Subclinical hyperthyroidism: the cardiovascular point of view.

OBJECTIVE: Subclinical hyperthyroidism (SHyper), defined as reduced thyrotropin with free hormones within the reference range, is a common medical finding, in particular in elderly people. In the last years has gained attention due to its health-related conditions, in particular at the cardiovascular level. MATERIALS AND METHODS: We searched electronic database (PubMed) and search engines (Google Scholar) of articles and reviews using the terms "subclinical hyperthyroidism", "Atrial fibrillation", Ischemic stroke", "Hypertension", Heart failure", and "Mortality". RESULTS: Subclinical hyperthyroidism was clearly associated with the onset of atrial fibrillation and, consequently, with ischemic stroke. However, the latter association is less clear. The effect on hypertension is doubtful and fair. Subclinical hyperthyroidism could increase the risk of acute heart failure, possibly by increasing heart rhythm. Data on mortality are scanty but seem to suggest a possible association, probably linked to the detrimental effect on the cardiovascular system. CONCLUSIONS: Current findings mainly described possible associations with rhythm alterations, heart failure, and stroke but the effective beneficial effects of the treatment of subclinical hyperthyroidism are still lacking.

Focal nodular hyperplasia: new findings at Doppler ultrasonography.

OBJECTIVE: The aim of our study was to explore the features of focal nodular hyperplasia (FNH) at Doppler ultrasonography, analyzing specifically the presence of intratumoral venous flow in patients with an established diagnosis of FNH. Previous studies showed that using a venous Doppler spectrum, intratumoral vessels are often depicted in hepatocellular adenoma (HCA) but less frequently in FNH. PATIENTS AND METHODS: Forty-five FNHs from thirty-three consecutive patients (26 female, 7 male; mean±SD age: 40±13) underwent color Doppler ultrasonography and spectral analysis according to a standardized protocol. FNH diagnosis was established by the presence of typical behavior at contrast-enhanced ultrasound (CEUS) associated with another imaging technique (contrast-enhanced computed tomography [ceCT] or contrast-enhanced magnetic resonance [ceMR]). A biopsy was performed when imaging was inconclusive. All data concerning Doppler analysis were reviewed by two more operators, blinded to the final diagnosis, and the interobserver agreement for the presence of venous Doppler signal was determined by Cohen's Kappa. RESULTS: Of the 33 patients, 24 had a single solitary focus, and 9 had multiple foci. Lesion diameter ranged between 1.2 and 8.9 cm (mean ± SD 3.2±1.6 cm). The central feeding artery with the typical arterial spectrum was detected in all 45 lesions, whereas the spoke-wheel sign was observed in 18 cases (40%). A venous Doppler signal was detected in 35 FNHs (77.8%), and in 60% of them, it was identified in the center of the lesion. CONCLUSIONS: Venous Doppler signal located in the center of the lesion suspected to be a hypervascular benign lesion cannot be considered a typical HCA feature since it has been detected in a high percentage of FNH cases.

The burden of HIV-associated neurocognitive disorder (HAND) in post-HAART era: a multidisciplinary review of the literature.

OBJECTIVE: The purpose of the present multidisciplinary review is to give an updated insight into the most recent findings regarding the pathophysiology, diagnosis and therapeutics of HIV-associated neurocognitive disorder (HAND). MATERIALS AND METHODS: We performed a comprehensive search, through electronic databases (Pubmed - MEDLINE) and search engines (Google Scholar), of peer-reviewed publications (articles and reviews) and conferences proceedings on HAND pathophysiology, diagnosis, and therapy, from 1999 to 2016. RESULTS: It seems to be increasingly clear that neurodegeneration in HIV-1 affected patients is a multi-faceted disease involving numerous factors, from chronic inflammation to central nervous system (CNS) compartmentalization of HIV. Diagnosis of HAND may benefit from both laboratory analysis and advanced specific neuroimaging techniques. As regards HAND therapy, modified HAART combinations and simplification strategies have been tested, while novel exciting frontiers seem to involve the use of nanoparticles with the ability to cross the Blood-Brain Barrier (BBB). CONCLUSIONS: Albeit highly active antiretroviral therapy (HAART) allowed a major decrease in morbidity and mortality for AIDS patients, CNS involvement still represents a challenge in HIV patients even today, affecting up to 50% of patients with access to combination antiretroviral therapy (cART). Future studies will have to focus on CNS compartmentalization, drugs' ability to penetrate and suppress viral replication in this compartment, and on new approaches to reduce HIV-associated neuroinflammation.

