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Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood–brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P = .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P = .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P < .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P = .002), followed by CNS progression of disease (POD) >24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P = .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P = .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P = .502) as the morphological variant (classical vs others, P = .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option.

Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n=36) and relapsed (n=27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.

Background: Understanding healthcare workers (HCWs) willingness to receive a future vaccination against coronavirus disease 2019 (COVID-19) may be useful. Methods: Cross-sectional study, conducted in Italy from September 14th to November 30th, 2020, among 811 HCWs who undergo a voluntary antibody-testing for anti-SARS-CoV-2. Results: The perceived risk level of developing COVID-19, measured on a Likert-type scale ranging from 1 to 10, was 6.6 and it was higher among females, older HCWs, and in those who agreed that COVID-19 is a severe disease. Married/cohabitant, not physicians, and those who needed additional information regarding the vaccination against COVID-19 were more likely to be concerned that COVID-19 vaccination might not be safe. Males, physicians, those who did not have had any symptom compatible with COVID-19, those who agreed that COVID-19 is a severe disease, those who perceived to be at higher risk of developing COVID-19, those who were not concerned about the vaccine's safety, and those who had received information regarding the COVID-19 vaccination from scientific journals expressed willingness to receive vaccination against COVID-19. Conclusions: Communication and education targeted to groups with lowest willingness are needed to raise awareness regarding the safety and benefits of the vaccination and to improve vaccine uptake.

Objective To perform a meta-analysis to determine the effect of loco-regional radiation therapy (RT) compared to no loco-regional RT for operated patients in clinical stage cN2 breast cancer at diagnosis and ypN0 after preoperative chemotherapy (PST). Material and Methods Eligible studies were identified through a systematic search of the medical literature performed independently by two researchers using a validated search strategy. An electronic search of Medline via PubMed and Embase (Breast cancer AND preoperative chemotherapy AND radiation therapy) was conducted with no language or publication status restrictions. The effect of loco-regional RT on overall (OS), disease free (DFS), loco-regional recurrence-free (LRRFS) survival and local recurrence was evaluated. An electronic search of Medline via PubMed and Embase (Toxicity AND radiation therapy breast cancer AND preoperative therapy; toxicity AND breast surgery AND preoperative chemotherapy) was conducted for outcomes of harm: major acute and late skin toxicity, lymphedema and cardiac events. Results Of 333 studies identified, 4 retrospective studies reporting on a total of 1107 patients were included in the meta-analysis. Six and 3 reported data of acute and late skin toxicity, while 2 studies provided information on cardiac events. Pooled results showed no difference in terms of hazard ratio for loco-regional RT versus no loco-regional RT [hazard ratio (HR) = 0.82, 95% confidence interval (CI) 0.63–1.68]. Loco-regional RT was associated with an OS benefit in the subgroup analysis: IIIB-C (loco-regional RT 79.3% vs no loco-regional RT 71.2%, p = 0.027) and T3-T4 (loco-regional RT 82.6% vs no loco-regional RT 76.6%, p = 0.025). No difference was shown in terms of 5-year DFS (loco-regional RT 91.2% vs no loco-regional RT 83%, p = 0.441) and LRRFS (loco-regional RT 98.1% vs no loco-regional RT 92.3%, p = 0.148). There was no significant difference between the groups in terms of acute and late skin toxicities, lymphedema and cardiac events. Conclusions Because of the limitations due to the small number of studies and heterogeneity in the analysis, the present study does not allow to draw any definitive conclusion, highlighting the need for well-controlled trials to determine the effect of loco-regional RT in patients with cN2 having a pathological complete response in the axillary nodes after preoperative chemotherapy., Highlights • The prognostic impact of pCR after primary systemic therapy on DFS and OS has been shown in meta-analyses of randomized phase III trials. • The association of treatment response with loco-regional recurrence has been studied only in retrospective reports. • RNI should be strongly considered in patients with clinically involved lymph nodes regardless of the response to primary systemic therapy, especially in the presence of further risk factors. • In patients with cN2 at diagnosis and ypN0 at surgery after PST, loco-regional RT should be evaluated for each patient in the multidisciplinary team.

Facial pore enlargement is considered a significant esthetic and health concern in skincare cosmetics. The pores fulfill the critical function of keeping the skin surface hydrated and protected against microbial infections. The hyperseborrhea, the stress factors, and the hormonal triggers can cause pore size enlargement, causing higher susceptibility of the skin to microbe aggressions and inflammatory reactions. Thus, reducing excessive sebum production and keeping functional pores are two of the most requested activities in skincare cosmetics. A Cirsium eriophorum cell culture extract was investigated for its role in sebum regulation, stratum corneum desquamation, and anti-inflammation. The extract was able to regulate essential markers associated with sebum secretion and pore enlargements, such as the enzyme 5α-reductase, which plays a central role in sebum production, and the trypsin-like serine protease Kallikrein 5, which promotes skin exfoliation and antimicrobial response. Moreover, the extract showed a sebum-normalizing and pore refining activity in individuals having seborrheic or acne-prone skins, suggesting a role of the C. eriophorum extract in rebalancing altered skin conditions responsible for pore enlargement.

To evaluate the effects of rehabilitation (physical and cognitive) treatments on the diagnosis severity and Disability Rating Scale (DRS) scores, adjusted for a number of potential confounders measured at baseline, in a large cohort of patients with disorders of consciousness across time.An observational, longitudinal (2 evaluations), multicenter project was made in 90 Italian centers.Patients (N=364) with a diagnosis of disorders of consciousness.Primary outcome was the severity of diagnosis, expressed on an ordinal scale (OtherMCSVSdeath). In the Other group were included patients who emerged from an MCS and recovered consciousness. The secondary outcome was the DRS score (range of 0-30 with 30 being the worst value). The DRS is a tool used to define the level of residual disability, commonly used to classify the level of functional impairment in patients with acquired brain injury. Both outcomes were measured for each wave.A total of 364 subjects having a complete set of demographic, clinical, and pharmacologic data were included in the propensity score (PS) analysis. Results showed that the rehabilitation treatments (physical and cognitive) reduced the clinical worsening over time in both severity diagnosis and DRS (around 6.5 points) in patients with disorders of consciousness across different propensity score strategies (ie, PS matching, PS adjustment, and PS-weighted procedures). In addition, cognitive protocols seem to be limited to patients with a median value of DRS=23.Our propensity score analysis suggests that rehabilitation treatment protocols seem effective and should be applied to a broader spectrum of patients with disorders of consciousness.

It is well-known that the Coronavirus Disease 2019, which is caused by the beta-coronavirus severe acute respiratory syndrome (SARS-CoV-2), emerged in December 2019 followed by an outbreak first reported in Wuhan, China. Thus far, vaccination appears to be the only way to bring the pandemic to an end. In the present study, immunogenicity data was evaluated using LIAISON® SARS-CoV-2 TrimericS IgG assay (DiaSorin S.p.A) among a sample of 52 vaccinated healthcare workers, five of whom were previously infected with SARS-CoV-2 and 47 who were seronegative, over a time span of ≤90 days following the second dose of the BNT162b2 mRNA vaccine. The test detects antibodies against the Trimeric complex (S1, S2 and receptor binding domain). The overall mean value of the serum levels of IgG antibodies to SARS-CoV-2 30 days following the second dose of the vaccine was 1,901.8 binding arbitrary unit (BAU)/ml, after 60 days the mean value declined to 1,244.9 BAU/ml. The antibody levels then reached a plateau, as confirmed by the antibody test carried out 90 days following the second dose, which revealed a mean value of 1,032.4 BAU/ml (P

Background: Interoception is the basic process enabling evaluation of one’s own internal state of body, but its alteration in brain-damaged patients has not been adequately investigated. Our study aimed to investigate awareness of visceral and somatosensorial sensations in brain-damaged patients with unilateral stroke. Methods: Sixty patients (22 with left brain damage, LP; 25 with right brain damage without neglect, RPN-; and 13 with right brain-damage and extrapersonal and/or personal neglect, RPN+) and 45 healthy controls (HC) completed the Self-Awareness Questionnaire (SAQ), a self-report tool for assessing interoceptive awareness with two domains related to visceral (VD) and somatosensory feelings (SD), respectively. Results: Comparing the SAQ subdomains scores between three groups of patients (LP, RPN-, and RPN+) and HC, we found that RPN+ had significantly lower scores on VD than HC and LP, whereas no significant difference was found on scores of SD between groups. Conclusion: Our results support the hypothesis of a right-hemispheric dominance for “interoceptive neural network” suggesting that processing of visceral sensations would be located mainly in the right hemisphere. Therefore, a careful assessment of interoceptive awareness in clinical practice would be useful to improve rehabilitation and to engage patients with deficit of interoceptive awareness in developing greater accuracy of body signals.

