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Although vascular and autonomic nervous system have been involved in the regulation of morning surge in blood pressure (MBPS), data on clinical correlates of MBPS in diabetic population are scarce, in particular with regard to diabetic complications. This study was aimed at investigating predictors and correlates of MBPS in diabetes. In a cross-sectional study including 167 patients with diabetes (age 58.5 ± 11.1 years, duration 15.9 ± 12.1 years), clinical variables, diabetic and neuropathic complications, and MBPS (using 24-h ambulatory blood pressure monitoring) were measured. The upper quartile of MBPS (>30.5 mmHg) was associated with higher values of waist circumference (P = 0.027), triglycerides (P = 0.021), and Michigan Diabetic Neuropathy Score (P = 0.042), with lower HDL cholesterol (P = 0.030), and with the presence of cardiovascular autonomic neuropathy (CAN) (P = 0.016) and peripheral vascular disease (PVD) (P < 0.0001). In a logistic regression analysis, PVD (odds ratio: 10.2, P = 0.001), CAN (odds ratio: 6.09, P = 0.016), and diastolic blood pressure (BP) (odds ratio: 1.06, P = 0.022) predicted MBPS upper quartile (r 2  = 0.20, P = 0.0005). In a multiple regression analysis, PVD (P = 0.002) and diastolic BP (P = 0.003) were the only determinants of MBPS (r 2  = 0.20). MBPS upper quartile was associated with BP dipping (systolic BP day-night reduction > 10%) (P = 0.012), and MBPS was positively related to systolic (rho = 0.41, P < 0.0001) and diastolic BP day-night reduction. In conclusion, metabolic syndrome stigmata, diastolic BP, CAN and PVD are the main predictors of MBPS in the diabetic population. Excessive MBPS and nondipping are not concurrent 24-h BP alterations. Autonomic dysfunction might exert an exacerbating effect on MBPS phenomenon.

Background: Our aim was to assess both the credibility and strength of evidence arising from systematic reviews with meta-analyses of observational studies and physical health outcomes associated with human immunodeficiency virus (HIV) but not acquired immunodeficiency syndrome., Methods: We performed an umbrella review of observational studies. Evidence was graded as convincing, highly suggestive, suggestive, weak, or nonsignificant., Results: From 3413 studies returned, 20 were included, covering 55 health outcomes. Median number of participants was 18 743 (range 403-225 000 000). Overall, 45 (81.8%) of the 55 unique outcomes reported nominally significant summary results (P < .05). Only 5 outcomes (9.0%; higher likelihood of presence of breathlessness, higher chronic obstructive pulmonary disease [COPD] prevalence, maternal sepsis, higher risk of anemia, and higher risk of all fractures among people living with HIV [PLWHIV]) showed suggestive evidence, with P values < 10-3; only 3 (5.5%; higher prevalence of cough in cross-sectional studies, higher incidence of pregnancy-related mortality, and higher incidence of ischemic heart disease among PLWHIV in cohort studies) outcomes showed stronger evidence using a stringent P value (<10-6). None of the unique outcomes presented convincing evidence (Class I), yet 3 outcomes presented highly suggestive evidence, 5 outcomes presented suggestive evidence, and 37 outcomes presented weak evidence., Conclusions: Results show highly suggestive and suggestive evidence for HIV and the presence of a cough, COPD, ischemic heart disease, pregnancy-related mortality, maternal sepsis, and bone fractures. Public health policies should reflect and accommodate these changes, especially in light of the increases in the life expectancy and the incidence of comorbidities in this population., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

At the end of 2019 a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing severe acute respiratory syndrome expanded globally from Wuhan, China. In March 2020 the World Health Organization declared the SARS-Cov-2 virus a global pandemic. We performed a narrative review to describe existing literature with regard to Corona Virus Disease 2019 (COVID-19) epidemiology, pathophysiology, diagnosis, management and future perspective. MEDLINE, EMBASE and Scopus databases were searched for relevant articles. Although only when the pandemic ends it will be possible to assess the full health, social and economic impact of this global disaster, this review represents a picture of the current state of the art. In particular, we focus on public health impact, pathophysiology and clinical manifestations, diagnosis, case management, emergency response and preparedness.

Sierra Leone is the country with highest maternal mortality and infections are the underlying cause in 11% of maternal deaths, but the real burden remains unknown. This study aims to determine the incidence and risk factors of surgical site infection (SSI) post-caesarean section (CS) in women admitted to Princess Christian Maternity Hospital (PCMH) in Freetown, Sierra Leone. A prospective case-control (1:3 ratio) study was implemented from 1 May 2018 to 30 April 2019 and 11 women presenting with suspected or confirmed infection post-CS were screened for inclusion as a case. For each case, three patients undergoing CS on the same day and admitted to the same ward, but not presenting with SSI, were selected as controls. The post-CS infection rate was 10.9%. Two hundred and fifty-four clinically confirmed cases were enrolled and matched with 762 control patients. By multivariable analysis, the risk factors for SSI were: being single (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.36-1.66), low education level (OR 1.68, 95% CI 1.55-1.84), previous CS (OR 1.27, 95% CI 1.10-1.52), presenting with premature membranes rupture (OR 1.49, 95% CI 1.18-1.88), a long decision-incision time (OR 2.08, 95% CI 1.74-2.24) and a high missing post-CS antibiotic doses rate (OR 2.52, 95% CI 2.10-2.85).

4,000 new HIV diagnoses and approximately 800 AIDS cases are still reported annually in Italy. Improving public awareness and bringing out HIV-undiagnosed individuals are keystones to progress towards the control of the HIV epidemic. For this purpose, the Open HIV TEST project was organized and delivered by the Italian NGO Anlaids, together with local infectious diseases specialists, in order to provide free access to HIV testing outside the healthcare setting. Between October 2017 and February 2019 six Open HIV TEST initiatives were delivered in six Italian cities (3 northern cities, 1 central and 2 southern cities). In all, 581 people were tested: the overall prevalence of HIV test reactivity was 0.7%. Participants were also asked about previous screenings and about their satisfaction with the initiative: previous HIV screening due to pregnancy or surgical procedures was reported mainly by participants in northern centres (p<0.001); finally, the initiative was considered useful and noteworthy by 99% of participants. Prevalence of HIV test reactivity in our experience was in line with national data. Our experience suggests that active testing and counselling strategies in community settings should be recommended and institutionalized by local health authorities in line with the 90-90-90 global strategy.

