Launching a multidisciplinary European collaboration towards a cure for HIV: The EU2Cure Consortium.

We felt the urgency to launch the EU2Cure Consortium to support research and find a cure for the human immunodeficiency virus (HIV) infection through intensified collaboration within Europe. This consortium is open to stakeholders on cure in Europe from academia and the community to connect. The aim of this consortium is to intensify the research collaboration amongst European HIV cure groups and the community and facilitate interactions with other academic and community cure consortia, private parties, and policy makers. Our main aim is to create a European research agenda, data sharing, and development of best practice for clinical and translational science to achieve breakthroughs with clinically feasible HIV cure strategies. This consortium should also enable setting up collaborative studies accessible to a broader group of people living with HIV. Besides reservoir studies, we have identified three overlapping scientific interests in the consortium that provide a starting point for further research within a European network: developing "shock and kill" cure strategies, defining HIV cure biomarkers, and connecting cure cohorts. This strategy should aid stakeholders to sustain progress in HIV cure research regardless of coincidental global health or political crises.

Highlights of the 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV-positive persons version 9.0.

BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV-positive persons in geographically diverse areas. GUIDELINE HIGHLIGHTS: Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management. Recommendations on the clinical situations in which tenofovir alafenamide may be considered over tenofovir disoproxil fumarate are provided, and recommendations on which antiretrovirals can be used safely during pregnancy have been revised. Renal and bone toxicity and hepatitis C virus (HCV) treatment have been added as potential reasons for ART switches in fully virologically suppressed individuals, and dolutegravir/rilpivirine has been included as a treatment option. In contrast, dolutegravir monotherapy is not recommended. New recommendations on non-alcoholic fatty liver disease, chronic lung disease, solid organ transplantation, and prescribing in elderly are included, and human papilloma virus (HPV) vaccination recommendations have been expanded. All drug-drug interaction tables have been updated and new tables are included. Treatment options for direct-acting antivirals (DAAs) have been updated and include the latest combinations of sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Recommendations on management of DAA failure and acute HCV infection have been expanded. For treatment of tuberculosis (TB), it is underlined that intermittent treatment is contraindicated, and for resistant TB new data suggest that using a three-drug combination may be as effective as a five-drug regimen, and may reduce treatment duration from 18-24 to 6-10 months. CONCLUSIONS: Version 9.0 of the EACS Guidelines provides a holistic approach to HIV care and is translated into the six most commonly spoken languages.

Successful pharmacogenetics-based optimization of unboosted atazanavir plasma exposure in HIV-positive patients: a randomized, controlled, pilot study (the REYAGEN study).

BACKGROUND: Atazanavir without ritonavir, despite efficacy and tolerability, shows low plasma concentrations that warrant optimization. METHODS: In a randomized, controlled, pilot trial, stable HIV-positive patients on atazanavir/ritonavir (with tenofovir/emtricitabine) were switched to atazanavir. In the standard-dose arm, atazanavir was administered as 400 mg once daily, while according to patients' genetics (PXR, ABCB1 and SLCO1B1), in the pharmacogenetic arm: patients with unfavourable genotypes received 200 mg of atazanavir twice daily. EudraCT number: 2009-014216-35. RESULTS: Eighty patients were enrolled with balanced baseline characteristics. The average atazanavir exposure was 253 ng/mL (150-542) in the pharmacogenetic arm versus 111 ng/mL (64-190) in the standard-dose arm (P < 0.001); 28 patients in the pharmacogenetic arm (75.7%) had atazanavir exposure >150 ng/mL versus 14 patients (38.9%) in the standard-dose arm (P = 0.001). Immunovirological and laboratory parameters had a favourable outcome throughout the study with non-significant differences between study arms. CONCLUSIONS: Atazanavir plasma exposure is higher when the schedule is chosen according to the patient's genetic profile.

Detection of enteroviruses from urban sewage in Parma.

