PET/MRI for staging patients with Hodgkin lymphoma: equivalent results with PET/CT in a prospective trial.

To compare FDG-PET/unenhanced MRI and FDG-PET/diagnostic CT in detecting infiltration in patients with newly diagnosed Hodgkin lymphoma (HL). The endpoint was equivalence between PET/MRI and PET/CT in correctly defining the revised Ann Arbor staging system. Seventy consecutive patients with classical-HL were prospectively investigated for nodal and extra-nodal involvement during pretreatment staging with same-day PET/CT and PET/MRI. Findings indicative of malignancy with the imaging procedures were regarded as lymphoma infiltration; in case of discrepancy, positive-biopsy and/or response to treatment were evidenced as lymphoma. Sixty of the 70 (86%) patients were evaluable having completed the staging program. Disease staging based on either PET/MRI or PET/CT was correct for 54 of the 60 patients (90% vs. 90%), with difference between proportions of 0.0 (95% CI, -9 to 9%; P=0.034 for the equivalence test). As compared with reference standard, invasion of lymph nodes was identified with PET/MRI in 100% and with PET/CT in 100%, of the spleen with PET/MRI in 66% and PET/CT in 55%, of the lung with PET/MRI in 60% and PET/CT in 100%, of the liver with PET/MRI in 67% and PET/CT in 100%, and of the bone with PET/MRI in 100% and PET/CT in 50%. The only statistically significant difference between PET/MRI and PET/CT was observed in bony infiltration detection rates. For PET/CT, iodinate contrast medium infusions' average was 86 mL, and exposure to ionizing radiation was estimated to be 4-fold higher than PET/MRI. PET/MRI is a promising safe new alternative in the care of patients with HL.

2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography Deauville scale and core-needle biopsy to determine successful management after six doxorubicin, bleomycin, vinblastine and dacarbazine cycles in advanced-stage Hodgkin lymphoma.

BACKGROUND: The clinical impact of the positivity of the Deauville scale (DS) of positron emission tomography (PET) performed at the end of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in patients with advanced Hodgkin lymphoma (HL), in terms of providing rationale to shift poor responders onto a more intensive regimen, remain to be validated by histopathology. PATIENTS AND METHODS: This prospective trial involved patients with stage IIB/IV HL who after six ABVD cycles underwent PET (PET6) and core-needle cutting biopsy (CNCB) of 2-deoxy-2[F-18] fluoro-d-glucose (FDG)-avid lymph nodes. Patients received high-dose chemotherapy/autologous haematopoietic stem cell rescue (HDCT/AHSCR) if CNCB was positive for HL, alternatively, if CNCB or PET was negative, received observation or consolidation radiotherapy (cRT) on residual nodal masses, as initially planned. The end-point was 5-year progression-free survival (PFS). RESULTS: In all, 43 of the 169 (25%) evaluable patients were PET6 positive (DS 4, 32; DS 5, 11). Among them, histology showed malignancy (HL) in 100% of DS 5 scores and in 12.5% of DS 4 scores. Fifteen patients with positive biopsy received HDCT/AHSCR, whereas 28 patients with negative biopsy, as well as 126 patients with negative PET6, continued the original plan (cRT, 78 patients; observation, 76 patients). The 5-year PFS in the negative PET6 group, negative biopsy group and positive biopsy group was 95.4%, 100% and 52.5%, respectively. CONCLUSION: DS positivity of end-of-ABVD PET in advanced HL carried a certain number of CNCB-proven non-malignant FDG-uptakes. The DS 4 scores which were found to have negative histology appeared to benefit from continuing the original non-intensive therapeutic plane as indicated by the successful outcome in more than 95% of them by obtaining similar 5-year PFS to the PET6-negative group. By contrast, the DS 5 score had consistently positive histology and was associated with unsuccessful conventional therapy, promptly requiring treatment intensification or innovative therapeutic approaches.

Brentuximab vedotin followed by bendamustine supercharge for refractory or relapsed Hodgkin lymphoma.