Pregnant women, especially those with comorbidities, compared to those non-pregnant, have higher risk of developing a severe form of COVID-19. However, COVID-19 vaccine uptake is very low among them.An anonymous questionnaire was administered to randomly selected women 18 years of age that were currently pregnant or had just given birth between September 2021 and May 2022 in the geographic area of Naples. Vaccine hesitancy was assessed using the vaccine hesitancy scale (VHS).A total of 385 women participated. Women who had not been infected by SARS-CoV-2 and who needed information about vaccination against COVID-19 had a higher perceived risk of being infected with SARS-CoV-2. More than half (54.3%) of the women were very afraid of the potential side effects of the COVID-19 vaccination on the fetus. There was higher concern of the side effects of the vaccine on the fetus among those who did not have a graduate degree, those with high-risk pregnancy, those who had not been infected by SARS-CoV-2, those who were more concerned that they could be infected by SARS-CoV-2, those who did not know that this vaccination was recommended for them, and those trusting mass media/internet/social networks for information. Only 21.3% were vaccinated when pregnant, mostly women with a university degree, those who had been infected by SARS-CoV-2 before pregnancy, those who did not need information, and those who acquired information about the vaccination from gynecologists. Almost three-quarters (71.9%) were willing to receive the vaccination and those more likely were those with a university degree, those who have had at least one relative/cohabitant partner/friend who had been infected by SARS-CoV-2, those who were more concerned that they could be infected by SARS-CoV-2, and those who were not extremely concerned of the side effects of the vaccine on the fetus. A total of 86.4% were highly hesitant. Highly hesitant were respondents who did not get a graduate degree, those less concerned that they could be infected by SARS-CoV-2, and those trusting mass media/internet/social networks for information.Public health efforts and education campaigns for pregnant women are needed for changing their perception patterns and for supporting gynecologists in promoting the uptake of this vaccination.

Purpose In the current study, we evaluated whether neoadjuvant chemoradiotherapy with reduced treatment volumes due to the exclusion of elective pelvic nodal irradiation is a feasible strategy for selected patients with locally advanced rectal cancer. Methods and Materials Patients with T2 low-lying/T3, N0-N1 rectal lesions without evidence of disease in the lateral lymph nodes were prospectively recruited. All patients underwent pretreatment testing, including computed tomography imaging of the chest, abdomen, and pelvis with intravenous contrast, pelvic magnetic resonance imaging with intravenous contrast, and 18-fluorodeoxyglucose positron emission/computed tomography. The clinical target volume included the primary tumor and the mesorectum with vascular supply containing the perirectal and presacral nodes, with the upper border at the S2/S3 interspace. The total radiation dose was 50.4 Gy, and fluoropyrimidine-based chemotherapy was associated concomitantly. The primary endpoint of the study was the reduction of gastrointestinal (GI) toxicity, and the secondary endpoints were pathologic complete response, local control, overall survival, and disease-free survival. Results Fifty-two patients (30 men, 22 women) with a median age of 67 years (range, 45-85 years) were enrolled in the study. Acute grade 3 GI toxicity was 7.6%, and there were no cases of grade 4 toxicity. Three patients (5.7%) developed a local recurrence. No relapse occurred in the lateral lymph nodes. The local control rate at 5 years was 96.1%. With a median follow-up time of 72.9 months (range, 2.5-127.6 months), the 3- and 5-year overall survival rates were 89.4% and 87%, respectively. The 3- and 5-year disease-free survival rates were 82.4% and 82.4%, respectively. Conclusions De-escalation of radiation therapy target volume reduces GI side effects without compromising efficacy in patients with rectal cancer. These results cannot be clearly extended to high-risk disease and need further evaluation in future randomized trials.

BACKGROUND About 1%-5% of acquired haemophilia A cases affect mothers in the postpartum setting. AIMS This study delineates the characteristics of this disease, specific to the postpartum setting, notably relapse in subsequent pregnancies. METHODS Report of two cases and literature study (1946-2019), yielding 73 articles describing 174 cases (total 176 cases). RESULTS Patients were aged 29.9 years (17-41) and 69% primigravidae. Diagnosis was made at a median of 60 days after delivery (range 0-308). Bleeding types were obstetrical (43.4%), cutaneous (41.3%), and muscular (36.7%). In >90% of the cases, FVIII at diagnosis was

BACKGROUND/AIM: Extraordinary restrictions aimed to limit Sars-CoV-2 spreading; they imposed a total reorganization of the health-system. Oncological treatments experienced a significant slowdown. The aim of our multicentric retrospective study was to evaluate screening suspension and surgical treatment delay during COVID-19 and the impact on breast cancer presentation. PATIENTS AND METHODS: All patients who underwent breast surgery from March 11, 2020 to May 30, 2020 were evaluated and considered as the Lockdown group. These patients were compared with similar patients of the previous year, the Pre-Lockdown group. RESULTS: A total of 432 patients were evaluated; n=223 and n=209 in the Lockdown and Pre-lockdown-groups, respectively. At univariate analysis, waiting times, lymph-nodes involvement and cancer grading, showed a statistically significant difference (p

We report final results of a phase II trial addressing efficacy and feasibility of lenalidomide maintenance in patients with chemosensitive relapse of diffuse large B-cell lymphoma (DLBCL) not eligible for or failed after autologous stem cell transplantation (ASCT). Patients with relapsed DLBCL who achieved at least a partial response to salvage chemoimmunotherapy were enrolled and treated with lenalidomide 25 mg/day for 21 of 28 days for 2 years or until progression or unacceptable toxicity. Primary endpoint was 1-year PFS. Forty-six of 48 enrolled patients were assessable. Most patients had IPI ≥2, advanced stage and extranodal disease before the salvage treatment that led to trial registration; 28 (61%) patients were older than 70 years. Lenalidomide was well tolerated. With the exception of neutropenia, grade-4 toxicities occurred in

Essentials Predictive ability of pro-hemostatic Gas6 for recurrent venous thromboembolism (VTE) is unknown. We measured Gas6 levels in 864 patients with VTE over 3 years. High Gas6 (> 157%) at diagnosis is associated with VTE recurrence, major bleeding and mortality. Gas6 plasma levels measured 12 months after the index VTE are discriminatory for VTE recurrence. SUMMARY: Background Growth arrest-specific gene 6 (Gas6) is a prohemostatic protein with an unknown predictive ability for recurrent venous thromboembolism (VTE). In the elderly, VTE results in higher mortality but does not have a higher rate of recurrence than in younger patients. Consequently, anticoagulation management in the elderly is challenging. Objective To prospectively investigate the performance of Gas6 in predicting VTE recurrence, major bleeding and mortality in the elderly. Methods Consecutive patients aged ≥ 65 years with acute VTE were followed for a period of 3 years. Primary outcomes were symptomatic VTE recurrence, major bleeding, and mortality. Plasma Gas6 was measured with ELISA. Results Gas6 levels were measured in 864 patients at the time of the index VTE (T1) and, in 70% of them, also 12 months later (T2). The Gas6 level at T1 was discriminatory for VTE recurrence (C-statistic, 0.56; 95% confidence interval [CI] 0.51-0.62), major bleeding (0.60, 95% CI 0.55-0.65) and mortality (0.69, 95% CI 0.65-0.73) up to 36 months. VTE recurrence up to 24 months after T2 was discriminated by the Gas6 level at T2 (0.62, 95% CI 0.54-0.71). High Gas6 levels (> 157%) and continuous Gas6 levels at T1 were associated with VTE recurrence up to 6 months and 12 months, respectively. Conclusions In elderly patients, a high Gas6 level is associated with higher risks of VTE recurrence, major bleeding, and death. These findings support further studies to assess the performance of Gas6 in adjusting the length of anticoagulation.

