pazienti affetti da attacco ischemico transitorio (TIA) e ictus ischemico nello studio di popolazione OXVASC

Parte 1 BACKGROUND: One-third of TIA and ischaemic strokes are of undetermined aetiology (cryptogenic). It has been previously shown that cryptogenic events had fewest atherosclerotic markers and no excess of long-term risks of new AF or recurrent cardioembolic stroke or systemic embolism. Another emerging hypothesis suggests that atrial cardiopathy could be a risk factor for thromboembolism independent of underlying arrhythmia. Therefore in the current study, we aimed to determine the prevalence of electrocardiogram (ECG) makers of atrial function in ischaemic stroke subtypes. METHODS: In a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from 2002-2015, we compared cryptogenic events versus other aetiological subtypes (TOAST classification). We studied ECG markers of atrial function (P wave inconsistency, maximum P wave duration, P wave dispersion, and RR interval variation) and echocardiographic makers of atrium structure (enlargement of the left atrium-LA). FINDINGS: Of 2213 eligible patients, 812 (36.7%) had cryptogenic events. As expected, patients with cardioembolic events were significantly more likely to have enlarged LA on echocardiogram compared to patients with non-cardioembolic events (p<0.0001). However, the prevalence of enlarged LA did differ in patients with cryptogenic events vs. patients with large artery/smal vessel disease (24.3% vs. 24.0%, p=0.93). Among the 1881 patients in sinus rhythm on ECG at baseline, although compared to patients with cardioembolic events, the prevalence of ECG markers of atrial function in patients with cryptogenic events were significantly lower (all p<0.0001), compared to patients with large artery/small vessel disease, patients with cryptogenic events had a significantly higher prevalence of P wave inconsistency (cryptogenic vs. large artery/small vessel \u2013p<0.0001), P wave dispersion ( 6560ms, p=0.01) and RR interval variation ( 6580ms, p<0.0001). Results were consistent for analyses when paroxysmal AF episodes from prolonged cardiac monitoring were not included for aetiological classification, and when stratified by age groups, or excluding patients with TIA. INTERPRETATION: Compared to patients with large artery or small vessel stroke/TIA, patients with cryptogenic events have a higher prevalence of ECG markers of abnormal atrial function, with no excess of significant left atrium structure abnormality or new AF. Parte 2 BACKGROUND: Little is known about the relationship between QTc interval and incident stroke. Prolonged QTc has been reported in 38% to 71% of patients during acute stroke (the most frequent ECG abnormality in this setting). The pathophysiology of this phenomenon has not been elucidated. The autonomic dysfunction has been suggested as one of potential mechanism, however, it is also possible that prolonged QTc ante data the development of stroke and its presence during the acute phase reflects a higher risk for recurrent stroke, death and unfavourable outcome METHODS: In a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from 2002-2015, we measured manually the QT interval in precordial leads. The absolute QT interval was adjusted for heart rate by using the Bazett\u2019s formula. The QTc interval was defined as \u201cprolonged\u201d based on the widely accepted values in relation to sex categories. The aims of the study were: to evaluate the association between the prolongation of QTc and risk of recurrent stroke, death, myocardial infarction and the severity of the event; to investigate the possible aetiological mechanism analysing the association with dementia pre-event, blood pressure variation and white matter disease detected on brain CT or MRI. FINDINGS: Of 2213 eligible patients, 2132 had QTc measurement. We found a significant association between the prolonged QTc and recurrent stroke (p<0.0001, age-adjusted and sex-adjusted p<0.0001), recurrent myocardial infarction (p<0.0001, age-adjusted and sex-adjusted p<0.0001), death (p<0.0001, age-adjusted and sex-adjusted p<0.0001) at 3 months and 10 years follow up and the severity of stroke (p<0.0001, age-adjusted and sex-adjusted p<0.0001) classified according to NIHSS at the event. After exclusion of prolonging QTc drugs, heart disease, cardiac pacing, AF, electrolyte disturbance and complete BBB the relation remained unchanged. A prolonged QTc was significant associated with dementia (p<0.0001, age-adjusted and sex-adjusted p<0.0001); white matter disease measured using a visual scale on a brain MRI (p<0.0001, age-adjusted and sex-adjusted p= 0.041) or brain CT (p= <0.0001, age-adjusted and sex-adjusted p=0.033), and blood pressure variation calculated using the blood pressure measurements in the 5 years before the event (p= 0.0009, age-adjusted and sex-adjusted p=0.0001). INTERPRETATION: QT prolongation is a predictive marker of recurrent cerebrovascular events, cardiac morbidity and mortality in patients with a first TIA or ischaemic stroke

