Efficacy of somatostatine analogues in survival and quality of life of a frail patient with poorly differentiated biliary neuroendocrine tumour

We describe the case of a 71-year-old woman with poorly differentiated neuroendocrine tumor of third distal biliary duct and osteolytic metastasis. The patient was evaluated as a third stage of Balducci’s criteria for the recognition of frailty. The patient received radiotherapy and octreotide LAR. This treatment allowed a good tumour progression rate (18 months), a good quality of life and a good survival (35 months). The case report describes the role of octreotide in the therapy of neuroendocrine tumours, and underlines the importance of a multidisciplinary management of cancer in frail patients

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Partial Discharges on IGBT Modules: are Sinusoidal Waveforms Sufficient to Evaluate Behavior?

In recent years, the increasing use of AC-DC converters, especially in the field of renewable energy sources has led to the implementation of new modulation techniques, in particular the ones based on the pulse width modulation. The purpose of the present work is to verify the different behavior that is obtained when the components are subjected to the partial discharge test carried out with a sinusoidal waveform, and when they are subjected to PWM stress-type, similar to the actual signal generated by this type of electronic components. By considering equal rms value of the fundamental sine wave, the comparison has shown different partial discharges patterns

Persistent Organic Pollutants and Fatty Acid Profile in a Typical Cheese from Extensive Farms: First Assessment of Human Exposure by Dietary Intake

Dairy products represent an important source of beneficial substances for humans. At the same time, they can expose the consumers to environmental contaminants ingested by animals through their diet, influencing their health negatively. This experiment aims to evaluate the risk and benefits related to the consumption of typical stretched cheeses, considering their fatty acid (FA) profile and persistent organic pollutants (POPs) content. Six representative farms, two of them organic, raising Cinisara cattle were selected, considering the typical extensive management systems, based on feeding of natural pasture integrated with concentrate and hay depending on the availability of forage on pastures. A total of 18 cheeses produced in winter, spring and summer with bulk milk of each farm were sampled and analyzed. The chemical composition of cheeses was influenced by farm management, and the FA profile mainly by the season. In particular, cheeses made in spring showed a healthier FA profile with the content of polyunsaturated fatty acids (PUFA), of omega3-PUFA and omega6/omega3 ratio pair to 7.29%, 1.44% and 1.32, respectively, while in winter 5.44%, 0.98% and 2.55, respectively, and in summer 4.77% 0.49% and 3.04, respectively. Due to high levels of feeding integration, cheese made in winter presented unhealthier characteristics compared to the cheeses made in spring and summer, showing high levels of saturated FA (66.2%, 64.2% and 65.5%, respectively), and large contents of polycyclic aromatic hydrocarbons (PAH) (57.07 ng/g fat, 36.25 ng/g fat and 10.22 ng/g fat, respectively) and polychlorinated biphenyls (PCBs) (36.19 ng/g fat, 4.68 ng/g fat and 3.73 ng/g fat, respectively), mainly in those from non-organic farms. Levels of PCBs considered to be hazardous to human health were found in nine samples

Comparing the Hydrological Response of Forested Headwaters (Unregulated and Regulated with Check Dams) under Mediterranean Semi-Arid Conditions

This study has evaluated the runoff and erosion rates in torrents of Southern Italy, two forested headwaters with very similar climatic, hydrological and geomorphological characteristics; in one headwater, 15 check dams were installed in the mid-1950s, while the other is not regulated with engineering works. To this aim, the hydrological variables have been modeled over 15 years after check dam installation using the HEC-HMS (Hydrologic Engineering Center-Hydrologic Modeling System) model coupled to the MUSLE (Modified Universal Soil Loss Equation) equation. The model simulations have shown that check dams have not played a significant role in reducing the surface runoff compared to the unregulated torrent; in both catchments, the well-developed forest cover determined very low runoff coefficients (lower than 0.3%) with a scarce runoff generation capacity. Additionally, the reduction in peak flow due to the check dams was not significant, on average −7.4% compared to the unregulated headwater. Check dams have retained sediments for about 8–10 years after their installation, reducing erosion by about 35%, although soil loss was much lower than the tolerance limit in both catchments. After the sediment retention capacity of the dam sediment wedge was depleted, the sediment yield in the regulated torrent was even higher (by about 20%) compared to the unregulated catchment. Overall, the study has shown that the use of check dams as a catchment management strategy of forested headwaters under semi-arid Mediterranean conditions should be considered with caution, since the structures could be ineffective to reduce water and sediment flows during floods or, in some cases, check dams may increase erosion rates

Longitudinal Strain Analysis and Correlation with TIMI Frame Count in Patients with Ischemia with No Obstructive Coronary Artery (INOCA) and Microvascular Angina (MVA)