We evaluated the impact on progression-free survival (PFS) of achieving a deep metabolic response at 2-deoxy-2[18F] fluoro-d-glucose positron emission tomography (FDG-PET) in patients with refractory or relapsed (R/R) classic Hodgkin lymphoma (cHL) following a new salvage regimen named Bv+Bs (brentuximab vedotin + bendamustine supercharge), from 2013 to 2017. In this real-life study, 20 consecutive patients (aged <60 years) with R/R cHL after failure of ≥1 salvage treatments received Bv+Bs regimen consisting of 3-days outpatient IV infusions of 1.8 mg/kg of Bv on day 1 of each 3-week cycle combined in sequence to bendamustine on days 2 and 3 of the treatment cycle at a fixed dose of 120 mg/m2 per day, for a total of 4 courses. A robust primary prophylaxis approach, including premedication, antimicrobials, stimulating factors, and cytomegalovirus monitoring, was systematically performed. The 20 patients (all evaluable) underwent 4 courses of Bv+Bs with a median dose intensity of 100% for both Bv and Bs. Ten patients (50%) experienced grade ≥3 treatment-related adverse events, without requiring hospitalization. At post-Bv+Bs reevaluation, 80% of patients had deep metabolic responses with Deauville 5-point scale scores ≤2. Thereafter, 14 patients (70%) received autologous hematopoietic stem cell transplantation (HSCT; peripheral blood stem cells previously harvested in 12 cases), and 4 patients (10%) received allogeneic HSCT. At a median follow-up of 27 months from Bv+Bs regimen initiation, the 2-year PFS of the entire population was 93.7% (95% confidence interval, 62.7% to 99.6%). Our data suggest that Bv+Bs regimen-driven strategy may be a promising salvage option to improve long-term control of high-risk Hodgkin lymphoma.

Circulation dynamics of Salmonella enterica subsp. enterica ser. Gallinarum biovar Gallinarum in a poultry farm infested by Dermanyssus gallinae.

Dermanyssus gallinae (Mesostigmata: Dermanyssidae, De Geer, 1778) is an ectoparasite of poultry, suspected to play a role as a vector of Salmonella enterica subsp. enterica ser. Gallinarum. Despite an association between them being reported, the actual dynamics in field remain unclear. Therefore, the present study aimed to confirm the interactions among mites, pathogen and chickens. The study was carried out in an industrial poultry farm infested by D. gallinae, during an outbreak of fowl typhoid. The presence of S. Gallinarum in mites was assessed and quantified by a semi-nested polymerase chain reaction (PCR) and real-time PCR, respectively, in mites collected during two subsequent productive cycles and the sanitary break. The anti-group D Salmonella antibodies were quantified by an enzyme-linked immunosorbent assay. During the outbreak and the sanitary break, S. Gallinarum was constantly present in mites. In the second cycle, scattered positivity was observed, although hens did not exhibit signs of fowl typhoid, as a result of the vaccination with BIO-VAC SGP695 (Fatro, Ozzano Emilia Bo, Italy). The data strongly suggest that D. gallinae acts as reservoir of S. Gallinarum, thus allowing the pathogen to persist in farms. Furthermore, the present study has highlighted the interactions among D. gallinae, S. Gallinarum and hens with respect to enhancing the mite-mediated circulation of S. Gallinarum in an infested poultry farm.

First report of Coxiella burnetii and Borrelia burgdorferi sensu lato in poultry red mites, Dermanyssus gallinae (Mesostigmata, Acari), related to urban outbreaks of dermatitis in Italy.

The poultry red mite (PRM), Dermanyssus gallinae, is a nonburrowing haematophagous nest-dwelling ectoparasite of birds; occasionally it bites humans, inducing dermatitis. The possibility that this parasite may also be involved in transmission of pathogens is an additional concern. We investigated the presence of zoonotic agents in PRMs from bird nests and pets, and related them to urban outbreaks of dermatitis. A total of 98 PRMs from 12 outbreaks of PRM dermatitis that occurred in Italian cities from 2001 to 2017 were molecularly investigated for detection of Coxiella spp. (16S rRNA), Chlamydophila spp. (16S rRNA), Rickettsia spp. (17 kDa protein-encoding gene), Borrelia burgdorferi sensu lato (groEL gene) and Bartonella spp. (16S-23S rRNA intergenic spacer). Of the 12 tested mite pools, one was positive for Coxiella burnetii (100% identity) and two for B. burgdorferi sensu lato (99% with Borrelia afzelii). For the first time, the presence of B. burgdorferi sensu lato and C. burnetii is reported in PRMs from urban areas. Birds, mainly pigeons, can harbour both pathogens. Therefore, birds and their nest-dwelling PRMs may play a role in the epidemiology of these infections.

Efficacy of a novel neem oil formulation (RP03™) to control the poultry red mite Dermanyssus gallinae.

