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The partial loss of SMARCB1/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1/INI1 and the underlying genetic alterations in the SMARCB1 gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the SMARCB1 gene. Partial loss of SMARCB1/INI1 was correlated with cervical–thoracic–lumbar tumor location (p = 0.033) and inadequate surgical margins (p = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins.

Introduction: The term theragnostic refers to the combination of a predictive imaging biomarker with a therapeutic agent. The promising application of prostate-specific membrane antigen (PSMA)-based radiopharmaceuticals in the imaging and treatment of prostate cancer (PCa) patients opens the way to investigate a possible role of PSMA-based radiopharmaceuticals in cancers beyond the prostate. Therefore, the aim of this review was to evaluate the role of 177Lu-PSMA radioligand therapy (RLT) in malignancies other than prostate cancer by evaluating preclinical, clinical studies, and ongoing clinical trials. Methods: An extensive literature search was performed in three different databases using different combinations of the following terms: “Lu-PSMA”, “177Lu-PSMA”, “preclinical”, “mouse”, “salivary gland cancer”, “breast cancer”, “glioblastoma”, “solid tumour”, “renal cell carcinoma”, “HCC”, “thyroid”, “salivary”, “radioligand therapy”, and “lutetium-177”. The search had no beginning date limit and was updated to April 2024. Only articles written in English were included in this review. Results: A total of four preclinical studies were selected (breast cancer model n = 3/4). PSMA-RLT significantly reduced cell viability and had anti-angiogenic effects, especially under hypoxic conditions, which increase PSMA binding and uptake. Considering the clinical studies (n = 8), the complexity of evaluating PSMA-RLT in cancers other than prostate cancer was clearly revealed, since in most of the presented cases a sufficient tumour radiation dose was not achieved. However, encouraging results can be found in some types of diseases, such as thyroid cancer. Some clinical trials are still ongoing, and results from prospective larger cohorts of patients are awaited. Conclusions: The need for larger patient cohorts and more RLT cycles administered underscores the need for further comprehensive studies. Given the very preliminary results of both preclinical and clinical studies, ongoing clinical trials in the near future may provide stronger evidence of both the safety and therapeutic efficacy of PSMA-RLT in malignancies other than prostate cancer.

Abstract Background Chikungunya is associated with high morbidity and the natural history of symptomatic infection has been divided into three phases (acute, post-acute, and chronic) according to the duration of musculoskeletal symptoms. Although this classification has been designed to help guide therapeutic decisions, it does not encompass the complexity of the clinical expression of the disease and does not assist in the evaluation of the prognosis of severity nor chronic disease. Thus, the current challenge is to identify and diagnose musculoskeletal disorders and to provide the optimal treatment in order to prevent perpetuation or progression to a potentially destructive disease course. Methods The study is the first product of the Clinical and Applied Research Network in Chikungunya (REPLICK). This is a prospective, outpatient department-based, multicenter cohort study in Brazil. Four work packages were defined: i. Clinical research; ii) Translational Science – comprising immunology and virology streams; iii) Epidemiology and Economics; iv) Therapeutic Response and clinical trials design. Scheduled appointments on days 21 (D21) ± 7 after enrollment, D90 ± 15, D120 ± 30, D180 ± 30; D360 ± 30; D720 ± 60, and D1080 ± 60 days. On these visits a panel of blood tests are collected in addition to the clinical report forms to obtain data on socio-demographic, medical history, physical examination and questionnaires devoted to the evaluation of musculoskeletal manifestations and overall health are performed. Participants are asked to consent for their specimens to be maintained in a biobank. Aliquots of blood, serum, saliva, PAXgene, and when clinically indicated to be examined, synovial fluid, are stored at -80° C. The study protocol was submitted and approved to the National IRB and local IRB at each study site. Discussion Standardized and harmonized patient cohorts are needed to provide better estimates of chronic arthralgia development, the clinical spectra of acute and chronic disease and investigation of associated risk factors. This study is the largest evaluation of the long-term sequelae of individuals infected with CHIKV in the Brazilian population focusing on musculoskeletal manifestations, mental health, quality of life, and chronic pain. This information will both define disease burden and costs associated with CHIKV infection, and better inform therapeutic guidelines.

Amyloidosis is a rare infiltrative condition resulting from the extracellular accumulation of amyloid fibrils at the cardiac level. It can be an acquired condition or due to genetic mutations. With the progression of imaging technologies, a non-invasive diagnosis was proposed. In this study, we discuss the role of CMR in cardiac amyloidosis, focusing on the two most common subtypes (AL and ATTR), waiting for evidence-based guidelines to be published.

Abstract The amount of evidence for guideline‐directed new heart failure (HFrEF) disease‐modifying drugs in the context of chronic kidney disease (CKD) is relatively modest, especially in end‐stage CKD. We report a case of dramatic reverse remodelling and disease regression in a naïve HFrEF young woman on haemodialysis treated with sacubitril/valsartan and SGLT2i. At 10‐month follow‐up, the patient normalized left ventricle and atrial volumes and improved ejection fraction to the normal range, assessed both by echocardiography and cardiac magnetic resonance. Cardiac biomarkers and exercise performance improved consensually. The haemodialysis protocol and the loop diuretic dose were unchanged within the whole period.

We present the case of an 82-year-old man with a history of inferior vena cava filter implantation and concomitant severe mitral regurgitation requiring transcatheter edge-to-edge repair. Despite being deemed ineligible for transfemoral access as technically challenging, he successfully underwent mitral transcatheter edge-to-edge repair after crossing and dilatation of the inferior vena cava filter. (Level of Difficulty: Intermediate.)