Introduction COVID-19 is a declared worldwide pandemic. In our country, due to shortage of hospitals and beds in intensive care unit, oncological and breast cancer (BC) resources are temporarily shifted to COVID-19 patients. In addition, risk of cross-infections should be considered in these frail patients. To accomplish more surgical procedures and to reduce the length of hospital stay (LOS), fast track awake BC surgery should be implemented. The aim of the study is to estimate the effects of surgical shift in our facility during the early COVID-19 outbreak. Materials and methods From 30th January 2020 to 30th of March 2020, 86 consecutive patients were retrospectively enrolled and divided into pre-COVID-19-BC and COVID-19-BC. Clinical parameters and anamnestic data were collected and analyzed. Surgical procedures, relative complications and type of anaesthesia were reported. The effect on surgical time (ST), operative room time (ORT) and length of stay (LOS) were described and examined. Results No statistical difference was found in complications rate, clinical data and surgical procedures (p > 0.05). Awake breast conservative surgery (BCS) was the most frequent procedure in COVID-19-BC (p = 0.006). A statistically significant decrease in ORT and LOS was reported in COVID-19-BC (p = 0.040 and p = 0.0015 respectively), while comparable time resulted for ST (p = 0.976). Mean ORT and LOS reduction were 20.79 min and 0.57 hospital bed days. Conclusion In the “COVID-19 era”, fast track awake breast surgery provides a reduction of ORT, LOS and potentially surgical treatment for a wider number of oncological patients.

Background/Aim: Despite the large amount of clinical data available of Coronavirus-19 (COVID-19), not many studies have been conducted about the psychological toll on Health Care Workers (HCWs). Patients and Methods: In this multicentric descriptive study, surveys were distributed among 4 different Breast Cancer Centers (BCC). BCCs were distinguished according to COVID-19 tertiary care hospital (COVID/No-COVID) and district prevalence (DP) (High vs. Low). DASS-21 score, PSS score and demographic data (age, sex, work) were evaluated. Results: A total of 51 HCWs were analyzed in the study. Age, work and sex did not demonstrate statistically significant values. Statistically significant distribution was found between DASS-21-stress score and COVID/No-COVID (p=0.043). No difference was found in the remaining DASS-21 and PSS scores, dividing the HCWs according to COVID-19-hospital and DP. Conclusion: Working in a COVID-19-hospital represents a factor that negatively affects psychosocial well-being. However, DP seems not to affect the psychosocial well-being of BCC HCWs. During the outbreak, psychological support for low risk HCWs should be provided regardless DP.

Background/Aim: In 2016, in the United States, more than 50% of breast cancer (BC) cases were diagnosed in patients older than 60 years of age. Our study aimed to estimate the risk of locoregional recurrence (LR) in patients who underwent breast-conservative treatment (BCT), according to age. Patients and Methods: This retrospective monocentric study analyzed 613 cases of patients who underwent BCT between 2003 and 2014. Patients were divided into groups according to age: Under70 (under 70 years old) and Over70 (above 70 years old). Margins width, histology results, prognostic and predictive factors were compared. Subgroup analysis was performed for patients who experienced LR. Results: LR Incidence among Under70 and Over70 was 5.4% and 1.7%, respectively (p

Background: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. Objective: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. Methods: Observational study in a tertiary care hospital in Milan, Italy. Results: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. Conclusions: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

The Vaccination Calendar for Life is an alliance of scientific and professional societies of public health physicians, paediatricians and general practitioners in Italy which provides a periodical update on the ideal, scientifically driven vaccination calendar throughout lifetime. Since 2012, the Lifetime Immunization Schedule has represented a benchmark for Regional and National Authorities to set up the updated list of vaccines provided actively and free of charge to infants, children, adolescents, adults and the elderly by inclusion in the Triennial National Vaccination Plan (TNVP), and in the Essential Levels of Care (LEA). The impact of the different editions of the Lifetime Immunization Schedule on the TNVP was deep, representing the inspiring source for the present vaccination policy. The 2019 edition called for more attention to pregnant women immunization; risk groups vaccination; uniform high coverage with the MMRV vaccine; extension of Meningococcal B vaccination also at adolescent age; use of quadrivalent conjugate meningococcal vaccine also at 1 year of life; progressive decrease of the age of free-of-charge offer of influenza to ≥ 60 and then to ≥ 50 year-old population; implementation of flu immunization ages 6 months-6 years; HPV vaccination also offered to 25-year old women at the time of the first screening (gender neutral immunization already offered); sequential PCV13-PPV23 pneumococcal vaccination in 65 year-old subjects; increased coverage with rotavirus vaccine in infants and zoster vaccine in the elderly.

BACKGROUND: As a legacy of the large asbestos consumption until the definitive ban in 1992, Italy had to tackle a real epidemic of asbestos related diseases. The Italian National Registry of Malignant Mesotheliomas (ReNaM) is a permanent surveillance system of mesothelioma incidence, with a regional structure. Aims, assignments and territorial network of ReNaM are described, as well as data collection, recording and coding procedures. OBJECTIVES: To describe the Italian epidemiological surveillance system of mesothelioma incidence, to provide updated data about occurrence of malignant mesothelioma in Italy, and to discuss goals, attainments, and expectations of registering occupational cancer. DESIGN: Analysis of data by malignant mesothelioma incident cases surveillance system. SETTING AND PARTICIPANTS: Italy, network of regional sur-veillance system, all Italian regions. MAIN OUTCOME MEASURES: A Regional Operating Centre (COR) is currently established in all the Italian regions, actively searching incident malignant mesothelioma cases from health care institutions. Occupational history, lifestyle habits, and residential history are obtained using a standardized questionnaire, administered to the subject or to the next of kin by a trained interviewer. The extent of dataset, epide-miological parameters, and occupations involved are reported updated at 31.12.2016, and standardized incidence rates are calculated. RESULTS: At December 2016, ReNaM has collected 27,356 malignant mesothelioma cases, referring to the period of incidence between 1993 and 2015. The modalities of exposure to asbestos have been investigated for 21,387 (78%) and an occupational exposure has been defined for around 70% of defined cases (14,818). CONCLUSIONS: The Italian experience shows that epidemiological systematic surveillance of asbestos related diseases incidence has a key importance for assessing and monitoring the public health impact of occupational and/or environmental hazards, programming preventive interventions, including remediation plans and information campaigns, and supporting the efficiency of insurance and welfare system. Monitor-ing the incidence of malignant mesothelioma through a specialized cancer registry is essential to follow-up the health effects of changing modalities and extent of occupational exposures over years and of environmental contamination. Such consolidated surveillance system is recommended also for occupational cancers with low aetiological fraction.

