Primary stroke prevention for sickle cell disease in north-east Italy: the role of ethnic issues in establishing a Transcranial Doppler screening program

<p>Abstract</p> <p>Background</p> <p>Stroke is a serious complication of sickle cell disease (SCD) in children. Transcranic Doppler (TCD) is a well-established predictor of future cerebrovascular symptoms: a blood flow velocity >200 cm/sec in the Middle Cerebral Artery (MCA) correlates with a high risk of stroke in cohorts of African-american HbS/HbS patients. In North-East Italy the recent increase in SCD patients is mainly due to immigration from Africa. A comprehensive care program for children with SCD was established in our Center since 2004, but a wide and routine screening for Primary stroke prevention needs to be developed.</p> <p>Methods</p> <p>In order to verify the feasibility of TCD and Transcranial color coded Sonography (TCCS) screening in our setting and the applicability of international reference values of blood velocities to our population of African immigrants with HbS/HbS SCD, we performed TCD and TCCD in 12 HbS/HbS African children and two groups of age-matched controls of Caucasian and African origin respectively. TCD and TCCS were performed on the same day of the scheduled routine hematologic visit after parental education.</p> <p>Results</p> <p>All parents accepted to perform the sonography to their children. TCD and TCCD were performed in all patients and an adequate temporal window could be obtained in all of them. Pulsatility index and depth values in both the MCA and the Basilar Artery (BA) were similar at TCD and TCCS evaluation in the three groups while time-average maximum velocities (TAMM), peak systolic velocity and diastolic velocity in the MCA and BA were higher in the patients' group on both TCD and TCCS evaluation. African and Caucasian healthy controls had similar lower values.</p> <p>Conclusion</p> <p>Our preliminary data set the base to further evaluate the implementation of a primary stroke prevention program in our setting of HbS/HbS African immigrants and HbS/beta thalassemia Italians. Parental education-preferably in the native language- on stroke risk and prevention in SCD increases compliance and should be a necessary part of the program. Ethnic background does not seem to influence TCD velocity and internationally accepted reference values already validated in African-American SCD pediatric patients can be used, but long prospective trials are needed to verify their efficacy in defining stroke risk in our setting.</p

Adolescents and young adults with oncohematological disease: use of social networks, impact of SARS-COV-2, and psychosocial well-being

ObjectiveAdolescents and young adults (AYA) with oncohematological diseases could have important psychosocial difficulties that could be worsened by the effects of the COVID19 pandemic. At this developmental stage, it is also important to assess the use of social networks (SNs). This study aims to investigate the type of social network use and the consequences of the COVID19 period. These patients are compared with matched healthy peers.MethodsAfter the informant consent signature, the adolescents completed a series of self-report questionnaires on the use of SNs, on communication preferences, on social anxiety and on Covid19 impact through the online platform of LimeSurvey. Most of the adolescents belonged to the 18–20 age group (42.5%), were female (62%) and mainly off therapy (72%).ResultsAdolescents spent more than 2 h/day on Instagram and 1 h and half on Whatsapp, while Tik Tok use was on average 1 h/day, especially used by younger patients (r = −0.33, p = 0.023). Males used Twitch (t45 = −2.06, p = 0.05) and Youtube (t45 = −2.18, p = 0.03) for longer than females. AYA in therapy used more Tik Tok (U = 137.50; p = 0.03), Ask/Tellonym (U = 172.50; p = 0.05) and Twitch (U = 144; p = 0.017) than those off therapy. Healthy AYA showed lower levels of exposure (Z = −4.17; p = 0.00001) and impact (Z = −5.12; p = 0.00001) to Covid19, while the level of social anxiety is comparable and is in the normal range in both groups.DiscussionSome clinical considerations and suggestions could be given based on these empirical results to health professionals in the care of AYA cancer patients

Whole Lung Irradiation after High-Dose Busulfan/Melphalan in Ewing Sarcoma with Lung Metastases: An Italian Sarcoma Group and Associazione Italiana Ematologia Oncologia Pediatrica Joint Study

SIMPLE SUMMARY: The lung is the most frequent site of metastasis in Ewing sarcoma, the second most common bone cancer affecting children, adolescents and young adults. The five-year overall survival of patients with isolated lung metastasis is approximately 50% after multimodal treatments including chemotherapy, surgery and radiotherapy. This retrospective study aimed to investigate the feasibility and the predictors of survival in 68 Ewing sarcoma patients with lung metastases who received high-dose chemotherapy with busulfan and melphalan, followed by reduced dose whole-lung irradiation, as part of two prospective and consecutive treatment protocols. This combined treatment strategy is feasible and might contribute to the disease control in lung metastatic Ewing sarcoma with responsive disease. Furthermore, the results of this study provide support to explore the treatment stratification for lung metastatic Ewing sarcoma based on the histological response of the primary tumor. ABSTRACT: Purpose: To analyze toxicity and outcome predictors in Ewing sarcoma patients with lung metastases treated with busulfan and melphalan (BU-MEL) followed by whole-lung irradiation (WLI). Methods: This retrospective study included 68 lung metastatic Ewing Sarcoma patients who underwent WLI after BU-MEL with autologous stem cell transplantation, as part of two prospective and consecutive treatment protocols. WLI 12 Gy for <14 years old and 15 Gy for ≥14 years old patients were applied at least eight weeks after BU-MEL. Toxicity, overall survival (OS), event-free survival (EFS) and pulmonary relapse-free survival (PRFS) were estimated and analyzed. Results: After WLI, grade 1–2 and grade 3 clinical toxicity was reported in 16.2% and 5.9% patients, respectively. The five-year OS, EFS and PRFS with 95% confidence interval (CI) were 69.8% (57.1–79.3), 61.2% (48.4–71.7) and 70.5% (56.3–80.8), respectively. Patients with good histological necrosis of the primary tumor after neoadjuvant chemotherapy showed a significant decreased risk of pulmonary relapse or death compared to patients with poor histological necrosis. Conclusions: WLI at recommended doses and time interval after BU-MEL is feasible and might contribute to the disease control in Ewing sarcoma with lung metastases and responsive disease. Further studies are needed to explore the treatment stratification based on the histological response of the primary tumor

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Me and my shadow

Threee Person Exhibition: Emma Talbot UK, Marta Pierobon IT, Jennifer Cohen USA

ral ssBioMed CentItalian Journal of Pediatrics

Primary stroke prevention for sickle cell disease in north-east Italy: the role of ethnic issues in establishing a Transcranial Doppler screening progra

Isolati, multipli, ereditari: Le tante facce dei polipi intestinali

This article provides a critical review of the clinical presentation, pathology, genetics and management of the polyposis in childhood starting from the isolated juvenile polyp to the hereditary polyposis syndromes. These include the juvenile polyposis syndrome, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndromes and familial adenomatous polyposis (FAP). These conditions typically outbreak in the second decade of life but early detection and proper screening and surveillance can minimize the risk of intestinal and extracolonic cancers. While juvenile polyp could be easily removed, the amartomatosis syndromes will require a specific endoscopic surveillance and a periodic polypectomy. In the case of FAP, the paediatrician has a decisive role in defining the colonscopic follow-up and the timing of the total colectomy