Abstract Background Head and neck squamous cell carcinoma (HNSCC) represents the 6th leading cancer worldwide. In most cases, patients present a locally advanced disease at diagnosis and non-surgical curative treatment is considered the standard of care. Nowadays, [18F]FDG PET/CT is a validated tool in post-treatment evaluation, with a high level of evidence. However, to standardize imaging response, several visual scales have been proposed with none of them approved yet. The study’s aim is a head-to-head comparison between the diagnostic performance of the Hopkins criteria, the Deauville score, and the new proposed Cuneo score, to establish their prognostic role. Secondly, we investigate the possible value of semiquantitative analysis, evaluating SUVmax and ΔSUVmax of the lymph node with the highest uptake on the restaging PET scan. Moreover, we also considered morphological features using the product of diameters measured on the co-registered CT images to assess the added value of hybrid imaging. Methods We performed a retrospective analysis on histologically proven HNSCC patients who underwent baseline and response assessment [18F]FDG PET/CT. Post-treatment scans were reviewed according to Hopkins, Deauville, and Cuneo criteria, assigning a score to the primary tumor site and lymph nodes. A per-patient final score for each scale was chosen, corresponding to the highest score between the two sites. Diagnostic performance was then calculated for each score considering any evidence of locoregional progression in the first 3 months as the gold standard. Survival analysis was performed using the Kaplan–Meier method. SUVmax and its delta, as well as the product of diameters of the lymph node with the highest uptake at post-treatment scan, if present, were calculated. Results A total of 43 patients were finally included in the study. Sensitivity, specificity, PPV, NPV, and accuracy were 87%, 86%, 76%, 92%, and 86% for the Hopkins score, whereas 93%, 79%, 70%, 96%, and 84% for the Deauville score, respectively. Conversely, the Cuneo score reached the highest specificity and PPV (93% and 78%, respectively) but the lowest sensitivity (47%), NPV (76%), and accuracy (77%). Each scale significantly correlated with PFS and OS. The ROC analysis of the combination of SUVmax and the product of diameters of the highest lymph node on the restaging PET scan reached an AUC of 0.822. The multivariate analysis revealed the Cuneo criteria and the product of diameters as prognostic factors for PFS. Conclusions Each visual score statistically correlated with prognosis thus demonstrating the reliability of point-scale criteria in HNSCC. The novel Cuneo score showed the highest specificity, but the lowest sensibility compared to Hopkins and Deauville criteria. Furthermore, the combination of PET data with morphological features could support the evaluation of equivocal cases.

Nowadays, there is still no consensus on the most accurate PET radiopharmaceutical to early detect prostate cancer (PCa) relapse. A tailored radiotracer choice based on a specific patient’s profile could ensure prompt disease detection and an improvement in patients management. We aimed to compare the [18F]fluciclovine and [18F]fluorocholine PET/CT detection rate (DR) in PCa patients restaged for early biochemical recurrence (BCR), according to clinical and biochemical features. A cohort of 138 PCa patients with early BCR (mean age: 71 y, range: 50–87 y) were homogeneously randomized 1:1 to a [18F]fluciclovine or a [18F]fluorocholine PET/CT group. The respective PET/CT DR, according to per-patient and per-region analysis, and the impact of the biochemical, clinical, and histological parameters, were compared. The PSA cut-off values predictive of a positive scan were also calculated. Overall, the [18F]fluciclovine PET/CT DR was 64%, significantly higher than the [18F]fluorocholine PET/CT DR of 35% (p = 0.001). Similarly, in the per-region analysis, the [18F]fluciclovine PET/CT DR was 51% in the prostate region, significantly higher compared to 15% of [18F]fluorocholine (p < 0.0001). Furthermore, a statistically significant higher DR in per-patient and per-region (prostate/prostate bed) analysis was observed in the [18F]fluciclovine group for 0.5–1 ng/mL (p = 0.018, p = 0.049) and >1 ng/mL (p = 0.040, p < 0.0001) PSA values. A PSA of 0.45 ng/mL for [18F]fluciclovine and of 0.94 ng/mL for [18F]fluorocholine was identified as the optimal cut-off value in predicting a positive PET/CT scan. Our results demonstrated a better [18F]fluciclovine PET/CT DR compared to [18F]fluorocholine for restaging PCa patients in early BCR, particularly in the detection of locoregional recurrence. The significantly higher [18F]fluciclovine DR for low PSA values (PSA < 1 ng/mL) supports its use in this setting of patients.

Abstract Immunity with SARS-CoV-2 infection during the acute phase is not sufficiently well understood to differentiate mild from severe cases and identify prognostic markers. We evaluated the immune response profile using a total of 71 biomarkers in sera from patients with SARS-CoV-2 infection, confirmed by RT-PCR and controls. We correlated biological marker levels with negative control (C) asymptomatic (A), nonhospitalized (mild cases-M), and hospitalized (severe cases-S) groups. Among angiogenesis markers, we identified biomarkers that were more frequently elevated in severe cases when compared to the other groups (C, A, and M). Among cardiovascular diseases, there were biomarkers with differences between the groups, with D-dimer, GDF-15, and sICAM-1 higher in the S group. The levels of the biomarkers Myoglobin and P-Selectin were lower among patients in group M compared to those in groups S and A. Important differences in cytokines and chemokines according to the clinical course were identified. Severe cases presented altered levels when compared to group C. This study helps to characterize biological markers related to angiogenesis, growth factors, heart disease, and cytokine/chemokine production in individuals infected with SARS-CoV-2, offering prognostic signatures and a basis for understanding the biological factors in disease severity.

