Hyperprogression and Immune Checkpoint Inhibitors: Hype or Progress?

There are currently seven approved immune checkpoint inhibitors (ICIs) for the treatment of various cancers. These drugs are associated with profound, durable responses in a subset of patients with advanced cancers. Unfortunately, in addition to individuals whose tumors show resistance, there is a minority subgroup treated with ICIs who demonstrate a paradoxical acceleration in the rate of growth or their tumors-hyperprogressive disease. Hyperprogressive disease is associated with significantly worse outcomes in these patients. This phenomenon, though still a matter of dispute, has been recognized by multiple groups of investigators across the globe and in diverse types of cancers. There are not yet consensus standardized criteria for defining hyperprogressive disease, but most commonly time to treatment failure less than 2 months and an increase in pace of progression of at least twofold between pre-immunotherapy and on-treatment imaging has been used. In some patients, the change in rate of progression can be especially dramatic-up to 35- to 40-fold. MDM2 amplification and EGFR mutations have been suggested as genomic correlates of increased risk of hyperprogression, but these correlates require validation. The underlying mechanism for hyperprogression is not known but warrants urgent investigation

Oral health status and periodontitis in Alzheimer's disease patients: A case control Study in a Sicilian rural community

Aim. Dementia is a common disorder among the elderly. Alzheimer’s disease (AD) is the most common cause of dementia. In addition to known risk factors (e.g. age and familiarity) of AD, recently it has been suggested a possible promoting role for chronic inflammatory infective diseases. Periodontal disease (PD) is a frequent chronic multi-bacterial infection involving the tissues supporting the teeth; in addition to promoting inflammation locally, the periodontal pathogens possess mechanisms able to influence the systemic balance of inflammatory mediators. Similarly to other systemic diseases (e.g. cardiovascular disease, diabetes, renal diseases and low birth weight), a possible link has been proposed between PD and the development and progression of AD. Aim of the present study was to evaluate the oral health status and the prevalence/severity of PD in a group of patients affected by AD compared to a control group of healthy subjects. Materials and methods. A case-controlled clinical trial was designed to compare patients with AD (Test group - T; n = 16; M: 8; F: 8, range age 64-93 yrs) with healthy controls (Control group - C; n = 16; M: 8; F:8; range age 64-92 yrs). The population study was named ZAP (Zabut Aging Project) and all participants, enrolled in a Sicilian rural community (Sambuca di Sicilia, AG, Italy), were matched for age and sex. Following variables were recorded: smoking and drinking habits, number of teeth, Decayed Missed Filled Teeth scoring (DMFT), measurement of the probing depth (CPI and PSR index). The association between AD and PD, socio-demographic and behavioural-clinical variables was assessed using the χ2 test or Fisher’s exact test, as appropriate. To measure the association level, crude OR and the 95% Confidence Interval (CI) were calculated. Statistical significance of the difference in the average DMFT between cases and controls was assessed using the Student’s t-test. A p value ≤0.05 was considered statistically significant. Results. One patient of T group was a smoker versus four of C group; four T patients were drinker versus two of C group. Seven of T group (43.7%) were totally edentulous, conversely only 2 (12.5%) of controls have the same condition (p=0.04). With respect to oral status, DMFT index was 23.7 ±9.0 in T patients versus 25.2±7.8 in controls (p=0.633). There were no significant differences between T and C groups regarding periodontal index: high PSR and CPI scores (>3) were recorded in 77.8% of AD patients and 46.1% of health cases (p >0.05). A similar distribution among two groups was observed regarding the other investigated variables (e.g. smoking and drinking habits). Conclusions. In this rural Sicilian adult/elderly community, poor oral health is frequent with a DMFT score higher than general population. The obtained data do not support the hypothesis of a major prevalence and severity of PD among AD patients. However, to confirm these preliminary results the recruitment of a wider sample size and further data, regarding proteomic salivary profiles and RT PCR-based microbiological investigation on sub-gingival plaque samples, still need in order to better clarify the role of PD and periodontal pathogens in the AD natural history

Infectious endocarditis during pregnancy, problems in the decision-making process: a case report

Infective endocarditis in pregnancy has a low incidence, often being associated with a previous history of rheumatic or congenital heart disease. In most reports the disease tends to run a subacute course and to appear more frequently in the third trimester of pregnancy. We present the case of a 36-year-old woman with large vegetations on the mitral valve due to infective endocarditis detected at the 32nd week of her first pregnancy. The difficulties in selecting the appropriate management strategy, particularly optimal time and mode of delivery, optimal time and type of valve surgery, are emphasized

Is hyperprogressive disease a specific phenomenom of immunotherapy?