There is an unmet need for predictive biomarkers of the clinical benefit of antiangiogenic drugs. The aim of the present study was to prospectively evaluate the value of 18 F-FDG PET/CT performed during and after preoperative chemoradiotherapy with bevacizumab for the prediction of complete pathologic tumor regression and survival in patients with MRI-defined high-risk locally advanced rectal cancer. Methods: Sixty-one patients treated in a nonrandomized phase II study (BRANCH) with concomitant or sequential (4 d before chemoradiotherapy) administration of bevacizumab with preoperative chemoradiotherapy were included. 18 F-FDG PET/CT was performed at baseline, 11 d after the beginning of chemoradiotherapy (early), and before surgery (late). Metabolic changes were compared with pathologic complete tumor regression (TRG1) versus incomplete tumor regression (TRG2-TRG5), progression-free survival, cancer-specific survival, and overall survival. Receiver-operating-characteristic curves were calculated for those 18 F-FDG PET/CT parameters that significantly correlated with TRG1. Results: Early total-lesion glycolysis and its percentage change compared with baseline (ΔTLG-early) could discriminate TRG1 from TRG2-TRG5. Only receiver-operating-characteristic analysis of ΔTLG-early showed an area under the curve greater than 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4% specificity), for identifying TRG1. Late metabolic assessment could not discriminate between the 2 groups. After a median follow-up of 98 mo (range, 77-132 mo), metabolic responders (ΔTLG-early ≥ 59.5%) demonstrated a significantly higher 10-y progression-free survival (89.3% vs. 63.6%, P = 0.02) and cancer-specific survival (92.9% vs. 72.6%, P = 0.04) than incomplete metabolic responders. Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy. The findings provide further support for the use of early 18 F-FDG PET/CT evaluation to predict pathologic response and survival in the preoperative treatment of patients with locally advanced rectal cancer. ΔTLG-early showed the best accuracy in predicting tumor regression and may be particularly useful in guiding treatment-modifying decisions during preoperative chemoradiotherapy based on expected response., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: To assess the trends concerning utilisation of maternal and child health (MCH) services before, during and after the Ebola outbreak, quantifying the contribution of a reorganised referral system (RS)., Design: A prospective observational study of MCH services., Setting: Pujehun district in Sierra Leone, 77 community health facilities and 1 hospital from 2012 to 2017., Main Outcome Measures: MCH utililization was evaluated by assessing: (1) institutional deliveries, Cesarean-sections, paediatric and maternity admissions and deaths, and major direct obstetric complications (MDOCs), at hospital level; (2) antenatal care (ANC) 1 and 4, institutional delivery and family planning, at community level. Contribution of a strengthened RS was also measured., Results: At hospital level, there is a significant difference between trends Ebola versus pre-Ebola for maternal admissions (7, 95% CI 4 to 11, p<0.001), MDOCs (4, 95% CI 1 to 7, p=0.006) and institutional deliveries (4, 95% CI 2 to 6, p=0.001). There is also a negative trend in the transition from Ebola to post-Ebola for maternal admissions (-7, 95% CI -10 to -4, p<0.001), MDOCs (-4, 95% CI -7 to -1, p=0.009) and institutional deliveries (-3, 95% CI -5 to -1, p=0.001). The differences between trends pre-Ebola versus post-Ebola are only significant for paediatric admissions (3, 95% CI 0 to 5, p=0.035). At community level, the difference between trends Ebola versus pre-Ebola and Ebola versus post-Ebola are not significant for any indicators. The differences between trends pre-Ebola versus post-Ebola show a negative difference for institutional deliveries (-7, 95% CI -10 to -4, p<0.001), ANC 1 (-6, 95% CI -10 to -3, p<0.001), ANC 4 (-8, 95% CI -11 to -5, p<0.001) and family planning (-85, 95% CI -119 to -51, p<0.001)., Conclusions: A stronger health system compared with other districts in Sierra Leone and a strengthened RS enabled health facilities in Pujehun to maintain service provision and uptake during and after the Ebola epidemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Splenic nodules are uncommon entities that occur rarely in the general population. Although an infectious etiology (primarily bacteria, followed by mycobacteria) is usually found, noninfectious diseases, including malignancies and autoimmune disorders, can also be involved. For instance, in course of inflammatory bowel diseases (IBDs), in particular Crohn's Disease, aseptic splenic abscesses have been reported in patients with a long history of illness, or in those unresponsive to medical treatments, while are only anecdotally reported in the early phase of the disease. Hence, we presented the case of aseptic splenic nodules as a first manifestation of Crohn's Disease., Case Presentation: A 21-year-old woman with a silent medical history was admitted to the Emergency Department of our hospital complaining of fever of 38-39 °C (mainly in the evening) for the past 10 days and left flank abdominal pain, accompanied by sweating and fatigue. An abdominal computed tomography showed multiple splenic nodules of unknown origin. Because of the absence of clinical improvement after several antibiotic therapiesand a positron emission tomography (PET) with hypercaptation strictly localized to spleen, she underwent splenectomy, in suspicion of lymphoma. For persistence of symptoms after splenectomy, she underwent many instrumental examination, including a colonoscopy with bowel and intestinal biopsies that poses diagnosis of Crohn's disease. A second PET confirmed this diagnosis showing this time also the gastrointestinal involvement., Conclusion: An unusual onset of Crohn's disease with multiple splenic nodules is reported. This case suggests that in light of splenic nodules of unknown etiology attention should be paid to all possible diagnoses of aseptic abscesses, including IBDs (primarily Crohn's Disease).

Rationale: In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term., Objective: The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain., Methods and Results: Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m 2 in the change of indexed LV end-systolic volume in favor of G-CSF group (P=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (P=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (P=0.04). Global circumferential strain significantly improved in G-CSF group only (P=0.006)., Conclusions: Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.

Breast tuberculosis (TB) is rarely reported and poorly described. This review aims to update the existing literature on risk factors, clinical presentations, constitutional symptoms, diagnostic procedures, and medical and surgical treatments for breast TB. In all, 1,478 cases of breast TB were collected. Previous history of TB was reported in 19% of cases. The most common clinical appearance of the lesion was breast lump (75%). The most common associated finding was axillary lymphadenitis (33%) followed by sinus or fistula (24%). The most common symptoms were pain and fever, reported in 42% and 28% of cases, respectively. The most used diagnostic method was fine-needle aspiration cytology (32%), followed by biopsy (27%), acid-fast bacteria Ziehl-Neelsen stain (26%), culture (13%), and polymerase chain reaction (2%). These tested positive in 64%, 93%, 27%, 26%, and 58% of cases, respectively. The majority (69%) of patients received a 6-month anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol). Surgery consisted of excision in 39% of cases, drainage in 23%, and mastectomy in 5%. The great majority of patients had a positive outcome. It often mimics breast cancer, which makes it difficult to diagnose. Most patients, when diagnosed in time, respond to antitubercular therapy alone.

Tuberculosis (TB) of the testicle is a rarely reported and poorly described disease localization. There are no well-defined clinical features suggestive of testicular TB, which makes the diagnosis difficult to establish, especially in low-income settings like Mozambique, where TB is endemic and often associated with HIV-infection; both considered leading causes of death worldwide. We reported the case of a 45-year-old male, HIV positive, naïve to antiretroviral treatment, admitted to the Department of Medicine of the Central Hospital of Beira to investigate chronic enlargement of the testicles.

Papillary thyroid carcinomas (PTCs) have an excellent prognosis, but a fraction of them show aggressive behavior, becoming radioiodine (RAI)-resistant and/or metastatic. AXL (Anexelekto) is a tyrosine kinase receptor regulating viability, invasiveness and chemoresistance in various human cancers, including PTCs. Here, we analyze the role of AXL in PTC prognosis and as a marker of RAI refractoriness. Immunohistochemistry was used to assess AXL positivity in a cohort of human PTC samples. Normal and cancerous thyroid cell lines were used in vitro for signaling, survival and RAI uptake evaluations. 38.2% of human PTCs displayed high expression of AXL that positively correlated with RAI-refractoriness and disease persistence or recurrence, especially when combined with v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation. In human PTC samples, AXL expression correlated with V-akt murine thymoma viral oncogene homolog 1 (AKT1) and p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation levels. Consistently, AXL stimulation with its ligand growth arrest-specific gene 6 (GAS6) increased AKT1- and p65 NF-kB-phosphorylation and promoted survival of thyroid cancer cell lines in culture. Enforced expression or activation of AXL in normal rat thyroid cells significantly reduced the expression of the sodium/iodide symporter (NIS) and the radioiodine uptake. These data indicate that AXL expression levels could be used as predictor of RAI refractoriness and as a possible novel therapeutic target of RAI resistant PTCs.

