Clinical and radiological presentation of parasellar ectopic pituitary adenomas: case series and systematic review of the literature.

PURPOSE: Parasellar ectopic pituitary adenomas (pEPAs) are extremely rare tumors located out of the sella turcica. PEPAs are heterogeneous entities in terms of anatomical localization and secretion of anterior pituitary hormones. METHODS: Multicenter retrospective study. Clinical charts' consultation of patients diagnosed with parasellar lesions, to identify all subjects fulfilling the diagnostic criteria of parasellar EPAs. Systematic review of the literature focused on the medical management of prolactin-secreting pEPAs and on the prevalence of radiological bone invasion in pEPAs. RESULTS: We identified four cases of pEPAs: (1) 54-year-old female with a prolactin-secreting suprasellar EPA successfully treated with cabergoline; (2) 74-year-old male with a non-functioning EPA of the sphenoidal sinus treated with endoscopic transsphenoidal surgery; (3) 75-year-old female with a giant lesion of the skull base (maximum diameter 7.2 cm) diagnosed as a non-functioning EPA after biopsy; (4) 49-year-old male with a silent corticotroph EPA of the sphenoidal sinus and clivus. Three out of four cases had radiological evidence of invasion of the surrounding bone structures. A systematic review of the literature highlighted that medical therapy can be effective in prolactin-secreting pEPAs. Overall, we found mention of local invasiveness in 65/147 cases (44.2%), confirmed by radiological signs of bone invasion/erosion. CONCLUSION: Our experience confirms the heterogeneity of pEPAs in terms of clinical and radiological presentation, as well as hormone secretion. PEPAs show a high frequency of radiological bone invasion, though similar to that of sellar pituitary adenomas. Although extremely rare, pEPAs need to be considered in the differential diagnosis of parasellar lesions.

Insomnia and menopause: a narrative review on mechanisms and treatments.

The menopausal transition is associated with an increased frequency of sleep disturbances. Insomnia represents one of the most reported symptoms by menopausal women. According to its pathogenetic model (3-P Model), different predisposing factors (i.e. a persistent condition of past insomnia and aging per se) increase the risk of insomnia during menopause. Moreover, multiple precipitating and perpetuating factors should favor its occurrence across menopause, including hormonal changes, menopausal transition stage symptoms (i.e. hot flashes, night sweats), mood disorders, poor health and pain, other sleep disorders and circadian modifications. Thus, insomnia management implies a careful evaluation of the psychological and somatic symptoms of the individual menopausal woman by a multidisciplinary team. Therapeutic strategies encompass different drugs but also behavioral interventions. Indeed, cognitive behavioral therapy represents the first-line treatment of insomnia in the general population, regardless of the presence of mood disorders and/or vasomotor symptoms (VMS). Different antidepressants seem to improve sleep disturbances. However, when VMS are present, menopausal hormone therapy should be considered in the treatment of related insomnia taking into account the risk-benefit profile. Finally, given its good tolerability, safety, and efficacy on multiple sleep and daytime parameters, prolonged-released melatonin should represent a first-line drug in women aged ≥ 55 years.

Functional Clustering approach for the analysis of Stereo-EEG activity patterns in correspondence of epileptic seizures.

In this study, a functional clustering approach is proposed and tested for the identification of brain functional networks emerging during sleep-related seizures. Stereo-EEG signals recorded in patients with Type II Focal Cortical Dysplasia (FCD type II), were analyzed. This novel approach is able to identify the network configuration changes in pre-ictal and early ictal periods, by grouping Stereo-EEG signals on the basis of the Cluster Index, after wavelet multiscale decomposition. Results showed that the proposed method is able to detect clusters of interacting leads, mainly overlapped on the Epileptogenic Zone (EZ) identified by a clinical expert, with distinctive configurations related to analyzed frequency ranges. This suggested the presence of coupling activities between the elements of the epileptic system at different frequency scales.

Nonvitamin K-dependent oral anticoagulants (NOACs) in chronic kidney disease patients with atrial fibrillation.

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance <25ml/min who were excluded from all pivotal phase 3 NOACs trials. This review focuses on the current pharmacokinetic, observational, and prospective data on NOACs in patients with moderate to advanced chronic kidney disease (creatinine clearance 15-49ml/min) and those on dialysis.

Suppression of interictal spikes during phasic rapid eye movement sleep: a quantitative stereo-electroencephalography study.

Tonic and phasic rapid eye movement (REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non-REM (NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra-temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity.

Visualisation of dual radiolabelled poly(lactide-co-glycolide) nanoparticle degradation in vivo using energy-discriminant SPECT.

