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Background The differential diagnosis of Fever of Unknown Origin (FUO) is very extensive, and includes infectious diseases (ID), neoplasms and noninfectious inflammatory diseases (NIID). Many FUO remain undiagnosed. Factors influencing the final diagnosis of FUO are unclear. Methods To identify factors associated with FUO diagnostic categories, we performed a systematic review of classical FUO case-series published in 2005–2015 and including patients from 2000. Moreover, to explore changing over time, we compared these case-series with those published in 1995–2004. Results Eighteen case-series, including 3164 patients, were included. ID were diagnosed in 37.8% of patients, NIID in 20.9%, and neoplasm in 11.6%, FUO were undiagnosed in 23.2%. NIIDs significantly increased over time. An association exists between study country income level and ID (increasing when the income decreases) and undiagnosed FUO (increasing when the income increases); even if not significant, the use of a pre-defined Minimal Diagnostic Work-up to qualify a fever as FUO seems to correlate with a lower prevalence of infections and a higher prevalence of undiagnosed FUO. The multivariate regression analysis shows significant association between geographic area, with ID being more frequent in Asia and Europe having the higher prevalence of undiagnosed FUO. Significant associations were found with model of study and FUO defining criteria, also. Conclusions Despite advances in diagnostics, FUO still remains a challenge, with ID still representing the first cause. The main factors influencing the diagnostic categories are the income and the geographic position of the study country.

Introduction and Purpose. Diffusion weighted imaging (DWI) has been proven to be valuable in the diagnosis of middle ear cholesteatoma. The aims of our study were to evaluate the advantage of multi-shot turbo spin echo (MSh TSE) DWI compared to single-shot echo-planar (SSh EPI) DWI for the diagnosis of cholesteatoma. Material and Methods. Thirty-two patients with clinical suspicion of unilateral cholesteatoma underwent preoperative MRI (1.5T) with SSh EPI and MSh TSE. Images were separately analyzed by 4 readers with different expertise to confirm the presence of cholesteatoma. Sensitivity, specificity, diagnostic accuracy, and positive (PPV) and negative predictive values (NPV) were assessed for each observer and interrater agreement was assessed using kappa statistics. Diagnosis was obtained at surgery. Results. Overall MSh TSE showed higher diagnostic accuracy and lower negative predictive value (NPV) compared to conventional SSh EPI. Interreader agreement between the observers revealed the superiority of MSh TSE compared to SSh EPI. Interrater agreement among all the four observers was higher by using MSh TSE compared to SSh EPI. Conclusion. Our findings suggest that MSh TSE DWI has higher sensitivity for detection of cholesteatoma and lower probability of misdiagnosis. MSh TSE DWI is useful in guiding less experienced observers to the diagnosis.

Atraumatic vertebral compression fractures are a common clinical problem, especially in elderly population. Metastases are the most frequent source of bone tumors, and the spine is a common site of metastatic disease; in case of cortical involvement or osteolysis, they may result in pathological compression fractures. Atraumatic compression fractures may result from other primary neoplasms of vertebrae and also from osteomyelitis, Paget’s disease, hyperparathyroidism and other metabolic processes. Osteoporosis is a common source of vertebral compression fractures in elderly population, which may be indistinguishable from those of metastatic origin. The differentiation between osteoporotic compression fractures and malignant fracture is necessary to establish an appropriate staging and a therapeutic planning, especially in the acute and subacute stages. Anamnestic data about preexisting disease can be useful to individuate the potential cause of vertebral collapse. Plain radiography shows some difficulties in distinguishing whether the fracture represents a consequence of osteoporosis, a metastatic lesion or some other primary bone neoplasm. Computed tomography is one of the most suitable imaging techniques for the evaluation of bone structure and fragments and to establish the degree of cortical bone destruction; MR imaging (MRI) is the most helpful radiological investigation in order to provide the basis for the distinction between metastatic and acute osteoporotic compression fractures. The most relevant MRI findings to establish a differential diagnosis are described.