Dermanyssus gallinae (Mesostigmata: Dermanyssidae) is the most harmful ectoparasite of laying hens, represents an occupational hazard for poultry workers, and a growing threat to medical science per se. There is increasing demand for alternative products, including plant-derived acaricides, with which to control the mite. The present study investigated the efficacy of neem oil against D. gallinae on a heavily infested commercial laying hen farm. A novel formulation of 20% neem oil, diluted from a 2400-p.p.m. azadirachtin-concentrated stock (RP03™), was administered by nebulization three times in 1 week. Using corrugated cardboard traps, mite density was monitored before, during and after treatment and results were statistically analysed. Mite populations in the treated block showed 94.65%, 99.64% and 99.80% reductions after the first, second and third product administrations, respectively. The rate of reduction of the mite population was significantly higher in the treated block (P < 0.001) compared with the control and buffer blocks. The results suggest the strong bioactivity of neem, and specifically of the patented neem-based formulation RP03™, against D. gallinae. The treatment was most effective in the 10 days following the first application and its effects persisted for over 2 months. Further studies will aim to overcome observed side effects of treatment represented by an oily layer on equipment and eggs.

Polyomavirus Infection in Gouldian Finches (Erythrura gouldiae) and Other Pet Birds of the Family Estrildidae.

A syndrome characterized by apathy, diarrhoea and high mortality of nestlings was observed in a flock of pet birds of the family Estrildidae. Enlargement of the liver, pulmonary congestion and urate accretions in the kidney were observed. Microscopically, there was glomerular atrophy, oedema and congestion of the lungs and necrosis and fibrosis of the liver. Cowdry type B intranuclear inclusion bodies were detected in the tissues. Polyomavirus was detected by polymerase chain reaction. The entire genome of the virus was amplified and sequenced, revealing 99 % identity to the sequence of finch polyomavirus isolated from the Eurasian bullfinch (family Fringillidae).

Measurement of myocardial amyloid deposition in systemic amyloidosis: insights from cardiovascular magnetic resonance imaging.

BACKGROUND: Cardiac involvement in systemic amyloidosis is caused by the extracellular deposition of misfolded proteins, mainly immunoglobulin light chains (AL) or transthyretin (ATTR), and may be detected by cardiovascular magnetic resonance (CMR). The aim of this study was to measure myocardial extracellular volume (ECV) in amyloid patients with a novel T1 mapping CMR technique and to determine the correlation between ECV and disease severity. METHODS: Thirty-six patients with biopsy-proven systemic amyloidosis (mean age 70 ± 9 years, 31 men, 30 with AL and six with ATTR amyloidosis) and seven patients with possible amyloidosis (mean age 64 ± 10 years, six men) underwent comprehensive clinical and CMR assessment, with ECV estimation from pre- and postcontrast T1 mapping. Thirty healthy subjects (mean age 39 ± 17 years, 21 men) served as the control group. RESULTS: Amyloid patients presented with left ventricular (LV) concentric hypertrophy with impaired biventricular systolic function. Cardiac ECV was higher in amyloid patients (definite amyloidosis, 0.43 ± 0.12; possible amyloidosis, 0.34 ± 0.11) than in control subjects (0.26 ± 0.04, P < 0.05); even in amyloid patients without late gadolinium enhancement (0.35 ± 0.10), ECV was significantly higher than in the control group (P < 0.01). A cut-off value of myocardial ECV >0.316, corresponding to the 95th percentile in normal subjects, showed a sensitivity of 79% and specificity of 97% for discriminating amyloid patients from control subjects (area under the curve of 0.884). Myocardial ECV was significantly correlated with LV ejection fraction (R(2)  = 0.16), LV mean wall thickness (R(2)  = 0.41), LV diastolic function (R(2)  = 0.21), right ventricular ejection fraction (R(2)  = 0.13), N-terminal fragment of the pro-brain natriuretic peptides (R(2)  = 0.23) and cardiac troponin (R(2)  = 0.33). CONCLUSION: Myocardial ECV was increased in amyloid patients and correlated with disease severity. Thus, measurement of myocardial ECV represents a potential noninvasive index of amyloid burden for use in early diagnosis and disease monitoring.

Detection of the new emerging rabbit haemorrhagic disease type 2 virus (RHDV2) in Sicily from rabbit (Oryctolagus cuniculus) and Italian hare (Lepus corsicanus).

Rabbit haemorrhagic disease virus (RHDV), a member of the genus Lagovirus, causes rabbit haemorrhagic disease (RHD), a fatal hepatitis of rabbits, not previously reported in hares. Recently, a new RHDV-related virus emerged, called RHDV2. This lagovirus can cause RHD in rabbits and disease and mortality in Lepus capensis (Cape hare). Here we describe a case of RHDV2 infection in another hare species, Lepus corsicanus, during a concurrent RHD outbreak in a group of wild rabbits. The same RHDV2 strain infected rabbits and a hare, also causing a RHD-like syndrome in the latter. Our findings confirmed the capability of RHDV2 to infect hosts other than rabbits and improve the knowledge about the epidemiology and the host range of this new lagovirus.