The determination of nanoparticle (NP) stability and degradation in vivo is essential for the accurate evaluation of NP biodistribution in medical applications and for understanding their toxicological effects. Such determination is particularly challenging because NPs are extremely difficult to detect and quantify once distributed in a biological system. Radiolabelling with positron or gamma emitters and subsequent imaging studies using positron emission tomography (PET) or single-photon emission computerised tomography (SPECT) are some of the few valid alternatives. However, NPs that degrade or radionuclides that detach or are released from the NPs can cause artefact. Here, submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) were dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. To label the core, 111In-doped iron oxide NPs were encapsulated inside PLGA-NPs during NP preparation, and the BSA coating was labelled by electrophilic substitution using 125I. After intravenous administration into rats, energy-discriminant SPECT resolved each radioisotope independently. Imaging revealed different fates for the core and coating, with a fraction of the two radionuclides co-localising in the liver and lungs for long periods of time after administration, suggesting that NPs are stable in these organs. Organ harvesting followed by gamma counting corroborated the SPECT results. The general methodology reported here represents an excellent alternative for visualising the degradation process of multi-labelled NPs in vivo and can be extended to a wide range of engineered NPs.

Inflammation and iron metabolism in adult patients with epilepsy: does a link exist?

PURPOSE: Inflammation has been shown to play a key role in epilepsy, and may also affect both the iron status and metabolism. Consequently, a relationship between iron metabolism and neuronal excitability and seizures could be expected. METHODS: We aimed at characterizing in 37 adult patients affected by focal epilepsy during the interictal period serum inflammatory cytokines, such as interleukin 6 (IL-6), IL-6 soluble receptor (IL6-sR), interleukin 1 (IL-1), IL-1 receptor-antagonist (IL-1RA), tumor necrosis factor-α (TNF-α), and markers of iron status and metabolism: hemoglobin concentration (Hgb), mean corpuscular volume (MCV), hematocrit (Hct) red blood cell (RBC) count, serum iron and copper concentrations, ceruloplasmin (iCp), the ceruloplasmin enzymatic activity (eCp), the specific ceruloplasmin activity (eCp/iCp), total ferroxidase activity, transferrin (Tf), serum ferritin (SF), Tf saturation (Sat-Tf), and ratio of ceruloplasmin to transferrin (Cp/Tf). We investigated the correlations between these biological markers as well their relationship with patients' clinical features. A group of 43 healthy subjects had the same serologic measurements to serve as controls. RESULTS: Our findings showed in the group of patients with epilepsy an increase of IL-6 (p=0.026) and a decrease of TNF-α (p=0.002) with respect to healthy subjects. For the first time, we also detected significant changes in iron metabolism as an increase of Cp/Tf (p=0.011) and a decrease of Tf (p=0.031), possibly driven by cytokine modifications and consistent with inflammation as acute phase and antioxidant activity markers. Accordingly, TNF-α positively correlated with Tf (p=0.005). Finally, a significant positive correlation between seizures frequency and eCp (p=0.046) and inversely with Hgb (p=0.038) and Hct (p=0.041), and an inverse correlation between TNF-α and the duration of epilepsy (p=0.021) was detected. CONCLUSIONS: Our findings demonstrate a relevant relationship between epilepsy and systemic inflammation, with a consistent link between seizures, inflammatory cytokines (IL-6 and TNF-α) and iron regulation and metabolism, as acute phase and antioxidant markers.

Coll2-1, Coll2-1NO2 and myeloperoxidase serum levels in erosive and non-erosive osteoarthritis of the hands.

OBJECTIVE: Erosive osteoarthritis of the hand (EHOA) is thought to be an aggressive variant of hand osteoarthritis (HOA) characterised by prominent local inflammation and radiographic aspects of bone erosions in interphalangeal (IP) joints. However, rare studies have until now investigated the value of biomarkers in these patients. Thus, we determined Coll2-1, a marker of type II collagen denaturation, its nitrated form (Coll2-1NO2) and myeloperoxidase (MPO) levels in serum of patients with EHOA vs non-EHOA and subsequently evaluated their relationships with disease indices of severity and activity. METHODS: Coll2-1, Coll2-1NO2 and MPO were measured using specific immunoassays in 82 patients, 57 with EHOA, all females, median age 59 (41-74 yrs) and 20 with non-EHOA, all females, median age 55 (43-73 yrs), fulfilling the American College of Rheumatology (ACR) criteria for hand OA. EHOA was characterized by the presence of at least one central bone erosion on radiograph in the IP joints. Patients were also evaluated for disease duration, number of affected (swollen and painful or tender) joints, radiographic score (RS) by Kallman scale and high sensitivity C-reactive protein (hsCRP). RESULTS: Serum levels of MPO were higher in EHOA (230.0 ± 152.1 ng/ml) than in non-EHOA (160.2 ± 111.5 ng/ml, P=0.037). Coll2-1NO2 levels trended towards an elevation in EHOA compared non-EHOA (0.40 ± 0.86 vs 0.22 ± 0.14 nmol/l, P=0.06), while Coll2-1 levels were not different. Correlations were found for disease duration and both MPO (R(2)=0.48, P=0.001) and Coll2-1NO2 (R(2)=0.73, P=0.01) after the splitting of the population in subgroups according to a cut off value above the 50th percentile. A correlation was found between hsCRP and MPO (R(2)=0.57, P=0.01). CONCLUSIONS: This study clearly demonstrates an elevation of some serum biomarkers in EHOA, in comparison with non-EHOA. In particular, MPO, hsCRP and the ratio Coll2-1NO2/Coll2-1 discriminated the two subsets of hand osteoarthritis (HOA), and a trend was also observed for Coll2-1NO2. These data suggest that these biomarkers could be helpful for the diagnosis of EHOA.