Laparoscopic surgery does not reduce the need for red blood cell transfusion after resection for colorectal tumour: a propensity score match study on 728 patients

Background: Patients with colorectal tumour often present with anaemia, and up to 60% will receive red blood cells (RBC) transfusion. Some evidence suggests a correlation between RBC transfusion and worse outcomes. Since laparoscopy minimizes intraoperative blood loss, we retrospectively investigated its role in reducing haemoglobin (Hb) drop and requirements for postoperative RBC transfusions. Methods: Patients were identified from consecutive cases undergone elective surgery for non-metastatic colorectal tumour between 2005 and 2019. Laparoscopic cases were matched 1:1 with open controls through propensity score matching (PSM). The main outcome measures were postoperative Hb drop and requirement for RBC. The secondary aim was evaluation of risk factors for postoperative RBC transfusions. Results: After application of PSM, 364 patients treated by laparoscopy were matched with 364 patients undergone open surgery. The two groups presented similar clinical and pathological characteristics, as well as comparable postoperative outcomes. 56 patients in the open group and 47 in the laparoscopic group required postoperative RBC (P = 0.395). No difference was observed in terms of mean number of RBC units (P = 0.608) or Hb drop (P = 0.129). Logistic regression analysis identified preoperative anaemia and occurrence of postoperative complications as relevant risk factors for postoperative RBC transfusion, while surgical approach did not prove statistically significant. Conclusion: Laparoscopy did not influence postoperative requirements for RBC transfusions after elective colorectal surgery. Preoperative anaemia and occurrence of postoperative complications represent the major determinants for postoperative transfusions after open as well as laparoscopic surgery

Treatment of locally advanced rectal cancer in the era of total neoadjuvant therapy: a systematic review and network meta-analysis

Importance: Treatment of locally advanced rectal cancer (LARC) involves neoadjuvant chemoradiotherapy plus total mesorectal excision and adjuvant chemotherapy. However, total neoadjuvant therapy (TNT) protocols (ie, preoperative chemotherapy in addition to radiotherapy) may allow better adherence and early treatment of distant micrometastases and may increase pathological complete response (pCR) rates. Objective: To assess the efficacy and tolerability of TNT protocols for LARC. Data sources: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science Core Collection electronic databases and ClinicalTrials.gov for unpublished studies were searched from inception to March 2, 2024. Study selection: Randomized clinical trials including adults with LARC who underwent rectal resection as a final treatment were included. Studies including nonoperative treatment (watch-and-wait strategy), treatments other than rectal resection, immunotherapy, or antiangiogenic agents were excluded. Among the initially identified studies, 2.9% met the selection criteria. Data extraction and synthesis: Two authors independently screened the records and extracted data. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant pairwise and network meta-analyses with a random-effects model were performed in a frequentist framework, and the certainty of evidence was assessed according to the confidence in network meta-analysis approach. Main outcomes and measures: The primary outcome was pCR, defined as the absence of residual tumor at pathological assessment after surgery. Secondary outcomes included tolerability, toxic effects, perioperative outcomes, and long-term survival. Results: Of 925 records identified, 27 randomized clinical trials, including 13 413 adults aged 18 years or older (median age, 60.0 years [range, 42.0-63.5 years]; 67.2% male) contributed to the primary network meta-analysis. With regard to pCR, long-course chemoradiotherapy (L-CRT) plus consolidation chemotherapy (relative risk [RR], 1.96; 95% CI, 1.25-3.06), short-course radiotherapy (S-RT) plus consolidation chemotherapy (RR, 1.76; 95% CI, 1.34-2.30), and induction chemotherapy plus L-CRT (RR, 1.57; 95% CI, 1.09-2.25) outperformed standard L-CRT with single-agent fluoropyrimidine-based chemotherapy. Considering 3-year disease-free survival, S-RT plus consolidation chemotherapy (RR, 1.08; 95% CI, 1.01-1.14) and induction chemotherapy plus L-CRT (RR, 1.12; 95% CI, 1.01-1.24) outperformed L-CRT, in spite of an increased 5-year locoregional recurrence rate of S-RT plus consolidation chemotherapy (RR, 1.65; 95% CI, 1.03-2.63). Conclusions and relevance: In this systematic review and network meta-analysis, 3 TNT protocols were identified to outperform the current standard of care in terms of pCR rates, with good tolerability and optimal postoperative outcomes, suggesting they should be recognized as first-line treatments

Protopine/Gemcitabine Combination Induces Cytotoxic or Cytoprotective Effects in Cell Type-Specific and Dose-Dependent Manner on Human Cancer and Normal Cells