Chlamydia psittaci infection in canaries heavily infested by Dermanyssus gallinae.

Dermanyssus gallinae is a haematophagous ectoparasite responsible for anemia, weight loss, dermatitis and a decrease in egg production. Dermanyssus gallinae may play a role in the modulation of the host immune system, maybe predisposing the host to some bacterial infections such as chlamydiosis. This is an important zoonosis. Humans are exposed to Chlamydia psittaci through inhalation of the agent dispersed from the infected birds. In this study, a syndrome observed in an aviary of canaries was investigated. A heavy infestation by D. gallinae was reported. Simultaneously, a C. psittaci infection was molecularly confirmed in the canaries. Combined therapy was applied successfully. The association of C. psittaci with the examined mites has been confirmed. Therefore, we think that D. gallinae have played a role in the spreading of C. psittaci infection among the canaries. Moreover, D. gallinae could have played an important role predisposing the canaries to the development of chlamydiosis, by inducing anemia and debilitation. The control of mites in the aviaries may represent a crucial step for the prevention of important infection such as chlamydiosis in birds and humans.

Hydromyelia secondary to spinal epidural abscess. A case report.

Spinal epidural abscess (SEA) is a rare condition that can be fatal if untreated. Risk factors are immunocompromised states as well as spinal procedures including epidural anesthesia and spinal surgery. The signs and symptoms of SEA are nonspecific and can range from low back pain to sepsis. The treatment of choice is surgical decompression followed by four to six weeks of antibiotic therapy. The most common causative organism in SEA is staphylococcus aureus and spread is usually haematogenous or contiguous from psoas, paraspinal or retropharyngeal abscesses. The exact mechanism by which an epidural abscess causes spinal cord damage is unclear. In fact, the damage is often out of proportion to the degree of compression demonstrated radiologically. There is only a report of a patient with syrinx formation secondary to epidural abscess. We describe the case of a 48-year-old woman with a two-week history of thoracic back pain and evidence of dorsal SEA probably from contiguous psoas abscess. Neurological examination revealed flaccid paraplegia and loss of sphincter control. A spinal MRI scan with Gd-enhancement revealed focal high intensity signal in the T2-weighted and FLAIR images at the level of the vertebral bodies in segments D3-D11. The patient was treated with posterior decompression and drainage of the SEA, but with a poor outcome. Six weeks after the onset of symptoms, an MRI scan showed a newly-formed hydromyelia formation from D4 to D8. The case reported is the second to describe hydromyelia formation secondary to epidural abscess and a poor outcome, experiencing partial improvement without recovery. For this reason, we confirmed that the essential problem of SEA lies in the need for early diagnosis, because the early signs and symptoms may be vague and the "classic" triad of back pain, fever and variable neurological deficits occur in only 13% of patients by the time of diagnosis. Only timely treatment will avoid or reduce permanent neurological deficits before massive neurological symptoms occur. The clear message is that a high index of suspicion and modern imaging techniques are essential.

SXT-related integrating conjugative element and IncC plasmids in Vibrio cholerae O1 strains in Eastern Africa.

OBJECTIVES: The objective of this study was to investigate the extent of resistance patterns and associated mobile genetic elements in epidemic V. cholerae O1 El Tor strains isolated from Eastern Africa in the late 1990s. METHODS: Self-transmissible genetic elements and associated clusters of genes encoding resistance were detected by conjugation experiments. Detection of SXT-related integrating conjugative elements (ICEs) and associated antibiotic resistance genes was performed by PCR to amplify the SXT element-integrase gene (int), right SXT element-chromosome junction (attP-prfC) and genes conferring resistance to chloramphenicol (floR), sulfamethoxazole (sulII), streptomycin (strA) and trimethoprim (dfrA1). Genomic relatedness was established by random amplified polymorphic DNA patterns. RESULTS: Of 224 strains analysed, 200 isolates exhibited resistance to four or more antimicrobials. An IncC plasmid, encoding resistance to ampicillin, chloramphenicol, streptomycin, sulfamethoxazole and trimethoprim, conferred multidrug resistance to 113 strains isolated from Somalia and Ethiopia, whereas an SXT-related ICE, encoding resistance to chloramphenicol, streptomycin, sulfamethoxazole and trimethoprim, conferred multidrug resistance to 74 strains isolated from Sudan, Kenya and Tanzania. CONCLUSIONS: This study has shown the spread of SXT-related ICEs among V. cholerae O1 African isolates. It has also highlighted the role of two distinct genetic elements in conferring multiple resistance to the two distinct groups of V. cholerae O1 strains that, in the late 1990s, spread through Eastern Africa, a critical geographic region for the persistence and transmission of cholera to the entire continent.

