Abstract Background Atrial myopathy is a complex condition due to a variety of causes resulting in mechanical and/or electrical remodeling and dysfunction. This can lead to arrhythmias (e.g. atrial fibrillation – AF) and/or heart failure (HF) symptoms. Surface 12-lead electrocardiogram (ECG) may provide the first clues about the presence of left atrial (LA) abnormalities. Interatrial blocks (IAB, partial – pIAB or advanced - aIAB) and abnormal P wave terminal force in lead V1 (aPtfV1) are recognized markers of electromechanical LA dysfunction. Chronic systemic inflammatory diseases are associated with increased cardiovascular risk. An increased incidence of AF has been reported in patients with rheumatoid arthritis (RA). However, the role of ECG with its markers of atrial myopathy in the context of RA have been never investigated so far. Purpose This observational cross-sectional study aimed to investigate: 1) the prevalence of ECG signs of atrial myopathy in RA and to compare it with that found in a selected cohort of control subjects; and 2) to assess the independent determinants of the presence of ECG features of atrial myopathy. Methods Two-hundred and eighteen patients with RA and 109 controls matched by age, gender and overall cardiovascular-risk profile underwent clinical evaluation and 12-lead ECG. The presence of IAB and or aPtfV1 was carefully investigated in all the ECG tracings. Patients with previous cardiovascular diseases and atrial fibrillation were excluded from the present study. Results Mean duration of the P wave on ECG was significantly longer in patients with RA than in controls (118±12 msec vs 112±10 msec, p<0.001). Similarly, pIAB was present in 43% of RA patients vs 21% of controls (p<0.001). The presence of aIAB was a rare finding being present only in 2 patients with RA. An abnormal PtfV1 was more frequently found in RA (27% vs 10%, p<0.001). Overall ECG features of atrial myopathy (i.e. aIAB or pIAB + abnormal PtfV1) were highly prevalent (15% vs 4%, p=0.003) in the RA group. There was a higher percentage of males in the subgroup of patients with RA and atrial myopathy (50% vs 28%, p=0.013). We did not find any relationship between RA disease duration and ECG features of atrial myopathy. On multivariate regression analysis male gender (OR [95% CI] = 3.07 [1.47–6.41], p=0.003) and RA (OR [95% CI] = 4.76 [1.51–14.4], p=0.006) were the only independent predictors of the presence of atrial myopathy on ECG. Conclusions ECG signs of atrial myopathy are highly prevalent in patients with RA compared to controls. A low-cost and easily available tool such as surface 12-lead ECG should be used in RA for the investigation and possibly early identification of LA myopathy. Further studies with advanced imaging techniques and specific laboratory markers could confirm these preliminary findings and help clarify the underlying pathophysiological mechanisms and the clinical correlates. Funding Acknowledgement Type of funding sources: None.