The natural alkaloid protopine (PRO) exhibits pharmacological properties including anticancer activity. We investigated the effects of PRO, alone and in combination with the chemotherapeutic gemcitabine (GEM), on human tumor cell lines and non-tumor human dermal fibroblasts (HDFs). We found that treatments with different PRO/GEM combinations were cytotoxic or cytoprotective, depending on concentration and cell type. PRO/GEM decreased viability in pancreatic cancer MIA PaCa-2 and PANC-1 cells, while it rescued the GEM-induced viability decline in HDFs and in tumor MCF-7 cells. Moreover, PRO/GEM decreased G1, S and G2/M phases, concomitantly with an increase of subG1 phase in MIA PaCa-2 and PANC-1 cells. Differently, PRO/GEM restored the normal progression of the cell cycle, altered by GEM, and decreased cell death in HDFs. PRO alone increased mitochondrial reactive oxygen species (ROS) in MIA PaCa-2, PANC-1 cells and HDFs, while PRO/GEM increased both intracellular and mitochondrial ROS in the three cell lines. These results indicate that specific combinations of PRO/GEM may be used to induce cytotoxic effects in pancreatic tumor MIA PaCa-2 and PANC-1 cells, but have cytoprotective or no effects in HDFs

Impact of the COVID-19 pandemic on paediatric otolaryngology: a nationwide study

Objective: The COVID-19 pandemic profoundly modified the work routine in healthcare; however, its impact on the field of paediatric otorhinolaryngology (ORL) has been rarely investigated. The aim of this study was to assess the impact of COVID-19 on paediatric ORL. Methods: A questionnaire was developed by the Young Otolaryngologists of the Italian Society of ORL-Head and Neck Surgery (GOS). The questionnaire consisted of 26 questions related to workplace and personal paediatric ORL activities. The link was advertised on the official social media platforms and sent by e-mail to 469 Italian otolaryngologists. Results: The questionnaire was completed by 118 responders. During the pandemic, the main reduction was observed for surgical activity (78.8%), followed by outpatient service (16.9%). The conditions that were mostly impacted by a delayed diagnosis were respiratory infections in 45.8% of cases and sensorineural hearing loss in 37.3% of cases. Conclusions: Paediatric ORL was highly impacted by the COVID-19 pandemic, with a significant reduction of surgical and outpatient activities and a delay in time-sensitive diagnosis. Therefore, the implementation of new strategies, such as telemedicine, is recommended

COVID-19 and slowdown of residents' activity: Feedback from a novel e-learning event and overview of the literature

Objective: To evaluate the impact of an e-learning online event, created for supporting resident's training during the slowdown of surgical and clinical activities caused by COVID-19 pandemic. An overview of PubMed literature depicting the state of the art of urology residency in the COVID-19 era was performed as well, to contextualize the issue.Methods: An online learning event for residents was set up at the beginning of the pandemic; the faculty consisted of experts in urology who provided on-line lectures and videos on surgical anatomy, procedures, updates in guidelines, technology, training. The audience was composed of 30-500 attendees from Italy, USA, India and Belgium. A questionnaire to analyze relevance, satisfaction and popularity of the lessons was mailed to 30 local residents.Results and limitations: Almost all residents defined the web environment suitable to achieve the learning outcomes; the method, the number and the competence of the faculty were appropriate/excellent. Most of the younger residents (81.8%) stated their surgical knowledge would improve after the course; 72.7% declared they would take advantage into routine inpatients clinical activity. Nineteen more expert residents agreed that the course would improve their surgical knowledge and enhance their practical skills; almost all stated that the initiative would change their outpatients and inpatients practice. Overall, 44 articles available in PubMed have addressed the concern of urological learning and training during the pandemic from different standpoints; four of them considered residents' general perception towards web-based learning programs.Conclusions: The paper confirms residents' satisfaction with e-learning methods and, to our knowledge, is the first one focusing on a specific event promptly settled up at the beginning of the outbreak. Web-based educational experience developed during the pandemic may represent the very basis for the implementation of prospective on-site training and overall scientific update of future urologists

Herpes Zoster Vaccine Uptake and Active Campaign Impact, a Multicenter Retrospective Study in Italy