BackgroundConduction disorders (CD) are the most common complications after Transcatheter Aortic Valve Implantation (TAVI). The last generation of Edwards balloon expandable valves, the SAPIEN 3 Ultra (S3U), is provided with an external sealing skirt that aims to further reduce paravalvular leakage (PVL) compared to SAPIEN 3 (S3) and could potentially lead to higher CD rate. We sought to investigate the rate of new-onset CD in patients undergoing TAVI with the S3 or S3U valve.MethodsWe included 582 consecutive patients undergoing TAVI in a single high-volume Center. Patients with previously implanted pacemaker and Valve in valve procedures were excluded. CD rate was evaluated early after implantation and at discharge.ResultsNo significant difference in the overall CD rate was found between S3 and S3U patients both immediately after the procedure (S3 45.5% vs. S3U 41.8%, p = 0.575) and at discharge (S3 30.4% vs. S3U 35.6%, p = 0.348) with low rate of permanent pacemaker implantation (S3 6.3% vs. S3U 5.5%, p = 0.749). No significant differences were found also in patients with pre-existing atrial fibrillation (S3 8.2% vs. S3U 5%, p = 0.648). A significantly lower rate of PVL was found with S3U compared to S3 (S3 42% vs. S3U 26%, p = 0.007). According to the manufacturer’s guidelines we confirmed that S3U were implanted in a significantly higher position compared to S3 (S3 4.89 ± 1.57 mm vs. S3U 4.47 ± 1.36 mm, p = 0.001).ConclusionNo significant difference in the rate of CD, including the need for PPM implantation, was found in patients undergoing TAVI with the S3 compared to S3U. Moreover, S3U significantly reduced the PVL rate.

Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the IGF2BP3, a gene that codes for an oncofetal RNA-binding protein demonstrated to be important for EWS patient’s risk stratification, and five SNPs of SENCR, a long non-coding RNA shown to regulate IGF2BP3. An association between polymorphisms and EWS susceptibility was observed for three IGF2BP3 SNPs - rs112316332, rs13242065, rs12700421 - and for four SENCR SNPs - rs10893909, rs11221437, rs12420823, rs4526784 -. In addition, IGF2BP3 rs34033684 and SENCR rs10893909 variants increased the risk for female respect to male subgroup when carried together, while IGF2BP3 rs13242065 or rs76983703 variants reduced the probability of a disease later onset (> 14 years). Moreover, the absence of IGF2BP3 rs10488282 variant and the presence of rs199653 or rs35875486 variant were significantly associated with a worse survival in EWS patients with localized disease at diagnosis. Overall, our data provide the first evidence linking genetic variants of IGF2BP3 and its modulator SENCR to the risk of EWS development and to disease progression, thus supporting the concept that heritable factors can influence susceptibility to EWS and may help to predict patient prognosis.

Lung cancer is the second most frequently diagnosed cancer in the world, and surgery is an integral part of the treatment for spinal metastases. The aims of this retrospective study were to assess the overall survival of surgically treated patients affected by lung cancer spinal metastases and identify any factors related to a better survival rate. We recruited 56 consecutive patients (34 male and 22 female) surgically treated for metastatic lung cancer in the spine from 2009 to 2019. Surgical indications were based on a previously published and validated flow chart following a multidisciplinary evaluation. We assessed the localization of vertebral metastases, the presence of other bone or visceral metastases, neurological status according to the Frankel score, ambulatory autonomy, and general status, measured with the Karnofsky performance scale. The expected prognosis was retrospectively assessed according to the revised Tokuhashi score. The median survival was 8.1 months, with over a third of patients surviving more than 1 year. We observed a global improvement in all clinical parameters after surgical treatment. The Tokuhashi predictive score did not correlate with survival after surgery. The results of this study suggest that the surgical treatment of symptomatic spinal metastases from lung cancer can improve quality of life, even in patients with a shorter life expectancy, by controlling pain and improving autonomy.

IntroductionTakayasu's arteritis (TA) is a systemic inflammatory disease that affects aorta and its major branches. There are several cardiac manifestations of TA and an association with Takotsubo syndrome (TTS) – but not coronary vasospasm - has been previously reported. The role of emotional stress in this context is unknown.Case presentationA 58-year-old Caucasian female elementary school teacher, with a history of generalized anxiety disorder (GAD), severe asymptomatic aortic regurgitation (AR), and TA in remission under corticosteroids, was admitted in the emergency department with worsening chest pain and dyspnea, initiated after a period of intense emotional stress (increased workload during COVID-19 pandemic). Physical examination revealed signs of heart failure (HF) with hemodynamic stability and an early diastolic heart murmur. The electrocardiogram showed sinus tachycardia, T wave inversion in left precordial and lateral leads, and a corrected QT of 487 ms. Laboratorial evaluation presented high values of high-sensitivity troponin I (3494 ng/L) and B-type natriuretic peptide (4759 pg/mL). The transthoracic echocardiogram revealed severe dilation of left ventricle (LV) with moderate systolic dysfunction, due to apical and midventricular akinesia, and severe AR. The coronary angiography showed normal coronary arteries. An acetylcholine provocative test induced spasm of both the left anterior descending and circumflex arteries, accompanied by chest pain and ST depression, completely reverted after intracoronary nitrates administration. The patient was switched to diltiazem and a drug multitherapy for HF was started. A cardiac magnetic resonance revealed severe dilation of the LV, mild apical hypokinesia, improvement of ejection fraction to 53%, signs of myocardial edema and increased extracellular volume in apical and mid-ventricular anterior and anterolateral walls, and absence of myocardial late gadolinium enhancement, compatible with TTS. At discharge, the patient was clinically stable, without signs of HF, and a progressive reduction of troponin and BNP levels was observed. A final diagnosis of TTS and coronary vasospasm in a patient with GAD and TA was done.DiscussionWe present the first case of acute HF showing coexistence of TA, TTS and coronary vasospasm. TA is a rare inflammatory disease that can be associated with TTS and coronary vasospasm. Besides that, coronary vasospasm may also be involved in TTS pathophysiology, suggesting a complex interplay between these diseases. Mood disorders and anxiety influence the response to stress, through a gain of the hypothalamic-pituitary-adrenal axis and an increased cardiovascular system sensitivity to catecholamines. Therefore, although the mechanisms behind these three pathologies are not yet fully studied, this case supports the role of inflammatory and psychiatric diseases in TTS and coronary vasospasm.

