Extracellular volume measured by whole body CT scans predicts chronic cardiotoxicity in breast cancer patients treated with neoadjuvant therapies based on anthracyclines: A retrospective study.

INTRODUCTION: Neoadjuvant chemotherapies for breast cancer (BC) are effective but potentially cardiotoxic, and expose long survivors at risk of chemotherapy-related cardiac dysfunction (CTRCD). Unfortunately, early screening for CTRCD has actual diagnostic limits. Myocardial extracellular volume (mECV) is a radiological marker used in cardiac CT scans and cardiac magnetic resonance for diagnosis and follow-up of CTRCD. It can be measured in whole-body CT (WB-CT) scan, routinely performed in patients at high risk of relapse, to evaluate CTRCD occurrence during oncological follow-up. METHODS: 82 WB-CT scans were examined at baseline (T0) and during oncological follow-up at first year (T1) and fifth year (T5) after the end of neoadjuvant treatment. mECV was measured at 1 min (PP) and 5 min (DP) after contrast injection. 31 echocardiograms were retrieved in T1 to perform a linear correlation between mECV and left ventricular ejection fraction (LVEF). RESULTS: mECV values in T0 were similar between the two groups both in PP and in DP. Significant results were found for PP values in T1 (37.0 % vs 32 %, p = 0.0005) and in T5 (27.2 % vs 31.2 %, p = 0.025). A cut-off value of 35 % in PP proved significant in T1 (OR = 12.4, p = 0.004), while mECV was inversely correlated with LVEF both in PP (adj-S = -3.54, adj-p = 0.002) and in DP (adj-S = -2.51, adj-p = 0.0002), suggesting a synergistic action with the age at diagnosis (p < 0.0001, respectively). CONCLUSIONS: WB-CT scans performed during oncological reassessment in patients at high-risk of recurrence could be used for CTRCD screening in cardiovascular low-risk patients, especially in aging patients with mECV values above 35 %.

Ankle sprain and podoscopic footprint pattern in female volleyball players.

Ankle sprain (AS) is the most common sports injury that can be complicated by chronic joint instability. The aim of this study was to examine the relationship between foot types and the ankle sprain events suffered during the sport career in female volleyball players. In this retrospective study, we randomly selected 98 female volleyball players competing in several divisions. Data were obtained from self-administered questionnaires in which the athlete noted data about volleyball practice, whether they had had ankle sprains and the number of these events. Plantar footprint was photographed by a plantoscope classifying each foot as normal, flat or cavus (196 feet). Of the 196 feet, 145 (74.0%) were normal, 8 (4.1%) were flat 43 and (21.9%) were cavus. Thirthy-five athletes reported at least one AS during volleyball practice. In total 65 sprain injuries were reported (35 to the right side and 30 to the left side). In 22 ankles (14 right, 8 left) sprain reinjure (AS >1) have been reported. A higher AS reinjury rate is correlated to the cavus footprint pattern (p = 0,005). Cavus foot associates to a higher risk of reinjury for ankle sprains in female volleyball players. Knowing the athletes which are more likely to sustain a reinjure may be helpful for the orthopedic surgeon to plan preventive strategies.

One year of surgical mask testing at the University of Bologna labs: Lessons learned from data analysis.

The outbreak of SARS-CoV-2 pandemic highlighted the worldwide lack of surgical masks and personal protective equipment, which represent the main defense available against respiratory diseases as COVID-19. At the time, masks shortage was dramatic in Italy, the first European country seriously hit by the pandemic: aiming to address the emergency and to support the Italian industrial reconversion to the production of surgical masks, a multidisciplinary team of the University of Bologna organized a laboratory to test surgical masks according to European regulations. The group, driven by the expertise of chemical engineers, microbiologists, and occupational physicians, set-up the test lines to perform all the functional tests required. The laboratory started its activity on late March 2020, and as of the end of December of the same year 435 surgical mask prototypes were tested, with only 42 masks compliant to the European standard. From the analysis of the materials used, as well as of the production methods, it was found that a compliant surgical mask is most likely composed of three layers, a central meltblown filtration layer and two external spunbond comfort layers. An increase in the material thickness (grammage), or in the number of layers, does not improve the filtration efficiency, but leads to poor breathability, indicating that filtration depends not only on pure size exclusion, but other mechanisms are taking place (driven by electrostatic charge). The study critically reviewed the European standard procedures, identifying the weak aspects; among the others, the control of aerosol droplet size during the bacterial filtration test results to be crucial, since it can change the classification of a mask when its performance lies near to the limiting values of 95 or 98%.

A systematic review and meta-analysis of PD-1/PD-L1 inhibitors in specific patient subgroups with advanced gastro-oesophageal junction and gastric adenocarcinoma.

BACKGROUND: immune checkpoint inhibitors(ICIs) have shown contradictory results in patients with advanced gastro-oesophageal junction/gastric cancer(GOJ/GC). AIM: to identify specific patient subgroups that would derive survival benefit from ICIs. METHODS: a subgroup meta-analysis of randomised clinical trials(RCTs) was carried out. RESULTS: four phase-III-RCTs were identified with data on the following variables: primary location(Gastric vs GOJ); age(≤ 65 vs >65); gender(male vs female); ECOG PS(0 vs 1); ethnicity (Asian vs non-Asian), histology(intestinal vs diffuse), PD-L1 expression(≥ 1% vs < 1%). PD-L1 positivity was significantly associated with survival benefit from ICIs (HR: 0.82, p 0.047), with a significant interaction between PD-L1 expression and ICI efficacy (interaction HR: 1.41, p 0.02). Numerically, the second most relevant interaction was ICI efficacy and gender, with ICI being more effective in males. CONCLUSION: The PD-L1 positive patient subgroup derives significant survival benefit from ICI in GOJ/GC, however other predictors are eagerly needed to further refine patient selection.

