Canine Cerebral Intravascular Lymphoma: Neuropathological and Immunohistochemical Findings

Intravascular lymphoma (IVL) is a rare angiotropic large-cell lymphoma in which neoplastic lymphocytes proliferate within the lumina of small blood vessels in the absence of a primary extravascular mass or leukemia. This study included 10 cases of canine IVL restricted to the CNS. Dogs had an average age of 8 years and neurological signs mainly referred to brain involvement such as depression, seizures, and ambulatory deficits. Gross examination at necropsy showed focal extensive or multiple hemorrhagic areas mainly distributed in the telencephalon and diencephalon. Histopathologically, numerous veins and capillaries were filled with neoplastic lymphoid cells, accompanied by edema, hemorrhage, and thrombosis. Immunohistochemistry (IHC) for CD3, CD20, and PAX5 was performed to phenotype the neoplastic lymphocytes. IHC for CD44 and CD29 were used to investigate the pathogenetic mechanism leading to the intravascular aggregation of the neoplastic lymphocytes. The same IHC panel was applied to 8 cases of primary and metastatic canine CNS lymphoma in order to compare IVL immunoreactivity. Three IVLs were typified as T-cell, 3 as B-cell, and 4 as non-T non-B. Neoplastic lymphocytes showed marked expression of CD44 in all IVL cases, and CD29-immunolabeled cells were observed in 4 IVLs. CD44 immunoreactivity was consistent with the findings reported in human IVL, suggesting a predisposition to the formation of lymphocyte aggregates. CD29 was inconsistently immunonegative in canine IVL, confirming only partially the pathogenetic mechanism suggested for the human counterpart

Quantitation of regional ejection fractions using gated tomographic imaging with Tc-99m-sestamibi

BACKGROUND: A new oro-dispersible film (ODF) formulation of sildenafil has been developed for the treatment of erectile dysfunction (ED) to overcome the drawbacks that some patients experience when taking the conventional film-coated tablet (FCT). AIM: To assess the effectiveness and safety of sildenafil ODF formulation in patients with ED who were using the conventional FCT. METHODS: From May 2017 through July 2017, 139 patients with ED were enrolled. Data from penile color-duplex ultrasound, medical history, hormonal evaluation, and patient self-administered questionnaires were collected. All patients were administered sildenafil 100-mg FCT for 4 weeks. Thereafter, they underwent a 2-week washout period and subsequently took sildenafil 75-mg ODF for 4 weeks. OUTCOMES: The International Index of Erectile Function (IIEF-15), Hospital Anxiety and Depression Scale (HADS), Patient Global Impressions of Improvement (PGI-I), and Clinician Global Impressions of Improvement (CGI-I) questionnaires were administered and severity of ED was classified as severe (IIEF-15 score ≤ 10), moderate (IIEF-15 score 11-16), or mild (IIEF-15 score = 17-25). RESULTS: All patients completed the final protocol. Differences in mean IIEF scores for erectile function, orgasmic function, sexual desire, and intercourse satisfaction were significantly in favor of sildenafil 100-mg FCT, whereas the mean score for overall satisfaction was in favor of sildenafil 75-mg ODF. A significant difference in changes in HADS score was found from washout to final follow-up (mean difference = -0.19; P < .01). For the ODF formulation, the median CGI-I score was 3.5 (interquartile range [IQR] = 2.5-4.5) and the median PGI-I score was 3.0 (IQR = 2.0-4.0). The median action time was 20.0 minutes (IQR = 15.0-30.0) and the median mouth time was 60.0 seconds (IQR = 30.0-120.0). CLINICAL IMPLICATIONS: The ODF formulation of a widely known drug, with the same safety and effectiveness of the FCT, was better appreciated by patients in overall satisfaction. STRENGTHS AND LIMITATIONS: This is the first clinical trial to assess the efficacy of a new formulation of sildenafil in patients with ED. The limitations of the study are related to the methodology used: it was not a case-control study and the patients were not drug-naïve for ED treatment. Therefore, only the "additional" side effects of the ODF formulation compared with FCT are reported. CONCLUSION: The new ODF formulation is as efficient and safe as the FCT formulation and offers a new choice of treatment to specialists for more precisely tailored therapy. Cocci A, Capece M, Cito G, et al. Effectiveness and Safety of Oro-Dispersible Sildenafil in a New Film Formulation for the Treatment of Erectile Dysfunction: Comparison Between Sildenafil 100-mg Film-Coated Tablet and 75-mg Oro-Dispersible Film. J Sex Med 2017;X:XXX-XXX