AIM: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. METHODS: Data recorded in a multicenter (n = 17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial [18F]FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET scans, and both the obtained responses were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31–89 years) in all. The most common neoplasm was lung cancer (56.9%), followed by malignant melanoma (32.5%). Nivolumab was administered in 46.3%, and pembrolizumab in 40.5% of patients. Baseline PET and a first PET scan performed at a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. After a median 18 (1–137) months, 113 (36.3%) patients had died. On Kaplan–Meier analysis, metabolic responders on the first two serial PET scans showed a better prognosis than non-responders, while clinical response became prognostically informative from the second assessment after starting immunotherapy onwards. CONCLUSIONS: [18F]FDG PET/CT could have a role in the assessment of response to immunotherapy in patients with some solid tumors. It can provide prognostic information and thus contribute to a patient’s appropriate treatment. Prospective randomized controlled trials are mandatory.

Abstract Background The outcomes of patients with lung metastases from giant cell tumor of bone (GCTB) vary from spontaneous regression to uncontrolled growth. To investigate whether observation is an appropriate first-line management approach for patients with lung metastases from GCTB, we evaluated the outcomes of patients who were initially managed by observation. Methods We retrospectively reviewed the data of 22 patients with lung metastases from histologically confirmed GCTB who received observation as a first-line treatment approach. The median follow-up period was 116 months. Results Disease progression occurred in 12 patients (54.5%). The median interval between the discovery of lung metastases and progression was 8 months. Eight patients underwent metastasectomy following initial observation. The median interval between the discovery of lung metastases and treatment by metastasectomy was 13.5 months. None of the patients experienced spontaneous regression. Of the 22 patients, 36.4% needed a metastasectomy, and 9.1% required denosumab treatment during the course of the follow-up period. Disease progression occurred in 45.5% of the 11 patients with lung nodules ≤ 5 mm, while all five of the patients with lung nodules > 5 mm experienced disease progression. Progression-free survival was significantly worse in the group with lung nodules > 5 mm compared to the group with lung nodules ≤ 5 mm (p = 0.022). Conclusions Observation is a safe first-line method of managing patients with lung metastases from GCTB. According to radiological imaging, approximately half of the patients progressed, and approximately half required a metastasectomy or denosumab treatment. However, patients with lung nodules > 5 mm should receive careful observation because of the high rate of disease progression in this group.

ObjectivesThis study aims to describe the outcome of intravascular lithotripsy (IVL) when used with different indications and to assess the short- and long-term outcomes of IVL-facilitated percutaneous coronary intervention (PCI).BackgroundIntravascular lithotripsy can improve the results of PCI of calcified coronary lesions with a low rate of periprocedural complications.MethodsA total of 105 consecutive patients with 110 calcified lesions underwent IVL. A total of 87 de novo lesions were treated by IVL with the following indications: 25 before attempting other balloon-based devices (primary IVL), 51 after the failure of non-compliant balloon dilatation (secondary IVL), and 11 after stent implantation because of stent under expansion (bailout IVL). In 23 lesions, IVL was used for the treatment of in-stent restenosis (ISR). Effectiveness (angiographic success) and safety [major adverse cardiovascular events (MACEs) and IVL-related procedural complications] endpoints were assessed.ResultsAngiographic success was achieved in 84.6% of lesions. Early MACEs were periprocedural MI only, ranging from 6.7 to 20% depending on MI definition. The flow-limiting dissections rate was 2.7%. A total of five (4.5%) IVL balloons ruptured during treatment with subsequent vessel perforation in 1 case. MACEs at 12 months were 13.3%, with TLR occurring in 8 lesions (12% primary IVL, 0% secondary IVL, 0% bailout IVL, and 21.7% IVL for ISR, p = 0.002).ConclusionTreatment of calcified coronary lesions with IVL in a “real-world” setting can be performed with high success, low rate of procedural complications, and an acceptable MACEs rate. Target lesion failure may be more frequent when IVL is performed for the treatment of ISR due to calcium-mediated stent under expansion.

To evaluate the foraging behaviour of yearling bulls grazing on Marandu grass, we conducted two experiments. In the first experiment (Exp. 1), three grazing heights of 15, 25, and 35 cm were evaluated, with bulls receiving 0.3% of body weight (BW) of supplement (161 g kg–1 crude protein (CP) and 20.1 MJ kg–1 gross energy (GE)); in the second experiment (Exp. 2), supplementation levels were decreased as grazing height increased: (1) low height (15 cm) and high supplementation (0.6% BW: 142 g kg–1 CP and 18.9 MJ kg–1 GE (LH-HS)); (2) moderate height (25 cm) and moderate supplementation (0.3% BW: 161 g kg–1 CP and 20.1 MJ kg–1 GE (MH-MS)) or (3) high height (35 cm) without supplementation (HH-WS). Ingestive behaviour was evaluated by direct visual observations, and intake using markers. It was used 9 paddocks each experiment. The experimental design was completely randomized, analysing effects by polynomial orthogonal contrasts (Exp. 1) and Tukey test (Exp. 2). In Exp. 1, a linear decreasing response to daily grazing time (P

Abstract Background The treatment of metastatic osteosarcoma (OS) remains a challenge for oncologists, and novel therapeutic strategies are urgently needed. An understanding of the pathways that regulate OS dissemination is required for the design of novel treatment approaches. We recently identified Rho-associated coiled-coil containing protein kinase 2 (ROCK2) as a crucial driver of OS cell migration. In this study, we explored the impact of ROCK2 disruption on the metastatic capabilities of OS cells and analyzed its functional relationship with Yes-associated protein-1 (YAP), the main transcriptional mediator of mechanotransduction signaling. Methods The effects of ROCK2 depletion on metastasis were studied in NOD Scid gamma (NSG) mice injected with U-2OS cells in which ROCK2 expression had been stably silenced. Functional studies were performed in vitro in human U-2OS cells and in three novel cell lines derived from patient-derived xenografts (PDXs) by using standard methods to evaluate malignancy parameters and signaling transduction. The nuclear immunostaining of YAP and the evaluation of its downstream targets Cysteine Rich Angiogenic Inducer 6, Connective Tissue Growth Factor and Cyclin D1 by quantitative PCR were performed to analyze YAP activity. The effect of the expression and activity of ROCK2 and YAP on tumor progression was analyzed in 175 OS primary tumors. Results The silencing of ROCK2 markedly reduced tumor growth and completely abolished the metastatic ability of U-2OS cells. The depletion of ROCK2, either by pharmacological inhibition or silencing, induced a dose- and time-dependent reduction in the nuclear expression and transcriptional activity of YAP. The nuclear expression of YAP was observed in 80/175 (46%) tumor samples and was significantly correlated with worse patient prognosis and a higher likelihood of metastasis and death. The use of verteporfin, a molecule that specifically inhibits the TEAD–YAP association, remarkably impaired the growth and migration of OS cells in vitro. Moreover to inhibiting YAP activity, our findings indicate that verteporfin also affects the ROCK2 protein and its functions. Conclusions We describe the functional connection between ROCK2 and YAP in the regulation of OS cell migration and metastasis formation. These data provide support for the use of verteporfin as a possible therapeutic option to prevent OS cell dissemination.