BACKGROUND AND AIM OF THE WORK: The human enteroviruses (EV) are the most common and widespread human viruses in the world. They have bowel as their natural habitat and they can spread in the environment through the faecal excretion. In the continental climate Regions these viruses may cause epidemic outbreaks in summer and fall, while in the tropical Regions the EV infections present a high incidence during all year. The symptoms can be minor or subclinic, but they can be also associated to rare and serious diseases. The aim of this study was to evaluate the environmental circulation of polioviruses and non-polio enteroviruses (NPEV) using standard methods of urban wastewater surveillance recommended by the WHO. METHODS: A total of 188 wastewater samples were collected between February 2005 and December 2008 from two sewage treatment plants in Parma. The sampling was carried out twice a month. Environmental variables were collected for each day of sampling. RESULTS: Out of the 188 examined wastewater samples, 78.7% were positive to the enterovirus research. One out of the 148 positive samples was identified as poliovirus Sabin-like type 3. The remaining 147 positive samples were enteroviruses non polio: Coxsakieviruses and Echoviruses. All Coxsakieviruses isolated were of type B. CONCLUSIONS: The proposed method has shown high sensibility, also in presence of very low expected prevalence of vaccine poliovirus. It allows to verify the kind and relative frequency of enteric viruses circulating in the country, whose characteristics (virulence and pathogenicity) may vary with reference to a different epidemiologic and demographic structure of the resident population.

Familial membranous nephropathy.

Numerous HLA studies suggest that genetic factors play an important role in the development of membranous nephropathy (MN). We studied seven patients with idiopathic MN, from three unrelated families of Italian ancestry. Complement phenotype analysis and restriction fragment length polymorphism (RFLP) typing of HLA class II and of the switch region genes were done in family members. In the first family, the father, one son, and one daughter had MN; another daughter had clinical glomerulonephritis. The three members with MN shared one HLA haplotype carrying DR beta 11; in the two siblings with the disease, the second HLA haplotype carried the DR beta 3.2 allele. In families 2 and 3, two brothers had MN: in family 2, they differed in at least one haplotype; in family 3, they differed in both haplotypes. Only family 3 was informative with regard to the RFLP of the switch region genes: the two siblings were identical for both Ig heavy chain haplotypes. No clinical, laboratory or morphologic features consistent with a secondary form of the disease were found. Familial clustering of MN suggests a genetically transmitted mechanism.

Cholesterol atheromatous embolism: an increasingly recognized cause of acute renal failure.

BACKGROUND: Cholesterol atheromatous embolism is a systemic disease resulting from cholesterol crystal embolization to many organs, including the kidney. Vascular surgery, vascular radiology investigations and anticoagulation have been identified as inciting factors. METHODS: Fifteen patients with extensive atherosclerosis, presenting with simultaneous occurrence of acute renal failure and peripheral ischaemic changes were diagnosed as having acute renal failure due to cholesterol atheromatous embolism. RESULTS: The patients, 12 men and three women, had an average age of 65 years. In one patient, spontaneous occurrence of the disease was observed. An inciting factor was identified in 14 patients: aortography in 10, aortic surgery in two, and thrombolysis in two. Clinical course of acute renal failure was quite variable. Four patients required dialysis; 11 were conservatively managed. All patients had concomitant skin lesions, including digital mottling, cyanosis and gangrene of the toes, and livedo reticularis of the lower limb and abdomen. Eosinophilia was the most common laboratory abnormality. The diagnosis of cholesterol atheromatous embolism was confirmed by tissue examination in eight; in three it was based on the finding of retinal cholesterol emboli; in four patients it was made on clinical grounds. Seven patients died within 36 months. Death was most commonly from cardiac causes. CONCLUSIONS: Since the population at risk for cholesterol embolism is growing and the disease is iatrogenic in origin, we should expect to detect cholesterol embolism with greater frequency as cause of acute renal failure in the future.

Supratentorial cavernous angiomas and epileptic seizures: preoperative course and postoperative outcome.

OBJECTIVE: Patients operated on for supratentorial cavernous angiomas were studied to define the incidence and the course of seizures in their clinical history. Electroclinical and neuroradiological data were correlated with the location of cavernomas. The impact of lesionectomy on the outcome of seizures was evaluated. METHODS: Preoperative clinical data on the history of the seizures, semeiology, incidence, severity, and response to antiepileptic drugs were analyzed. The location of the cavernomas, revealed by magnetic resonance imaging, was correlated with electroencephalographic and clinical data. Postoperative clinical and neuroradiological data were evaluated, with particular consideration to the outcome of the seizures, antiepileptic drug withdrawal, and the completeness of the lesion excision. RESULTS: A higher incidence of severe epilepsy was observed in the patients with mesiotemporal and cortical angiomas. In most of the patients (78.7%), a good concordance between the site of the lesion and the electroclinical data was found. The complete removal of the lesion led to a favorable outcome, with discontinuation of antiepileptic drugs achieved in one-quarter of the patients. CONCLUSION: A high percentage of patients with cortical cavernomas had epileptic seizures. They often presented with chronic intractable epilepsy (44.7% in our series). In cases of good concordance between the electroclinical data and the location of the angioma, complete lesionectomy led to the disappearance of seizures. Removal of the hemosiderin ring did not correlate with better outcome. Preoperative ictal scalp recordings to assess the topographic relationship between the cavernoma and the epileptic seizures could improve outcome, which suggests different surgical strategies (lesionectomy versus enlarged resection) in patients without a clear-cut concordance between the site of the lesion and the ictal semeiology.