The Herpes Zoster (HZ) vaccination has proven both safe and effective in alleviating conditions related to HZ, leading to significant cost savings in national healthcare and social systems. In Italy, it is recommended and provided free of charge to individuals aged 65 and older. To achieve broad vaccination coverage, alongside ordinary immunization campaigns, active and catch-up campaigns were implemented. This retrospective observational study aimed to observe the vaccination coverage achieved in the Romagna Local Health Authority (LHA) during the 2023 active campaign, with a secondary goal of assessing the impact of the 2022 catch-up campaign and the 2023 active campaign compared to ordinary campaigns. As of 3 July 2023, an overall vaccine uptake of 13.5% was achieved among individuals born in 1958, with variations among the four LHA centers ranging from 10.2% to 17.7%. Catch-up and active campaigns together contributed to nearly half of the achieved coverage in Center No. 1 and a quarter in Center No. 2. Notably, individuals born in 1957, not included in the Center No. 2 catch-up campaign, reached significantly lower vaccination coverage compared to other cohorts and centers. Analyzing the use of text messages for active campaigns, it was observed that cohort groups did not show substantial differences in text-message utilization for warnings. However, having relatives who had experienced HZ-related symptoms significantly reduced the reliance on text messages as warnings. These results highlighted how catch-up and active campaigns effectively increased vaccine coverage. Nevertheless, differences in uptake among different centers within the same LHA and the limited contribution of other information sources compared to text messages suggest the necessity of designing campaigns involving all available channels and stakeholders to maximize vaccine uptake

Cauliflower Mosaic Virus TAV, a Plant Virus Protein That Functions like Ribonuclease H1 and is Cytotoxic to Glioma Cells

Recent comparisons between plant and animal viruses reveal many common principles that underlie how all viruses express their genetic material, amplify their genomes, and link virion assembly with replication. Cauliflower mosaic virus (CaMV) is not infectious for human beings. Here, we show that CaMV transactivator/viroplasmin protein (TAV) shares sequence similarity with and behaves like the human ribonuclease H1 (RNase H1) in reducing DNA/RNA hybrids detected with S9.6 antibody in HEK293T cells. We showed that TAV is clearly expressed in the cytosol and in the nuclei of transiently transfected human cells, similar to its distribution in plants. TAV also showed remarkable cytotoxic effects in U251 human glioma cells in vitro. *ese characteristics pave the way for future analysis on the use of the plant virus protein TAV, as an alternative to human RNAse H1 during gene therapy in human cells

Impact of the COVID-19 pandemic on paediatric otolaryngology: a nationwide study

Objective: The COVID-19 pandemic profoundly modified the work routine in healthcare; however, its impact on the field of paediatric otorhinolaryngology (ORL) has been rarely investigated. The aim of this study was to assess the impact of COVID-19 on paediatric ORL. Methods: A questionnaire was developed by the Young Otolaryngologists of the Italian Society of ORL-Head and Neck Surgery (GOS). The questionnaire consisted of 26 questions related to workplace and personal paediatric ORL activities. The link was advertised on the official social media platforms and sent by e-mail to 469 Italian otolaryngologists. Results: The questionnaire was completed by 118 responders. During the pandemic, the main reduction was observed for surgical activity (78.8%), followed by outpatient service (16.9%). The conditions that were mostly impacted by a delayed diagnosis were respiratory infections in 45.8% of cases and sensorineural hearing loss in 37.3% of cases. Conclusions: Paediatric ORL was highly impacted by the COVID-19 pandemic, with a significant reduction of surgical and outpatient activities and a delay in time-sensitive diagnosis. Therefore, the implementation of new strategies, such as telemedicine, is recommended

Pre-diagnostic prognostic value of leukocytes count and neutrophil-to-lymphocyte ratio in patients who develop colorectal cancer

IntroductionEmerging evidence is pointing towards a relevant role of immunity in cancer development. Alterations in leukocytes count and neutrophil-to-lymphocyte ratio (NLR) at diagnosis of colorectal cancer (CRC) seems to predict poor prognosis, but no data is available for the pre-diagnostic values.MethodsRetrospective analysis of patients who underwent surgery for CRC at our center (2005 – 2020). 334 patients with a complete blood count dating at least 24 months prior to diagnosis were included. Changes in pre-diagnosis values of leukocytes (Pre-Leu), lymphocytes (Pre-Lymph), neutrophils (Pre-Neut), and NLR (Pre-NLR) and their correlation with overall- (OS) and cancer-related survival (CRS) were analyzed.ResultsPre-Leu, Pre-Neut and Pre-NLR showed an increasing trend approaching the date of diagnosis, while Pre-Lymph tended to decrease. The parameters were tested for associations with survival after surgery through multivariable analysis. After adjusting for potential confounding factors, Pre-Leu, Pre-Neut, Pre-Lymph and Pre-NLR resulted independent prognostic factors for OS and CRS. On sub-group analysis considering the interval between blood sampling and surgery, higher Pre-Leu, Pre-Neut, and Pre-NLR and lower Pre-Lymph were associated with worse CRS, and the effect was more evident when blood samples were closer to surgery.ConclusionTo our knowledge, this is the first study showing a significant correlation between pre-diagnosis immune profile and prognosis in CRC