Background and Purpose: The Active Connection Matrixes (ACMs) are unsupervised artificial adaptive systems able to extract from digital images features of interest (edges, tissue differentiation, etc.) unnoticeable with conventional systems. In this proof-of-concept study, we assessed the potentiality of ACMs to increase measurement precision of morphological structures (e.g., stenosis and lumen diameter) and to grasp morphological features (arterial walls) from quantitative coronary angiography (QCA), unnoticeable on the original images.Methods: Archive images of QCA and intravascular ultrasound (IVUS) of 10 patients (8 men, age 69.1 ± 9.7 years) who underwent both procedures for clinical reasons were retrospectively analyzed. Arterial features derived from “IVUS images,” “conventional QCA images,” and “ACM-reprocessed QCA images” were measured in 21 coronary segments. Portions of 1-mm length (263 for lumen and 526 for arterial walls) were head-to-head compared to assess quali-quantitative between-methods agreement.Results: When stenosis was calculated on “ACM-reprocessed QCA images,” the bias vs. IVUS (gold standard) did not improve, but the correlation coefficient of the QCA–IVUS relationship increased from 0.47 to 0.83. When IVUS-derived lumen diameters were compared with diameters obtained on ACM-reprocessed QCA images, the bias (−0.25 mm) was significantly smaller (p < 0.01) than that observed with original QCA images (0.58 mm). ACMs were also able to extract arterial wall features from QCA. The bias between the measures of arterial walls obtained with IVUS and ACMs, although significant (p < 0.01), was small [0.09 mm, 95% CI (0.03, 0.14)] and the correlation was fairly good (r = 0.63; p < 0.0001).Conclusions: This study provides proof of concept that ACMs increase the measurement precision of coronary lumen diameter and allow extracting from QCA images hidden features that mirror well the arterial walls derived by IVUS.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. After first-line therapy, 30–40% of patients relapse or experiment with refractory disease. 18F-FDG PET/CT represents a validated diagnostic tool in post-treatment evaluation of FDG-avid lymphoma, and the Deauville Score (DS), a five-point visual scale, is usually used to assess response. However, the increased number of false positive findings suggested the need to search for new parameters. The aim of this study is to evaluate the prognostic value of End-of-Treatment-PET, comparing DS to the semi-quantitative Lesion-to-Liver ratio (LLR). Methods: newly diagnosed DLBCL patients who underwent 18F-FDG PET/CT were retrospectively analyzed. End-of-Treatment PET findings were assessed first using DS; secondly, assigned the LLR. Results: a total of 105 patients were finally enrolled. ROC analysis showed an LLR of 1.80 as the optimal cutoff value for predicting a disease progression (sensitivity 58%, specificity 95%). Both DS and LLR showed a statistically significant correlation with PFS and OS. LLR resulted in a better diagnostic performance than DS. Conclusions: LLR showed to be a reliable diagnostic method to assess treatment response in DLBCL. The integration of visual and semi-quantitative criteria could help in decision making, improving specificity and PPV.

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease.Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020.Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5–9 years and lymphopenia were statistically related to ICU admission (p < 0.05).Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission.

Background and PurposeVolumetric modulated arc radiotherapy (RT) has become pivotal in the treatment of prostate cancer recurrence (RPC) to optimize dose distribution and minimize toxicity, thanks to the high-precision delineation of prostate bed contours and organs at risk (OARs) under multiparametric magnetic resonance (mpMRI) guidance. We aimed to assess the role of pre-treatment mpMRI in ensuring target volume coverage and normal tissue sparing.Material and MethodsPatients with post-prostatectomy RPC eligible for salvage RT were prospectively recruited to this pilot study. Image registration between planning CT scan and T2w pre-treatment mpMRI was performed. Two sets of volumes were outlined, and DWI images/ADC maps were used to facilitate precise gross tumor volume (GTV) delineation on morphological MRI scans. Two rival plans (mpMRI-based or not) were drawn up.ResultsTen patients with evidence of RPC after prostatectomy were eligible. Preliminary data showed lower mpMRI-based clinical target volumes than CT-based RT planning (p = 0.0003): median volume difference 17.5 cm3. There were no differences in the boost volume coverage nor the dose delivered to the femoral heads and penile bulb, but median rectal and bladder V70Gy was 4% less (p = 0.005 and p = 0.210, respectively) for mpMRI-based segmentation.ConclusionsmpMRI provides high-precision target delineation and improves the accuracy of RT planning for post-prostatectomy RPC, ensures better volume coverage with better OARs sparing and allows non-homogeneous dose distribution, with an aggressive dose escalation to the GTV. Randomized phase III trials and wider datasets are needed to fully assess the role of mpMRI in optimizing therapeutic strategies.