Objective To evaluate the early toxicity of concurrent use of radiotherapy in association with CDK4/6 inhibitors (palbociclib or ribociclib) in patients with hormone-receptors positive metastatic breast cancer. Material and methods Records of patients with histologically proven metastatic or locally advanced breast cancer treated in our institution were reviewed. Patients who received radiotherapy and concurrent palbociclib or ribociclib were selected. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE V4.0). Results Sixteen consecutive metastatic breast cancer patients with 24 radiotherapy treatments were studied. Thirteen patients (81.3%) received palbociclib, 3 (18.7%) patients received ribociclib concurrently with RT (18 and 5 radiotherapy courses respectively). The majority of patients (68.7%) received palliative radiotherapy to the bones (median dose 30 Gy, range 8–36 Gy). Five patients (31.2%) were treated in oligo-metastatic or oligo-progressive sites of disease with higher doses (median dose = 50 Gy, range 39.6–60 Gy). The most common toxicity observed was hematological toxicity. Neutropenia was common (grade 2 = 12.5%; grade 3 = 25%, grade 4 = 6.3%); 60% of patients experiencing grade ≥ 3 neutropenia had already experienced neutropenia during previous cycles of palbociclib. One patient (6.3%) completed the RT course earlier (48 Gy of 50 Gy prescribed) and another patient (6.3%) suspended RT for 2 days. Conclusion concomitant treatment of CDK4/6 and radiotherapy seems well tolerated; high grade hematological toxicity is common, but did not change treatment course in the majority of patients. Previous toxicity should be carefully evaluated as it usually reoccurs.

Several solid malignancies trigger lymphangiogenesis, facilitating metastasis. Tumor-associated lymphatic vessels significantly contribute to the generation of an immunosuppressive tumor microenvironment (TME). Here, we have investigated the ability of tumoral lymphatic endothelial cells (LEC) to function as MHC class II-restricted antigen-presenting cells in the regulation of antitumor immunity. Using murine models of lymphangiogenic tumors engrafted under the skin, we have shown that tumoral LECs upregulate MHC class II and the MHC class II antigen-processing machinery, and that they promote regulatory T-cell (Treg) expansion ex vivo In mice with LEC-restricted lack of MHC class II expression, tumor growth was severely impaired, whereas tumor-infiltrating effector T cells were increased. Reduction of tumor growth and reinvigoration of tumor-specific T-cell responses both resulted from alterations of the tumor-infiltrating Treg transcriptome and phenotype. Treg-suppressive functions were profoundly altered in tumors lacking MHC class II in LECs. No difference in effector T-cell responses or Treg phenotype and functions was observed in tumor-draining lymph nodes, indicating that MHC class II-restricted antigen presentation by LECs was required locally in the TME to confer potent suppressive functions to Tregs. Altogether, our study suggests that MHC class II-restricted antigen-presenting tumoral LECs function as a local brake, dampening T cell-mediated antitumor immunity and promoting intratumoral Treg-suppressive functions.

Background: Aim of this study was to evaluate the prevalence of blood-borne chronic viral infections in immigrants living in southern Italy and identify factors associated to viral infections. Methods: A prospective screening program was performed in seven clinical centers operating in Campania, Apulia and Calabria regions in southern Italy, in order to identify immigrants with HBV, HCV or HIV infections. Results: Of 4,125 immigrants observed in the study period, 3,839 (93.0%) agreed to be screened: 381 (9.9%) resulted HBsAg-positive, 136 (3.5%) anti-HCV, 62 (1.6%) anti-HIV and 1,448 (37.7%) HBsAg-negative and anti-HBc-positive. Ongoing or previous HBV infection was observed more frequently in males (p = 0.02 and p < 0.001, respectively), whereas HIV infection in females (p = 0.01). Immigrants from western Africa showed a higher rate of HBsAg positivity (p < 0.0001), HBsAg negativity/anti-HBc positivity (p < 0.0001) and anti-HIV positivity (p = 0.004) compared with those from other geographical areas. At multivariate analysis, ongoing HBV infection was associated with male sex (OR 1.49, 95% CI: 1.04–2.14) and origin from western Africa (OR 4.67, 95% CI: 1.70–12.80) and eastern Europe (OR 3.44, 95% CI: 1.17–10.08). HCV infection showed the tendency to be more frequent among males (OR 1.84, 95% CI: 0.99–3.42). HIV infection was associated with an older age (OR 1.04, 95% CI: 1.01–1.06), origin from western Africa (OR 4.09, 95% CI: 1.26–13.29) and female sex (OR 2.38, 95% CI: 1.29–4,39; p = 0.006). Conclusions: The high prevalence of HBV, HCV and HIV infections in our large cohort of immigrants should definitively prompt Italian Healthcare Authorities to develop adequate cost-effective screening policies.

Chronic lymphocytic leukaemia (CLL) cells are strongly influenced by microenvironmental signals through the activation of distinct membrane receptors including the B-cell receptor and toll-like receptors (TLR). Recapitulating TLR stimulation in vitro by treating CLL cells with the TLR9 ligand CpG can induce metabolic activation and protection from apoptosis. We hypothesized that interfering with TLR signalling may be beneficial for treating CLL, and we tested in preclinical studies the effect of a specific interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitory small molecule on primary leukaemic cells isolated from the peripheral blood of patients. We observed that IRAK4, an upstream kinase of the TLR pathway, is expressed in patients with CLL, and lower IRAK4 mRNA levels associate with a better outcome. The specific IRAK4 inhibitor disrupted TLR signalling as assessed by reduction of the specific biomarkers NFKBIZ and interleukin-6 mRNAs, and restrained the protective effect of in vitro TLR stimulation on cell viability. To note, IRAK4 inhibitor induced p53 and triggered apoptosis. Co-treatment of CLL cells with increasing concentrations of IRAK4i and the Bruton tyrosine kinase inhibitor ibrutinib demonstrated a synergistic effect. Our results suggest that targetting IRAK4 may represent a novel approach in CLL and may be combined with other signalling inhibitors.

This study was designed to investigate the knowledge, beliefs, and behaviors about rotavirus infection and its vaccination in a sample of parents in Naples, Italy. The survey was conducted between June and December 2018 among parents of children aged 3 months to 3 years. A total of 40.7% of the study subjects declared that they had heard about rotavirus infection and 60.8% and 59.2% were aware about the vaccination and of its availability in Italy. Parents with a child aged &lt, 1 year and those who reported the physicians as source of information were more likely to have heard about rotavirus infection and to know that the vaccination is available in Italy. More than half (56.4%) were worried that their children could have a rotavirus gastroenteritis and this was most likely to occur in those who have heard about rotavirus infection. Only 15.3% declared that they had immunized their children against rotavirus infection. Parents who considered it dangerous for their children to contract the rotavirus gastroenteritis, those who considered the rotavirus vaccine useful, and those who had received information by physicians were more likely to have vaccinated their children against the infection. More than half of the parents who did not immunize their children expressed their willingness to vaccinate them. Developing and implementing additional public education programs are needed for better knowledge toward rotavirus infection and vaccination and a high coverage among parents.

The objectives of this survey were to assess the knowledge, attitudes, and behaviors toward eating disorders among adolescents in Italy. The survey was undertaken between May and June 2017 among a random sample of 420 adolescents aged 14&ndash, 20 years. Data were collected through a self-administered questionnaire. Only 22.8% correctly knew both the definition of anorexia and bulimia nervosa. Female, overweight or obese individuals, and who had at least one parent with a college degree or higher level of education were more likely to have this knowledge. More than one third (38.8%) had a fear of getting fat. Female, overweight or obese individuals, who did not know the definition of anorexia and bulimia nervosa, who avoided eating when they were hungry, and who always and usually were engaged in dieting behavior were more likely to have a fear of getting fat. Only 10.1% and 11.9% always and usually were engaged in dieting behavior, and 40.8% never did so. Respondents who usually/always had a strong desire to be thinner and who had a fear of getting fat were more likely to be engaged in dieting behavior. There is an urgent need to inform Italian adolescents about eating disorders, and healthcare workers may play a crucial role in distributing eating disorder-related knowledge.