Neuroendocrine Neoplasms (NEN) are a group of heterogeneous malignancies derived from neuroendocrine cell compartment, with different roles in both endocrine and nervous system. Most NETs have gastroentero-pancreatic (GEP) origin, arising in the foregut, midgut, or hindgut. The 2010 WHO classification divides GEP-NETs into two main subgroups, neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC), according with Ki-67 levels. NET are tumors with low (<20 %) Ki-67 value, and NECs, including small cell lung carcinomas and Merkel Cell carcinomas, are all NETs with high Ki-67 levels (>20 %–G3). Poorly differentiated neuroendocrine carcinomas (NEC) are usually treated with cisplatin-based chemotherapy regimens. Here we present a case of a patient with pancreatic NEC progressing after cisplatin and etoposide, treated with temozolomide as palliative, second line treatment. According with the poor Performance Status (PS = 2) and to reduce the toxicity of the treatment was chosen an intermittent dosing regimen of metronomic temozolomide (75 mg/m 2 /day—one-week-on/on-week-off). MGMT resulted methylated. On July 2014 the patient started the treatment. On August 2014 the patient obtained a significant clinical benefit (PS = 0) and the total body CT scan performed on October 2014 showed a RECIST partial response on all the sites of disease. No drug-related side effects were reported by the patient. After 18 months of therapy the treatment continues without significant toxicity, and with further remission of the metastases. Treatment with metronomic “one-week-on/on-week-off” Temozolomide can be considered a good treatment option in patients with poor performance status, affected by pNEC with MGMT methylation.

Background The debate on the benefits and limitations of off-pump (OPCAB) coronary artery bypass grafting (CABG) on long-term outcomes is not yet settled. This study aimed to compare the impact of OPCAB vs on-pump CABG on long-term outcomes and to evaluate possible public health implications linked to their use. Methods The PRIORITY project was planned to evaluate the long-term outcomes of two prospective multicenter studies on CABG conducted between 2002-2004 and 2007-2008. Data on isolated CABG were linked to administrative data in order to retrieve patients' late outcome. Time-to-event distributions were analyzed accordingly to primary event-type (death, major adverse cardiac events (MACEs)) using the Kaplan-Meier and the Cox proportional hazards methods. Results The study population consisted of 11 021 patients who underwent isolated CABG (27.2% OPCAB). The median follow-up time was 8.0 years (interquartile range 7.6-10.0 years). OPCAB had comparable late all-cause mortality to on-pump CABG (HR 0.94, 95%CI 0.85-1.03, p = 0.19), but it was associated to an increased risk of MACE (adjusted HR 1.14, 95%CI 1.06-1.23, p = 0.001). In particular, OPCAB had an increased risk of repeated revascularization with percutaneous cardiac intervention (PCI) (adjusted HR 1.33, 95%CI 1.16-1.53, p < 0.001) compared to on-pump CABG. Conclusions OPCAB does not affect long-term mortality, but it significantly increases the risk of MACEs. In particular, OPCAB had an increased risk of repeated revascularization with PCI. These findings may have important implications towards health resources allocation. Key messages Off-pump coronary artery bypass grafting strategy is associated with an increased long-term risk of MACE and repeated PCI. Off-pump strategy is mainly based on operator preferences and can have important implications in terms of healthcare costs.