Studio clinicopatologico ed immunofenotipico del linfoma intravascolare del Sistema Nervoso Centrale nel cane

Riassunto Il linfoma intravascolare (IVL) è una rara forma di linfoma non-Hodgkin a grandi cellule, angiotropico, nel quale i linfociti neoplastici proliferano all’interno del lume vascolare in assenza di una massa primaria extravascolare o di leucemia. In questo studio è stata condotta un’analisi retrospettiva su 10 casi di IVL del sistema nervoso centrale (SNC) del cane. Le presentazioni cliniche più frequenti sono state: ottundimento del sensorio (3 casi), crisi convulsive (2 casi), deficit deambulatori (4 casi), ipertermia (1 caso). L’acquisizione di sequenze GE T2, FLAIR, FSE T2 e SE T1 pesate nei tre piani dello spazio, prima e dopo somministrazione endovenosa di mezzo di contrasto paramagnetico (gadolinio) mostrava aree d’iperintensità a livello dei lobi parietali e occipitali (in 4 casi), del talamo (in 5 casi), dell’ippocampo (in 2 casi), delle leptomeningi (in 2 casi), nuclei della base (in 1 caso), dell’area sottocorticale (in 1 caso). A livello macroscopico le lesioni osservate con maggiore frequenza si riferiscono ad aree emorragiche focali (2 casi) o multiple (4 casi) che spesso interessavano gran parte del parenchima cerebrale. In 4 casi non si sono osservate lesioni macroscopiche apprezzabili. In un caso era evidente deviazione della falce cerebrale per aumento di volume di un lobo e concomitante compressione del ventricolo laterale ipsilaterale alla tumefazione. La diagnosi dei campioni fissati in formalina e inclusi in paraffina è stata eseguita tramite colorazione con ematossilina–eosina e in seguito si è proceduto alla tipizzazione dei linfociti neoplastici con specifici marker immunoistochimici (CD3 e CD20). È stato inoltre utilizzato un pannello di anticorpi comprendente CD29 (ITGB1), CD44 (Hermes-3), CD11a/CD18 (LFA-1) e CD49d al fine di indagare sui meccanismi patogenetici responsabili dell’aggregazione dei linfociti neoplastici e della loro localizzazione intravascolare. Lo stesso pannello anticorpale è stato applicato anche su 14 casi di linfoma primario e secondario del SNC del cane allo scopo di evidenziare eventuali differenze di immunoreattività rispetto ai casi di IVL. Come campioni di controllo sono stati utilizzati linfonodi normali di cane e sezioni di encefalo di cane affetto da fenomeni infiammatori non suppurativi. Negli IVL numerose strutture vascolari, principalmente venule e capillari, apparivano parzialmente o totalmente occluse da una popolazione cellulare neoplastica morfologicamente interpretabile come linfoblasti. In 6 casi le lesioni vascolari erano responsabili dello sviluppo di ampie aree infartuali emorragiche ed edema perilesionale. Tre casi sono risultati linfomi a cellule T (CD3+), 3 casi a cellule B (CD20+) e 4 casi non-B non-T (CD3–, CD20–). I risultati hanno evidenziato differenze nel comportamento degli anticorpi anti-CD44 e anti-CD29 tra i linfomi primari e secondari e gli IVL. Il CD44 è risultato espresso in tutti gli IVL, mentre nei linfomi primari e metastatici l’immunoreattività è stata osservata in 5 casi su 14. Tali risultati sono in accordo con quanto riportato anche in letteratura umana. Il CD29 non sempre è risultato immunonegativo (6 su 10), tendendo quindi a confermare solo parzialmente quanto