Response to "Imaging to diagnose acute appendicitis".

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Treatment of osteolytic solitary painful osseous metastases with radiofrequency ablation or cryoablation: a retrospective study by propensity analysis

The present study aimed to measure the improvement in pain relief and quality of life in patients with osteolytic solitary painful bone metastasis treated by cryoablation (CA) or radiofrequency ablation (RFA). Fifty patients with solitary osteolytic painful bone metastases were retrospectively studied and selected by propensity analysis. Twenty-five patients underwent CA and the remaining twenty-five underwent RFA. Pain relief, in terms of complete response (CR), the number of patients requiring analgesia and the changes in self-rated quality of life (QoL) were measured following the two treatments. Thirty-two percent of patients treated by CA experienced a CR at 12 weeks versus 20% of patients treated by RFA. The rate of CR increased significantly with respect to baseline only in the group treated by CA. In both groups there was a significant change in the partial response with respect to baseline (36% in the CA group vs. 44% in the RFA group). The recurrence rate in the CA and RFA groups was 12% and 8%, respectively. The reduction in narcotic medication requirements with respect to baseline was only significant in the group treated by CA. A significant improvement in self-rated QoL was observed in both groups. The present study seems to suggest that CA only significantly improves the rate of CR and decreases the requirement of narcotic medications. Both CA and RFA led to an improvement in the self-rated QoL of patients after the treatments. However, the results of the present study should be considered as preliminary and to serve as a framework around which future trials may be designed

Treatment of Solitary Painful Osseous Metastases with Radiotherapy, Cryoablation or Combined Therapy: Propensity Matching Analysis in 175 Patients

aim of this study was to identify outcomes in pain relief and quality of life in patients with a solitary painful osseous metastasis treated by radiotherapy, cryoablation or the combination using a propensity score matching study design

The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome. The aim of this study was to evaluate the involvement and the possible interaction between these two molecular cascades in the pathogenesis and prognosis of GBM. Immunohistochemistry (IHC) was performed on microdissected GBM samples, collected from 14 patients (6 men and 8 women) ranging in age from 43 to 74 years. The patients were previously divided, on the basis of their overall survival (OS), into two groups: short and long OS. Patients with poor prognosis showed hyperexpression of HDAC4 and HDAC6, an activation of the TGF-β/Smad pathway, with high levels of IL-13, Smad2, PDGF and MMP3 expression, compared to the long survivors. The short OS group exhibits a decrease in Smad 7 expression and also low levels of p21 immunostaining, which represents a common target of the two pathways. The IHC data was confirmed by quantitative analysis and Immunoblotting. Our preliminary results suggest that both HDAC4 and HDAC6 together with the TGF-β/Smad pathway may be involved in progression of GBM and this cross talking could be a useful prognostic marker in this deadly disease

Hypoxia sustains glioblastoma radioresistance through ERKs/DNA-PKcs/HIF-1α functional interplay

The molecular mechanisms by which glioblastoma multiforme (GBM) refracts and becomes resistant to radiotherapy treatment remains largely unknown. This radioresistance is partly due to the presence of hypoxic regions, which are frequently found in GBM tumors. We investigated the radiosensitizing effects of MEK/ERK inhibition on GBM cell lines under hypoxic conditions. Four human GBM cell lines, T98G, U87MG, U138MG and U251MG were treated with the MEK/ERK inhibitor U0126, the HIF-1α inhibitor FM19G11 or γ-irradiation either alone or in combination under hypoxic conditions. Immunoblot analysis of specific proteins was performed in order to define their anti‑oncogenic or radiosensitizing roles in the different experimental conditions. MEK/ERK inhibition by U0126 reverted the transformed phenotype and significantly enhanced the radiosensitivity of T98G, U87MG, U138MG cells but not of the U251MG cell line under hypoxic conditions. U0126 and ERK silencing by siRNA reduced the levels of DNA protein kinase catalytic subunit (DNA-PKcs), Ku70 and K80 proteins and clearly reduced HIF-1α activity and protein expression. Furthermore, DNA-PKcs siRNA-mediated silencing counteracted HIF-1α activity and downregulated protein expression suggesting that ERKs, DNA-PKcs and HIF-1α cooperate in radioprotection of GBM cells. Of note, HIF-1α inhibition under hypoxic conditions drastically radiosensitized all cell lines used. MEK/ERK signal transduction pathway, through the sustained expression of DNA-PKcs, positively regulates HIF-1α protein expression and activity, preserving GBM radioresistance in hypoxic condition

Modic I changes size increase from supine to standing MRI correlates with increase in pain intensity in standing position: uncovering the "biomechanical stress" and "active discopathy" theories in low back pain

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Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

Purpose: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). Results: Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls. In xenograft models, vosaroxin reduced tumor growth and showed enhanced activity with RT; vosaroxin/RT combined was more effective than temozolomide/RT. Vosaroxin/ RT triggered rapid and massive cell death with characteristics of necrosis. A minor proportion of treated cells underwent caspase-dependent apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced autophagy, increasing necrosis. This was associated with increased recruitment of granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells. Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin. Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS) significantly compared with RT, vosaroxin alone, temozolomide, and temozolomide/RT in the U251-luciferase orthotopic model. Materials and Methods: Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in orthotopic intrabrain models using luciferasetransfected U251 cells by bioluminescence and magnetic resonance imaging. Conclusions: Vosaroxin demonstrated significant activity in vitro and in vivo in GBM models, and showed additive/synergistic activity when combined with RT in O6- methylguanine methyltransferase-negative and -positive cell lines

Short term outcome of myocarditis and pericarditis following COVID-19 vaccines: a cardiac magnetic resonance imaging study

To evaluate clinical and cardiac magnetic resonance (CMR) short-term follow-up (FU) in patients with vaccine-associated myocarditis, pericarditis or myo-pericarditis (VAMP) following COVID-19 vaccination. We retrospectively analyzed 44 patients (2 women, mean age: 31.7 +/- 15.1 years) with clinical and CMR manifestations of VAMP, recruited from 13 large tertiary national centers. Inclusion criteria were troponin raise, interval between the last vaccination dose and onset of symptoms < 25 days and symptoms-to-CMR < 20 days. 29/44 patients underwent a short-term FU-CMR with a median time of 3.3 months. Ventricular volumes and CMR findings of cardiac injury were collected in all exams. Mean interval between the last vaccination dose and the onset of symptoms was 6.2 +/- 5.6 days. 30/44 patients received a vaccination with Comirnaty, 12/44 with Spikevax, 1/44 with Vaxzevria and 1/44 with Janssen (18 after the first dose of vaccine, 20 after the second and 6 after the "booster" dose). Chest pain was the most frequent symptom (41/44), followed by fever (29/44), myalgia (17/44), dyspnea (13/44) and palpitations (11/44). At baseline, left ventricular ejection fraction (LV-EF) was reduced in 7 patients; wall motion abnormalities have been detected in 10. Myocardial edema was found in 35 (79.5%) and LGE in 40 (90.9%) patients. Clinical FU revealed symptoms persistence in 8/44 patients. At FU-CMR, LV-EF was reduced only in 2 patients, myocardial edema was present in 8/29 patients and LGE in 26/29. VAMPs appear to have a mild clinical presentation, with self-limiting course and resolution of CMR signs of active inflammation at short-term follow-up in most of the cases

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell