El papel de la resonancia magnética multiparamétrica en el diagnóstico de la recidiva local tras la prostatectomía radical y antes de la radioterapia de rescate / The role of multiparametric magnetic resonance imaging in the diagnosis of local recurrence after radical prostatectomy and before salvage radiotherapy

Objetivo Evaluar la precisión diagnóstica de la resonancia magnética multiparamétrica (RMmp) en la detección de la recidiva local del cáncer de próstata (CaP) después de la prostatectomía radical (PR) y antes de la radioterapia (RT). Materiales y métodos Un total de 188 pacientes se sometieron a una RMmp de 1,5T después de la PR y antes de la RT. Los pacientes se dividieron en 2 grupos: con recidiva bioquímica (grupo A) y sin recidiva bioquímica, pero con alto riesgo de recidiva local (grupo B). Las variables continuas se compararon entre los 2 grupos mediante la prueba t de Student; las variables categóricas se analizaron mediante chi-cuadrado de Pearson. El análisis ROC se realizó considerando como variables de agrupación el PSA antes de la RT, el grado ISUP, el pT y el pN. Resultados La recidiva del CaP (reducción de los niveles de PSA después de la RT) fue del 89,8% en el grupo A y del 80,3% en el grupo B. Al comparar los pacientes con y sin recidiva del CaP, hubo una diferencia significativa en los valores de PSA antes de la RT para el grupo A, y en los valores de PSA antes y después de la RT para el grupo B. En el grupo A hubo una correlación significativa entre el PSA antes de la RT y el diámetro de la recidiva, y entre el PSA antes de la RT y el tiempo transcurrido hasta la recidiva. La precisión diagnóstica de la RMmp en la detección de la recidiva local del CaP tras la RT es del 62,2% en el grupo A y del 38% en el grupo B. La imagen potenciada en difusión es la secuencia de RM más específica y la perfusión dinámica con contraste la más sensible. Para el PSA=0,5ng/ml, el AUC disminuye, mientras que la sensibilidad y la precisión aumentan para cada secuencia de RM. Para el PSA=0,9ng/ml, el AUC de la perfusión dinámica con contraste aumenta significativamente (AU)

Purpose Assess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of prostate cancer (PCa) after radical prostatectomy (PR) and before radiation therapy (RT). Materials and methods A total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into 2 groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between 2 groups using Student-t test; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. Results PCa recurrence (reduction of PSA levels after RT) was 89.8% in group A and 80.3% in group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. Diffusion weighted imaging is the most specific MRI-sequence and dynamic contrast enhanced the most sensitive. For PSA=0.5ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA=0.9ng/ml, dynamic contrast enhanced-AUC increases significantly. Conclusion mp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of diffusion weighted imaging for PSA≤0.5ng/ml (AU)

The role of multiparametric mri in the diagnosis of local recurrence after radical prostatectomy and before salvage radiotherapy.

PURPOSE: Assess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of Prostate Cancer (PCa) after Radical Prostatectomy (PR) and before Radiation Therapy (RT). MATERIALS AND METHODS: A total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into two groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between two groups using T-Student; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. RESULTS: PCa recurrence (reduction of PSA levels after RT) was 89.8% in the group A and 80.3% in the group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. DWI is the most specific MRI-sequence and DCE the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, DCE-AUC increases significantly. CONCLUSION: mp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of DWI for PSA ≤ 0.5 ng/ml.

Development of a solute and defect concentration dependant Ising model for the study of transmutation induced segregation in neutron irradiated W-(Re, Os) systems.

In this study, radiation-induced precipitation of transmutation products is addressed via the development of a new solute and vacancy concentration dependant Ising model for the W-Re-Os system. This new model includes interactions between both Os and Re atoms with vacancies, thus facilitating more representative simulations of transmutation in fusion reactor components. Local solute concentration dependencies are introduced for the W-Re, W-Os and Re-Os pair interactions. The model correctly accounts for the repulsion between small clusters of vacancies and the attraction between larger clusters/voids, via the introduction of local vacancy concentration dependant interaction coefficients between pairs of atoms and vacancies. To parameterise the pair interactions between atoms and/or vacancies, the enthalpy of mixing, ΔHmix, for various configurations and solute/defect concentrations, was calculated using density functional theory, within 6 binary systems: W-Re, W-Os, Re-Os, W-vacancy, Re-vacancy and Os-vacancy. The new energy model was implemented into the SPPARKS Monte Carlo code, and successfully used to predict the formation of voids decorated with Re and Os solute atoms. Analysis suggests that there is a strong thermodynamic tendency for Os to bind to these voids with a comparatively weaker binding from Re atoms. The binding energies of various solute/vacancy clusters were calculated and showed that Re and Os solute atoms tend to stabilise small clusters of vacancies, increasing the attractive binding energy between the constituents.

Recurrent Cesarean scar pregnancy: case series and literature review.

OBJECTIVES: To determine the rate of recurrent Cesarean scar pregnancy (CSP) in our clinical practices and to evaluate whether the mode of treatment of a CSP is associated with the risk of recurrent CSP, as well as to review the published literature on recurrent CSP. METHODS: We performed a retrospective search of our six obstetric and gynecological departmental ultrasound databases for all CSPs and recurrent CSPs between 2010 and 2019. We extracted various data, including number of CSPs with follow-up, number of cases attempting and number achieving pregnancy following treatment of CSP and number of recurrent CSPs, as well as details of the treatment of the original CSP. After analyzing the clinical data, we evaluated whether the mode of treatment terminating the previous CSP was associated with the risk of recurrent CSP. We also performed a PubMed search for: 'recurrent Cesarean scar pregnancy' and 'recurrent Cesarean scar ectopic pregnancy'. Articles were reviewed for year of publication, and extraction and analysis of the same data as those obtained from our departmental databases were performed. RESULTS: Our database search identified 252 cases of CSP. The overall rate of clinical follow-up ranged between 71.4% and 100%, according to treatment site (mean, 90.9%). Among these, 105 women had another pregnancy after treatment of the previous CSP. Of these, 36 (34.3%) pregnancies were recurrent CSP, with 27 women having a single recurrence and three women having multiple recurrences, one with two, one with three and one with four. We did not find any particular single or combination treatment mode terminating the previous CSP to be associated with recurrent CSP. The literature search identified 17 articles that yielded sufficient information for us to evaluate their reported prevalence of recurrent CSP. These reported 1743 primary diagnoses of CSP, of which 944 had reliable follow-up. Data were available for 489 cases that attempted to conceive again after treatment of a previous CSP, and on the 327 pregnancies achieved. Of these, 67 (20.5%) were recurrent CSP. CONCLUSIONS: On the basis of our pooled clinical data and review of the literature, recurrent CSP is apparently more common than was previously assumed based upon mostly single-case reports or series with few cases. This should be borne in mind when counseling patients undergoing treatment for CSP regarding their risk of recurrence. We found no obvious causal relationship or association between the type of treatment of the previous CSP and recurrence of CSP. Patients who become pregnant after treatment of a CSP should be encouraged to have an early (5-7-week) first-trimester transvaginal scan to determine the location of the gestation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Correction to: A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches.

Following publication of the original article [1], we have been notified that the name of author five was spelled incorrectly as M. Ferrili, when the correct spelling is MAN Ferilli.

Are paediatric headaches in the emergency department increasing? An Italian experience.

The aim of this study was to assess admissions, for headache, to the emergency department (ED) of the Di Cristina Children's Hospital in Palermo over a decade. The total number of ED admissions for headache was retrospectively analysed considering two 24- month periods: 2009-2010 and 2017-2018. Total admissions to the ED decreased from 55,613 to 50,096 (-10%) between the two periods considered, while the number of admissions for headache increased by 63.56% (p < 0.0001). There was also a significant increase in the number of multiple ED admissions by single children (9.5% versus 17.98% of the patients accessing the ED for headache). This significant increase in admissions for paediatric headache is probably due to limited efficacy of the Italian and international guidelines and of the educational strategies implemented in this setting, and also to communication difficulties, both with patients and between primary care networks and hospitals.

A PRISMA-compliant systematic review of the endpoints employed to evaluate symptomatic treatments for primary headaches.

BACKGROUND: Primary headache are prevalent and debilitating disorders. Acute pain cessation is one of the key points in their treatment. Many drugs have been studied but the design of the trials is not usually homogeneous. Efficacy of the trial is determined depending on the selected primary endpoint and usually other different outcomes are measured. We aim to critically appraise which were the employed outcomes through a systematic review. METHODS: We conducted a systematic review of literature focusing on studies on primary headache evaluating acute relief of pain, following the PRISMA guideline. The study population included patients participating in a controlled study about symptomatic treatment. The comparator could be placebo or the standard of care. The collected information was the primary outcome of the study and all secondary outcomes. We evaluated the studied drug, the year of publication and the type of journal. We performed a search and we screened all the potential papers and reviewed them considering inclusion/exclusion criteria. RESULTS: The search showed 4288 clinical trials that were screened and 794 full articles were assessed for eligibility for a final inclusion of 495 papers. The studies were published in headache specific journals (58%), general journals (21.6%) and neuroscience journals (20.4%). Migraine was the most studied headache, in 87.8% studies, followed by tension type headache in 4.7%. Regarding the most evaluated drug, triptans represented 68.6% of all studies, followed by non-steroidal anti-inflammatories (25.1%). Only 4.6% of the papers evaluated ergots and 1.6% analyzed opioids. The most frequent primary endpoint was the relief of the headache at a determinate moment, in 54.1%. Primary endpoint was evaluated at 2-h in 69.9% of the studies. Concerning other endpoints, tolerance was the most frequently addressed (83%), followed by headache relief (71.1%), improvement of other symptoms (62.5%) and presence of relapse (54%). The number of secondary endpoints increased from 4.2 (SD = 2.0) before 1991 to 6.39 after 2013 (p = 0.001). CONCLUSION: Headache relief has been the most employed primary endpoint but headache disappearance starts to be firmly considered. The number of secondary endpoints increases over time and other outcomes such as disability, quality of life and patients' preference are receiving attention.

Local arterial nanoparticle delivery of siRNA for NOX2 knockdown to prevent restenosis in an atherosclerotic rat model.

Both atherosclerosis and arterial interventions induce oxidative stress mediated in part by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases that have a pivotal role in the development of neointimal hyperplasia and restenosis. For small interfering RNA (siRNA) targeting of the NOX2 (Cybb) component of the NADPH oxidase to prevent restenosis, gene transfer with viral vectors is effective, but raises safety issues in humans. We developed a new approach using the amino-acid-based nanoparticle HB-OLD7 for local delivery of siRNA targeting NOX2 to the arterial wall. siRNA-nanoparticle complexes were transferred into the regional carotid artery walls after angioplasty in an atherosclerotic rat model. Compared with angioplasty controls, Cybb gene expression (measured by quantitative reverse transcriptase-PCR) in the experimental arterial wall 2 weeks after siRNA was reduced by >87%. The neointima-to-media-area ratio was decreased by >83%, and the lumen-to-whole-artery area ratio was increased by >89%. Vital organs showed no abnormalities and splenic Cybb gene expression showed no detectable change. Thus, local arterial wall gene transfer with HB-OLD7 nanoparticles provides an effective, nonviral system for efficient and safe local gene transfer in a clinically applicable approach to knock down an NADPH oxidase gene. Local arterial knockdown of the Cybb gene significantly inhibited neointimal hyperplasia and preserved the vessel lumen without systemic toxicity.

Ribavirin up-regulates IL-12 p40 gene expression and restores IL-12 levels in Leishmania-treated PBMCs.

Ribavirin, a nucleoside analogue that interferes with viral mRNA synthesis and inhibits the replication of RNA and DNA viruses, has been recently proposed as an effective immune response modulator. In the present report, we studied the effect of ribavirin on IL-12 p40 gene expression in peripheral blood mononuclear cells (PBMCs) of healthy subjects. We also studied ribavirin effects on PBMCs activated with lipopolysaccharide (LPS) and phytohaemagglutinin (PHA) and treated with Leishmania donovani antigens. We provide evidence that ribavirin was able to up-regulate IL-12 p40 gene expression and to restore levels of IL-12 p40 gene expression and IL-12 secretion in fully activated PBMCs that were strongly inhibited by L. donovani antigens. Because effective management of leishmanial disease is usually associated with a prevalent T-helper 1 immune response with elevated production of IL-12,our preliminary results may be of particular interest, provided that they will be confirmed by further in vitro and in vivo studies, when considering a possible use of ribavirin as adjuvant in severe leishmanial disease.

Optimization of adenovirus-mediated endothelial nitric oxide synthase delivery in rat hindlimb ischemia.

Adenovirus-mediated overexpression of endothelial nitric oxide synthase (eNOS) induces collateral artery development and substantially increases blood flow after induction of experimental acute hindlimb ischemia. However, the optimal technique of gene delivery for this or any other form of gene therapy in limb ischemia is still unknown. The purpose of this study was to determine the effect of the two most commonly used techniques, intra-arterial and intramuscular injection, on blood flow recovery, collateral artery development, and preservation of muscle mass. We compared intra-arterial injection under vascular isolation, intra-arterial injection under transient vascular occlusion, and intramuscular injection of phosphate buffered saline (PBS) or adenovirus encoding either the eNOS (AdeNOS) or LacZ (AdlacZ) gene after induction of acute hindlimb ischemia. Delivery of AdeNOS by both intra-arterial injection techniques increased eNOS activity (22.30 versus 10.56, P<0.01), blood flow (0.90+/-0.02 versus 0.69+/-0.07, P<0.001) and collateral artery development (17.56484 versus 13.74259, P<0.05) more than by intramuscular delivery. Intra-arterial injection under transient vascular occlusion led to better preservation of muscle mass, muscle architecture, and clinical ischemic index, but led to greater transgene expression in distant organs and contralateral limb muscles. Intra-arterial injection of AdeNOS under transient vascular occlusion is the optimal technique to reverse severe hindlimb ischemia in the rat. This is the first systematic comparison of different delivery techniques used in gene therapy of experimental hindlimb ischemia.

Applying Telemedicine to Remote and Rural Underserved Regions in Brazil using eMedical Consulting Tool.

In this paper, we are going to depict a medical tele-consultation network for medical imaging that has been deployed in Brazil. Preliminary outcomes of the medical network will be presented. In addition, the medical application used for tele-consultations will be shown. Eighty nine ultrasound acquisitions took place in the period of five months of the operation of the medical network and five hundred fifty six medical consultations performed.

The incidence of iliac aneurysms in patients with abdominal aortic aneurysms: comparison of four centers in Europe and the USA.

BACKGROUND: The purpose of this study was to compare the anatomy of the aortoiliac vessels in patients scheduled for infrarenal abdominal aortic aneurysm (AAA) repair in four different countries. MATERIAL AND METHODS: Consecutives series of 100 preoperative CT-scans were evaluated at each center. Diameters of the suprarenal aorta, maximal diameter of the aneurysm, right and left common and external iliac artery as well as the hypogastric arteries were recorded and compared between each center. RESULTS: Configuration of the AAA above bifurcation was similar at each center. The dimensions of the aortic bifurcation and the common iliac arteries were different among the centers. Common iliac arteries with diameters over 25 mm were significantly more common at center 1 (p < 0.001, p = 0.002 and p < 0.001). Among centers 2, 3 and 4 there was no significant difference in common iliac diameters. CONCLUSIONS: Configuration of the iliac arteries in AAA was significantly different for Swiss patients compared to American, Austrian and German patients. Reasons for these differences are unclear, epidemiological or genetic factors may be responsible.

Cardiac changes in subclinical and overt hyperthyroid women: retrospective study.

BACKGROUND: This retrospective and descriptive 4-year study was undertaken to describe cardiac changes in subclinical and overt hyperthyroidism. METHODS: We revised the charts of 386 consecutive cardiopathic women whose blood samples were referred to the Radioimmunoassay Laboratory to evaluate thyroid function from 1 January 1997 through 31 December 2000. RESULTS: After excluding women because euthyroid or hypothyroid, or taking amiodarone and women with hypertension, rheumatic disease, myocardial infarction, a total of 31 hyperthyroid women were thus selected for the study: 19 with subclinical hyperthyroidism and 12 with overt hyperthyroidism. The prevalence of atrial fibrillation did not differ between subclinical (48%) and overt (67%) hyperthyroid women, as well as left atrial dimension; the latter was larger in hyperthyroid (27.8+/-7.8 cm(2)/m(2)) than in control women (18.9+/-2.8 cm(2)/m(2)) (P<0.001). In the subclinical and overt hyperthyroidism, the heart rate (HR) was increased and left ventricular end diastolic (LVED) volume was reduced; in addition, only in overt hyperthyroidism, left ventricular (LV) mass was increased. A significant correlation between LV mass and free triiodothyronine was found. CONCLUSION: HR increase and LVED decrease, both in subclinical and overt hyperthyroidism, indicate a global impairment of diastolic heart performance, complicated in overt hyperthyroidism by LV concentric hypertrophy. So, in our opinion, subclinical hyperthyroidism, far from being considered a simple laboratory finding, in clinical practice should be taken into serious consideration.

C-reactive protein levels and viable Chlamydia pneumoniae in carotid artery atherosclerosis.

