Emerging Respiratory Viruses of Cats

In recent years, advances in diagnostics and deep sequencing technologies have led to the identification and characterization of novel viruses in cats as protoparviruses and chaphamaparvoviruses, unveiling the diversity of the feline virome in the respiratory tract. Observational, epidemiological and experimental data are necessary to demonstrate firmly if some viruses are able to cause disease, as this information may be confounded by virus- or host-related factors. Also, in recent years, researchers were able to monitor multiple examples of transmission to felids of viruses with high pathogenic potential, such as the influenza virus strains H5N1, H1N1, H7N2, H5N6 and H3N2, and in the late 2019, the human hypervirulent coronavirus SARS-CoV-2. These findings suggest that the study of viral infections always requires a multi-disciplinary approach inspired by the One Health vision. By reviewing the literature, we provide herewith an update on the emerging viruses identified in cats and their potential association with respiratory disease.     

Bone fractal analysis

Fractal analysis is a quantitative method used to evaluate complex anatomic findings in their elementary component. Its application to biologic images, particularly to cancellous bones, has been well practiced within the past few years. The aims of these applications are to assess changes in bone and the loss of spongious architecture, indicate bone fragility, and to show the increased risk for fracture in primary or secondary osteoporosis. The applications are very promising to help complete the studies that can define bone density (bone mineral density by dual energy x-ray absorptiometry or quantitative computed tomography), and also have the capacity to distinguish the patients with a high or low risk for fracture. Their extension to the clinical fields, to define a test for fracture risk, is still limited by difficult application to the medical quantitative imaging of bones, between correct application at superficial bones and unreliable application to deep bones. The future evolution and validity do not depend upon fractal methods but upon well-detailed imaging of the bones in clinical conditions.     

Radiolabelled monoclonal antibodies against alpha-fetoprotein for in vivo localization of human hepatocellular carcinoma by immunotomoscintigraphy

Two high affinity monoclonal antibodies, designated AF01 and AF04, directed against distinct epitopes of human alpha-fetoprotein (AFP) and the Fab fragments of one of them, were labelled with ¹³¹I and injected into 18 patients with AFP producing hepatocellular carcinoma (HCC) in order to carry out imaging studies by tomoscintigraphy. Twelve patients were injected with whole antibody, only three of seven patients injected with AF01 and two of five patients injected with AF04 had a positive scan. In contrast, five out of six patients injected with labelled Fab fragments of AF04 had positive imaging. These results confirm that tumour imaging of HCC using ¹³¹I labelled monoclonal antibody against AFP is feasible. Moreover, utilization of tomoscintigraphy in place of linear scintigraphy and Fab fragments instead of whole immunoglobulin may improve the sensitivity of radioimmunolocalization. This technique provides useful information on the in vivo distribution of monoclonal antibodies directed against AFP and on the practicability of the eventual therapeutic use of anti-AFP antibodies in HCC.This work was supported by Grant number 84D16 from the Institut Gustave-Roussy     

A one-to-one telestroke network: the first Italian study of a web-based telemedicine system for thrombolysis delivery and patient monitoring

Over 10 years after European approval, thrombolysis is still limited by a restricted time window and non-optimal territorial coverage. Implementation of telestroke can give a growing number of patients access to treatment. We hereby present the first Italian telemedicine study applied to both the acute and the monitoring phase of stroke care. From January 2011 to December 2013, we tested a web-based, drip, and treat interaction model, connecting the cerebrovascular specialist of one hub center to the Emergency Department of a Spoke center. We then compared thrombolysis delivered using the telestroke model with thrombolysis provided at the Hub Stroke Unit at the time when the telemedicine program was activated. Telethrombolysis data were then compared with data from the two main international telestroke projects (TEMPiS and REACH), and other European telestroke studies performed at the time of writing. We collected a total of 131 thrombolysis procedures (25 telethrombolysis and 106 thrombolysis patients at the Stroke Unit). Statistical analysis with the t test yielded no statistically significant differences between the two populations in door-to-scan, door-to-needle (DTN), and onset-to-treatment times (OTT). Our OTT and DTN pathway times were longer than the TEMPiS and REACH studies but comparable with other European telemedicine trials, despite different models of interaction and number of centers. Our study in a northeastern province of Italy confirms the potential of applying telemedicine to a cerebrovascular pathology.     

The Poor Outcome of Ischemic Stroke in Very Old People: A Cohort Study of Its Determinants

OBJECTIVES: To assess how much of the excess risk of poor outcome from stroke in people aged 80 and older aging per se explains, independent of other prognostic determinants.
DESIGN: Cohort, observational.
SETTING: University hospital.
PARTICIPANTS: One thousand five hundred fifty-five patients with first-ever ischemic stroke consecutively referred to an in-hospital Clinical Pathway program were studied.
MEASUREMENTS: The relationship between age and 1-month outcome (death, disability (modified Rankin Scale 3–5), and poor outcome (modified Rankin Scale 3–6)) was assessed, with adjustment for several prognostic factors.
RESULTS: Six hundred twelve patients aged 80 and older showed worse outcome after 1 month than those who were younger, in terms of mortality (19% vs 5%, hazard ratio (HR)=3.85, 95% confidence interval (CI)=2.8–5.4) and disability (51% vs 33%, odds ratio (OR)=3.16, 95% CI=2.5–4.0), although in multivariate models, the adjusted HR for mortality decreased to 1.47 (95% CI=1.0–2.16) and the ORs for disability and poor outcome decreased to 1.76 (95% CI=1.32–2.3.) and 1.83 (95% CI=137–2.43), respectively. Stroke severity, the occurrence of at least one medical complication, and premorbid disability explained most of the risk excess in the oldest-old.
CONCLUSION: Stroke outcome is definitely worse in very old people, and most of the excess risk of death and disability is attributable to the higher occurrences of the most-severe clinical stroke syndromes and of medical complications in the acute phase. These represent potential targets for preventive and therapeutical strategies specifically for elderly people.     