Jagged 1 is a major Notch ligand along cholangiocarcinoma development in mice and humans.

Intrahepatic cholangiocarcinoma (ICC) is a rare yet deadly malignancy with limited treatment options. Activation of the Notch signalling cascade has been implicated in cholangiocarcinogenesis. However, while several studies focused on the Notch receptors required for ICC development, little is known about the upstream inducers responsible for their activation. Here, we show that the Jagged 1 (Jag1) ligand is almost ubiquitously upregulated in human ICC samples when compared with corresponding non-tumorous counterparts. Furthermore, we found that while overexpression of Jag1 alone does not lead to liver tumour development, overexpression of Jag1 synergizes with activated AKT signalling to promote liver carcinogenesis in AKT/Jag1 mice. Histologically, tumours consisted exclusively of ICC, with hepatocellular tumours not occurring in AKT/Jag1 mice. Furthermore, tumours from AKT/Jag1 mice exhibited extensive desmoplastic reaction, an important feature of human ICC. At the molecular level, we found that both AKT/mTOR and Notch cascades are activated in AKT/Jag1 ICC tissues, and that the Notch signalling is necessary for ICC development in AKT/Jag1 mice. In human ICC cell lines, silencing of Jag1 via specific small interfering RNA reduces proliferation and increases apoptosis. Finally, combined inhibition of AKT and Notch pathways is highly detrimental for the in vitro growth of ICC cell lines. In summary, our study demonstrates that Jag1 is an important upstream inducer of the Notch signalling in human and mouse ICC. Targeting Jag1 might represent a novel therapeutic strategy for the treatment of this deadly disease.

Diagnostic features of real-time contrast-enhanced ultrasound in focal nodular hyperplasia of the liver.

PURPOSE: The typical appearance of focal nodular hyperplasia (FNH) in radiological contrast techniques (helical CT or MRI) includes homogeneous enhancement in the arterial phase, but the exact timing for the best visualization of this pattern is unknown. The aim of the present study was to assess the ultrasound pattern of FNH with special attention to real-time contrast-enhanced ultrasonography (CEUS) appearance and specifically to the timing of perfusion patterns. MATERIALS AND METHODS: 72 patients (60 females, 12 males) with a total of 90 FNH nodules with a diameter ranging from 8 to 100 mm (mean +/- SD, 40.6 +/- 21.5 mm) were examined continuously for at least 4 minutes using CnTI and CPS methods (ESAOTE, Genoa, Italy and Acuson-Siemens) after bolus injection of SonoVue (BRACCO, Milan, Italy). RESULTS: 87 of 90 nodules showed the typical coin-like hyperechogenicity in the arterial phase. The remaining three nodules were all in the same patient and were diagnosed as FNH after resection. Contrast started to appear within the lesions after a mean of 15.7 +/- 4.6 seconds (range 7 - 27 s) and reached peak signal intensity, with the greatest differentiation between the lesion and the surrounding parenchyma, at around 22.6 +/- 7.0 seconds (range 14 - 72 s). In the late phase, 65 lesions (72.2 %) became isoechoic (after a mean of 80.8 +/- 85.7 s, range 20 - 300 s), 22 (24.4 %) slightly hyperechoic and 3 (3.3 %) faintly hypoechoic. CONCLUSION: FNH shows a typical homogeneous hyperechoic pattern during the arterial phase in real-time CEUS which disappears slowly on average but occasionally even as soon as 20 seconds after contrast injection. If the first scans are taken later than 20 seconds after injection (which is still considered to be a full arterial phase), the ultrasound hyperechogenicity may be missed in some cases. Real-time study of these lesions is therefore strongly recommended to avoid possible false-negative results.