Purpose: To evaluate the image quality and radiation dose exposure of low-dose coronary CTA (cCTA) study, reconstructed with the new model-based iterative reconstruction algorithm (IMR), compared with standard hybrid-iterative reconstruction (iDose 4 ) cCTA in patients with suspected coronary artery disease., Materials and Methods: Ninety-eight patients with an indication for coronary CT study were prospectively enrolled. Fifty-two patients (study group) underwent 256-MDCT low-dose cCTA (80 kV; automated-mAs; 60 mL of CM, 350 mgL/mL) with prospective ECG-triggering acquisition and IMR. A control group of 46 patients underwent 256-MDCT standard prospective ECG-gated protocol (100 kV; automated-mAs; 70 mL of CM, 400 mgL/mL; iDose 4 ). Subjective and objective image quality (attenuation value, SD, SNR and CNR) were evaluated by two radiologists subjectively. Radiation dose exposure was quantified as DLP, CTDIvol and ED., Results: Mean values of mAs were significantly lower for IMR-cCTA (167 ± 62 mAs) compared to iDose-cCTA (278 ± 55 mAs), p < 0.001. With a significant reduction of 38% in radiation dose exposure (DLP: IMR-cCTA 91.7 ± 26 mGy cm vs. iDose-cCTA 148.6 ± 35 mGy cm; p value < 0.001), despite the use of different CM, we found higher mean attenuation values of the coronary arteries in IMR group compared to iDose 4 (mean density in LAD: 491HU IMR-cCTA vs. 443HU iDose-cCTA; p = 0.03). We observed a significant higher value of SNR and CNR in study group due to a lower noise level. Qualitative analysis did not reveal any significant differences between the two groups (p = 0.23)., Conclusions: Low-dose cCTA study combined with IMR reconstruction allows to correctly evaluate coronary arteries disease, offering high-quality images and significant radiation dose exposure reduction (38%), as compared to standard cCTA protocol.

Objective: Our cross-sectional study aimed at evaluating the diagnostic performance of Focused Assessment with Sonography for HIV-associated tuberculosis (FASH) to detect extrapulmonary tuberculosis in extremely resource-limited settings, with visceral leishmaniasis as a differential diagnosis with overlapping sonographic feature., Design: Cross-sectional study., Setting: Voluntary Counselling and Testing Centre (VCT) of Yirol Hospital, South Sudan., Participants: From May to November 2017, 252 HIV-positive patients out of 624 newly admitted to VCT Centre were registered for antiretroviral treatment. According to the number of trained doctors available to practise ultrasound (US) scan, a sample of 100 patients were screened using the FASH protocol., Interventions: Following a full clinical examination, each patient was scanned with a portable US scanner in six different positions for pleural, pericardial, ascitic effusion, abdominal lymphadenopathy and hepatic/splenic microabscesses, according to the FASH protocol. A k39 antigen test for visceral leishmaniasis was also performed on patients with lymphadenopathy and/or splenomegaly. All demographic, clinical and HIV data, as well as FASH results and therapy adjustments, were recorded following the examination., Results: The FASH protocol allowed the detection of pathological US findings suggestive of tuberculosis in 27 out of the 100 patients tested. Overall, FASH results supported tuberculosis treatment indication for 16 of 21 patients, with the treatment being based exclusively on FASH findings in half of them (8 patients). The group of FASH-positive patients had a significantly higher proportion of patients with CD4 count below 0.2 x10 9 /L (n=22, 81%) as compared with FASH-negative patients (n=35, 48%) (p=0.003). Moreover, 48% (n=13) of FASH-positive patients had CD4 below 100 cells/mm 3 . All patients tested had a negative result on k39 antigen test., Conclusion: FASH was found to be a relevant diagnostic tool to detect signs of tuberculosis. Further research is needed to better define a patient profile suitable for investigation and also considering diagnostic accuracy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cataract is a major cause of visual impairment in people with diabetes, yet a paucity of data is available in low- and middle-income countries (LMICs) on this comorbidity. Thus we assessed the association between diabetes and cataract in 6 LMICs., Methods: Cross-sectional, community-based data from the Study on Global Ageing and Adult Health (SAGE) was analyzed (n = 42,469 aged ≥18 years). Five years information on self-reported diagnosis of cataract was collected. Three definitions for cataract were used: (a) Self-reported diagnosis and/or past 12-month symptoms; (b) Solely self-reported diagnosis; and (c) Surgical treatment for cataract in the past five years. Diabetes was based on self-reported diagnosis. Multivariable logistic regression was conducted to assess the associations., Results: Overall, the prevalence of diabetes was 3.1% (95%CI = 2.7-3.5%) and that of cataract based on the three different definitions was: (a) 13.3% (95%CI = 12.4-14.3%); (b) 4.4% (95%CI = 3.9-4.8%), (c) 1.7% (95%CI = 1.5-2.0%). After adjustment the association was significantly elevated: (a) OR = 2.10 (95%CI = 1.59-2.76); (b) OR = 2.62 (95%CI = 2.00-3.42); (c) OR = 2.80 (95%CI = 1.78-4.40). These associations were particularly pronounced among those aged <50 years., Conclusions: A strong association between diabetes and cataract was observed in LMICs. Considering the impact on health and quality of life and the limited treatment options especially for cataract it is mandatory to promote the prevention through bi-directional screening and treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background : Chest ultrasound (CUS) has been shown to be a sensitive and specific imaging modality for pneumothorax, pneumonia, and pleural effusions. However, the role of chest ultrasound in the diagnosis of thoracic tuberculosis (TB) is uncertain. We performed a systematic search in the medical literature to better define the potential role and value of chest ultrasound in diagnosing thoracic tuberculosis. Aim : To describe existing literature with regard to the diagnostic value of chest ultrasound in thoracic tuberculosis. Methods : MEDLINE, EMBASE, and Scopus databases were searched for relevant articles. We included studies that used chest ultrasound for the diagnosis or management of any form of thoracic tuberculosis, including pulmonary, pleural, mediastinal, and military forms. Results : We identified five main fields of chest ultrasound application: (1) Detection, characterization, and quantification of TB; (2) detection of residual pleural thickening after evacuation; (3) chest ultrasound-guided needle biopsy; (4) identification of pathologic mediastinal lymph nodes in children; and (5) identification of parenchymal ultrasound patterns. Effusion was also detected, in early stages, with signs of organization in 24⁻100% of patients. A low to moderate (10⁻23%), false negative rate was reported for chest ultrasound-guided needle biopsy. CUS was able to identify mediastinal lymph nodes in as many as 67% of patients with negative chest radiography. Conclusions : Very few studies with important methodological limitations analyze the role of chest ultrasound in the diagnosis of TB. The scarce available data suggests potential targets of future diagnostic or feasibility trials, such as the detection of tuberculosis⁻related pleural effusion, residual pleural thickening, lymphadenopathy, TB parenchymal patterns, or the use of CUS in biopsy guidance.

Purpose: Great veins invasion is considered as a rare and prognostically unfavourable event in thyroid cancer. However, current knowledge about this issue is mainly based on single case reports. Follicular thyroid cancer (FTC) represents the histotype with the most pronounced angioinvasive feature. This study is aimed at assessing the actual prevalence of great veins invasion in FTC and providing information about prognosis and the proper clinical management of these patients., Methods: Clinico-pathological and radiological data of patients with thyroid cancer undergoing thyroidectomy in our institution were retrospectively retrieved. Inclusion criteria were as follows: (a) histological diagnosis of FTC; (b) instrumental and histological evidence of great veins invasion and (c) documented follow-up entirely performed at our institution. Pre-surgical assessment of great veins status was performed in all patients by means of Doppler ultrasonography., Results: Out of 637 patients operated from 2003 to 2013, four subjects, all affected with FTC, showed great veins involvement (0.62% of the overall cohort and 7.85% of the FTC group). One of them was lost at follow-up. All three patients with available follow-up were subjected to aggressive surgery obtaining a complete eradication of neck disease. All of them achieved the 5-year survival target (60, 63 and 96 months of survival for patients 1, 2 and 3, respectively)., Conclusions: Great veins invasion may not be uncommon in FTC and preoperative detection and characterisation of such condition may optimise surgical approach and improve survival.