[The natural history of ankylosing spondylitis in the 21st century]. / La storia naturale della spondilite anchilosante nel XXI secolo.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects the axial skeleton and evolves in stiffness followed by ankylosis and disability. However, it may be difficult to exactly establish the natural history of the disease and the influence of risk factors of progression, since most patients are treated with various pharmacologic or non-pharmacologic agents, which may potentially influence the natural progression of the disease. In this context, we report here a very interesting case of a 40 year old man, presented to our outpatient clinic, 28 years after the onset of AS. Previously for personal reasons, did not choose not to undergo any treatment. This case allows us to evaluate the natural radiological progression of the disease and the influence of predictive risk factors.

Transverse and normal interfacial stiffness of solids with randomly rough surfaces.

Using a theoretical approach and computer simulations, we calculate the normal stiffness K(perpendicular) and the transverse stiffness K(parallel) of the interface between two contacting isotropic solids with randomly rough surfaces and Poisson ratio ν. The theoretical predictions for K(perpendicular) agree well with the simulations. Moreover, the theoretical result for the ratio K(perpendicular)/K(parallel) is (2 - ν)/(2 - 2ν), as predicted by Mindlin for a single circular contact region. Finally, we compare the theory to experimental ultrasonic data.

Immunogenetic aspects of erosive osteoarthritis of the hand in patients from northern Italy.

OBJECTIVES: To compare the distribution of human leucocyte antigen (HLA) class I and II alleles in patients with erosive hand osteoarthritis (EHOA) to that of patients with non-erosive hand OA (non-EHOA) and in healthy Italian Bone Marrow Donors (IBMDs), in order to evaluate possible immunogenetic associations with EHOA. In the EHOA group we also sought possible associations between HLA alleles and disease severity. METHODS: Ninety-four patients with EHOA (82 women, 12 men; mean age 61.4 ± 8.45 years) and 37 with non-EHOA (28 women, nine men; mean age 59.21 ± 9.07 years) were studied. Disease severity was measured by the number of clinically active joints (NCAJ) and by the radiographic score (RS) using the Kallman scale. HLA typing was undertaken for A, B, C, and DRB1 loci; HLA-DRB1* genotyping was determined using polymerase chain reaction (PCR) with sequence-specific primers. Frequencies were compared with those of the healthy IBMDs. RESULTS: The alleles found more frequently in EHOA patients than in non-EHOA patients and healthy controls were: A23, A26, and A29; B38, B44, and HLA DRB1*01 and *07. The RS was more severe in the EHOA compared to the non-EHOA group (63.60 ± 23.14 vs. 34.34 ± 20.24, p < 0.001). Within the EHOA group, HLA-DRB1*07 was associated with a higher RS (67.36 ± 23 vs. 64.5 ± 18.5, p = 0.029). CONCLUSION: In this study of North Italian patients affected with EHOA, the HLA-DRB1*07 allele was found to be associated with both the development and greater severity of the disease.

The tailored medical therapy in patients with advanced heart failure referred for cardiac transplantation.