Histological correlation of 17 prospective immunoscintigraphies of recurrences of colorectal carcinomas using indium-111-labeled anti-cea and(or) 19-9 monoclonal antibodies

Seventeen patients (mean age 55 years) with suspected recurrence in previously operated and histologically confirmed colorectal adenocarcinomas were explored by immunoscintography (IS) associating planar and emission computed tomography (ECT) and using the ¹¹¹In-labeled anti carcinoembryonic antigen (CEA) and(or) 19-9 monoclonal antibodies (MoAbs). The results of IS were compared blind with those of computed tomography (CT) and ultrasonography (US). The final diagnosis of recurrence and(or) metastasis was done in 16 cases by second-look surgery and in another patient by rectal biopsy. Overall per-patient sensitivity for the pelvis and extrahepatic abdomen was 69% for IS and 31% and 25% respectively for computed tomography and ultrasonography. No false positive of IS, as well as US and CT, for the pelvis and the extrahepatic abdomen was seen. Based on the number of anatomical sites tested, sensitivity of IS was 91% in the pelvis. In our series, scintigraphic computer subtraction did not allow adequate resolution of the problem of intense liver uptake of ¹¹¹In-labeled MoAbs. It is concluded that IS using ¹¹¹In-labeled anti CEA and(or) 19-9 MoAbs should be carried out prospectively in patients at high risk of recurrence of colorectal cancer.     

Histological correlation of 17 prospective immunoscintigraphies of recurrences of colorectal carcinomas using indium-111-labeled anti-cea and(or) 19-9 monoclonal antibodies

Seventeen patients (mean age 55 years) with suspected recurrence in previously operated and histologically confirmed colorectal adenocarcinomas were explored by immunoscintography (IS) associating planar and emission computed tomography (ECT) and using the 111In-labeled anti carcinoembryonic antigen (CEA) and(or) 19-9 monoclonal antibodies (MoAbs). The results of IS were compared blind with those of computed tomography (CT) and ultrasonography (US). The final diagnosis of recurrence and(or) metastasis was done in 16 cases by second-look surgery and in another patient by rectal biopsy. Overall per-patient sensitivity for the pelvis and extrahepatic abdomen was 69% for IS and 31% and 25% respectively for computed tomography and ultrasonography. No false positive of IS, as well as US and CT, for the pelvis and the extrahepatic abdomen was seen. Based on the number of anatomical sites tested, sensitivity of IS was 91% in the pelvis. In our series, scintigraphic computer subtraction did not allow adequate resolution of the problem of intense liver uptake of 111In-labeled MoAbs. It is concluded that IS using 111In-labeled anti CEA and(or) 19-9 MoAbs should be carried out prospectively in patients at high risk of recurrence of colorectal cancer.     

Effectiveness and toxicity of "BELD" polychemotherapy in advanced malignant melanoma

From January 1985 to December 1987, 17 patients with advanced malignant melanoma were treated with the polychemotherapy regimen BELD (bleomycin, 15 mg subcutaneously on day 1 and 4, vindesine 3 mg/m2 intravenously on day 1 and 5, CCNU 80 mg/m2 orally on day 1 and DTIC 200 mg/m2 intravenously on day 1 through 5) proposed as effective (CR + PR 45%) and tolerable. All patients were evaluable for toxicity and 14/17 also for response after 2 BELD cycles (total n. of cycles was 54). Criteria for response were just the same as those used by Young et al. A complete remission and a partial remission (2/14) have been observed at lymph nodal level, the unique sites of the disease in these two patients. Remission lasted 6 and 4 months, respectively. Two other patients showed a minimal response of 2 and 3 months duration (lymphonodal and cutis, respectively); 9 patients had stabilized disease of 5 months median duration. One case of progression of disease was observed. However, toxicity was relevant because of 2 early deaths after the first cycle, most probably therapy related, nausea and vomiting (82%), leukopenia (17%) and muscle rigors (11%).     

A novel adoptive transfer model of chronic lymphocytic leukemia suggests a key role for T lymphocytes in the disease

Chronic lymphocytic leukemia (CLL) is an incurable adult disease of unknown etiology. Understanding the biology of CLL cells, particularly cell maturation and growth in vivo, has been impeded by lack of a reproducible adoptive transfer model. We report a simple, reproducible system in which primary CLL cells proliferate in nonobese diabetes/severe combined immunodeficiency/γc(null) mice under the influence of activated CLL-derived T lymphocytes. By co-transferring autologous T lymphocytes, activated in vivo by alloantigens, the survival and growth of primary CFSE-labeled CLL cells in vivo is achieved and quantified. Using this approach, we have identified key roles for CD4(+) T cells in CLL expansion, a direct link between CD38 expression by leukemic B cells and their activation, and support for CLL cells preferentially proliferating in secondary lymphoid tissues. The model should simplify analyzing kinetics of CLL cells in vivo, deciphering involvement of nonleukemic elements and nongenetic factors promoting CLL cell growth, identifying and characterizing potential leukemic stem cells, and permitting preclinical studies of novel therapeutics. Because autologous activated T lymphocytes are 2-edged swords, generating unwanted graph-versus-host and possibly autologous antitumor reactions, the model may also facilitate analyses of T-cell populations involved in immune surveillance relevant to hematopoietic transplantation and tumor cytoxicity.