Background: The aim of the study is to evaluate the subclinical alterations of cardiac mechanics detected using speckle-tracking echocardiography and compare these data with the coronary angiography indices used during coronary angiography in a population of patients diagnosed with ischemia with no obstructive coronary artery (INOCA) and microvascular angina (MVA). Methods: The study included 85 patients admitted to our center between November 2019 and January 2022 who were diagnosed with INOCA compared with a control group of 70 healthy patients. A collection of anamnestic data and a complete cardiovascular physical examination, and echocardiogram at rest with longitudinal strain were performed for all patients. Furthermore, the TIMI frame count (TFC) for the three coronary vessels was calculated according to Gibson’s indications. All parameters were compared with a control population with similar characteristics. Results: Patients with INOCA compared to the control population showed statistically significant changes in the parameters assessed on the longitudinal strain analysis. In particular, patients with INOCA showed statistically significant changes in GLS (−16.71) compared to the control population (−19.64) (p = 0.003). In patients with INOCA, the total TIMI frame count (tTFC) correlated with the GLS value with a correlation coefficient of 0.418 (p = 0.021). Conclusions: In patients with angina, documented myocardial ischemia, the absence of angiographically significant stenosis (INOCA) and LVEF > 50%, the prevalence of microvascular dysfunction documented by TFC was extremely represented. A statistically significant reduction in GLS was observed in these patients. TFC and longitudinal strain, therefore, appear to be two reliable, sensitive and easily accessible methods for the study of alterations in coronary microcirculation and the characterization of patients with INOCA and microvascular angin

Leptospira interrogans Serogroup Pomona in a Dairy Cattle Farm in a Multi-Host Zootechnical System

Bovine leptospirosis is an infectious zoonotic disease causing reproductive problems and economic losses in livestock. This work reports, for the first time in Sicily (South Italy), an outbreak of Leptospira interrogans serogroup Pomona that occurred in cattle farms within the Nebrodi Park and was mainly characterized by full-term abortion. Blood and urine samples were collected at different time points from animals of six different farms (Farms A–F) sharing the same grazing area. Research of antibodies against pathogenic Leptospira species in serum samples was carried out via Micro Agglutination Test (MAT). Urine samples were subjected to pathogen isolation and molecular analyses via TaqMan Real Time-PCR. Genotyping of Leptospira species was obtained by Multi-locus sequence typing. MAT detected antibodies against Leptospira interrogans serogroup Pomona in serum samples of all the farms. Pathogenic Leptospira spp. DNA and culture isolation was obtained from urine samples. Genotyping confirmed the excretion of L. interrogans serogroup Pomona. This study describes clinical manifestations, diagnostic implications and epidemiological characteristics of an outbreak in cattle due to L. interrogans Pomona in a protected multi-host area, where domestic and wild animals share the same habitat, suggesting a role of wild species in transmission and persistence of Pomona serogroup among cattle

Lysin (K)-specific demethylase 1 inhibition enhances proteasome inhibitor response and overcomes drug resistance in multiple myeloma

Abstract Background Multiple myeloma (MM) is an incurable plasma cell malignancy, accounting for approximately 1% of all cancers. Despite recent advances in the treatment of MM, due to the introduction of proteasome inhibitors (PIs) such as bortezomib (BTZ) and carfilzomib (CFZ), relapses and disease progression remain common. Therefore, a major challenge is the development of novel therapeutic approaches to overcome drug resistance, improve patient outcomes, and broaden PIs applicability to other pathologies. Methods We performed genetic and drug screens to identify new synthetic lethal partners to PIs, and validated candidates in PI-sensitive and -resistant MM cells. We also tested best synthetic lethal interactions in other B-cell malignancies, such as mantle cell, Burkitt’s and diffuse large B-cell lymphomas. We evaluated the toxicity of combination treatments in normal peripheral blood mononuclear cells (PBMCs) and bone marrow stromal cells (BMSCs). We confirmed the combo treatment’ synergistic effects ex vivo in primary CD138+ cells from MM patients, and in different MM xenograft models. We exploited RNA-sequencing and Reverse-Phase Protein Arrays (RPPA) to investigate the molecular mechanisms of the synergy. Results We identified lysine (K)-specific demethylase 1 (LSD1) as a top candidate whose inhibition can synergize with CFZ treatment. LSD1 silencing enhanced CFZ sensitivity in both PI-resistant and -sensitive MM cells, resulting in increased tumor cell death. Several LSD1 inhibitors (SP2509, SP2577, and CC-90011) triggered synergistic cytotoxicity in combination with different PIs in MM and other B-cell neoplasms. CFZ/SP2509 treatment exhibited a favorable cytotoxicity profile toward PBMCs and BMSCs. We confirmed the clinical potential of LSD1-proteasome inhibition in primary CD138+ cells of MM patients, and in MM xenograft models, leading to the inhibition of tumor progression. DNA damage response (DDR) and proliferation machinery were the most affected pathways by CFZ/SP2509 combo treatment, responsible for the anti-tumoral effects. Conclusions The present study preclinically demonstrated that LSD1 inhibition could provide a valuable strategy to enhance PI sensitivity and overcome drug resistance in MM patients and that this combination might be exploited for the treatment of other B-cell malignancies, thus extending the therapeutic impact of the project