Background. The impetuous entrance of the COVID-19 pandemic in Italy in March 2020, after the onset and diffusion in China, found the health system widely unfit to face the large amount of infected patients. The matter of this investigation was to evaluate how pandemic fear and guidelines for limiting the diffusion of SARS-CoV-2 virus could have impacted the regular supply of radiotherapy (RT) and the outcome of the treatments. Materials and Methods. From March 9, 2020, to May 29, 2020, a register has been established to record patients that cancelled or postponed the RT appointment. The reasons were as follows: (1) patients whose appointments were postponed by the staff according to national guidelines; (2) patients who asked themselves to postpone the appointment; (3) patients who interrupted the treatment for causes directly or indirectly related to the pandemic; (4) patients who cancelled their care path. Results. A total number of 277 patients started regular RT, and 384 respected their computed tomography (CT) simulation appointment, but 60 of them had alteration of their therapeutic pathway. Among these, 18 cancelled their appointment. 42 patients asked to postpone their procedure. Twenty-seven out of 42 adduced directly or indirectly SARS-CoV-2 infection-related reasons. Conclusions. The COVID-19 pandemic affected the regular RT delivery to oncologic patients, owing to the delay or cancellation of procedures with the likely effect to observe worsening of local disease control and reduced survival rates in the future.

Background and PurposeDyspnea is an important symptomatic endpoint for assessment of radiation-induced lung injury (RILI) following radical radiotherapy in locally advanced disease, which remains the mainstay of treatment at the time of significant advances in therapy including combination treatments with immunotherapy and chemotherapy and the use of local ablative radiotherapy techniques. We investigated the relationship between dose-volume parameters and subjective changes in dyspnea as a measure of RILI and the relationship to spirometry.Material and MethodsEighty patients receiving radical radiotherapy for non-small cell lung cancer were prospectively assessed for dyspnea using two patient-completed tools: EORTC QLQ-LC13 dyspnea quality of life assessment and dyspnea visual analogue scale (VAS). Global quality of life, spirometry and radiation pneumonitis grade were also assessed. Comparisons were made with lung dose-volume parameters.ResultsThe median survival of the cohort was 26 months. In the evaluable group of 59 patients there were positive correlations between lung dose-volume parameters and a change in dyspnea quality of life scale at 3 months (V30 p=0.017; V40 p=0.026; V50 p=0.049; mean lung dose p=0.05), and a change in dyspnea VAS at 6 months (V30 p=0.05; V40 p=0.026; V50 p=0.028) after radiotherapy. Lung dose-volume parameters predicted a 10% increase in dyspnea quality of life score at 3 months (V40; p=0.041, V50; p=0.037) and dyspnea VAS score at 6 months (V40; p=0.027) post-treatment.ConclusionsWorsening of dyspnea is an important symptom of RILI. We demonstrate a relationship between lung dose-volume parameters and a 10% worsening of subjective dyspnea scores. Our findings support the use of subjective dyspnea tools in future studies on radiation-induced lung toxicity, particularly at doses below conventional lung radiation tolerance limits.

Bevacizumab plus FOLFOX-4 regimen represents the first-line therapy in patients affected by metastatic colorectal cancer (mCRC). Hyperthermia has been considered an effective ancillary treatment for cancer therapy through several anti-tumor mechanisms, sharing with Bevacizumab the inhibition of angiogenesis. Up to now, scientific literature offers very few clinical data on the combination of bevacizumab plus oxaliplatin-based chemotherapy with deep electro-hyperthermia (DEHY) for metastatic colon cancer (mCC) patients. Therefore, we aimed at evaluating the efficacy of this combination based on the possible interaction between the DEHY and bevacizumab anti-tumor mechanisms. We conducted a retrospective analysis on 40 patients affected by mCC treated with the combination of bevacizumab plus FOLFOX-4 (fluorouracil/folinic acid plus oxaliplatin) and DEHY (EHY2000), between January 2017 and May 2020. DEHY treatment was performed weekly, with capacitive electrodes at 80–110 W for 50 min, during and between subsequent bevacizumab administrations, on abdomen for liver or abdominal lymph nodes metastases and thorax for lung metastases. Treatment response assessment was performed according to the Response Evaluation Criteria for Solid Tumors (RECIST). The primary endpoints were disease control rate (DCR) and progression-free survival (PFS). The secondary endpoint was overall survival (OS). DCR, counted as the percentage of patients who had the best response rating [complete response (CR), partial response (PR), or stable disease (SD)], was assessed at 90 days (timepoint-1) and at 180 days (timepoint-2). DCR was 95% and 89.5% at timepoint-1 and timepoint-2, respectively. The median PFS was 12.1 months, whereas the median OS was 21.4 months. No major toxicity related to DEHY was registered; overall, this combination regimen was safe. Our results suggest that the combined treatment of DEHY with bevacizumab plus FOLFOX-4 as first-line therapy in mCC is feasible and effective with a favorable disease control, prolonging PFS of 2.7 months with respect to standard treatment without DEHY for mCC patients. Further studies will be required to prove its merit and explore its potentiality, especially if compared to conventional treatment.

The aim of this study was to characterize four corn and sorghum co-products (DDG) in terms of their protein and carbohydrate fractions; we also evaluated the effects of substituting the protein source of the conventional supplement by DDG on consumption and nutrient digestibility in confined finishing cattle. Thirty-six male Nellore cattle with a mean age of 24 months were used. The treatments were: FA: concentrate with corn as an energy source and cottonseed meal as a protein source; DDG50: concentrate with a 50% substitution of the FA protein source by DDG; DDG100: concentrate with 100% substitution of the FA protein source by DDG. The experimental design was completely randomized with three treatments and three replicates (pens) containing four animals per pen. We found that the use of DDG in the finishing phase did not interfere with the animals’ food intake or the digestibility of the nutrients (p > 0.05). Nutrients were used by the animals; therefore, DDGs may be viable substitutes of cottonseed meal. We conclude that the bromatological composition of this co-product is influenced a lot during processing; therefore, the nutritional values of this co-product present in the composition tables may not be true.