ipotizzato in patologia umana. La mancata immunoreattività del complesso CD11a/CD18 e del CD49d non ha permesso di validare le relative teorie patogenetiche sostenute in medicina umana per tale rara forma neoplastica. Parole chiave: linfoma, linfoma intravascolare, immunoistochimica, CD29, CD44, CD11a/CD18, CD49d, sistema nervoso centrale, cane. Abstract Intravascular lymphoma (IVL) is a rare angiotropic large-cell non-Hodgkin lymphoma in which neoplastic lymphocytes proliferate within the lumina of blood vessels in absence of a primary extravascular mass or leukemia. A retrospective study was performed on 10 cases of canine IVL of the central nervous system. Depression (3 cases), seizures (2 cases), deambulatory deficit (4 cases), and hyperthermia (1 case) dominated the clinical presentations. The acquisition of GE T2, FLAIR, FSE T2 and T1-weighted SE in the three planes of space, before and after intravenous paramagnetic contrast (gadolinium) administration showed areas of enhancement in the parietal and occipital lobes (4 cases), thalamus (5 cases), hippocampus (2 cases), leptomeninges (2 cases), basal ganglia (1 case), and subcortical area (1 case). Grossly, lesions included focal extensive (2 cases) or multiple (4 cases) hemorrhagic areas often involving large neuroparenchyma areas. In 4 cases, the macroscopical pictures were unremarkable. In one case, shifting of the midline structures and compression of the contralateral hemisphere was observed. Diagnosis was achieved by microscopical examination of formalin-fixed paraffin wax-embedded tissues stained with hematoxylin-eosin. Immunohistochemistry (IHC) was performed to typify the neoplastic lymphocytes using T-cell (CD3+) and B-cell (CD20+) markers. A panel of antibodies including CD29 (ITGB1), CD44 (Hermes-3), CD11a/CD18 (LFA-1) and CD49d were used in order to investigate on the pathogenetic mechanisms leading to the intravascular aggregation of the neoplastic lymphocytes. The same IHC panel was applied to 14 primary and secondary canine CNS lymphomas in order to verify any different immunoreactivity of neoplastic lymphocytes compared to IVL. Control tissues were normal canine lymph nodes and canine brain sections with non suppurative inflammatory lesions. Numerous vessels, predominantly small veins and capillaries, were partially or completely filled with neoplastic lymphocytes. Frequently, focal extensive or multifocal hemorrhage, necrosis, and edema of the neuroparenchyma were associated with the vascular occlusions. The tumors were classified as T-cell (CD3+) in 3 cases, as B-cell (CD20+) in 3 cases, and as non-B, non-T lymphoma (CD3–, CD20–) in the remaining 4 cases. CD44 appeared markedly expressed in IVL, whereas in primary and secondary lymphomas CD44-posivite cells were detected in 5 out of 14 cases. These results were consistent with the findings reported in human IVL. CD29 was inconsistently immunonegative (6 out of 10 cases) then it only partially confirmed the pathogenetic mechanism as suggested for human IVL. Failure of CD11a/CD18 and CD49d operations did not allow to hypothesize other pathogenetic theories. Keywords: lymphoma, intravascular lymphoma, immunohistochemistry, CD29, CD44, CD11a/CD18, CD49d, central nervous system, dog

Sliding doors: how their opening affects particulate matter levels?