Hyperprogressive disease (HPD) is a novel pattern of response during immunotherapy treatment. Several retrospective studies have evaluated its prevalence among various cancer types and, in particular, in non-small cell lung cancer patients, based on different definition criteria. If HPD is a just a typical phenomenon of immunotherapy is still an unsolved concern. This paper summarized the available data about HPD in other cancer treatments. Hyperprogressive disease (HPD) is a novel pattern of response during immunotherapy treatment. Several retrospective studies have evaluated its prevalence among various cancer types and, in particular, in non-small cell lung cancer patients, based on different definition criteria. If HPD is a just a typical phenomenon of immunotherapy is still an unsolved concern. This paper summarized the available data about HPD in other cancer treatments

Hydrogeological Features and Sustainable Use of Geothermal Resources: Selected Case Studies in Italy

Within the framework of the activities aimed at studying current and future exploitation and the related sustainability of geothermal resources, and considering the key role hydrogeology plays in the study of geothermal systems and design of installations, in October 2012 the Working Group IDROGEOTER was set-up within the IAH (International Association of Hydrogeologists) Italian Chapter. The first activity of IDROGEOTER‘s workplan is the analysis of state of the art in current use of low-to high enthalpy geothermal resources in Italy and of the hydrogeological settings resulting from features (e.g.: hydrostratigraphy, hydraulic and hydrodynamic conditions, hydrogeochemistry, …) influencing the availability of the resource and the potential of the systems. Detailed studies supporting the possible optimization of the use of geothermal resources, carried out in different areas (see figure) and under different hydrogeological conditions in Italy, are described in the paper. In the Piedmont Region (NW Italy) several experimental sites have been investigated in order to assess the potential subsurface effects of open-loop Groundwater Heat Pumps (GW-HPs) plants for the cooling and heating of buildings. A comparison between field measures and numerical modelling results reveals that the most important aquifer parameters affecting the developing of the Thermal Affected Zone (TAZ) around the injection wells are those related to advective heat transfer. The Lombardy Region (N Italy) is currently the most populated and industrialized region in Italy and therefore the area where the highest number of GWHP plants (open and closed loop) are installed, from which a representative sample will be selected with the objective of identifying the critical hydrogeological factors contributing both to the geothermal potential and to a sustainable use of the resource. In the Veneto Region (NE Italy), the Euganean Geothermal Field is the most important thermal field in northern Italy (about 250 active wells) and the thermal waters (65-86 °C) are mainly used for spas; recently, a new conceptual model of the Euganean Geothermal System has been proposed and tested in a numerical model; with regard to low enthalpy, studies on sites potentially suitable for closed-loop and open-loop systems, together with data from automated monitoring of several wells, could be used for advanced analysis of different hydrogeothermal systems. Research activities in the Lazio Region (Central Italy) focus also on low enthalpy and are specifically aimed at the mapping of the geothermal potential of aquifers, and at pilot studies of sites characterized by gravel aquifers, alluvial Holocene deposits of the Tevere River and alluvial pre-volcanic Pleistocene deposits. In the Campania Region (S Italy - Mondragone plain), in the framework of the geothermal exploration programme “VIGOR” (Evaluation of Geothermal Potential in Convergence Region), a groundwater balance, verifying the recharge area of thermal springs (temperature 33-54 °C) connected to a large carbonate aquifer, has permitted the identification of the most suitable area in which to drill a geothermal well. In the Apulia Region (SE Italy) the thermal field trends consequent to groundwater advection and the influence of seawater intrusion have been reconstructed for two karstic coastal aquifers (Murgia and Salento) at various elevation between -5 and -100 m amsl. These reconstructions are intended to provide required base knowledge for correctly implementing low enthalpy HP plants in the saturated zones. Further studies and inventory of data and applications will be part of the activities of IDROGEOTER, which will also include the preparation of a proposal of guidelines for hydro-geothermal studies

Iodine Intake Estimated by 24 h Urine Collection in the Italian Adult Population: 2008–2012 Survey

Monitoring the population iodine status is essential for iodine deficiency eradication. This study assessed the average dietary iodine intake and the iodine status of a random sample of the Italian general adult population. The study population included 2378 adults aged 35–79 years (1229 men and 1149 women) from all 20 Italian regions, participating in the Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey 2008–2012 (OEC/HES), and were examined for iodine intake in the framework of the MINISAL-GIRCSI Programme. Dietary iodine intake was assessed by the measurement of 24 h urinary iodine excretion. The median daily iodine intake of the whole population was lower (96 μg/d, interquartile range 51–165) than the daily adequate iodine intake according to both EFSA and WHO recommendation (150 μg/d), with a significantly lower value among women (85 μg/d) compared with men (111 μg/d). Iodine intake diminished with age and increased with BMI (body mass index) in male but not in female participants, without achieving the adequate intake in any sex, age, or BMI category. In this random sample of Italian general adult population examined in 2008–2012, iodine intake still remained lower than the recommended val- ues despite the implementation of a strategy of iodoprophylaxis based on salt iodization in 2005. These data represent a valuable reference for future monitoring of iodine status in our country