We investigated the [18F]Fluciclovine PET/CT reliability in the early detection of recurrent prostate cancer (PCa) and its impact on therapeutic decision making. We retrospectively analyzed 58 [18F]Fluciclovine PET/CT scans performed to identify early PCa recurrence. Detection rate (DR) and semiquantitative analysis were evaluated in relation to biochemical and clinical–histological features. Clinical follow-up data were collected and considered as gold standard to evaluate sensitivity, specificity, accuracy, positive and negative predictive value (PPV, NPV). The impact of [18F]Fluciclovine PET/CT on clinical management was also assessed. Overall DR resulted as 66%, while DR was 53%, 28%, and 7% in prostate/bed, lymph nodes, and bone, respectively. DR significantly increased with higher PSA values (p = 0.009) and 0.45 ng/mL was identified as the optimal cut-off value. Moreover, SUVmax and SUVmean resulted significant parameters in interpreting malignant from benign findings. [18F]Fluciclovine PET/CT reached a sensitivity, specificity, PPV, NPV, and accuracy of 87.10%, 80.00%, 87.10%, 80.00%, and 84.31%, respectively. Therapeutic strategy was changed in 51% of patients. Our results support [18F]Fluciclovine PET/CT as a reliable tool for early restaging of PCa patients, especially for local recurrence detection, leading to a significant impact on clinical management. Semiquantitative analysis could improve specificity in interpreting malignant from benign lesions.

Ewing’s sarcoma (EWS), an aggressive pediatric bone and soft-tissue sarcoma, has a very stable genome with very few genetic alterations. Unlike in most cancers, the progression of EWS appears to depend on epigenetic alterations. EWS–FLI1 and CD99, the two hallmarks of EWS, are reported to severely impact the malignancy of EWS cells, at least partly by regulating the expression of several types of non-coding RNAs. Here, we identify miR-214-3p as a common mediator of either EWS-FLI1 or CD99 by in silico analysis. MiR-214-3p expression was lower in EWS cells and in clinical samples than in bone marrow mesenchymal stem cells, and this miRNA was barely expressed in metastatic lesions. Silencing of EWS-FLI1 or CD99 restored the expression of miR-214-3p, leading to a reduced cell growth and migration. Mechanistically, miR-214-3p restoration inhibits the expression of the high-mobility group AT-hook 1 (HMGA1) protein, a validated target of miR-214-3p and a major regulator of the transcriptional machinery. The decrease in HMGA1 expression reduced the growth and the migration of EWS cells. Taken together, our results support that the miR-214-3p is constitutively repressed by both EWS-FLI1 and CD99 because it acts as an oncosuppressor limiting the dissemination of EWS cells.

Este artigo tem como objeto de análise o Programa de Desenvolvimento Educacional (PDE/PR), constituído a partir da parceria entre a Secretaria de Estado da Educação – SEED/PR, a Secretária de Estado de Ciência, Tecnologia e Ensino Superior – SETI/PR e as Instituições Públicas de Ensino Superior do Paraná – IPES. O referido programa de formação continuada objetiva a profissionalização de educadores da educação básica no estado do Paraná. Particularmente o presente artigo analisa as contribuições e desafios do PDE/PR para a melhoria da prática pedagógica dos professores da educação básica participantes da 1ª e 2ª edições, ofertadas em 2007 e 2008, no âmbito da Universidade Estadual do Centro-Oeste-PR, particularmente das áreas de Ciências e Biologia. A pesquisa é de cunho qualitativo e os dados foram coletados por meio de um questionário semiestruturado encaminhado a 37 professores PDE/UNICENTRO de Ciências e Biologia. O texto aponta a formação continuada como elemento crucial para o desenvolvimento profissional de professores e reforça a importância do professor como agente de mudanças que levem à melhoria da qualidade do ensino público no Paraná.

Introduction: The aim of this study was to investigate whether [18F]FDG PET/CT-derived semi-quantitative parameters can predict immunotherapy treatment response in non-small cell lung cancer (NSCLC) patients. Secondly, immune-related adverse events (irAEs) and lymphoid cell-rich organs activation were evaluated. Materials and Methods: Twenty-eight patients who underwent [18F]FDG PET/CT scans before and at first restaging therapy with immuno-checkpoint inhibitors (ICIs) were retrospectively analyzed. PET-based semi-quantitative parameters extracted from both scans were respectively: SUVmax and SUVpeak of the target lesion, whole-body metabolic tumor volume (MTVWB), and whole-body total lesion glycolysis (TLGWB), as well as their interval changes (ΔSUVmaxTL, ΔSUVpeakTL, ΔMTVWB, ΔTLGWB). These PET-derived parameters were correlated to controlled disease (CD) assessed by RECIST 1.1. IrAEs, if present, were also described and correlated with clinical benefit (CB). SUVmax of the spleen and bone marrow at restaging scans were also correlated to CB. Results: The CD was achieved in 54% of patients. Out of 28 eligible patients, 13 (46%) experienced progressive disease (PD), 7 showed SD, 7 had PR, and only in one patient CR was achieved. ΔSUVmaxTL (p = 0.002) and ΔSUVpeakTL (p < 0.001) as well as ΔMTVWB (p < 0.001) and ΔTLGWB (p < 0.005) were significantly associated with PD vs. non-PD. IrAEs and lymphoid cell-rich organs activation did not correlate with CB. Conclusions: [18F]FDG PET/CT by using interval changes of PET-derived semi-quantitative parameters could represent a reliable tool in immunotherapy treatment response evaluation in NSCLC patients.

The widespread COVID-19 vaccination led to unexpected PET findings. Notably, axillary and interpectoral lymphadenopathies ipsilateral to the vaccine inoculation were observed. We aimed to assess the hypermetabolic lymphadenopathy (HLN) detection rate on PET/CT. Secondly, we investigated factors that might help in HLN differential diagnosis. A retrospective analysis on 1196 consecutive patients referred for a PET/CT was performed. All patients were asked about the date, type and site of vaccine injections. HLNs were recorded and categorized according to risk classes and SUVmax grades. A statistical analysis was performed to assess the correlation between HLN detection and different clinical/vaccine data. HLN detection rate was 15% and 27% in the No Vac- and vac-groups (p < 0.001), respectively. In the Vac-group, age (p < 0.001) and time interval from vaccine-to-PET (p = 0.010) were inversely correlated with HLN detection. Furthermore, SUVmax significantly changed during time intervals, with lower values beyond 20 days (p < 0.001). In the era of mass COVID-19 vaccination, a higher axillary and interpectoral lymphadenopathies detection ipsilateral to vaccine injection was observed. These PET findings can be wrongly interpreted, complicating cancer patients’ management. To minimize these pitfalls, a detailed vaccination anamnesis must be recorded and should take into account the appropriate PET schedule.