Background: Operating theatres (OTs) have adequate conditions to perform safe operations and to prevent surgical site infections (SSIs). Opening doors can compromise these situations. Measurement of particulate contamination is a crucial point to check the effectiveness of preventive measures in the OTs. We analysed how opening the doors interact with particulate contamination in different designs of OTs. Methods: Between January and February 2020, a cross-sectional study was conducted in five different types of OTs of a teaching hospital in Siena. Two (OTs 1 and 2) had laminar flows, with 58 and 55 air changes/h, respectively. Three had turbulent flows: OT3 (18 air changes/h, with four inlets from the ceiling), OT4 (16 air changes/h, airflow directed from one wall to the opposite one and the main door laterally to the flow) and OT5 (23 air changes/ h and airflow from the ceiling plenum). Particulate matter (PM) measurements were carried out at seven different locations in each OT, alternating two conditions: 1) doors closed and 2) opening/closing the main door twice per minute. For each spot, in each condition, we recorded for several minutes the following parameters: particles (&gt;0.3, &gt;0.5, &gt;1, &gt;3, &gt;5 and &gt;10 μm), room temperature (RT), relative humidity (RH) and airflow velocity (AS). International Organization for Standardization (ISO) class for PM &gt; 0.5 μm was calculated. Comparison with the Wilcoxon signed-rank test was made using Stata 16 (StataCorp LLC, College Station, TX, USA). Results: All five OTs had differential pressure, but all fell to 0 at door opening; negligible changes were detected on microclimatic parameters although they may be affected by different types of airflows and design. Even though the variations in the turbulent flow rooms were broader and different, there were no changes in ISO class particle classification, given the already very high initial particulate levels. In laminar flow rooms, with a better ISO classification, the variations were smaller but sufficient to worsen the class. Conclusions: When opening the doors, the PM levels in OTs are influenced by different ventilation systems and room design. Different ventilation systems and the design of OTs influence particulate levels during door opening. Particulate variations in the laminar flows studied were smaller than in the turbulent flows, which, although lower in performance in our study, can be just as effective; however, as the heterogeneous construction and logistic characteristics of OTs result in significant variations in PMs, further research is needed to determine the actual effect of airflow on the SSI rate

Clinical characteristics, management and in-hospital mortality of patients with COVID-19 In Genoa, Italy

To describe clinical characteristics, management and outcome of COVID-19 patients; and to evaluate risk factors for all-cause in-hospital mortality

Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society

Cystic Fibrosis (CF) occurs most frequently in caucasian populations. Although less common, this disorder have been reported in all the ethnicities. Currently, there are more than 2000 described sequence variations in CFTR gene, uniformly distributed and including variants pathogenic and benign (CFTR1:www.genet.sickkids.on.ca/). To date,only a subset have been firmily established as variants annotated as disease-causing (CFTR2: www.cftr2.org). The spectrum and the frequency of individual CFTR variants, however, vary among specific ethnic groups and geographic areas. Genetic screening for CF with standard panels of CFTR mutations is widely used for the diagnosis of CF in newborns and symptomatic patients, and to diagnose CF carrier status. These screening panels have an high diagnostic sensitivity (around 85%) for CFTR mutations in caucasians populations but very low for non caucasians. Developed in the last decade, Next-Generation Sequencing (NGS) has been the last breakthrough technology in genetic studies with a substantial reduction in cost per sequenced base and a considerable enhancement of the sequence generation capabilities. Extended CFTR gene sequencing in NGS includes all the coding regions, the splicing sites and their flankig intronic regions, deep intronic regions where are localized known mutations,the promoter and the 5'-3' UTR regions. NGS allows the analysis of many samples concurrently in a shorter period of time compared to Sanger method . Moreover, NGS platforms are able to identify CFTR copy number variation (CNVs), not detected by Sanger sequencing. This technology has provided new and reliable approaches to molecular diagnosis of CF and CFTR-Related Disorders. It also allows to improve the diagnostic sensitivity of newborn and carrier screeningmolecular tests. In fact, bioinformatics tools suitable for all the NGS platforms can filter data generated from the gene sequencing, and analyze only mutations with well-established disease liability. This approach allows the development of targeted mutations panels with a higher number of frequent CF mutations for the target populationcompared to the standard panels and a consequent enhancement of the diagnostic sensitivity. Moreover, in the emerging challenge of diagnosing CF in non caucasians patients, the possibility of customize a NGS targeted mutations panel should increase the diagnostic sensitivity when the target population has different ethnicities