BACKGROUND AND PURPOSE: An elevated serum level of C-reactive protein, an inflammatory marker, is an independent predictor of stroke and coronary artery disease. To determine whether chronic infection with Chlamydia pneumoniae, which has been identified in atherosclerotic plaques, is responsible for systemic inflammation, we studied the association between serum C-reactive protein levels and infection of carotid artery atherosclerotic plaque with viable C pneumoniae. METHODS: Serum C-reactive protein levels were obtained before endarterectomy for carotid artery stenosis. Plaques were tested for C pneumoniae mRNA, an indicator of viability, and DNA by polymerase chain reaction of DNA and cDNA, respectively. RESULTS: Forty-eight samples were studied, of which 18 (38%; 95% CI, 23 to 50) were infected with viable C pneumoniae as evidenced by isolated chlamydial mRNA. All 18 of these samples, plus 1 additional sample, were positive for chlamydial DNA. Serum C-reactive protein levels were higher in those with viable C pneumoniae compared with those without infection (median, 8 mg/L versus undetectable; P=0.045 by Wilcoxon rank-sum test). In multivariable models, the only independent predictor of the presence of viable C pneumoniae was a detectable C-reactive protein level (odds ratio, 4.2; 95% CI, 1.1 to 17; P=0.04). CONCLUSIONS: Viable C pneumoniae are present in a substantial portion of carotid artery atherosclerotic plaques and are associated with increased serum C-reactive protein levels. These findings may explain the link between elevated C-reactive protein levels and the risk of cardiovascular disease and stroke but should be reproduced in a larger cohort.

Extended iliac exposure from the groin.

Knowledge of iliac artery and inguinal anatomy enables extraperitoneal exposure of the iliac arteries for surgical treatment of unilateral inflow disease. A method is presented for exposing the distal common iliac artery, the iliac bifurcation, and the full length of the external iliac artery by detachment and retraction of the inguinal ligament though a single extended groin incision. The indications for unilateral iliac artery exposure, revascularization, surgical anatomy, and technique of iliofemoral exposure through a single, extended groin incision are presented. Extended iliac exposure through a single, extraperitoneal exposure facilitates all methods of unilateral iliac revascularization and provides access for delivery of endovascular devices.

Administration of adenoviral vectors induces gangrene in acutely ischemic rat hindlimbs: role of capsid protein-induced inflammation.

PURPOSE: The initial purpose of this study was to determine the effects of intravascular adenoviral vector-mediated gene transfer of endothelial nitric oxide synthase (AdeNOS) on experimental hindlimb ischemia in the rat. Unexpectedly, administration of AdeNOS immediately after induction of acute limb ischemia led to limb gangrene. We subsequently sought to define the molecular mechanisms responsible for this unusual effect and to devise adenoviral gene transfer strategies to prevent the development of gangrene in acutely ischemic limbs. METHODS: Phosphate-buffered saline or adenoviral vectors containing the bovine endothelial nitric oxide synthase gene (AdeNOS) or no transgene (Ad-E1) were injected intra-arterially into the hindlimb of a rat under vascular isolation immediately after surgical induction of severe ischemia. Hematoxylin and eosin staining was performed on muscle sections to evaluate inflammation. A separate group of animals was injected with an adenovirus containing a nontranscribable genome, treated with cyclosporine, or received delayed administration of the adenoviral vector. Gene expression after delayed adenoviral gene transfer was assessed with immunohistochemistry, Western blotting, and nitric oxide synthase (NOS) activity assay. RESULTS: Both AdeNOS and Ad-E1 caused gangrene of the entire hindlimb within 12 days in a dose-dependent manner, at a threshold concentration of 1 x 10(9) plaque-forming unit/mL. Adenoviral delivery was associated with more inflammation and edema compared with phosphate-buffered saline histologically. Inactivation of adenoviral DNA transcription did not affect induction of gangrene. However, gangrene was prevented by concurrent immunosuppression with cyclosporine or delayed administration of the vector. Delayed administration allowed adenoviral gene expression as determined by immunohistochemistry, NOS protein levels, and an assay of NOS enzyme activity. CONCLUSION: Intra-arterial administration of adenoviral vectors, under vascular isolation, immediately after induction of acute ischemia causes inflammation and subsequent limb gangrene. The inflammatory response is unrelated to the expression of the recombinant transgene or the adenoviral genome and is likely due to the adenoviral capsid proteins. However, administration of cyclosporine or delayed injection of the adenoviral vector is a method that can be used for adenoviral mediated gene transfer in limb ischemia.