Co-infection between malaria and HIV has major public health implications. The aims of this study were to assess the malaria prevalence and to identify predictors of positivity to malaria Test in HIV positive patients admitted to the health center São Lucas of Beira, Mozambique. A retrospective cross-sectional study was performed from January 2016 to December 2016. Overall, 701 adult HIV patients were enrolled, positivity to malaria test was found in 232 (33.0%). These patients were found to be more frequently unemployed (76.3%), aged under 40 (72.0%), with a HIV positive partner (22.4%) and with a CD4 cell count <200 (59.9%). The following variables were predictors of malaria: age under 40 (O.R. = 1.56; 95%CI: 1.22⁻2.08), being unemployed (O.R. = 1.74; 95%CI: 1.24⁻2.21), irregularity of cotrimoxazole prophylaxis's (O.R. = 1.42; 95%CI: 1.10⁻1.78), CD4 cell count <200 (O.R. = 2.01; 95%CI: 1.42⁻2.32) and tuberculosis comorbidity (O.R. = 1.58; 95%CI: 1.17⁻2.79). In conclusion, high malaria prevalence was found in HIV patients accessing the out-patients centre of São Lucas of Beira. Our findings allowed us to identify the profile of HIV patients needing more medical attention: young adults, unemployed, with a low CD4 cell count and irregularly accessing to ART and cotrimoxazole prophylaxis.

Background: Pulmonary and mediastinal paragangliomas are rare tumors that may have neuroendocrine activity or be non-functional, incidental, in asymptomatic patients, or causing mass effect symptoms. Although being low-grade tumors, they can display an aggressive behaviour, developing local infiltration and distant metastases. We report our experience with three endothoracic paragangliomas and a Literature review, to point out diagnostic difficulties and problems related to surgical treatment., Methods: From 2009 to 2017, we treated 3 patients with histological diagnosis of paraganglioma: 2 pulmonary, 1 mediastinal. No one presented catecholamine-secreting syndromes; pulmonary cases were asymptomatic, while the mediastinal one had aspecific cough and dyspnea. Imaging diagnosis was based on chest computerized tomography (CT) and magnetic resonance imaging (MRI) scan. No patient had preoperative histological diagnosis. Intraoperative pathological examination was suggestive for malignancy: in pulmonary cases, wedge resection and lobectomy were performed; the middle mediastinal mass was completely removed after challenging dissection, isolation and section of numerous vascular pedicles., Results: Postoperative course was uneventful in all cases. No patient received adjuvant treatments. At a median follow-up of 47 months (range, 6-102 months), two patients are alive, without local or distant recurrence; one patient died 6 months after surgery, due to disease progression., Conclusions: Endothoracic paragangliomas, rare and often asymptomatic tumors, are of difficult diagnosis and should be considered malignant tumors, due to the potential aggressive behaviour of cases with high mitotic index and the frequent possibility of recurrence and metastases. Surgical resection is the treatment of choice and careful intraoperative manipulation is recommended, due to the high vascularity of these tumors, to prevent complications. After complete excision, long-term prognosis is generally good. However, even after surgical removal, a close, periodical and life-long follow-up is mandatory., Competing Interests: Conflicts of Interest: Presented on the 17th October 2017, as Poster, at the IASLC 18th World Conference on Lung Cancer, Yokohama, Japan, 15–18 October 2017.

A low-cost air quality station has been developed for real-time monitoring of main atmospheric pollutants. Sensors for CO, CO₂, NO₂, O₃, VOC, PM 2.5 and PM 10 were integrated on an Arduino Shield compatible board. As concerns PM 2.5 and PM 10 sensors, the station underwent a laboratory calibration and later a field validation. Laboratory calibration has been carried out at the headquarters of CNR-IBIMET in Florence (Italy) against a TSI DustTrak reference instrument. A MATLAB procedure, implementing advanced mathematical techniques to detect possible complex non-linear relationships between sensor signals and reference data, has been developed and implemented to accomplish the laboratory calibration. Field validation has been performed across a full "heating season" (1 November 2016 to 15 April 2017) by co-locating the station at a road site in Florence where an official fixed air quality station was in operation. Both calibration and validation processes returned fine scores, in most cases better than those achieved for similar systems in the literature. During field validation, in particular, for PM 2.5 and PM 10 mean biases of 0.036 and 0.598 µg/m³, RMSE of 4.056 and 6.084 µg/m³, and R² of 0.909 and 0.957 were achieved, respectively. Robustness of the developed station, seamless deployed through a five and a half month outdoor campaign without registering sensor failures or drifts, is a further key point.

The concept of &ldquo;children at risk&rdquo; changes worldwide according to each specific context. Africa has a large burden of overall risk factors related to childhood health and development, most of which are of an infective or social origin. The aim of this study was to report and analyze the volumes of activities of fifteen At Risk Child Clinics (ARCCs) within the Beira District (Mozambique) over a 3 year-period in order to define the health profile of children accessing such health services. We retrospectively analyzed the data from all of the children accessing one of the 15 Beira ARCCs from January 2015 to December 2017. From this, 17,657 first consultations were registered. The motivations for accessing the services were in order of relevance: HIV exposure (n. 12,300; 69.7%), other risk conditions (n. 2542; 14.4%), Moderate Acute Malnutrition (MAM) (n. 1664; 9.4%), Severe Acute Malnutrition (SAM) (n. 772; 4.4%), and TB exposure (n. 542; 3.1%). During the first consultations, 16,865 children were screened for HIV (95.5%), and 7.89% tested HIV-positive. In our three years of experience, HIV exposure was the main indication for children to access the ARCCs in Mozambique. ARCCs could represent a strategic point to better understand health demands and to monitor the quality of care provided to this vulnerable population group, however significant effort is needed to improve the quality of the data collection.

Background: In 2013, Mozambique implemented task-shifting (TS) from clinical officers to maternal and child nurses to improve care for HIV positive children < 5 years old. A retrospective, pre-post intervention study was designed to evaluate effectiveness of a new pathway of care in a sample of Beira District Local Health Facilities (LHFs), the primary, local, community healthcare services., Methods: The study was conducted by accessing registries of At Risk Children Clinics (ARCCs) and HIV Health Services. Two time periods, pre- and post-intervention, were compared using a set of endpoints. Variables distribution was explored using descriptive statistics. T-student, Mann Whitney and Chi-square tests were used for comparisons., Results: Overall, 588 HIV infected children (F = 51.4%) were recruited, 330 belonging to the post intervention period. The mean time from referral to ARCC until initiation of ART decreased from 2.3 (± 4.4) to 1.1 (± 5.0) months after the intervention implementation (p-value: 0.000). A significant increase of Isoniazid prophylaxis (O.R.: 2.69; 95%CI: 1.7-4.15) and a decrease of both regular nutritional assessment (O.R. = 0.45; 95%CI: 0.31-0.64) and CD4 count at the beginning of ART (O.R. = 0.46; 95%CI: 0.32-0.65) were documented after the intervention., Conclusions: Despite several limitations and controversial results on nutrition assessment and CD4 count at the initiation of ART reported after the intervention, it could be assumed that TS alone may play a role in the improvement of the global effectiveness of care for HIV infected children only if integrated into a wider range of public health measures.

Gynecomastia is a common finding in males, with an incidence that varies widely globally. In 10-25% of cases, it is caused by drugs. Its pathophysiologic mechanism includes exposure to exogenous estrogens and medications that cause hypogonadism, antiandrogenic effects and hyperprolactinemia. Gynecomastia is associated with exposure to antiretroviral therapy (ART), particularly efavirenz. Sometimes surgery may be required as treatment. We report a case of a 46-year-old man receiving ART presenting with a marked bilateral breast enlargement who underwent bilateral mastectomy as the only successful treatment in a low-income setting.