Diagnosis and management of hepatic focal nodular hyperplasia.

Focal nodular hyperplasia (FNH) is the second most common benign tumor of the liver, after hemangioma. It is generally found incidentally and is most common in reproductive-aged women, but it also affects males and can be diagnosed at any age. Patients are rarely symptomatic, but FNH sometimes causes epigastric or right upper quadrant pain. The main clinical task is to differentiate it from other hypervascular hepatic lesions such as hepatic adenoma, hepatocellular carcinoma, or hypervascular metastases, but invasive diagnostic procedures can generally be avoided with the appropriate use of imaging techniques. Magnetic resonance (MR) imaging is more sensitive and specific than conventional ultrasonography (US) or computed tomography (CT), but Doppler US and contrast-enhanced US (CEUS) can greatly improve the accuracy in the diagnosis of FNH. Once a correct diagnosis has been made, in most cases there is no indication for surgery, and treatment includes conservative clinical follow-up in asymptomatic patients.

Fitz-Hugh-Curtis-syndrome mimicking acute cholecystitis: value of new ultrasound findings in the differential diagnosis.

Fitz-Hugh-Curtis is a rare syndrome characterised by perihepatitis following pelvic inflammatory disease. We report the case of a patient with a right ovarian teratoma, abnormal liver tests and pain in the right abdomen and shoulder, initially attributed to an acalculous cholecystitis. Before gynaecological surgery, a repeat ultrasound scan found several small avascular peritoneal masses at the upper dome of the liver, not reported in the initial examination. This prompted laparoscopic exploration of the subdiaphragmatic space, and the final diagnosis of Fitz-Hugh-Curtis-syndrome was made. Such ultrasound finding appears to be a new diagnostic feature of this syndrome.

The role of pneumatic compression in the treatment of postmastectomy lymphedema. A randomized phase III study.

BACKGROUND: Pneumatic compression is a frequently prescribed physical therapy for patients affected by postmastectomy lymphedema but, despite its wide use, its efficacy has not been demonstrated in phase III studies. We performed a randomized study comparing pneumatic compression versus no treatment in patients with postmastectomy lymphedema. PATIENTS AND METHODS: Patients with monolateral postmastectomy lymphedema were randomized to receive two cycles of intermittent pneumatic compression (PC group), i.e., five two-hour sessions per week for two weeks, to be repeated after a five-week interval, or to no treatment (control group). The patients in both groups were instructed as to the prophylactic hygienic care of the limb. Lymphedema was assessed by the sum of differences in circumference measurements between affected and normal limbs ('delta'). Response was defined as a > or = 25% reduction in delta value. RESULTS: Eighty patients entered the study. No statistically significant differences in response rates between the two groups were observed: 20% in the control group (95% CI: 9%-36%), 25% in the PC group (95% CI: 13%-41%, P = 0.59). The absolute mean decrease in delta value was 1.9 +/- 3.7 cm in the PC group and 0.5 +/- 3.3 cm in the control group. CONCLUSIONS: We demonstrated that intermittent pneumatic compression has a limited clinical role in the treatment of postmastectomy lymphedema. Efforts to prevent this complication should be undertaken.

Control of refractory, chemotherapy-induced emesis with the serotonin antagonist ondansetron (GR38032F).

Twenty-four patients with severe post-chemotherapy emesis (greater than 15 emetic episodes) refractory to prior combination antiemetic therapy were treated with a selective 5-HT3 receptor antagonist ondansetron (GR38032F). Ondansetron was given as 8 mg three times daily orally for 5 days with the first dose given 1 h prior to chemotherapy. Control of emesis was evaluated over the 5-day period. All chemotherapy was administered on an outpatient basis. Worst day analysis of antiemetic response was 87.5%: complete protection in 9/24 patients (37.5%) and major protection (1-2 emetic episodes) in 12/24 patients (50%). No protection from emesis was observed in 3 patients (12.5%). No side effects and no alterations in liver function tests were observed. Ondansetron is a safe and highly effective antiemetic agent.