Does access to care play a role in liver cancer survival? The ten-year (2006-2015) experience from a population-based cancer registry in Southern Italy.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary invasive cancer of the liver. During the last decade, the epidemiology of HCC has been continuously changing in developed countries, due to more effective primary prevention and to successful treatment of virus-related liver diseases. The study aims to examine survival by level of access to care in patients with HCC, for all patients combined and by age. METHODS: We included 2018 adult patients (15-99 years) diagnosed with a primary liver tumour, registered in the Palermo Province Cancer Registry during 2006-2015, and followed-up to 30 October 2019. We obtained a proxy measure of access to care by linking each record to the Hospital Discharge Records and the Ambulatory Discharge Records. We estimated net survival up to 5 years after diagnosis by access to care ("easy access to care" versus "poor access to care"), using the Pohar-Perme estimator. Estimates were age-standardised using International Cancer Survival Standard (ICSS) weights. We also examined survival by access to care and age (15-64, 65-74 and ≥ 75 years). RESULTS: Among the 2018 patients, 62.4% were morphologically verified and 37.6% clinically diagnosed. Morphologically verified tumours were more frequent in patients aged 65-74 years (41.6%), while tumours diagnosed clinically were more frequent in patients aged 75 years or over (50.2%). During 2006-2015, age-standardised net survival was higher among HCC patients with "easy access to care" than in those with "poor access to care" (68% vs. 48% at 1 year, 29% vs. 11% at 5 years; p < 0.0001). Net survival up to 5 years was higher for patients with "easy access to care" in each age group (p < 0.0001). Moreover, survival increased slightly for patients with easier access to care, while it remained relatively stable for patients with poor access to care. CONCLUSIONS: During 2006-2015, 5-year survival was higher for HCC patients with easier access to care, probably reflecting progressive improvement in the effectiveness of health care services offered to these patients. Our linkage algorithm could provide valuable evidence to support healthcare decision-making in the context of the evolving epidemiology of hepatocellular carcinoma

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Objective To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the frst pandemic wave, Lombardia. Methods Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions We detected an increased incidence of GBS in COVID-19 patients which can refect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures

The role of clinical and neuroimaging features in the diagnosis of CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. METHODS: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. RESULTS: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. CONCLUSIONS: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.The Lombardia GENS project has received funding from the Regione Lombardia Government as a Research Independent Project (DGR n°VIII/006128-12/12/2007). Lombardia GENS is an investigator-driven, academic, non-profit consortium and is publicly funded. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by the Cambridge University Hospitals NIHR Biomedical Research Centr

Reducing time delays in the management of ischemic stroke patients in Northern Italy

Background and purpose Thrombolysis represents the best therapy for ischemic stroke but the main limitation of its administration is time. The avoidable delay is a concept reflecting the effectiveness of management pathway. For this reason, we projected a study concerning the detection of main delays with following introduction of corrective factors. In this paper we describe the results after these corrections. Materials and methods Consecutive patients admitted for ischemic stroke during a 3-months period to 35 hospitals of a macro-area of Northern Italy were enrolled. Each time of management was registered, identifying three main intervals: pre-hospital, in-hospital and total times. Previous corrective interventions were: 1.increasing of population awareness to use the Emergency Medical Service (EMS); 2.pre-notification of Emergency Department; 3.use of high urgency codes; 4.use of standardised operational algorithm. Statistical analysis was conducted using time-to-event analysis and Cox proportional hazard regression. Results 1084 patients were enrolled. EMS was alerted for 56.3% of subjects, mainly in females and severe strokes (p < 0.001). Thrombolytic treatment was performed in 4.7% of patients. Median pre-hospital and in-hospital times were 113 and 105 min, while total time was 240. High urgency codes at transport contributed to reduce pre-hospital and in-hospital time (p < 0.05). EMS use and high urgency codes promoted thrombolysis. Treatment within 4.5 hours from symptom onset was performed in 14% of patients more than the first phase of study. Conclusions The implementation of an organizational system based on EMS and concomitant high urgency codes use was effective to reduce avoidable delay and to increase thrombolysis

Berberine Affects Mitochondrial Activity and Cell Growth of Leukemic Cells from Chronic Lymphocytic Leukemia Patients

B-cell chronic lymphocytic leukemia (CLL) results from accumulation of leukemic cells that are subject to iterative re-activation cycles and clonal expansion in lymphoid tissues. The effects of the well-tolerated alkaloid Berberine (BRB), used for treating metabolic disorders, were studied on ex-vivo leukemic cells activated in vitro by microenvironment stimuli. BRB decreased expression of survival/proliferation-associated molecules (e.g. Mcl-1/Bcl-xL) and inhibited stimulation-induced cell cycle entry, irrespective of TP53 alterations or chromosomal abnormalities. CLL cells rely on oxidative phosphorylation for their bioenergetics, particularly during the activation process. In this context, BRB triggered mitochondrial dysfunction and aberrant cellular energetic metabolism. Decreased ATP production and NADH recycling, associated with mitochondrial uncoupling, were not compensated by increased lactic fermentation. Antioxidant defenses were affected and could not correct the altered intracellular redox homeostasis. The data thus indicated that the cytotoxic/cytostatic action of BRB at 10-30 μM might be mediated, at least in part, by BRB-induced impairment of oxidative phosphorylation and the associated increment of oxidative damage, with consequent inhibition of cell activation and eventual cell death. Bioenergetics and cell survival were instead unaffected in normal B lymphocytes at the same BRB concentrations. Interestingly, BRB lowered the apoptotic threshold of ABT-199/Venetoclax, a promising BH3-mimetic whose cytotoxic activity is counteracted by high Mcl-1/Bcl-xL expression and increased mitochondrial oxidative phosphorylation. Our results indicate that, while CLL cells are in the process of building their survival and cycling armamentarium, the presence of BRB affects this process