The purpose of this article is to provide insights into the demand for pregnancy-related health services by adolescent girls and young women in Mozambique. We analysed the patient registers for the first year of operation (2014) of the Servicios Amigos dos Adolescentes (SAAJ) [Friendly Services for Adolescents] clinics in Beira, Mozambique. These registers provide details of the service demands of, and services provided to the 8 290 adolescent girls and young women who accessed the 6 SAAJ clinics in 2014. Analysis of that record, with disaggregation of the patients according to age (9 years or less; 10-14; 15-19; 20-24; 25 and older), show that 3 021 (36%) were pregnant or had previously been pregnant; most being girls in the 15-19 age band (59%). Being pregnant or having been pregnant previously was associated with dropping out of school. Of all the girls and women, 60% agreed to HIV testing and counselling; the HIV prevalence rate amongst this group was 4-5% amongst adolescents and 25% amongst women 25 years and older. A minority of the girls and women who were pregnant or had been pregnant previously agreed to HIV testing and counselling. Notwithstanding the limitations for analysis, the results were alarming: substantially high HIV prevalence rates were indicated (2% amongst 10-14 year old girls; 8% amongst 15-19 year olds; 10% amongst 20-24 year olds; and 28% amongst >24 year olds). The data from the SAAJ clinics and results pertain only to conditions in Beira. However, as the first empirical assessment of pregnancy-related service demand amongst adolescent girls and young women in the country and involving a relatively large sample, we contend that this study affirms the need for expansion of sexual and reproductive health (SRH) services, including HIV services, for adolescent girls and young women in Mozambique.

Objective: Tuberculosis (TB) remains a major global health issue, ranking in the top ten causes of death worldwide. A deep understanding of factors influencing poor treatment outcomes may allow the development of additional treatment strategies, focused on the most vulnerable groups. Aims of the study were: (i) to evaluate the treatment outcome among TB subjects followed in an outpatient setting and (ii) to analyze factors associated with treatment failure in newly diagnosed patients with pulmonary TB in Beira, the second largest city of Mozambique., Results: A total of 301 TB adult patients (32.6% females) were enrolled. Among them, 62 (20.6%) experienced a treatment failure over a 6 months follow-up. On multivariate model, being males (O.R. = 1.73; 95% CI 1.28-2.15), absence of education (O.R. = 1.85; 95% CI 1.02-2.95), monthly income under 50 dollars (O.R. = 1.74; 95% CI 1.24-2.21) and being employed (O.R. = 1.57; 95% CI 1.21-1.70), low body mass index values (O.R. = 1.42; 95% CI 1.18-1.72) and HIV status (O.R. = 1.42; 95% CI 1.10-1.78) increased the likelihood of therapy failure over 6 months of follow-up. In this study, patients who need more medical attention were young males, malnourished, with low income and low educational degree and HIV positive. These subjects were more likely to fail therapy.

Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.

Deforestation and forest degradation cause the deterioration of resources and ecosystem services. However, there are still no operational indicators to measure forest status, especially for forest degradation. In the present study, we analysed the thermal response number (TRN, calculated by daily total net radiation divided by daily temperature range) of 163 sites including mature forest, disturbed forest, planted forest, shrubland, grassland, savanna vegetation and cropland. TRN generally increased with latitude, however the regression of TRN against latitude differed among vegetation types. Mature forests are superior as thermal buffers, and had significantly higher TRN than disturbed and planted forests. There was a clear boundary between TRN of forest and non-forest vegetation (i.e. grassland and savanna) with the exception of shrubland, whose TRN overlapped with that of forest vegetation. We propose to use the TRN of local mature forest as the optimal TRN (TRN opt ). A forest with lower than 75% of TRN opt was identified as subjected to significant disturbance, and forests with 66% of TRN opt was the threshold for deforestation within the absolute latitude from 30° to 55°. Our results emphasized the irreplaceable thermal buffer capacity of mature forest. TRN can be used for early warning of deforestation and degradation risk. It is therefore a valuable tool in the effort to protect forests and prevent deforestation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Data regarding the association between diabetes mellitus (DM) and tuberculosis (TB) in Africa are scarce. DM screening among TB patients in Mozambique was carried out., Methods: The study was implemented from January to August 2016 in three Urban Health Centers in Beira, Mozambique and recruited adult (>18 years) patients newly diagnosed with pulmonary TB., Results: Three hundred and one patients were enrolled (67.4%, males mean age 31.7(SD 11 years). Diabetes was diagnosed in only 3 patients (1%) and impaired glucose tolerance (IGT) in an additional 6 subjects (2%)., Conclusion: A lower than expected prevalence of DM was observed, which could be explained by the lack of traditional risk factors for DM (overweight, age over 45 years, hypertension and smoking) in Mozambique.

Aim: To validate the Composite Autonomic Symptom Score (COMPASS) 31, in its Italian version, for the diagnosis of diabetic cardiovascular autonomic neuropathy in a clinic-based, single-centre study., Methods: A total of 73 participants with diabetes (age 55 ± 14 years) completed the COMPASS 31 questionnaire before undergoing cardiovascular autonomic neuropathy and diabetic polyneuropathy assessment according to cardiovascular reflex tests, neuropathic symptoms and signs, and vibration and thermal thresholds., Results: The COMPASS 31 total weighted score differed between participants with and without cardiovascular autonomic neuropathy (29.9 ± 19.5 vs 16.1 ± 14.7; P = 0.003) and with and without diabetic polyneuropathy (28.9 ± 19.1 vs 12.7 ± 11.3; P < 0.0001). It was related to cardiovascular reflex tests score (rho = 0.38, P = 0.0013) as well as diabetic polyneuropathy symptoms (rho=0.61, P < 0.0001) and signs scores (rho = 0.49, P < 0.0001). Receiver-operating curve analysis showed a fair diagnostic accuracy of total score for cardiovascular autonomic neuropathy (area under the curve 0.748 ± 0.068, 95% CI 0.599-0.861) and diabetic polyneuropathy (area under the curve 0.742 ± 0.061, 95% CI 0.611-0.845). The best score thresholds were 16 for early cardiovascular autonomic neuropathy (sensitivity 75.0%, specificity 64.9%, positive predictive value 37.5% and negative predictive value 90.2%), and 17 for both confirmed cardiovascular autonomic neuropathy and diabetic polyneuropathy (sensitivity 70.0% and 65.5%, respectively; specificity 66.7% and 79.5%, respectively; positive predictive value 25.0% and 67.9%, respectively; and negative predictive value 93.0% and 77.8%, respectively). COMPASS 31 had a good internal consistency according to Cronbach's α coefficient of 0.73., Conclusions: COMPASS 31 can represent a valid, easy-to-use, quantitative assessment tool for autonomic symptoms in diabetic neuropathy, with a fair diagnostic accuracy for both cardiovascular autonomic neuropathy and diabetic polyneuropathy., (© 2016 Diabetes UK.)

Background: Imported cases of multidrug resistant Plasmodium falciparum and treatment failure with artemisinin-based regimens, although rare, have been described also in Western countries and their management is often challenging. This is also due to an inadequate knowledge and implementation of health prevention measures., Case Report: A complex case of imported malaria caused by Plasmodium vivax/P. falciparum isolates in a patient who was not taking chemoprophylaxis while he was travelling in Cambodia is reported in this article. After failures of artemisinin-based and both oral and intravenous quinine-based regimens, a multidrug resistant P. falciparum was detected. The patient was successfully treated with atovaquone-proguanil., Conclusions: This experience highlights the importance of a careful management that should be based not only on the most up-to-date guidelines, but also on the awareness of a rapidly evolving scenario.