The objectives of this investigation were to examine the travelers' knowledge, attitudes, and behavior about travel-related diseases and to evaluate the factors that influence their knowledge, attitudes, and behavior. A cross-sectional study was performed between May and September 2018 among a random sample of individuals attending randomly selected travel agencies in the geographical areas of Caserta and Naples, Italy. One fourth of participants (25.6%) had a poor level of knowledge, 50.2% a moderate, and only 24.2% a good level about the most common infectious diseases in the destination country. Those who had received information from physicians about the most common infectious diseases in the destination country and who do not need additional information were significantly more likely to have a good level of knowledge. A large majority (91%) showed no concern about the risk of getting an infectious disease during the travel. Almost half of the respondents had received information concerning the most common infectious diseases in the destination country and the related prevention measures. This information was more likely acquired by those graduated, those who know the foods that can cause the infectious diseases, and those who self-perceived a well health status, and less likely by those who had a poor level of knowledge about the most common infectious diseases in the destination country and who were going to Asia and South America. Education and communication activities regarding all aspects of travel-related diseases are needed to increase the knowledge and the access to preventive measures.

The purposes of this study were to explore the knowledge, attitudes, and behaviors towards the recommended vaccinations for adults between 19&ndash, 64 years of age and the associated factors among parents. The survey was conducted from October to December 2018 among a sample of parents randomly selected from five preschools and primary, secondary, and high schools in the geographic area of Naples, Italy. The mean age of participants was 45.2 years (range 19&ndash, 71). Only 16% of the parents knew all vaccinations recommended to adults between 19&ndash, 64 years of age. Those being healthcare professionals, having a chronic condition, having received information about vaccinations from physicians, and having a lower educational level were more likely to know the vaccinations recommended to adults between 19&ndash, 64 years of age. Female participants, those who had received information about vaccinations from physicians, and those who had a lower number of children were more likely to have a positive attitude toward the usefulness of the administration of vaccinations recommended to adults between 19&ndash, 64 years of age. Among unvaccinated respondents, more than half reported a positive attitude toward willingness to receive a recommended vaccination. This positive attitude was significantly higher among those who considered vaccinations as being useful and among who had received information from physicians. Only 16.9% self-reported to have received at least one vaccination recommended to adults between 19&ndash, 64 years of age. Those who were healthcare professionals, who had at least one chronic condition, and who considered the administration of the vaccinations as being useful were more likely to have received at least one recommended vaccination. Greater efforts by policy makers and healthcare providers are needed to increase parents&rsquo, knowledge on recommended vaccines, and it is also crucial that healthcare providers have a high knowledge and favorable attitudes in order to increase vaccine coverage.

Purpose We report long-term outcomes of phase 2 trial on patients with invasive breast cancer treated with accelerated partial-breast irradiation (APBI) using tomotherapy after breast conservative surgery. Methods and Materials From December 2010 to December 2018, we treated 338 women with APBI-tomotherapy: 38.5 Gy in 10 once-daily fractions. Patients selected were age ≥50 years old, with ≤3 cm in size unifocal tumor and at least 2 mm of clear margins. Disease outcomes were analyzed by clinicopathologic characteristics, molecular phenotypes, and American Society for Radiation Oncology (ASTRO) 2017 updated consensus groupings. Results The median age was 65 years (range, 50-86). The invasive ductal (87.5%) and the luminal A-like molecular phenotype (70%) were the most common tumors. Overall 242 patients (71.6%) were considered “suitable” for enrollment in APBI according to the eligibility criteria of the ASTRO-2017 consensus statement. With a median follow-up of 76 months (range, 17-113), 2 patients (0.6%) had an invasive ipsilateral breast tumor recurrence (IBTR), and 2 patients (0.6%) had an axillary ipsilateral failure. The rate of local control in terms of free of IBTR was 99.4% and locoregional control (no recurrence in ipsilateral breast as well as in regional nodes) was 98.8%. Progression-free survival was 98.4% and 92% at 5 and 10 years, respectively. Acute and late skin toxicity, graded according to the Common Terminology Criteria for Adverse Events, were 7.7% (G1) and 0.6% (G2) and 4.4% (G1) and 1.1% (G2), respectively. There were no grade 3/4 toxicities, however. Very few patients (2%) or physicians (2%) assessed cosmetic outcome as fair or poor at the 2-year follow-up. Conclusions This phase 2 trial on APBI-tomotherapy shows excellent long-term results. Once-daily fractionation schedule was well tolerated with a low rate of adverse events and worse cosmetic outcome. In this series, even among those deemed cautionary or unsuitable for APBI by ASTRO criteria, we demonstrated a low rate of IBTR.

The association of glycated hemoglobin (HbA1c) with venous thromboembolism (VTE) and death in the elderly is unknown. In the SWEETCO 65+ study we analyzed prospectively a Swiss Cohort of Elderly Patients with Venous Thromboembolism (SWITCO 65+). 888 patients were enrolled for the SWEETCO 65+ analysis. HbA1c was determined at baseline and divided into three categories (HbA1c 6.5%, diabetic range). Median follow-up was 2.5 years. The primary endpoint was recurrent VTE. Secondary endpoints included all-cause mortality and major bleeds. The total prevalence of diabetes was 22.1%. The risk of recurrent VTE was similar in patients with HbA1c with pre-diabetes (adjusted subhazard ratio (aSHR) 1.07 [0.70 to 1.63]) and diabetes (aSHR 0.73 [0.39 to 1.37]) as compared to those with a HbA1c in the normal range. However, a HbA1c ≥ 6.5% (median IQ range 7.0 [6.70;7.60]) was significantly associated with a higher risk of all-cause mortality (adjusted hazard ratio [aHR] 1.83 [1.21 to 2.75]). In summary we found no association between HbA1c and major bleeding. Elevated HbA1c levels are not associated with recurrent VTE but with increased all-cause mortality in an elderly population with acute VTE.

Background : The misuse of antibiotics is one of the leading causes of antibiotic resistance. Paediatric patients are highly involved in this issue, as they are those who receive the largest amount of prescriptions of these drugs. Therefore, this study aimed to investigate the general knowledge regarding the use of antibiotics, as well as the attitudes related to the administration of these drugs to children, amongst parents of children in the paediatric age-group. Methods : In 2014, a multicentre cross-sectional study was conducted amongst parents of children aged 0–14. A questionnaire made up of 33 items was administered in waiting rooms of outpatient departments. Multivariable logistic regression models were performed, in order to assess the potential predictors of a better knowledge about antibiotics. Results : A total of 1247 parents took part to the survey. Around 33% of the samples declared that antibiotics are useful for viral infections, 20.6% that antibiotics are useful for every kind of pain and inflammation, while 14% of the parents stated that they stop giving antibiotics to their children when they start feeling better. Multivariable models showed that males, unemployed and those with lower levels of education are less prone to answer correctly to the questions about antibiotics. Conclusion : The present study demonstrates that parents have a lack of knowledge regarding the use of antibiotics, which results in bad habits and inappropriate attitudes when it comes to giving antibiotics to their children. Attention should be particularly focused on disadvantaged parents.