Spinal dural arteriovenous fistulas: an underestimated cause of myelopathy.

13 patients with spinal dural arteriovenous fistulas (DAVF) diagnosed in our Institution have been the object of this study. The necessity to include the disease in the differential diagnosis with other pathologies affecting the lower thoracic cord, particularly in middle-aged and old males, is emphasized. Involvement of the spinal cord was always demonstrable on magnetic resonance studies, but pathologic vessels suggesting the possibility of DAVF were seldom recognizable. Myelography still remains an important complementary method. Spinal angiography is essential, taking into account that the fistula can be located far from the spinal cord. The therapy consisting in embolization in 7 cases and embolization associated with surgery in 6 cases led to improvement or stabilization of the disease in all cases. Our cases are discussed in comparison with the literature.

Superficial siderosis of the CNS: MR diagnosis and clinical findings.

PURPOSE: To report the clinical and neuroradiologic findings of superficial siderosis of the CNS, due to chronic subarachnoid bleeding of unknown origin. MATERIALS AND METHODS: We observed seven cases. The main clinical manifestations were progressive deafness and ataxia. Four patients had had previous cranial or cervical trauma, with root avulsion in two, many years before onset of deafness and ataxia. Neuroradiologic studies included MR (0.5 T in four and 1.5 T in three) and angiography of the brain in all cases, CT in six cases, MR of the spine in six, and myelography in four. RESULTS: MR demonstrated a rim of marked hypointensity in T2-weighted images, consistent with hemosiderin deposits, on the surface of cerebellum, brain stem, inferior part of cerebral hemispheres, and spinal cord. CT showed cerebellar atrophy in five cases, and a rim of mild hyperdensity around the brain stem in two. Angiographic studies were negative. Myelography showed cervical nerve root avulsion in two cases and a cervicodorsal extradural cyst in one. Cerebrospinal fluid contained RBCs in all the six examined cases. CONCLUSION: Although CT may occasionally suggest the diagnosis of superficial siderosis, MR demonstrates this abnormality to better advantage.

Superficial siderosis of the central nervous system: neuroradiological evaluation of two cases.

We present 2 cases of superficial siderosis of the central nervous system secondary to chronic subarachnoid bleeding. The diagnosis was made with MR and cerebrospinal fluid (CSF) examination. MR showed, in T2-weighted images, superficial hypointensity of the cervical cord, brainstem, cerebellum, and basal cisterns due to hemosiderin deposits. CSF was xanthochromic, with increased protein content. In 1 of the 2 cases also the CT examination was positive, showing a hyperdense rim around the brainstem. A complete neuroradiological evaluation (MR, CT, angiography and myelography) did not permit to detect the source of the bleeding.

MRI in internal carotid artery dissection.

We report two cases of internal carotid artery dissection in which MRI unequivocally demonstrated the intramural hematoma. We propose that, whenever the clinical presentation or the angiogram suggest arterial dissection, MRI be done to confirm the diagnosis.

Epidural anaesthesia and spinal arachnoiditis.

Six patients were referred to our hospital with spinal arachnoiditis after epidural anaesthesia performed one month to 3 years before the onset of symptoms. None had had previous lumbar surgery or trauma, intraspinal haemorrhage, infections or other known causative factors of arachnoiditis. All the patients were free of neurological symptoms before epidural anaesthesia and only two had transient distress in the period immediately following the procedure. The clinical signs and symptoms of spinal arachnoiditis were severe and in every case the diagnosis was confirmed by myelography. Three patients were confined to a wheelchair after 3 years of follow-up. To our knowledge, the anaesthetic procedures were performed according to standard methods. Arachnoiditis seems to be due to the epidural injection of foreign substances, and may be related to anaesthetic-vasoconstrictor solution or contaminants.

The natural history of repaired myelomeningocele.

With aggressive management based on careful evaluation, children afflicted with myelomeningocele can achieve their maximum potential. Sonography, MR imaging and CT myelography all play important roles in their evaluation.

Age and evolution of language area functions. A study on adult stroke patients.