Neuroradiological and neuropsychological study of a callosal infarct. A case report.

Corpus callosum infarcts are rare, constituing 0.6% of cerebral infarcts, most likely due to a rich blood supply from three main arterial systems. These infarcts may present with slowly evolving and non-localizing neurologic signs and symptoms that suggest the diagnosis of neoplasm rather than infarct. In addition, they may exhibit radiologic features more often associated with neoplasm, such as mass-like enhancement or extension across the midline. We describe a patient with corpus callosum infarct presenting with a non specific ataxia-like gait disorder, speech difficulty and left-side weakness. MR imaging disclosed an ischemic area in the body and splenium of the corpus callosum with extension to the right semiovalis centre. Neuropsychological study revealed constructive apraxia, attention reduction, motor programming and inhibiting control involvement. The atypical clinical presentation suggested involvement of the posterior circulation, while apraxia and attention impairment were in accordance with lesion localization. In-depth neuropsychological study is essential in patients with suspected corpus callosum involvement because the neurological signs and symptoms are confounding. The infarct localization in the body and semiovalis centre is an interesting neuroradiological feature.

[Churg-Strauss vasculitis and idiopathic hypereosinophyl syndrome: role of molecular biology in the differential diagnosis of hypereosinophyl syndrome]. / Vasculite di Churg-Strauss e sindrome ipereosinofila idiopatica: ruolo della biologia molecolare nella diagnosi differenziale delle sindromi ipereosinofile.

OBJECTIVE: Hypereosinophilic syndromes are a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia, tissue eosinophilia, or both, resulting in a wide variety of clinical manifestations, often without an identifiable cause. Churg-Strauss syndrome is a systemic vasculitis characterized by prominent peripheral eosinophilia, asthma and systemic involvement. The presence of mild to severe eosinophilia and systemic involvement raise the search of many trigger factor that need to be ruled out. Distinguishing CSS from idiopathic hypereosinophilic syndrome may be particularly challenging, especially in ANCA negative patients. METHODS: The aim of the present study was to present a small case series of patients referred to a Rheumatology Unit for mild to severe eosinophilia and signs and symptoms of systemic involvement and to outline the clinical significance of molecular biology in the work-up of hypereosinophilia. RESULTS: Eleven patients with moderate to severe peripheral eosinophylia, were referred to our Unit from 1996 to 2007. Female to male ratio was 7/4, mean age 40.54 (range 22-75). Three out of eleven patients resulted positive for molecular biology. The diagnosis of idiopathic hypereosinophylia was confirmed in one out of three on the basis of the clinical picture and bone marrow biopsy. CONCLUSIONS: Molecular biology may be useful in the screening and in the follow-up of a new hypereosinophylic patient.

Distal anterior cerebral artery aneurysms: endovascular or surgical treatment? A case report.

Cerebral aneurysms are occasionally associated with anomalies of the cerebral arteries. Most reports on anomalies of the anterior cerebral artery have been concerned with hypoplasia, fenestration and the infra-optic course of the A1, variant A1 perforators or Heubner's artery, multi-channeled anterior communicating artery, and azygos anterior cerebral artery. Distal anterior cerebral artery (ACA) aneurysms are known to have a poor clinical course and prognosis compared to other supratentorial aneurysms. The presence of the unpaired, distal, postcommunicating (A2) segment of the ACA is very rare in adults. We describe a patient with a ruptured aneurysm arising from the proximal end of the azygos ACA, first surgically treated with clipping and then with endovascular coiling. A 37-year-old woman at 34 weeks' gestation was transferred to our emergency room with sudden onset of severe headache and vomiting. Computed tomography (CT) revealed subarachnoid hemorrhage in the basal cisterna and the sylvian and interhemispheric fissures. Cerebral angiography showed an azygos ACA, a saccular aneurysm at the junction of the azygos ACA and the right A1 segment. A right fronto-temporal craniotomy was performed in the day of admission, and the neck of the aneurysm was clipped. One year later, an angiographic control examination revealed a regrowth of the aneurysm. The patient underwent endovascular treatment with coiling. Aneurysms of the azygos ACA are rare and their pathogenesis and course are still a matter of discussion. Developmental abnormalities or dynamic vessel wall stresses can explain the high incidence of aneurysms in these cases. The association of a rare anatomical variant with an aneurysm in the same location may suggest an embryogenesis alteration in the Willis circulation.