INTRODUCTION: Optimal pharmacologic management of heart transplant (HT) candidates is required prior to evaluation so as to obtain a reliable prognostic stratification and to address the donor shortage. The aim of this study was to determine whether a tailored medical approach was effectively achieved before HT waiting list enrollment. MATERIALS AND METHODS: This study concerned 40 consecutive patients referred for HT evaluation who underwent a clinical assessment, including hemodynamic, echocardiographic, and brain natriuretic peptide determinations. Medical therapy was optimized according to the clinical assessment to improve neurohormonal and hemodynamic profiles. We analyzed the distribution of the different drugs between the first and the following evaluation to demonstrate whether a significant improvement of medical therapy could be achieved in advanced chronic heart failure (ACHF). RESULTS: The mean age was 53 years, including 93% males. The etiology of disease was ischemic in 40% and idiopathic in 45%. The mean left ventricular ejection fraction was 23%, mean values of hemodynamic data were cardiac index (CI) 2+/-0.6 L/min/m(2), mean pulmonary arterial pressure (mPAP) 30+/-10 mm Hg, wedge pressure (PWP) 23+/-8 mm Hg; mean BNP was 618 pg/mL. Median follow-up was 397 days; 82% of candidates underwent HT waiting-list enrollment. The medical treatment was modified as follows: beta-blockers were introduced or uptitrated in 32%, angiotensin receptor blockers (ARB) were introduced in 7.5%, spironolactone was started in 42%, nitrates were introduced in 20%, and diuretics were uptitrated in 35% of patients. CONCLUSION: In patients with ACHF referred for HT, a further effort in the assessment of the medical treatment is strongly recommended.

[Sjögren's syndrome: comparison among the main imaging techniques in the study of major salivary glands]. / Sindrome di Sjögren: confronto fra le principali tecniche di imaging per lo studio delle ghiandole salivari maggiori.

Sjögren's syndrome (SS) is a chronic inflammatory disease with an autoimmune etiology, that affects exocrine glands, in particular salivary and lacrimal glands. Among the diagnostic criteria of SS, imaging techniques play an important role. The aim of our study is to compare three imaging techniques, such as sonography, scintigraphy and sialography in the evaluation of major salivary glands. The use of the these techniques is of great importance for the diagnosis of SS. Sonography is the most frequently used for its prompt execution, non invasivity, great acceptance by the patient and low cost. In the diagnostic patient management of SS, sonography results are eventually confirmed by the other imaging techniques, sialography and scintigraphy.

[Intrauterine growth restriction and pregnancy outcome]. / Ritardo di accrescimento intrauterino e outcome della gravidanza.

AIM: This prospective study was performed to evaluate perinatal outcome and maternal risk factors in pregnancies complicated by fetal intrauterine growth restriction (IUGR). METHODS: A total of 3 537 women pregnant with a singleton gestation were enrolled in the study: 219 of these pregnancies were complicated by fetal growth restriction (6.2%). Statistical analysis was performed using Wilcoxon test, Kruskall-Wallis test, c2 analysis of variance and ANOVA test. Statistical significance was set at P-value <0.05. Correlations were calculated by Spearman's coefficient. RESULTS: Ethnic group, physical demanding work, maternal smoking, alcohol abuse do not seem to be associated with lower birth weight and worse Apgar score. Sonographic assessment of fetal weight obtained by Hadlock's formula underestimate real newborn's weight. The difference between estimate weight and real weight is statistically significant. Women with intrauterine growth restriction underwent caesarean sections more often than women with appropriate fetal growth selected as controls (P<0.05). CONCLUSION: In conclusion, the obstetrician must recognize and accurately diagnose inadequate fetal growth and attempt to determine its cause (especially placental factors) in order to reduce fetal and maternal risks and establish the appropriate clinical management, timing and mode of delivery. If the growth-restricted fetus is identified and appropriate management instituted, perinatal mortality can be reduced.

Glioblastomas: correlation between oligodendroglial components, genetic abnormalities, and prognosis.

It has been demonstrated that a small percentage (approximately 15%) of glioblastomas (GBM) presents an oligodendroglial component with a variable frequency of chromosome 1p and 19q deletions, the genetic alteration related to chemotherapy response and longer survival in oligodendrogliomas. There is a growing interest in investigating 1p and 19q losses in hybrid gliomas and their impact on prognosis. A series of 88 GBMs was investigated regarding 1p and/or 19q losses, 24 with oligodendroglioma-like areas, using quantitative microsatellite analysis and/or fluorescent in situ hybridization. When present, the oligodendroglial and astrocytic components were independently investigated. Clinical data, histology, and 1p/19q status were correlated. Tumors with oligodendroglial components showed three cases each of 1p or 19q loss and one with combined 1p/19q loss. No difference in 1p or 19q status was observed between the oligodendroglial and astrocytic components. Conventional GBM demonstrated isolated 1p loss in four cases and 19q loss in five. No association was seen between 1p/19q status and histology. Deletions at 1p and/or 19q were infrequent in GBMs with oligodendroglial components. Despite the hybrid phenotype, the pattern of genetic changes at 1p and 19q was not different from that usually observed in conventional GBMs, nor did it show any correlation with survival.