Differentiated thyroid cancer (DTC) represents the most common thyroid cancer histotype. Generally, it exhibits a good prognosis after conventional treatments; nevertheless, about 20% of patients can develop a local recurrence and/or distant metastasis. In one-third of advanced DTC, the metastatic lesions lose the ability to take up iodine and become radioactive iodine-refractory (RAI-R) DTC. In this set of patients, the possibility to perform localized treatments should always be taken into consideration before the initiation of systemic therapy. In the last decade, some multi-tyrosine kinase inhibitor (MKI) drugs were approved for advanced DTC, impacting on patient’s survival rate, but at the same time, these therapies have been associated with several adverse events. In this clinical context, the role of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in the early treatment response to these innovative therapies was investigated, in order to assess the potentiality of this diagnostic tool in the early recognition of non-responders, avoiding unnecessary therapy. Herein, we aimed to present a critical overview about the reliability of [18F]FDG PET/CT in the early predictive response to MKIs in advanced differentiated thyroid cancer.

Primary renal lymphoma (PRL) is a rare form of non-Hodgkin’s lymphoma (NHL) restricted to and primarily involving one or both kidneys, with no lymph node extension. It accounts for

Acute pulmonary embolism (APE) is a cardiovascular emergency, representing the main cause of mortality, morbidity, and hospitalisation in Europe. We aim to evaluate the economic and healthcare impact of lung perfusion scintigraphy (LPS) used in patients with suspected APE, in the event of non-conclusive or contraindicated computed tomography pulmonary angiography (CTPA). We considered two alternative healthcare processes for APE diagnosis, with and without LPS. We performed a cost analysis with the aim of evaluating the average direct healthcare costs for diagnosis, risk assessment, and treatment of APE. We used data from a monocentric trial. Our economic model showed that the strategy with LPS was preferable in terms of costs. The average per-patient costs for the diagnosis and treatment of the acute phase of PE in low-risk patients with a non-conclusive or not-executable CTPA, with and without LPS, are EUR 2145.25 and EUR 4912.45, respectively. LPS is a simple, quick, and economic examination, useful in this setting of patients not only for an early diagnosis but also to exclude APE, demonstrating an advantage in terms of healthcare resources. To the best of our knowledge, this study is the first to analyse the economic and healthcare impact of the use of LPS in the diagnostic pathway of suspected APE.

Primary solitary fibrous tumor (SFT) of the bone is extremely rare, with only few cases reported in the literature. We retrieved all cases of primary SFT of the bone treated at our institution and we assessed the morphology and the immunohistochemical and molecular features to investigate the clinical outcome of primary SFT of the bone and any clinical relevance of clinical and histological criteria of aggressiveness currently adopted for the soft tissues counterpart. Morphologically, 15 cases evidenced high cellularity, cytologic atypia, and foci of necrosis and were associated with more than 4 mitotic figures/10 HPF. Immunohistochemical analysis showed an expression of CD34 and of STAT6 immunopositivity in 95% and in 100% of cases, respectively. The presence of NAB2-STAT6 chimeric transcripts was found in 10 out of 12 cases in which RT-PCR analysis was feasible, whereas TERT promoter mutations analysis was feasible in 16 cases and only a C-to-T substitution in a heterozygous state was found in one DNA sample for the C228T genetic variant. P53 variants were assessed in 12 cases: 11 (91.6%) cases showed a variation, while in one case, no alteration was found. Disease-specific survival was 64% at 5 years and 49% at 10 years. Statistical analysis showed no correlation between survival and all the clinicopathological and molecular parameters evaluated. In conclusion, at difference to SFT of soft tissues, aggressive behavior of primary SFT of the bone seems to be independent from mitotic count or any other clinicopathological and molecular features.

Abstract Introduction Epidemiological studies focused on prognostic factors associated with laryngeal cancer in the Brazilian population are poorly reported in the literature. Objective To evaluate the influence of certain risk factors on the survival rates of patients with squamous cell carcinoma (SCC) of the larynx. Methods This retrospective study was conducted on adult patients who were admitted to the outpatient clinic of the head and neck department in a tertiary care hospital. Evaluation of the influence of risk factors on the survival rates of patients registered in the hospital with laryngeal SCC was performed based on age, sex, initial stage, time of evolution, habits, educational levels and relapse and death. Overall survival (OS), disease-free survival (DFS) and clinical-demographic data were analyzed using the Kaplan-Meier method, Log-rank test and Cox regression. Results A total of 107 patients with a mean age of 59.8 years (range 19–81) were included in this study. Stages III and IV were associated with decreased DFS (p = 0.02) and OS (p = 0.02). Smoking patients had a greater period of disease evolution than non-smoking patients (p = 0.003). Alcohol consumption in smokers increased the risk of death by 2.8 (p = 0.002) compared with non-drinking smokers. Male patients presented lower DFS average when compared with female patients (p = 0.04). Conclusion Our study confirms that male gender, smoking habit combined with alcohol consumption, and advanced stages were strongly associated with poor prognosis.

Abstract INTRODUCTION Immunization is the primary method of preventing influenza. The objective of this study was to describe reasons and determine causes of acceptance or refusal of the influenza vaccine by elderly people. METHODS: This cross-sectional and descriptive study included elderly patients (aged >60 years) from the City of Jundiai, São Paulo, Brazil. RESULTS: The sample comprised 185 people; 71.9% reported receiving the vaccine and 21% claimed to have experienced complications. CONCLUSIONS: The vaccination coverage was below the national goal; the reasons for not being vaccinated was “did not want to receive the vaccine”, in addition to “forgot”.