Long-term tumor control, toxicity and cosmetic outcomes for accelerated partial breast irradiation (APBI) delivered with Helical Tomotherapy have not been studied before now. We report our phase II trial results on 338 women with invasive disease treated with APBI-Tomotherapy at one institution after breast conservative surgery (BCS). From December 2010 to December 2018, we followed women with early invasive breast cancer treated with APBI-Tomotherapy with 38.5Gy in 10 once-daily fractions. Patients selected were: age ≥ 50 years old, with unifocal disease up to 3 cm in size with at least 2 mm of clear margins, without extensive intraductal disease (less than 25%) or lymph/vascular invasion. Disease outcomes were analyzed by clinicopathologic characteristics, molecular phenotypes and American Society for Radiation Oncology (ASTRO) 2016 updated consensus groupings (suitable, cautionary, and unsuitable). Median age was 65 yrs (range:50-86) and median follow-up was 72 months (range 12-110 months). Of the 338 women, 242 (= 71,6%) were ASTRO "suitable," 60, (= 17,8%) were "cautionary," and 36 (= 10,6%) were "unsuitable". Invasive lobular were 42 (= 12.5%), pN1 were 34 (= 10%) and 90%were luminal type. Six-year rates of ipsilateral breast tumor recurrence (IBTR), progression free survival (PFS) and cancer specific survival CSS were 0.6%, 98.2% and 99.4% respectively. IBTR were in two patients at 8 and 15 months from BCS in different sites of the same breast and away from the primary surgical irradiated bed. Two patients are alive with metastatic disease, two patients had a contralateral breast cancer, and two patients (HER+ and TN) died from disease. Axillary failure occurred in one patient (HER+) with distant metastases and death from disease. Acute and late skin toxicity, graded according to Common Terminology Criteria for Adverse Events version 4.0, were 7,7% (G1), 0.6% (G2), and 4.4% (G1), 1,1% (G2) respectively. There was no grade 3/4 toxicities however. One patient had a cutaneous fibrosis G1 and very few patients or physicians (1-4%) assessed cosmetic outcome as fair or poor at 2 years follow-up. According to recent results of the RAPID and NSABP B-39/RTOG 0413 randomized trials, our phase II trial on APBI-Tomotherapy shows excellent long-term results with good to excellent cosmetic outcome. The schedule once daily APBI treatment could be predictive of low adverse post-treatment toxicity as well as optimal cosmetic results. Select women in "cautionary" or "unsuitable" ASTRO grouping seem not prognostic for IBTR.

Studies in animal models and humans suggested that glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetically inherited condition causing haemolytic anemia, may be considered a risk factor for cardiovascular disease. It is currently unknown whether enzymatic activity may impact the extent and severity of coronary atherosclerosis in patients with acute myocardial infarction. This hypothesis was tested in a cohort of acute coronary syndrome (ACS) patients undergoing invasive management from Northern Sardinia, where the population prevalence of G6PD deficiency is the highest in the Mediterranean area. The study was based on a prospective single-centre registry of consecutive ACS patients undergoing coronary angiography and subsequent percutaneous revascularization between January 2017 and December 2018, in which G6PD activity has been measured quantitatively using a biochemical assay based on G6PD/6GPD ratio in erythrocytes. Subjects were defined as deficient when the ratio was <0.80. The primary endpoint of the study was the severity of coronary artery disease as assessed by the SYNTAX I score at baseline angiography. Among the 466 enrolled patients, 41 (9%) showed G6PD deficiency. Patients with G6PD deficiency were less likely to have a history of dyslipidemia (27% vs 50%; p=0.005) or diabetes (12% vs 21%; p=0.105). As expected, at admission patients with deficiency had lower hemoglobin level (12.1 vs 13.7 g/dL; p=0.005) as compared with those without. By angiography, SYNTAX score resulted as 19±9 and 16±9 (p=0.039) in patients with and without G6PD deficiency; while the number of diseased (with >50% stenosis) vessels was 1.9 vs 1.6 (p=0.089) in the 2 study groups. Left main disease was detected in 15% and 7% (p=0.06) patients, respectively. G6PD deficiency emerged as an independent predictor of high SYNTAX score (OR=2.16, 95% CI 1.1–4.5; p=0.037). Angioplasty with coronary stenting of the culprit vessel was performed in all patients, while GP IIb/IIIa inhibitors were used in 30% and 14% (p=0.009) of patients with and without G6PD deficiency. Finally, in-hospital events were similar between the 2 study groups. An increased extent and severity of coronary artery disease was observed in ACS patients with G6PD deficiency as compared with those without, despite the lower prevalence of “classic” cardiovascular risk factors.

Introduction: In prostate cancer radiotherapy, the relationship between genitourinary (GU) toxicity and clinical and dosimetric parameters is debated. The aim of this study is to analyze the associations among GU toxicity and dosimetric and clinical parameters in patients treated with 3D conformal radiotherapy for localized prostate cancer.