Background: Social determinants influence health and the development of tuberculosis (TB). However, a paucity of data is available considering the relationship of social determinants influencing therapy failure and multi drug resistance (MDR). We conducted a review investigating the relationship of common social determinants on therapy failure and MDR in people with TB., Methods: PubMed and SCOPUS were searched without language restrictions until February 02, 2016 for studies reporting the association between socioeconomic factors (income, education and alcohol abuse) and therapy failure or MDR-TB. The association between social determinants and outcomes was explored by pooling data with a random effects model and calculating crude and adjusted odds ratios (ORs) ±95% confidence intervals (CIs)., Results: Fifty studies with 407,555 participants with TB were included. Analysis demonstrated that low income (unadjusted OR = 2.00 (95% CI: 1.69-2.38; I 2  = 88%; 33 studies, adjusted OR 1.77, p < 0.0001), low education (unadjusted OR 2.11, 95% CI 1.55-2.86, 26 studies, adjusted OR 1.69, p < 0.0001) and alcohol abuse (unadjusted OR = 2.43 (95% CI: 1.56-3.80, 16 studies, adjusted OR 2.13, p < 0.0001) were associated with therapy failure. Similarly, low income (unadjusted OR = 1.67; 95% CI: 1.12-2.41, p = 0.006; 14 studies, adjusted OR 2.16, p < 0.0001) and alcohol abuse (unadjusted OR = 1.88; 95% CI: 1.18-3.00, 7 studies, adjusted OR 1.43, p = 0.06) were associated with MDR-TB. Increasing age of the population was able to explain a consistent part of the heterogeneity found., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aims: To investigate the independent effect on depression of painless diabetic polyneuropathy, painful diabetic polyneuropathy, and general and diabetes-related comorbidities., Methods: In 181 patients, the presence of painless diabetic polyneuropathy, painful diabetic polyneuropathy, comorbidities and depression was assessed using the Michigan Neuropathy Screening Instrument Questionnaire, the Michigan Diabetic Neuropathy Score, nerve conduction studies, the Douleur Neuropathique en 4 Questions, the Charlson Comorbidity Index and the Beck Depression Inventory-II., Results: In all, 46 patients met the criteria of confirmed painless diabetic polyneuropathy and 25 of painful diabetic polyneuropathy. Beck Depression Inventory-II scores indicative of mild-moderate-severe depression were reached in 36 patients (19.7%). In a multiple logistic regression analysis (including age, sex, body mass index, being unemployed, duration, haemoglobin A1c, insulin treatment, systolic blood pressure, nephropathy, retinopathy, Charlson Comorbidity Index and painful diabetic polyneuropathy), female sex (odds ratio: 5.9, p = 0.005) and painful diabetic polyneuropathy (odds ratio: 4.6, p = 0.038) were the only independent predictors of depression. Multiple regression analysis, including Douleur Neuropathique en 4 Questions and Michigan Diabetic Neuropathy Score instead of painful diabetic polyneuropathy, showed that Douleur Neuropathique en 4 Questions, in addition to female sex, was a significant predictor of depressive symptoms severity (p =0.005)., Conclusion: Painful diabetic polyneuropathy is a greater determinant of depression than other diabetes-related complications and comorbidities. Painful symptoms enhance depression severity more than objective insensitivity., (© The Author(s) 2016.)

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome predisposing to many endocrine and neuroendocrine tumors (NET). Conventional imaging (CI) cannot provide satisfactory results for all the different types of MEN1-related tumors. Objective of this prospective observational study was to evaluate the role of (68)Ga-DOTATATE PET/CT in MEN1 compared to CI. Diagnostic performance of (68)Ga-DOTATATE PET/CT for the detection of NET was evaluated as well as the prognostic role of SUVmax. Eighteen patients with genetically confirmed MEN1 were evaluated by (68)Ga-DOTATATE PET/CT, endoscopic ultrasounds, multidetector-row computed tomography, magnetic resonance imaging, and hormone/markers serum measurements. Four MEN1-related tumor sites (pancreas, pituitary, parathyroids, adrenals) were considered. Sensitivity and specificity of (68)Ga-DOTATATE PET/CT for the detection of NET were calculated. There was (68)Ga-DOTATATE PET/CT uptake in 11/11 patients with pancreatic lesions, in 9/12 with pituitary adenoma, in 5/15 with parathyroid enlargements, and in 5/7 with adrenal lesions. (68)Ga-DOTATATE PET/CT showed sensitivity and specificity of 100 and 100 % in pancreas, 75 and 83 % in pituitary, 28 and 100 % in parathyroids, and 62.5 and 100 % in adrenals, respectively. Compared with CI, no significant difference in sensitivity for pancreas, pituitary, and adrenals was found, while CI had a better sensitivity for parathyroids (p = 0.002). On the ROC analysis, progression of pancreatic lesions was significantly associated to SUVmax <12.3 (p < 0.05). (68)Ga-DOTATATE PET/CT is greatly helpful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. There is also a prognostic role of (68)Ga-PET in patients with MEN1-pancreatic lesions.

This review outlines the association between tuberculosis and diabetes, focusing on epidemiology, physiopathology, clinical aspects, diagnosis and treatment, and evaluates future perspectives, with particular attention to developing countries., (© 2016 John Wiley & Sons Ltd.)

Background: We report short and long-term results with the dedicated Synthes(®) titanium plates system, introduced 5 years ago, for chest wall stabilization and reconstruction., Methods: We retrospectively analyzed (January 2010 to December 2014) 27 consecutive patients (22 males, 5 females; range 16-83 years, median age 60 years), treated with this system: primary [3] and secondary [8] chest wall tumor; flail chest [5]; multiple ribs fractures [5]; sternal dehiscence-diastasis [3]; sternal fracture [1]; sternoclavicular joint dislocation [1]; Poland syndrome [1]. Short-term results were evaluated as: operating time, post-operative morbidity, mortality, hospital stay; long-term results as: survival, plates-related morbidity, spirometric values, chest pain [measured with Verbal Rating Scale (VRS) and SF12 standard V1 questionnaire]., Results: Each patient received from 1 to 10 (median 2) titanium plates/splints; median operating time was 150 min (range: 115-430 min). Post-operative course: 15 patients (55.6%) uneventful, 10 (37%) minor complications, 2 (7.4%) major complications; no post-operative mortality. Median post-operative hospital stay was 13 days (range: 5-129 days). At a median follow-up of 20 months (range: 1-59 months), 21 patients (78%) were alive, 6 (22%) died. Three patients presented long-term plates-related morbidity: plates rupture [2], pin plate dislodgment [1]; two required a second surgical look. One-year from surgery median spirometric values were: FVC 3.31 L (90%), FEV1 2.46 L (78%), DLCO 20.9 mL/mmHg/min (76%). On 21 alive patients, 7 (33.3%) reported no pain (VRS score 0), 10 (47.6%) mild (score 2), 4 (19.1%) moderate (score 4), no-one severe (score >4); 15 (71.5%) reported none or mild, 6 (28.5%) moderate pain influencing quality of life., Conclusions: An optimal chest wall stabilization and reconstruction was achieved with the Synthes(®) titanium plates system, with minimal morbidity, no post-operative mortality, acceptable operating time and post-operative hospital stay. Long-term restoration of a normal respiratory function was achieved, with minimal plates-related morbidity and chest pain.

Background: Treatment of iron deficiency helps to improve cardiac and renal function in patients with chronic heart failure. However, the mechanism by which this occurs is currently unclear., Methods: We undertook a double-blind, randomised, placebo-controlled study of intravenous iron sucrose treatment (200mg/mL weekly for five weeks) in patients with chronic heart failure, chronic kidney disease and iron-deficiency anaemia receiving optimal treatment for chronic heart failure (N=60). Markers of disease severity, iron status, anaemia and inflammation were measured during a six-month follow-up period, and evaluation of echocardiographic parameters was performed at baseline and six months after treatment., Results: At six months after treatment initiation, intravenous iron was associated with reduced severity of the symptoms of chronic heart failure and improved renal function (both p<0.001 versus control). Also, ferritin and transferrin saturation levels were increased, as were haemoglobin levels, whereas inflammatory markers were reduced (all p<0.001 versus control). Left ventricular systolic and diastolic diameters were increased and improved left ventricular function correlated with iron status in patients receiving intravenous iron but not patients in the control group., Conclusions: Intravenous iron treatment was associated with improved myocardial functional parameters and cardiac dimensions in patients with anaemia and chronic kidney disease., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Fine-needle cytology (FNC) is frequently used to diagnose thyroid nodules discovered by palpation or imaging studies. Molecular tests on FNC material may increase its diagnostic accuracy. We report a case of a classic papillary thyroid carcinoma combined with a mucoepidermoid carcinoma correctly identified on FNC. The papillary component had a classic immunophenotype (CK19+, TTF1+), while the mucoepidermoid one was only focally CK19+. Point mutations (BRAF and RAS) and rearrangements (RET/PTC) of the papillary component have been also investigated on FNC samples, with resulting concurrent rearrangements of RET/PTC1 and RET/PTC3, but no point mutations. The histogenesis of combined papillary and mucoepidermoid carcinoma of the thyroid still remains partly unsettled, and further genomic studies are needed to shed some more light on this peculiar neoplasm.