Relationship between anxiety level and radiological investigation. Comparison among different diagnostic imaging exams in a prospective single-center study

Objective: Every patient could feel anxious when he waits in a radiological department to undergo diagnostic exams. The aim of our study is to evaluate the impact of the radiological exams on patient anxiety. Materials and methods: We evaluated 343 patients (mean age 54.83 years) who underwent different types of diagnostic exams in the Department of Diagnostic Imaging at our Hospital from April 2013 to August 2014. We administered to patients the State and Trait Anxiety Inventory Test, which detected with high sensitivity both state anxiety and trait anxiety. A team of clinical psychologists and radiologists evaluated the scores obtained. Results: 83 out of 343 patients were excluded because refused to file the questionnaire. 31 % of the patients were submitted to MR, 18 % to breast imaging, 10 % to X-ray, 22 % Computer Tomography and 19 % to ultrasound, as previously described. 41 % of patients were submitted to the examination because of an oncologic disease, while 59 % because of non-oncological disease. Therefore, it was found that high levels of anxiety were present in most (about 91 %) of the patients and the scores varied according to the imaging examination and to the examination’s reason: anxiety level was higher in non-oncological patients (54 %) and in patients waiting to undergo to MRI exams (29 %). Conclusion: Our data suggest that the diagnostic exams are stressful events for the patient, also in non-oncological patients. So, it is important to adequate the radiological staff to receive the patient, to inform him and perform exams with emotive involvement with a targeted education. Also, further studies are needed to evaluate the anxiety level and the quality of the images, because the anxiety can result in a somatic disorder with hyperactivity of the autonomic nervous system which may affect the patient’s physical examination, causing problems in the evaluation of radiological images making to non-cooperative patient. MRI imaging is the examination that more of all led to an anxious state of patients but the main stressor is not related to the type of diagnostic examination, but to the uncertainty of the diagnosis, therapy and prognosis

EPSILoN score: Validation cohort of a prognostic score in advanced non-small cell lung cancer (aNSCLC) patients treated with immunotherapy

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A giant mediastinal teratoma: From diagnosis to complete resection and restitutio ad integrum.

The current report highlights the integrated work-up of an unexpected giant mediastinal teratoma in 28 years old female. A comprehensive multi-modality imaging approach was implemented in order to define the diagnosis and tailor the most appropriate surgical intervention

Trend in potassium intake and Na/K ratio in the Italian adult population between the 2008 and 2018 CUORE project surveys

Abstract Background and aims Low potassium intake, in addition to high sodium, has been associated with higher risk of hypertension and CVD. The Study assessed habitual potassium intake and sodium/potassium ratio of the Italian adult population from 2008 to 2012 to 2018–2019 based on 24-h urine collection, in the framework of the CUORE Project/MINISAL-GIRCSI/MENO SALE PIU' SALUTE national surveys. Methods and results Data were from cross-sectional surveys of randomly selected age-and-sex stratified samples of resident persons aged 35–74 years in 10 (out of 20) Italian regions. Urinary electrolyte and creatinine measurements were performed in a central laboratory. Analyses considered 942 men and 916 women, examined in 2008–2012, and 967 men and 1010 women, examined in 2018–2019. In 2008–2012, the age-standardized mean of potassium intake (urinary potassium accounts for 70% of potassium intake) was 3147 mg (95% CI 3086–3208) in men and 2784 mg (2727–2841) in women, whereas in 2018–2019, it was 3043 mg (2968–3118) and 2561 mg (2508–2614) respectively. In 2008–2012, age-adjusted prevalence of persons with an adequate potassium intake (i.e. ≥ 3510 mg/day) was 31% (95% CI 28–34%) for men and 18% (16–21%) for women; in 2018–2019, it was 26% (23–29%) and 12% (10–14%) respectively. The sodium/potassium ratio significantly decreased both in men and women. Conclusions The average daily potassium intake of the Italian general adult population remains lower than the WHO and EFSA recommended level. These results suggest the need of a revision to strengthen initiatives for the promotion of an adequate potassium intake at the population level