This study attempted to verify some of the hypotheses advanced to explain the repeatedly reported finding that non-fluent aphasics are younger than fluent aphasics. One hundred and ninety eight vascular patients with cerebral infarcts documented by CT-scan were investigated. Also in this sample fluent patients were older than non-fluent patients. Age was found not to differ according to lesion site (anterior versus posterior). Patients with extensive lesions were, on average, younger than those with more restricted damage. The most interesting finding was that more than half patients with anterior lesion had fluent aphasia and that were remarkably older than anterior patients presenting with the classical non-fluent picture. It is inferred that anterior language areas undergo some kind of progressive functional evolution with age, though not in the sense postulated by Brown and Jaffe.

Relation between CT patterns, clinical findings and etiological factors in children born at term, affected by congenital hemiparesis.

In order to examine if specific findings from CT correlate with specific clinical or neurological findings, 30 children, 5 to 16 years old, born at term, affected by congenital hemiparesis without intellectual impairment, were submitted to neurofunctional and psychological assessment and examined by CT. 28 of the 30 children had pathological CT. Two morphological CT patterns were found: A) Cavity in the cortex and underlying subcortical white matter (11 cases); B) Unilateral ventricular enlargement and paraventricular lesions (17 cases). CT was normal in two cases. In our children, born at term, no statistical correlation between CT patterns and anamnestic data was found as described in other studies, although in the patients with cortical-subcortical lesions, there was a slight prevalence of a history of perinatal complications, and in the patients with paraventricular lesions there was an uneventful history or abnormal pregnancy history. The relation between specific CT patterns (type A and B) and specific clinical dysfunction is not statistically evident, (unless for astereognosis and type A CT pattern). However, the patients with cortical-subcortical lesions showed a slight prevalence of a lower function of the impaired hand, and a higher percentage of an I.Q. of less than 90, than the group with unilateral ventricular enlargement. No relation was found between CT lesional pattern and epilepsy. The absence of correlation between morphological aspects and clinical findings could be explained by the complexity of structural changes and remodelling properties of the central nervous system, following prenatal and perinatal brain damage.

The vascular territories in the cerebellum and brainstem: CT and MR study.

More than 100 CT and 15 MR studies of infarcts in the cerebellum and brainstem were reviewed to define the most typical distribution of infarcts in the different vascular territories. Posterior inferior cerebellar artery and anterior inferior cerebellar artery territories are variable in size and are in a sort of equilibrium with each other. The posterior inferior cerebellar artery territory in transverse sections reveals a characteristic posterior crescent caused by its cranial posterior extension. The anterior inferior cerebellar artery territory may be limited to the lateral inferior pontine and floccular regions but usually extends over the whole petrosal surface of the cerebellum up to the lateral angle. Superior cerebellar artery territory is the most extensive territory and includes the largest part of the deep white matter. Infarcts in a single-branch distribution, vermian or hemispheric, have a characteristic sagittal or oblique orientation. Watershed cerebellar infarcts can also be recognized. In the brainstem, paramedian, lateral, and dorsal penetrating arteries have characteristic distributions at the medullary, pontine, and mesencephalic levels. With MR, lateral medullary infarcts can be demonstrated. Paramedian penetrating arteries are paired, and symmetric and small infarcts at medullary and pontine levels are sharply delimited on the midline. At the mesencephalic level, infarcts in this distribution usually involve all the arteries originating from the tip of the basilar artery and from the precommunicating segment of the posterior cerebral arteries, resulting in a central mesencephalic infarct with bilateral upward extension in the thalami. The different vascular territories in the cerebellum and in the brainstem are illustrated in schematic drawings in transverse, coronal, and sagittal planes. Knowledge of the vascular territories gained by the multiplanar capabilities of MR, and knowledge of the CT patterns of enhancement and evolution, will improve recognition and definition of infarcts.

Radiologic demonstration of syringobulbia. Report of 8 cases.

Out of 75 syringomyelia cases, 8 had a syringobulbic extension. The cavity was demonstrated by magnetic resonance imaging (3 cases), syringography (3 cases), ventriculography (2 cases), and myelo-CT (2 cases). The cavities could be separated into 2 groups. In the first (5 cases) the cavity extended from the floor of the fourth ventricle, anterolaterally (3 cases) or anteriorly in the midline (2 cases). The communication with the fourth ventricle was usually wide. In the second group (3 cases), the syringobulbic cavity was located anteriorly; 2 of the 3 had no communication with the fourth ventricle and had an exceptional cranial extension (syringocephalia). In selected cases, invasive studies may help to recognize the connections of the cavities, and thus be useful in planning the surgical treatment.