Background: Patients with non-dialysis-dependent chronic kidney disease (ND-CKD) often receive an erythropoiesis-stimulating agent (ESA) and oral iron treatment. This study evaluated whether a switch from oral iron to intravenous ferric carboxymaltose can reduce ESA requirements and improve iron status and hemoglobin in patients with ND-CKD., Methods: This prospective, single arm and single-center study included adult patients with ND-CKD (creatinine clearance ≤40 mL/min), hemoglobin 11-12 g/dL and iron deficiency (ferritin <100 μg/L or transferrin saturation <20%), who were regularly treated with oral iron and ESA during 6 months prior to inclusion. Study patients received an intravenous ferric carboxymaltose dose of 1,000 mg iron, followed by a 6-months ESA/ ferric carboxymaltose maintenance regimen (target: hemoglobin 12 g/dL, transferrin saturation >20%). Outcome measures were ESA dose requirements during the observation period after initial ferric carboxymaltose treatment (primary endpoint); number of hospitalizations and transfusions, renal function before and after ferric carboxymaltose administration, number of adverse reactions (secondary endpoints). Hemoglobin, mean corpuscular volume, ferritin and transferrin saturation were measured monthly from baseline until end of study. Creatinine clearance, proteinuria, C-reactive protein, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase bimonthly from baseline until end of study., Results: Thirty patients were enrolled (age 70.1±11.4 years; mean±SD). Mean ESA consumption was significantly reduced by 83.2±10.9% (from 41,839±3,668 IU/patient to 6,879±4,271 IU/patient; p<0.01). Hemoglobin increased by 0.7±0.3 g/dL, ferritin by 196.0±38.7 μg/L and transferrin saturation by 5.3±2.9% (month 6 vs. baseline; all p<0.01). No ferric carboxymaltose-related adverse events were reported and no patient withdrew or required transfusions during the study., Conclusion: Among patients with ND-CKD and stable normal or borderline hemoglobin, switching from oral iron to intravenous ferric carboxymaltose was associated with significant improvements in hematological and iron parameters and a significant reduction in ESA dose requirements in this single-center pilot study., Trial Registration: ClinicalTrials.gov NCT02232906.

Thyroid carcinomas are rare and heterogeneous diseases representing less than 1% of all malignancies. The majority of thyroid carcinomas are differentiated entities (papillary and folliculary carcinomas) and are characterized by good prognosis and good response to surgery and radioiodine therapy. Nevertheless, about 10% of differentiated carcinomas recur and become resistant to all therapies. Anaplastic and medullary cancers are rare subtypes of thyroid cancer not suitable for radioiodine therapy. A small percentage of differentiated and all the anaplastic and medullary thyroid carcinomas often recur after primary treatments and are no longer suitable for other therapies. In the last years, several advances have been made in the field of molecular biology and tumorigenesis mechanisms of thyroid carcinomas. Starting from these issues, the targeted therapy may be employed as a new option. The MAP-Kinase pathway has been found often dysregulated in thyroid carcinomas and several upstream signals have been recognized as responsible for this feature. RET/PTC mutations are often discovered both in papillary and in medullary carcinomas, while B-RAF mutation is typical of papillary and anaplastic histologies. Also mTOR disruptions and VEGFR pathway disruption are common features in all advanced thyroid cancers. Some angiogenesis inhibitors and a number of RET/PTC pathway blocking agents are yet present in the clinical armamentarium. Vandetanib, cabozatinib and sorafenib have reached clinical use. A number of other biological compounds have been tested in phase II and III trials. Understanding the biology of thyroid cancers may help us to design a well shaped targeted therapy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: Hyperferritinemia is frequent in chronic liver diseases of any cause, but the extent to which ferritin truly reflects iron stores is variable. In these patients, both liver iron and fat are found in variable amount and association. Liver biopsy is often required to quantify liver fat and iron, but sampling variability and invasiveness limit its use. We aimed to assess single breath-hold multiecho magnetic resonance imaging (MRI) for the simultaneous lipid and iron quantification in patients with hyperferritinemia., Material and Methods: We compared MRI results for both iron and fat with their respective gold standards - liver iron concentration and computer-assisted image analysis for steatosis on biopsy. We prospectively studied 67 patients with hyperferritinemia and other 10 consecutive patients were used for validation. We estimated two linear calibration equations for the prediction of iron and fat based on MRI. The agreement between MRI and biopsy was evaluated., Results: MRI showed good performances in both the training and validation samples. MRI information was almost completely in line with that obtained from liver biopsy., Conclusion: Single breath-hold multiecho MRI is an accurate method to obtain a valuable measure of both liver iron and steatosis in patients with hyperferritinemia.

Thyroid carcinoma with distant metastases at initial presentation, is uncommon. Skull metastases occur very rarely, with a reported incidence of 2.5-5.8%. Here we report two cases of follicular thyroid cancer with skull involvement, and describe the diagnostic and therapeutic approach to metastatic thyroid cancer. We present the cases of a 70-year-old female and a 74-year-old female who presented with painless, large slow-growing masses of the skull. The patients underwent surgical excision of the skull masses, which were histologically diagnosed as metastatic follicular thyroid cancer, and total thyroidectomy, which confirmed the diagnosis of follicular thyroid carcinoma. They were treated with radioiodine and suppressive levothyroxine, which achieved local control of the disease. Management of metastatic thyroid cancer, requires a multidisciplinary approach and multimodality treatment. Distant metastases should be surgically removed whenever possible. Initial aggressive treatment is crucial in the management of metastatic thyroid carcinoma, providing the best chance to prolong patient survival.

The Virtual Family computational whole-body anatomical human models were originally developed for electromagnetic (EM) exposure evaluations, in particular to study how absorption of radiofrequency radiation from external sources depends on anatomy. However, the models immediately garnered much broader interest and are now applied by over 300 research groups, many from medical applications research fields. In a first step, the Virtual Family was expanded to the Virtual Population to provide considerably broader population coverage with the inclusion of models of both sexes ranging in age from 5 to 84 years old. Although these models have proven to be invaluable for EM dosimetry, it became evident that significantly enhanced models are needed for reliable effectiveness and safety evaluations of diagnostic and therapeutic applications, including medical implants safety. This paper describes the research and development performed to obtain anatomical models that meet the requirements necessary for medical implant safety assessment applications. These include implementation of quality control procedures, re-segmentation at higher resolution, more-consistent tissue assignments, enhanced surface processing and numerous anatomical refinements. Several tools were developed to enhance the functionality of the models, including discretization tools, posing tools to expand the posture space covered, and multiple morphing tools, e.g., to develop pathological models or variations of existing ones. A comprehensive tissue properties database was compiled to complement the library of models. The results are a set of anatomically independent, accurate, and detailed models with smooth, yet feature-rich and topologically conforming surfaces. The models are therefore suited for the creation of unstructured meshes, and the possible applications of the models are extended to a wider range of solvers and physics. The impact of these improvements is shown for the MRI exposure of an adult woman with an orthopedic spinal implant. Future developments include the functionalization of the models for specific physical and physiological modeling tasks.