Pharmacists should be educated about travel medicine, since they could influence their own choices and those of the individuals they encounter. This study aims to investigate the knowledge, attitudes, and behaviors towards infectious diseases related to travel among community pharmacists in Italy. The data was collected from September 2018 to September 2019 using semi-structured telephone interviews. Only 1.8% answered correctly to all seven questions regarding the infectious diseases related to travel. Community pharmacists who had heard about travel medicine and those who had received information were more likely to have good knowledge. More than two-thirds of the respondents believed that it is important to provide information to the public about travel medicine. Pharmacists who worked a higher number of hours per week, were more knowledgeable about the more frequent infectious diseases related to travel, believed that travel medicine was a pharmacist competency, believed that they could give advice to the public, and had received information from scientific journals and educational activities were more likely to have this positive attitude. More than two-thirds often/always informed the public about the importance of having travel health center counseling. Pharmacists who had heard about travel medicine and those who believed that they could give advice to the public were more likely to inform. Interventions are needed to improve knowledge in order that community pharmacists can play an active role in counseling the public.

Background The objectives of the present cross-sectional study were to investigate the level of knowledge and attitudes regarding Human papillomavirus (HPV) infection and its vaccination and to understand the impact of different determinants among immigrants and refugees in Italy. Methods Between September 2016 and March 2018, a total of 519 potential participants were randomly recruited. The information was collected through a questionnaire administered by two researchers. Results Only 15.9% reported that they had heard of HPV infection before completing the survey and 83.8% of them were aware that the infection could be transmitted through sexual intercourses, 32.3% that it can lead to cervical cancer, 22% to warts, 16.2% to penile cancer, 13.2% to oral cancer, 39.7% that cervical cancer is a very severe disease, 47.1% that receiving the vaccine could protect against the infection, and 44.1% that a vaccine against HPV is available in Italy. Females, those who originated from Eastern Europe, Asia and South America, those who lived in a house compared to those who lived in a street, and those who had 1–10 years and 11 or more years of education compared to those illiterate were more likely to have heard about the HPV infection before completing the survey. Only 3 participants (0.7%) received the HPV vaccination. Out of the unvaccinated who had heard of HPV, 50.7% and 59% of those between the ages of 12 and 26 and of those who had at least one child aged 12–26 years, were willing to receive vaccination for themselves as well as their children. Conclusion The results underscored the necessity to develop health education and promotion aimed at improving the knowledge and vaccination practice in immigrants and refugees.

The aims of this survey were to ascertain pregnant women's level of knowledge and acceptability on the vaccinations and to identify their associations with several characteristics. A cross-sectional study was performed from December 2017 through March 2018 in the geographic area of Naples, Italy. The study used two stages cluster sampling method for selection and recruitment of participants. Data were collected through face-to-face interviews with pregnant women present at the Obstetrics outpatient clinic of the selected hospitals. A total of 358 respondents agreed to be interviewed out of the 405 pregnant women selected. One-fourth knew at least one of the vaccinations recommended during pregnancy and only 2.8% correctly identified all of these. Women who had received information about the vaccinations during pregnancy from general practitioners or gynecologists or other sources and those with at least one child were more likely to know at least one of the recommended vaccinations, whereas women with middle school education were less knowledgeable. None of the women had received tetanus, diphtheria, and acellular pertussis vaccine and only 1.4% the seasonal influenza vaccination. Only 27.9% reported a positive willingness to receive all the recommended vaccinations during pregnancy. Pregnant women would be willing to get all recommended vaccinations if they had at least one child and if they needed additional information, whereas the willingness was significantly lower among women who had reported high school as the highest level of education, who were in the second trimester of pregnancy, and who felt that the recommended vaccines administered during pregnancy were less dangerous for them and for the unborn child. This study suggests important focus points to be taking into account for informing and for implementing education activities on the benefits regarding vaccinations in order to increase the level of knowledge and the uptake in pregnant women.

Finkelstein1 invited physicians and researchers interested in mesothelioma to investigate on past usage of talcum powders by affected people. In Italy, asbestos contamination in talc for industrial use has been documented,2 and, as he underlines tremolite contamination at low levels of cosmetic and pharmaceutical talc has been reported in USA by Blount3 and Gordon and colleagues.4 In the Italian National Mesothelioma Register (ReNaM), the analysis of intensive exposure to talc has been evaluated with respect to occupational and environmental history. The catalogue of possible asbestos exposure circumstances (a tool for the interviewers) reports the potential presence of industrial talcs in quarries or mines working activities, in leather tanning and in rubber industries. The use of intensive cosmetic talc for personal use is evaluated by means of a structured questionnaire,5 as reported in the ReNaM guidelines (see https://www.inail.it/cs/internet/docs/all-linee-guida-renam.pdf%3Fsection=attivita, p82, p98, in Italian). In our paper regarding gender differences in mesothelioma epidemiology,6 we have presented figures referring to 21 463 MM cases detected by ReNaM with a diagnosis between 1993 and 2012. Among female case list (6087 cases), 4374 cases (71.9%) have been interviewed for defining exposure. During the interview, 30 MM female cases referred an intensive use of talc in the context of occupational or life habits. For five of them, the regional centre has identified an exposure to asbestos due to intensive talc use, classifying such modality of exposure as ‘leisure activities’ (see ReNaM guidelines5). For the remaining 25 cases, an occupational exposure to asbestos in other working (or familiar or environmental) circumstances has been identified and coded. Registry data such as those provided by ReNaM cannot provide estimates of the mesothelioma risk associated with any particular exposure circumstance. We plan to include talc exposure at work and cosmetic talc usage in the analyses of a case–control study on pleural mesothelioma currently under way. A specific survey to compare and discuss how the modalities of exposure to talc have been evaluated in patients with mesothelioma in countries where epidemiological surveillance systems are active could improve knowledge and support prevention policies.

This cross-sectional survey was designed to assess the prevalence of vaccine hesitancy and to identify factors associated among a randomly selected sample of parents. A questionnaire was self-administered from October to December 2017 to a sample of parents of children aged 2 to 6 years attending five randomly selected pre-schools in the geographic area of Naples, Italy. Out of the 727 selected parents, 437 returned the questionnaires for a response rate of 60.1%. The median of Parent Attitudes about Childhood Vaccines Survey (PACV) score among participants was 45.8 with a total of 141 parents (34.7%) scored a value ≥50 and were defined hesitant about the childhood vaccinations. Vaccine hesitancy was significantly more common among those who were concerned and among those were not sure that any one of the childhood shots might not be safe, among those who were concerned that their children might have a serious side effect from a shot, among those who were concerned that a shot might not prevent the disease, among those who delayed and refused at least a shot of vaccine for their children, and in those who are not sure and uncertain in the pediatrician. More than half of parents (53.8%) expressed a desire to receive additional information about the childhood vaccinations. Parents who were not sure and uncertain that to follow the recommended shot schedule is a good idea for their children and those who were parents of first-born children were more likely to need additional information. This study finds a high prevalence of vaccine hesitancy among parents suggesting that in the immunization program is necessary to achieve a higher quality of the relationship between pediatricians and the community.

The objectives of this cross-sectional investigation among a random sample of immigrants and refugees in Italy were to gain an insight into the extent and type of the episodes of violence and to assess their association with different characteristics. Data was collected from September 2016 to July 2017 using a face-to-face structured interview. A total of 503 subjects participated. Overall, 46.5% and 40% of the sample reported having experienced some form of violence in Italy at least once since they arrived and during the last 12 months. Psychological violence was the most common form experienced by 53.2% of the participants, 40.3% experiencing physical violence, 18.9% economic violence, and only 6.5% intimate partner violence. The risk of experiencing at least one form of violence in the last 12 months in Italy was more likely to occur among immigrants who have been in Italy much longer and less likely in those who lived in a camp. The number of episodes of violence experienced since they arrived in Italy was significantly higher in female, in those who have been in Italy much longer and in those who had experienced at least one racially discriminatory episode of violence, whereas those with middle and high school or above educational level and those who did not experience psychological consequences of the violence had experienced a lower number of episodes. These results must be used to strengthen interventions and policies aimed at preventing violence among this population.