Conclusion:Treatment intensification in NSCLC via targeted dose escalation with modern delivery techniques offers the potential for a significant increase in tumour control probability without a clinically significant increase in predicted OAR toxicity.

Introduction: We analyzed the correlation between prostate movements and rectum and bladder filling during the treatment course.

Purpose or Objective: Image-guided intensity modulated radiotherapy (IG-IMRT) reduces dose to organs at risk (OARs) compared to 3D-conformal radiotherapy (3D-CRT).Currently it is not known to what extent this reduces late toxicity in prostate cancer patients.We previously reported on significant reductions in dose to OARs and acute toxicity.The aim of this study was to assess the therapeutic gain with IG-IMRT in terms of long-term toxicity reductions, and to establish to what extent acute toxicity was associated with late side effects.For that purpose we used prospective data of two randomized trials.

AIM:Fatigue can be defined as an unpleasant feeling of tiredness, weakness and lack of energy. It is found in about 80% of the patients receiving radiation therapy and has a significant impact on quality of life. The aim of this paper was to assess the frequency, severity and changes of fatigue before, during and after administration of a nutraceutical (mixture of whey protein with an high biological value, with an high content in native cysteine, albumin and lactoferrin in patients undergoing treatment for breast and prostate cancer.METHODS:Thirty patients (20 breast and 10 prostate ones) were enrolled in our test and they received a questionnaire about Fatigue developed by the University of Texas, MD Anderson Cancer Center, 1999. The patients who achieved a score between 4 and 6 were administered the nutraceutical (Prother) at a dose of 20 g / day for the first 10 days of radiation treatment and then 10 g/day for the following 20 days without considering the terms of the radiation oncology treatment [corrected]. Each patient was reassessed using the same Fatigue test after 10 and 30 days from the start of the administration of nutraceutical. We enrolled 30 control patients who did not receive Prother.RESULTS:The results showed the effectiveness of Prother in all patients with moderate-to-mild fatigue.CONCLUSION:The administration of Prother has therefore been effective in terms of both improving the compliance of the radiation treatment and the quality of life.

2nd ESTRO Forum 2013 S475 of 1.4 cm vertically, 1.6 cm longitudinally and 1 cm laterally in prostate cancer patients and 0.5 cm vertically or longitudinally and 0.7 cm laterally in H&N patients.In prostate cancer patients the 98% of the MTS were less then 1 cm, while in H&N patients the MTS was less than 0.5 cm in 92% of the cases.Therefore the mean (±SD) 3D vector of displacement was 0.3±0.7 cm and 0,2±0,4 cm for the prostate and H&N group respectively.The magnitude of roll variation was greater in both groups (mean (±SD) of -0.5±1.2° in prostate and a maximal value of 3.8° and a mean (±SD) of 1.3±1,2 ° in H&N with a maximal value of 3.4°).The pitch variations were greater for patients treated to the pelvis (means (±SD) of -0.4±1.1°vs -0.1±0.8° with a maximal value of 2.8° vs 1.9°), while the mean (±SD) interfractional yaw was 0.1±0.7° in prostate and 0.0±0.6° in H&N patients.No correlation was observed between the magnitude of translational and rotational shift in either group.The procedure of online correction added less than one minute to the treatment time when compared to IGRT without robotic 6 DOF couch.The total treatment time (±SD) (IGRT plus delivery) was: 14.52±2.02min., 15.26±1.52min., 24.53±5.47min.for prostate RapidArc, brain RapidArc and H&N IMRT respectively.Conclusions: This data confirms the relevance of rotational shifts in prostate and H&N patients.The correlation between immobilization systems and the rotational shift value is not strong enough to refrain from implementing the robotic couch in IGRT high precision radiotherapy treatments.