Objective: We hypothesized the meaningful coexistence of neuropathic pain and nondipping in painful diabetic polyneuropathy (PDPN)., Research Design and Methods: In 113 patients with PDPN, with painless diabetic polyneuropathy (DPN(+)) and without DPN (DPN(-)), neuropathic pain, sleep, risk for obstructive sleep apnea (OSA), autonomic function, and blood pressure (BP) circadian pattern were assessed using the Douleur Neuropathique en 4 Questions (DN4), the Medical Outcomes Study Sleep Scale, the Berlin Questionnaire, cardiovascular reflex tests, and ambulatory BP monitoring., Results: Patients with PDPN showed higher nighttime systolic BP (130.4 ± 15.6 mmHg) than both DPN(-) (119.9 ± 10.6 mmHg; P < 0.0001) and DPN(+) patients (124.2 ± 12.3 mmHg; P < 0.05), and lower day-night difference (∆) in systolic BP (5.5 ± 6.5 vs. 8.6 ± 7.7%; P < 0.05) and diastolic BP than DPN(-) patients. In a stepwise regression analysis, orthostatic hypotension, high risk for OSA, and PDPN (DN4 interview) were independent determinants of ∆ in systolic BP (r = 0.46; P = 0.0001), ∆ in diastolic BP, and nighttime systolic BP., Conclusions: PDPN is associated with higher nocturnal systolic BP and impaired BP circadian pattern independent of pain-related comorbidities, suggesting a condition of high cardiovascular risk., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Purpose: The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the extracellular matrix of tumours and on newly formed blood vessels and is thus a valuable target for radionuclide therapy. Tenarad is a fully human miniantibody or small immunoprotein (SIP, molecular weight 80 kDa) labelled with (131)I that is derived from a TC-A1-binding antibody. Previous phase I/II studies with a similar compound ((131)I-L19SIP) used for radioimmunotherapy (RIT) have shown preliminary efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad was administered to patients with recurrent Hodgkin's lymphoma (HL) refractory to conventional treatments., Methods: Eight patients (four men, four women; age range 19 - 41) were enrolled between April 2010 and March 2011. All patients had received a median of three previous lines of chemotherapy (range three to six) and seven had also undergone autologous stem cell transplantation (ASCT) or bone marrow transplantation. In addition, seven patients received external beam radiation. All patients had nodal disease, constitutional B symptoms and some showed extranodal disease in skeletal bone (four patients), lung (three), liver (two) and spleen (one). Baseline assessments included whole-body FDG PET with contrast-enhanced CT and diagnostic Tenarad planar and SPECT studies. Patients were considered eligible to receive a therapeutic dose of Tenarad (2.05 GBq/m(2)) if tumour uptake was more than four times higher than that of muscle., Results: All patients were eligible and received the therapeutic dose of Tenarad. Only one patient developed grade 4 thrombocytopenia and leucocytopenia, requiring hospitalization and therapeutic intervention. All other patients had haematological toxicity of grade 3 or lower, which resolved spontaneously. At the first response assessment (4 - 6 weeks after therapy), one patient showed a complete response, one showed a partial response (PR) and five had disease stabilization (SD). Five patients were given up to three repeated Tenarad treatments. One patient showed SD which then improved to a PR, three showed clinical benefit while maintaining SD and one patient showed disease progression., Conclusion: Tenarad RIT is effective in chemorefractory HL and resulted in objective responses or clinical benefit in the majority of patients. Toxicity was acceptable despite the high load of prior treatments, previous ASCT and multiple Tenarad administrations. Further studies are planned to define the most effective schedule for this type of RIT in HL patients.

Objective: To assess whether granulocyte colony-stimulating factor (G-CSF) treatment induces a sustained benefit on adverse remodelling in patients with large anterior ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction after successful reperfusion., Methods: The STEM-AMI Trial was a prospective, placebo-controlled, multicentre study. Sixty consecutive patients with a first anterior STEMI, who underwent primary percutaneous coronary intervention 2-12 h after symptom onset, with LV ejection fraction (LVEF) ≤45% measured by echocardiography within 12 h after successful revascularisation (TIMI flow score ≥2), were randomised 1:1 to G-CSF (5 µg/Kg body weight b.i.d.) or placebo. Clinical events and Major Adverse Cardiac and Cerebrovascular Event (MACCE) were monitored, and LVEF, LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes, and infarct size were evaluated by MRI at the final 3-year follow-up., Results: Fifty-four patients completed the study, of whom 35 with MRI. No significant differences were found in mortality and MACCE between G-CSF and placebo-treated groups. The 3-year infarct size was not different between groups, whereas LVEDV was significantly lower in G-CSF (n=20) than in placebo (n=15) patients (170.1±8.1 vs 197.2±8.9 mL, respectively; p=0.033 at analysis of covariance). A significant inverse correlation was detected in G-CSF patients between the number of circulating CD34 cells at 30 days after reperfusion and the 3-year absolute and indexed LVEDV (ρ=-0.71, 95% CI -0.90 to -0.30, and ρ=-0.62, -0.86 to -0.14, respectively), or their change over time (r=-0.59, -0.85 to -0.11, and r=-0.55, -0.83 to -0.06, respectively)., Conclusions: G-CSF therapy may be beneficial in attenuating ventricular remodelling subsequent to a large anterior STEMI in the long term. No differences have been detected in clinical outcome.

The Authors report the case of a patient who underwent resection of a huge anterior mediastinal mass, revealing to be a necrotic thymoma. The patient had been previously submitted to surgical biopsies of the mass yielding non-diagnostic results due to extensive necrosis. A sternotomy was then performed to resect the mediastinal mass originating from the thymus, en-bloc with the mediastinal fat and the apparently infiltrated lung. Histopathology showed a possible cyst/thymoma in massive necrosis, not further definable; revision by a specialized experienced pathologist (J. Rosai) confirmed total mass necrosis and no lung infiltration, thus orientating diagnosis towards a necrotic thymoma and excluding a lymphoblastic lymphoma, with similar histopathological features but more frequent in children or characterized by neoplastic infiltration of surrounding lung. Total body computed tomography (CT) scan and fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/CT, show neither local recurrence, nor distant metastases two years after surgery. In case of anterior mediastinal mass with difficult histopathological diagnosis due to massive necrosis, the hypothesis of a necrotic thymoma should be considered. After radical removal prognosis is generally favourable and no adjuvant treatment is required.

Purpose: The aim of the present study is to prospectively evaluate the prognostic value of previously defined [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) criteria of early metabolic response in patients with locally advanced rectal cancer (LARC) after long-term follow-up., Methods: Forty-two patients with poor prognosis LARC underwent three biweekly courses of chemotherapy with oxaliplatin, raltitrexed and 5-fluorouracil modulated by levofolinic acid during pelvic radiotherapy. FDG PET studies were performed before and 12 days after the beginning of the chemoradiotherapy (CRT) treatment. Total mesorectal excision (TME) was carried out 8 weeks after completion of CRT. A previously identified cutoff value of ≥52 % reduction of the baseline mean FDG standardized uptake value (SUV(mean)) was applied to differentiate metabolic responders from non-responders and correlated to tumour regression grade (TRG) and survival., Results: Twenty-two metabolic responders showed complete (TRG1) or subtotal tumour regression (TRG2) and demonstrated a statistically significantly higher 5-year relapse-free survival (RFS) compared with the 20 non-responders (86 vs 55 %, p = .014) who showed TRG3 and TRG4 pathologic responses. A multivariate analysis demonstrated that early ∆SUV(mean) was the only pre-surgical parameter correlated to the likelihood of recurrence (p = .05)., Conclusion: This study is the first prospective long-term evaluation demonstrating that FDG PET is not only an early predictor of pathologic response but is also a valuable prognostic tool. Our results indicate the potential of FDG PET for optimizing multidisciplinary management of patients with LARC.