Introduction Anatomical change of tumor during radiotherapy contributes to target missing. However, in the case of tumor shrinkage, adaptation of volume could result in an increased incidence of recurrence in the area of target reduction. This study aims to investigate the incidence of failure of the adaptive approach and, in particular, the risk for local recurrence in the area excluded after replanning. Methods In this prospective study, patients with locally advanced NSCLC treated with concomitant chemoradiation underwent weekly chest computed tomography simulation during treatment. In the case of tumor shrinkage, a new tumor volume was delineated and a new treatment plan outlined (replanning). Toxicity was evaluated with the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Patterns of failures were classified as in field (dimensional and/or metabolic progression within the replanning planning target volume [PTV]), marginal (recurrence in initial the PTV excluded from the replanning PTV), and out of field (recurrence outside the initial PTV). Results Replanning was outlined in 50 patients selected from a total of 217 patients subjected to weekly simulation computed tomography in our center from 2012 to 2014. With a median follow-up of 20.5 months, acute grade 3 or higher pulmonary and esophageal toxicity were reported in 2% and 4% of cases and late toxicity in 4% and 2%, respectively. Marginal relapse was recorded in 6% of patients, and 20% and 4% of patients experienced in-field and out-of-field local failure, respectively. Conclusions The reduced toxicity and the documented low rate of marginal failures make the adaptive approach a modern option for future randomized studies. The best scenario to confirm its application is probably in neoadjuvant chemoradiation trials.

Long-term predictors and causes of death are understudied in elderly patients with acute venous thromboembolism.We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was overall mortality. We explored the association between patient baseline characteristics and mortality, adjusting for other baseline variables and periods of anticoagulation as a time-varying covariate. Causes of death over time were adjudicated by a blinded, independent committee.The median age was 75 years. During a median follow-up period of 30 months, 206 patients (21%) died. Independent predictors of overall mortality were age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.05-1.65, per decade), active cancer (HR, 5.80; 95% CI, 4.22-7.97), systolic blood pressure100 mm Hg (HR, 2.77; 95% CI, 1.56-4.92), diabetes mellitus (HR, 1.50; 95% CI, 1.02-2.22), low physical activity level (HR, 1.92; 95% CI, 1.38-2.66), polypharmacy (HR, 1.41; 95% CI, 1.01-1.96), anemia (HR, 1.48; 95% CI, 1.07-2.05), high-sensitivity C-reactive protein40 mg/L (HR, 1.88; 95% CI, 1.36-2.60), ultra-sensitive troponin14 pg/mL (HR, 1.54; 95% CI, 1.06-2.25), and D-dimer3000 ng/mL (HR, 1.45; 95% CI, 1.04-2.01). Cancer (34%), pulmonary embolism (18%), infection (17%), and bleeding (6%) were the most common causes of death.Elderly patients with acute venous thromboembolism have a substantial long-term mortality, and several factors, including polypharmacy and a low physical activity level, are associated with long-term mortality. Cancer, pulmonary embolism, infections, and bleeding are the most common causes of death in the elderly with venous thromboembolism.

BACKGROUND Combining high-sensitivity cardiac Troponin T (hs-cTnT), NT-pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) may improve risk stratification of patients with pulmonary embolism (PE) beyond the PESI risk score. METHODS In the prospective multicenter SWITCO65+ study, we analyzed 214 patients ≥65 years with a new submassive PE. Biomarkers and clinical information for the PESI risk score were ascertained within 1 day after diagnosis. Associations of hs-TnT, NT-proBNP, hs-CRP and the PESI risk score with the primary endpoint defined as 6-month mortality were assessed. The discriminative power of the PESI risk score and its combination with hs-cTnT, NT-proBNP and hs-CRP for 6-month mortality was compared using integrated discrimination improvement (IDI) index and net reclassification improvement (NRI). RESULTS Compared with the lowest quartile, patients in the highest quartile had a higher risk of death during the first 6 months for hs-cTnT (adjusted HR 10.22; 95% CI 1.79-58.34; p=0.009), and a trend for NT-proBNP (adjusted HR 4.3; 95% CI 0.9-20.41; p=0.067) unlike hs-CRP (adjusted HR 1.97; 95% CI 0.48-8.05; p=0.344). The PESI risk score (c-statistic 0.77 (95% CI 0.69-0.84) had the highest prognostic accuracy for 6-month mortality, outperforming hs-cTnT, NT-proBNP and hs-CRP (c-statistics of 0.72, 0.72, and 0.54), respectively. Combining all three biomarkers had no clinically relevant impact on risk stratification when added to the PESI risk score (IDI = 0.067; 95% CI 0.012-0.123; p=0.018; NRI = 0.101 95% CI -0.099-0.302; p=0.321). CONCLUSIONS In elderly patients with PE, 6-month mortality can adequately be predicted by the PESI risk score alone. This article is protected by copyright. All rights reserved.

AIMS OF THE STUDY Iron deficiency (ID) and iron deficiency anaemia (IDA) are important conditions affecting a large proportion of the general population, causing the patients physical and psychosomatic symptoms, particularly fatigue, and significantly affecting their quality of life. General practitioners (GPs) are frequently consulted with nonspecific symptoms due to the ID. However, little evidence is available to guide iron treatment. The aim of the Swiss Delphi study was to generate a broad consensual Swiss expert opinion in various therapeutic areas on diagnosis and treatment of ID/IDA and their practical implications. METHODS Specific statements regarding clinical relevance, practical diagnostic and therapeutic approaches, and treatment were evaluated by Swiss experts in various therapeutic areas using the Delphi method. “Consensus” was defined as ≥80% agreement; the agreement of 50–79% was defined as “critical”, of

The diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (One hundred twenty-two patients with histologically proven mantle-cell lymphoma were included. PET/CT BM findings were considered positive if isolated/multiple focal uptake in the BM not explained by benign findings and/or diffuse BM uptake higher than liver with/without focal uptakes were present. PET/CT findings were considered positive for GI involvement in the presence of isolated/multiple focal uptake in the GI organ.All patients had positive PET/CT showing the presence of at least one hypermetabolic lesion, with the exception of one case. PET/CT results, compared to CT, detected more nodal and/or splenic lesions in 26 patients. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT for BM were 52%, 98%, 97%, 65%, and 74%; for GI 64%, 91%, 69%, 90%, and 85%; and for GI excluding diabetic patients, 78%, 92%, 72%, 94%, and 89%. PET/CT permitted upstaging of 21 cases and downstaging of 2.

BACKGROUND/PURPOSE Hemophagocytic lymphohistiocytosis (HLH) is a rare, life threatening hyperinflammatory syndrome. Sinusoidal hemophagocytosis is occasionally observed on liver biopsy in patients who do not have clinical suspicion of HLH. We aimed at comparing the clinical characteristics and outcomes of patients with signs of hemophagocytosis on liver biopsy meeting and not meeting the HLH diagnostic criteria. METHODS We reviewed the clinical, laboratory features and outcomes of all adult patients consecutively admitted in our center between 08/2011 and 08/2017 presenting with liver histology showing sinusoidal hemophagocytosis and of critically ill patients presenting with severe liver disease in whom hemophagocytosis was histologically confirmed. The characteristics of patients fulfilling and not fulfilling the diagnostic criteria of HLH were compared. RESULTS We identified 12 cases (58% male, median age 61, 75% with a chronic underlying disease) with liver histology showing sinusoidal hemophagocytosis. All had at least some of the clinical features typically associated with HLH. Six were critical ill patients. In 4 cases with insufficient laboratory and clinical criteria, liver biopsy allowed to confirm the HLH diagnosis. Six patients died, of which four met the diagnostic criteria for HLH. Two patients with chronic liver disease died despite not fulfilling the diagnostic criteria of HLH. CONCLUSION Hemophagocytosis on liver biopsy may contribute to confirming a diagnosis of HLH in suspected cases with indeterminate clinical and laboratory findings. Sinusoidal hemophagocytosis in patients with cirrhosis was associated with bad outcome.