In all species studied, the basic fibroblast growth factor (bFGF) gene is transcribed into multiple mRNAs, one of which is an antisense RNA (1B FGF-AS) probably involved in regulating the stability of the sense transcript. In this study we investigated whether the regulatory mechanisms of bFGF expression might be altered in endometrial stromal cells derived from women with endometriosis. bFGF and 1B FGF-AS mRNA levels were quantified in primary cultures of eutopic endometrial stromal cells derived from 29 women without endometriosis and 24 patients affected by the disease. When the data were analyzed according to the phase of the menstrual cycle, endometrial stromal cells derived from patients in the late proliferative phase showed significantly higher bFGF mRNA values and significantly lower 1B FGF-AS mRNA levels compared with control samples. Furthermore, the mean bFGF/1B FGF-AS mRNA ratio was significantly higher in endometrial stromal cells derived from patients compared with that in controls (mean +/- SEM, 2.31 +/- 0,55 and 0.77 +/- 0.14, respectively; P = 0.009). Moreover, for bFGF expression the differences existing at the mRNA level were maintained at the protein level. These findings support the hypothesis that 1B FGF-AS mRNA could regulate the expression of the sense transcript and suggest that in endometrial cells derived from patients, the presence of higher bFGF levels could improve their ability to proliferate at the ectopic site.

Endometriosis is a gynaecological disease with a certain genetic background, but the locations of possible genomic aberrations are still poorly clarified. Intercellular adhesion molecule-1 (ICAM-1), which is a surface glycoprotein that promotes adhesion in immunological and inflammatory reactions, seems to play a role in this condition. The aim of this study was to examine the potential associations of ICAM-1 gene polymorphisms with endometriosis and its severity. Specifically, we have studied two polymorphic sites located in codons 241 (G/R241) and 469 (E/K469) of the ICAM-1 gene. Three hundred and sixty-three Italian Caucasian women of reproductive age who underwent laparoscopy for benign pelvic conditions were enrolled in the study. Endometriosis was documented and staged in 188 women while 175 subjects, in whom endometriosis was laparoscopically ruled out, served as the control group. The frequency of the R241 allele was only marginally higher in endometriosis patients than in controls [5.8 versus 2.9%, P = 0.05; odds ratio (OR), 2.1; 95% confidence interval (CI), 1-4.5]. However, a strikingly high frequency of this allele was found in patients with Stage IV endometriosis versus controls (8.6 versus 2.8%, P = 0.008; OR, 3.2; 95% CI, 1.3-7.9). In contrast, the allele and genotype frequencies of the E/K469 polymorphism did not differ significantly between endometriosis and control groups. While the functional correlate of the G/R241 polymorphism remains unclear, this finding indicates that a genetic polymorphism in the ICAM-1 gene domain may contribute to the susceptibility to endometriosis.

We studied the potential role of innovative diagnostic tools for the management of patients with differentiated thyroid cancer (DTC). Several methods for the detection of the tumor marker thyroglobulin (Tg) have been employed in 36 patients in apparent remission at the moment of the study. All patients had negative anti-Tg antibodies and were evaluated during L-T(4) suppressive therapy before and after stimulation with recombinant human TSH (rhTSH). Serum Tg was measured by means of conventional [nonhighly sensitive (nhs)] or highly sensitive (hs) immunoassays with positive cut-off values set at 1.0 and 0.18 microg/liter, respectively. The RT-PCR conditions for the qualitative determination of Tg mRNA from peripheral blood were optimized to prevent interference by illegitimate transcription. The patients have been classified on the basis of a hs-basal Tg testing by taking into account the results of their baseline samples in hs immunoassay and RT-PCR method; hs-basal Tg testing was considered positive when the marker was detectable in at least one of the two tests. The predictive value of hs-basal Tg testing was estimated on the basis of a global clinical evaluation, including serum Tg response after rhTSH stimulation and reports of contemporary (131)I scan and neck ultrasound. The clinical evaluation was considered positive when at least one of these criteria yielded positive results. Although nhs-Tg measurement was poorly predictive of the clinical status, basal hs-Tg evaluation was found to be concordant with the clinical evaluation in 71% of cases. Results of basal Tg mRNA detection did not vary after rhTSH stimulation and were concordant with the clinical evaluation in 66% of cases. Tg mRNA evaluation alone showed 10 apparently false-positive results, and serum basal hs-Tg was falsely negative in 11 additional cases, suggesting that a suitable predictability could be obtained by the association of these 2 parameters. Indeed, the combination of hs-Tg assay and mRNA detection in the hs-basal Tg testing allowed the identification of 22 patients with a positive persistent/recurrent disease or normal thyroid residue, as well as identification of all 6 patients with a negative clinical evaluation. In conclusion, the combined evaluation of circulating Tg mRNA and serum Tg by means of hs noncompetitive immunoassay (hs-basal Tg testing) can give useful information on the clinical status of patients with DTC who are apparently disease-free, even on L-T(4) TSH-suppressive therapy. Therefore, these combined evaluations retain a potential role in the clinical monitoring of DTC patients. In particular, a negative hs-basal Tg testing would indicate disease remission and the opportunity to lengthen the intervals between rhTSH stimulations and/or to shift patients to a less profound TSH suppression with L-T(4).