Background The advantages to use the bilateral internal thoracic artery grafting (BITA) technique for coronary artery bypass grafting (CABG) have been recently questioned, but data on long-term follow-up is limited. Using data from the PRIORITY project, this study aims to assess the outcome with the use of BITA grafting and its implications for public health. Methods The PRIORITY project was planned to evaluate the long-term outcomes of two prospective multicenter studies on CABG conducted between 2002-2004 and 2007-2008. Data on isolated CABG were linked to administrative data in order to retrieve patients' late outcome. Time-to-event distributions were analyzed accordingly to primary event-type (death, major adverse cardiac events (MACEs)) using the Kaplan-Meier and the Cox proportional hazards methods. Results The study population consisted of 11021 patients who underwent isolated CABG. BITA grafting was employed in 24.6% of patients. The median follow-up time was 8.0 years (interquartile range 7.6-10.0 years). After adjustment for potential confounding factors, BITA grafting was significantly associated with better survival (HR 0.85, 95%CI 0.76-0.95, p = 0.003). Moreover, using BITA grafting reduced the incidence of MACE (HR 0.87, 95%CI 0.80-0.94, p = 0.001), showing to be a protective factor for recurrent acute myocardial infarction (HR 0.84, 95%CI 0.71-0.99, p = 0.05) and for rehospitalization for percutaneous cardiac intervention (HR 0.82, 95%CI 0.70-0.96, p = 0.013). Conclusions BITA grafting during isolated CABG is associated with survival advantage at 10-year with a significantly reduced incidence of MACE. Being the choice to perform isolated CABG with or without BITA based mainly on operator personal preferences, these findings may have important implications from a public health perspective. Key messages The choice to perform CABG with or without BITA grafting is associated to different outcomes. The choice to perform CABG with or without BITA grafting is mainly based on operator preferences and may have important implications in terms of healthcare expenditures.

Background Uncertainties on long-term outcomes after acute myocardial infarction (AMI) still exist, despite the ongoing progresses in the management of patients with AMI. This study aims to appraise early and 1-year outcome of patients hospitalized due to AMI and to describe the role of heart failure (HF) as complication affecting prognoses. Methods Retrospective nationwide cohort study based on administrative data on patients with AMI admitted in all Italian hospitals from 2007 to 2017. Index admission mortality rate (I-MR), 30-day and 1-year post-discharge mortality rate (PD-MR), and 30-day and 1-year total mortality rate (T-MR) were analysed; mortality average annual changes (AC) and their 95% CI were calculated; the Cox model, adjusting for age, sex, comorbidities and length of stay, was used to analyse 1-year PD-MR Results 1,148,820 patients were considered. From 2007 to 2017, both I-MR and T-MR up to 1 year decreased significantly (from 10.9 to 8.4%; AC: -0.28%; CI: -0.31 to -0.25 and from 20.2% to 17.1%: AC: -0.33%; CI: -0.39 to -0.28, respectively). From 2010, also the rate of PD-MR decreased significantly from 11.7% to 10.4%, with such favourable trend confirmed at multivariable analyses. The HF diagnosis at the index admission is always associated with a significant increase in the risk of death (1-year T-MR average: 43% and 12% in patients with or without HF, respectively; both patients with and without HF show a constant improvement in I-MR, T-MR and PD-MR over time. Conclusions In the last decade, the remarkable improvements in the in-hospital treatment of patients with AMI and in the overall prognosis up to 1 year are confirmed by a constant decrease in both early and long-term mortality. Since complication from HF remains a dangerous condition that significantly worsens the prognosis of the AMI patient, appropriate management strategies must be identified and implemented to guarantee best results from both clinic and public health perspective. Key messages Remarkable improvements achieved in overall prognosis after AMI over the past 10 years. HF confirms to be a condition able to worsen AMI patients’ prognosis.

Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive neurodegenerative disease, recently associated with mutations in the aprataxin gene. Main features are early onset cerebellar ataxia, oculomotor apraxia and peripheral neuropathy. The presence of choreoathetosis or dystonia in some patients suggests basal ganglia involvement, but these structures appear preserved in a single case in which neuropathological examination was performed. To evaluate in vivo the nigrostriatal function we studied dopamine transporter (DAT) density with [ 123 I] 2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FPCIT)-SPECT in four AOA1 patients and eight healthy volunteers. All patients showed ataxia and neuropathy; only one had chorea and none had dystonia. Comparing with controls, AOA1 patients showed a slight reduction of the average striatal DAT density, which was bilateral and uniform in caudate and putamen. Nigrostriatal impairment occurred even in the absence of extrapyramidal features. Our data suggest subclinical involvement of basal ganglia in AOA1.