Introduction: Targeted therapies against epidermal growth factor receptor (EGFR) have revolutionized the treatment of a subset of lung adenocarcinomas that have EGFR-activating mutations; however, all patients treated with EGFR tyrosine kinase inhibitors (TKIs) ultimately develop resistance. Histologic transformation of EGFR-mutant adenocarcinoma to small cell lung cancer (SCLC) is a resistance mechanism rarely reported in the literature. Case presentation: We describe the case of a woman with metastatic lung cancer adenocarcinoma with mutated EGFR with an initial response to gefitinib and radiation therapy, who progressed after 18 months due to the development of a resistance mechanism. The new biopsy performed after progression highlighted histologic transformation to SCLC, while maintaining the original EGFR mutation. Conclusions: To better identify patients who progress after TKIs and radiation therapy, it is important to perform tumor rebiopsy and collect data to study mechanisms of acquired EGFR TKI resistance.

Background. The objectives of the study were to document knowledge, attitudes, and behaviors of women regarding cardiovascular diseases (CVDs) and the determinants associated.Materials and Methods. The cross-sectional survey was conducted among a random sample of 830 women older than 18 years from the general population in Italy.Results. Almost all participants reported having heard about CVDs, and among them 89.4% and 74.7% identified smoking and high cholesterol level as risk factors. Only 26.5% identified the main CVDs risk factors. Women more knowledgeable were married and better educated and self-perceived a worse health status. Only 23% knew the main CVDs preventive measures and this knowledge was significantly higher in women who are unemployed, who are more educated, who have received information about CVDs from physicians, and who know the main risk factors. Respondents with lower education, those with at least three children, those who self-perceived a worse health status, and those who need information were most likely to have a positive attitude toward the perceived risk of developing CVDs. Women with two or three children or more were at high risk profiles 49% and 56% lower than women with one child.Conclusions. Educational programs are needed among women as support to improve knowledge and appropriate behavior about CVDs.

Background The aims of this study were to assess the knowledge, attitudes, and behaviors towards seasonal influenza and its vaccination among pregnant women. Methods A cross-sectional survey was carried out among a sample of women in the second or third trimester of pregnancy in Italy. Results The 64.2% of the sample knew that the influenza is more dangerous for pregnant women. Women of older age, Italian, and who had a pregnancy at high-risk were more likely to have this knowledge. This knowledge was lower among women with none, primary or secondary school education. The majority of the respondents considered the vaccine not very useful during pregnancy. Those younger, unmarried, who knew that influenza is more dangerous for pregnant women, who knew that the vaccine could protect them, who reported a higher self-rated health status, and who had received information about influenza and its vaccination were more likely to have a positive attitude toward the usefulness of influenza vaccination in pregnancy. Women with secondary school education and with more than one child revealed a lower perception. Only 9.7% had received the vaccine and 21.4% of those unvaccinated would be willing to receive it. This positive attitude was higher among women with one child, who knew that the vaccine could protect them against the influenza, and who have a positive attitude toward the usefulness of the vaccination during pregnancy. Conclusions Health educational programs are needed to improve the knowledge about seasonal influenza and vaccination rate in pregnancy. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-2138-2) contains supplementary material, which is available to authorized users.

The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of the FKBP5 gene, resulting in increased expression of its variant 4 in the peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript is translated into the truncated FKBP51s protein. Given the importance of co-inhibitory signalling in tumour immune escape, here we tested the potential for using FKBP51s expression to predict immunotherapy outcomes. To do this, we immunophenotyped PBMCs from 118 melanoma patients and 77 age- and sex-matched healthy controls. Blood samples were collected before patients underwent ipilimumab treatment. In 64 of the 118 patients, FKBP51s expression was also assessed in regulatory T cells (Tregs). We found that each PBMC subset analysed contained an FKBP51s(pos) fraction, and that this fraction was greater in the melanoma patients than healthy controls. In CD4 T lymphocytes, the FKBP51s(neg) fraction was significantly impaired. Tregs count was increased in melanoma patients, which is in line with previous studies. Also, by analyses of FKBP51s in Tregs, we identified a subgroup of ipilimumab nonresponder patients (p = 0.002). In conclusion, FKBP51s-based immunophenotyping of melanoma patients revealed several profiles related to a negative immune regulatory control and identified an unknown Treg subset. These findings are likely to be useful in the selection of the patients that are candidate for immunotherapy.

The objectives of the cross-sectional study were to delineate the knowledge, attitudes, and behavior among nurses regarding the prevention of central line-associated bloodstream infections (CLABSIs) and to identify their predisposing factors. A questionnaire was self-administered from September to November 2011 to nurses in oncology and outpatient chemotherapy units in 16 teaching and non-teaching public and private hospitals in the Campania region (Italy). The questionnaire gathered information on demographic and occupational characteristics; knowledge about evidence-based practices for the prevention of CLABSIs; attitudes towards guidelines, the risk of transmitting infections, and hand-washing when using central venous catheter (CVC); practices about catheter site care; and sources of information. The vast majority of the 335 nurses answered questions correctly about the main recommendations to prevent CLABSIs (use sterile gauze or sterile transparent semipermeable dressing to cover the catheter site, disinfect the needleless connectors before administer medication or fluid, disinfect with hydrogen peroxide the catheter insertion site, and use routinely anticoagulants solutions). Nurses aged 36 to 50 years were less likely to know these main recommendations to prevent CLABSIs, whereas this knowledge was higher in those who have received information about the prevention of these infections from courses. Nurses with lower education and those who do not know two of the main recommendations on the site’s care to prevent the CLABSIs, were more likely to perceive the risk of transmitting an infection. Higher education, attitude toward the utility allow to dry antiseptic, and the need of washing hands before wearing gloves for access to port infusion were predictors of performing skin antiseptic and aseptic technique for dressing the catheter insertion site. Educational interventions should be implemented to address the gaps regarding knowledge and practice regarding the prevention of CLABSIs and to ensure that nurses use evidence-based prevention interventions.

Background The aims of this cross-sectional survey were to examine the knowledge, the attitudes, and the behavior regarding the varicella infection and its vaccination and to get insight into their determinants among parents of children in Italy. Methods From May to June 2015 in the geographic area of Naples (Italy) a random sample of 675 parents of children aged 4-7 years received a self-administered anonymous questionnaire about socio-demographic characteristics, knowledge, attitudes, and behaviors towards varicella and its vaccination. Results A total of 414 parents responded to the questionnaire, for a response rate of 61.3%. A history of varicella was reported in 163 children (39.6%). Only 26.6% parents knew that the vaccine was available and the number of doses and this knowledge was significantly higher in those who had a university degree, in those who had received information on the vaccination from a health care provider, and in those who had vaccinated their child. The perceived utility towards vaccination had a mean value of 5.7. The positive attitude towards the utility of the vaccination was higher in parents with a level of education not higher than middle school, in those who had vaccinated their child, in those who considered the varicella a dangerous disease, and in those who had received information from a health care provider. More than one-third had vaccinated their child. Immunization was more frequent in parents who had knowledge about the vaccination, who beliefs that the immunization was useful, who believed that the disease was not dangerous, and who had not a history of varicella among their children. Conclusions Educational programs are needed among parents as support to improve knowledge about vaccination and immunization coverage. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2247-6) contains supplementary material, which is available to authorized users.