Basophil Activation Test in the Diagnosis of <i>Anisakis</i> Allergy: An Observational Study from an Area of High Seafood Consumption in Italy

The rising popularity of undercooked or raw seafood containing larvae of the Anisakis parasite has led to issues of public health concern due to allergic manifestations. We conducted an observational study on the use of an innovative Anisakis allergy diagnostic algorithm in a convenience sample of 53 allergic outpatients recruited in Western Sicily, between April 2021 and March 2022. We included individuals with an anamnesis suggestive of IgE sensitization to Anisakis reporting clinical manifestation in the last month due to allergic reactions after eating fresh fish, or in subjects at high exposure risk with sea products while abstaining from fish ingestion, excluding those with documented fish sensitization. Outpatients were tested via Skin Prick Test, IgE-specific dosage and Basophil Activation Test (BAT). Twenty-six outpatients were diagnosed with Anisakis, while 27 with Chronic Urticaria (CU). We found a seven-fold excess risk for Anisakis (p4) positivity in the Anisakis allergic outpatients, as compared to the CU ones. BAT showed the best diagnostic accuracy (92.45%) and specificity (100%), while specific IgE to Ascaris (p1) documented the best sensitivity (92.31%) but a very low specificity (37.04%). In conclusion, our findings may represent a potentially useful contribution to the future development of updated clinical guidelines

Covid-19-associated Guillain-Barré syndrome in the first wave of COVID-19 pandemic in Lombardia: Increased incidence or increased seroprevalence?

38noembargoed_20221015embargoed_20221015Filippo Martinelli Boneschi; Antonio Colombo; Nereo Bresolin; Maria Sessa; Mattia Pozzato; Giampiero Grampa; Pietro Bassi; Eugenio Magni; Maurizio Versino; Carlo Ferrarese; Davide Zarcone; Alberto Albanese; Giuseppe Micieli; Carla Zanferrari; Antonio Cagnana; Claudio Ferrante; Angelo Zilioli; Davide Locatelli; Maria Calloni; Maria Luisa Delodovici; Camillo Foresti; Barbara Frigeni; Stefania Canella; Rubjona Xhani; Massimo Crabbio; Alessandro Clemenzi; Marco Mauri; Simone Beretta; Isidoro La Spina; Simona Bernasconi; Anna Cavallini; Michela Ranieri; Elisabetta D{ extquotesingle}Adda; Maria Elisa Fruguglietti; Lorenzo Peverelli; Edoardo Agosti; Andrea Rigamonti; Andrea SalmaggiMartinelli Boneschi, Filippo; Colombo, Antonio; Bresolin, Nereo; Sessa, Maria; Pozzato, Mattia; Grampa, Giampiero; Bassi, Pietro; Magni, Eugenio; Versino, Maurizio; Ferrarese, Carlo; Zarcone, Davide; Albanese, Alberto; Micieli, Giuseppe; Zanferrari, Carla; Cagnana, Antonio; Ferrante, Claudio; Zilioli, Angelo; Locatelli, Davide; Calloni, Maria; Luisa Delodovici, Maria; Foresti, Camillo; Frigeni, Barbara; Canella, Stefania; Xhani, Rubjona; Crabbio, Massimo; Clemenzi, Alessandro; Mauri, Marco; Beretta, Simone; La Spina, Isidoro; Bernasconi, Simona; Cavallini, Anna; Ranieri, Michela; D( extquotesingle)Adda, Elisabetta; Elisa Fruguglietti, Maria; Peverelli, Lorenzo; Agosti, Edoardo; Rigamonti, Andrea; Salmaggi, Andre

Factors Associated with Primary Liver Cancer Survival in a Southern Italian Setting in a Changing Epidemiological Scenario

A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male), a flexible hazard-based regression model revealed factors influencing 5-year survival rates. High deprivation levels [HR = 1.41 (95%CI = 1.15–1.76); p &lt; 0.001], poor access to care [HR = 1.99 (95%IC = 1.70–2.35); p &lt; 0.0001], age between 65 and 75 [HR = 1.48 (95%IC = 1.09–2.01); p &lt; 0.05] or &gt;75 [HR = 2.21 (95%CI = 1.62–3.01); p &lt; 0.0001] and residing in non-urban areas [HR = 1.35 (95%CI = 1.08–1.69); p &lt; 0.01] were associated with poorer survival estimates. While deprivation appeared to be a risk factor for primary liver cancer patients residing within the urban area, the geographic distance from specialised treatment centres emerged as a potential determinant of lower survival estimates for residents in the non-urban areas. After balancing the groups of easy and poor access to care using a propensity score approach, poor access to care and a lower socioeconomic status resulted in potentially having a negative impact on primary liver cancer survival, particularly among urban residents. We emphasise the need to interoperate cancer registries with other data sources and to deploy innovative digital solutions to improve cancer prevention.Statistic