Objective: Basic fibroblast growth factor (bFGF) is a heparin-binding cationic peptide, member of a family of related proteins whose basic structure has been conserved throughout evolution. In all species studied, the bFGF gene is transcribed into multiple mRNAs deriving from different polyadenilation sites. It has been demonstrated, first in the Xenopus Laevis and subsequently in human and rat tissues, that one of these mRNAs is an antisense RNA (FGF-AS) transcribed from the opposite strand of the gene, likely involved in regulating stability of the sense transcript. The nucleotide sequence of this FGF-AS mRNA is strongly conserved among species. Basic FGF mitogenic and angiogenic properties have been well characterized in endometrial physiology but their involvement in endometriosis is still to be elucidated. We have previously demonstrated that endometriosis cells derived from large cysts have increased bFGF mRNA levels. Based on the evidence in this study we investigated whether the regulatory mechanisms of bFGF expression might be altered in endometrial stromal cells derived from women affected by endometriosis. Design: To this aim bFGF and FGF-AS mRNAs levels were evaluated in samples of eutopic endometrial stromal cells obtained from 34 consecutive women undergoing laparoscopy for pelvic pain and or infertility. Patients with no laparoscopic evidence of endometriosis served as control group. Materials/Methods: Basic FGF and FGF-AS mRNA levels were quantified in primary cultures of eutopic endometrial stromal cells derived from 19 controls and 15 patients using Competitive-PCR.The amplified DNA fragments were visualized on an agarose gel and analyzed by laser densitometer. Unpaired t-student was used to evaluate differences in mRNA values among the two groups studied. Results: Both transcripts were present in all samples, however, their expression resulted to be different between the two groups of women. When the data were analyzed according to the phases of the menstrual cycle, in the central phase (days 10–18) endometrial stromal cells derived from women affected by endometriosis showed significant higher bFGF mRNA values and significant lower FGF-AS mRNA levels compared to control samples. The ratio between bFGF mRNA and FGF-AS mRNA values was calculated and the mean ratio resulted significantly higher in endometrial cells derived from women affected by endometriosis when compared to that obtained from endometrial cells of control patients (mean ratio ± S.E : 2.69 ± 0.65 and 0.83 ± 0.15 respectively). Conclusions: The results of this study indicate that in eutopic endometrial cells of endometriosis women the expression of bFGF and FGF-AS mRNAs is inversely correlated. This finding further support the hypothesis that FGF-AS mRNA could regulate the expression of the sense transcript. Moreover, the higher expression of bFGF mRNA observed in these cells suggest that they have an increased capacity to synthetize bFGF. Based on these data, it is tempting to speculate that an altered regulation of bFGF expression could be among the factors that favour the proliferation of endometrial cells leading to endometriosis. Supported By: No support.