Biological and predictive role of ERCC1 polymorphisms in cancer.

Excision repair cross-complementation group 1 (ERCC1) is a key component in DNA repair mechanisms and may influence the tumor DNA-targeting effect of the chemotherapeutic agent oxaliplatin. Germline ERCC1 polymorphisms may alter the protein expression and published data on their predictive and prognostic value have so far been contradictory. In the present article we review available evidence on the clinical role and utility of ERCC1 polymorphisms and, in the absence of a 'perfect' trial, what we call the 'sliding doors' trial, we present the data of ERCC1 genotyping in our local patient population. We found a useful predictive value for oxaliplatin-induced risk of anemia.

Role of Serum and Glucocorticoid-Inducible Kinase (SGK)-1 in Senescence: A Novel Molecular Target Against Age-Related Diseases.

Senescence is a phenomenon characterized by a progressive decline of body homeostasis. Premature senescence acts when the cellular system is not able to adequately respond to noxious stimuli by synthesis of stressor molecules. Among those, serum-and-glucocorticoidinducible kinase-1 (SGK-1) dramatically increases under typical physiopathological conditions, such as glucocorticoid or mineralcorticoids exposure, inflammation, hyperglycemia, and ischemia. SGK-1 has been implicated in mechanism regulating oxidative stress, apoptosis, and DNA damage, which are all leading to a state of accelerating aging. Moreover, SGK-1-sensitive ion channels participate in the regulation of renal Na(+)/K(+) regulation, blood pressure, gastric acid secretion, cardiac action potential, and neuroexcitability. Recently, we demonstrated in endothelial cells as an increase in SGK-1 activity and expression reduces oxidative stress, improves cell survival and restores insulin-mediated nitric oxide production after hyperglycemia. Moreover, we showed as SGK-1 delays the onset of senescence by increasing telomerase activity, significantly decreasing reactive oxygen species (ROS) production, and by directly interacting with hTERT. Therefore, SGK-1 may represent a specific target to further develop novel therapeutic options against chronic diseases such as diabetes typical of aging. SGK-1 has been also associated with cancer, neurodegenerative diseases, and cardiovascular disease, among other age-related diseases. However, to date, the data available on SGK-1 and aging, are sparse, controversial, and only from C. elegans experimental models. In this review we sought to discuss the possible implication of SGK-1 in mechanisms regulating senescence and age-related diseases. Moreover, we aimed to discuss and identify the possible role of SGK-1 as possible molecular target to counteract and prevent aging.

Predictive value of HDL cholesterol for cancer-associated venous thromboembolism during chemotherapy.

BACKGROUND: Dyslipidemia is a well-known risk factor for the development of atherothrombosis; however, its involvement in venous thromboembolism (VTE) is still debated. Low levels of HDL cholesterol (HDL-C) have been found to be associated with VTE, which is a common complication of cancer and its treatment. VTE incidence is increased in cancer patients, especially those undergoing chemotherapy. OBJECTIVE: We sought to investigate the value of pretreatment HDL-C in the risk prediction of future VTE in a population of ambulatory cancer patients undergoing chemotherapy. PATIENTS AND METHODS: Blood lipid composition was retrospectively evaluated in 592 consecutive patients with primary (n = 373) or relapsing/recurrent (n = 219) solid cancers at the start of a new chemotherapy regimen (12% neoadjuvant, 31% adjuvant, 57% metastatic). RESULTS: VTE occurred during chemotherapy in 38 patients (median time-to-event: 3 months). Mean HDL-C levels were lower in patients who developed VTE during chemotherapy (41 mg dL(-1) ; standard deviation [SD] 13 mg dL(-1) ) than in those who did not (48 mg dL(-1) ; SD 14 mg dL(-1) ). Cox proportional hazard survival analysis showed that HDL-C levels ≤ 43 mg dL(-1) were able to significantly predict a first VTE episode, with a hazard ratio of 2.87 (95% confidence interval 1.45-5.68). Moreover, patients with HDL-C levels ≤ 43 mg dL(-1) had worse 1-year VTE-free survival (86%) than those with HDL-C levels > 43 mg dL(-1) (96%; log rank test, 3.14). CONCLUSIONS: Patients with low HDL-C levels have a three-fold higher risk of developing a first VTE episode during chemotherapy. Baseline analysis of HDL-C levels might be of clinical value in predicting VTE in cancer outpatients treated with anticancer drugs.

Clinical models and biochemical predictors of VTE in lung cancer.

Venous thromboembolism (VTE) is a frequent complication of lung cancer and its treatment, especially in the advanced stages of disease. The risk of a pro-thrombotic state might increase through the activation of hemostasis, occurring both via the induction of a pro-coagulant activity and with platelet involvement, ultimately leading to the development of metastases. Despite the acknowledgement of an increased thrombophilic condition in cancer patients, and the experimental evidence that heparin compounds may have direct anticancer benefits, there is no univocal consent regarding VTE prevention in cancer outpatients receiving therapy. Thus, many authors highlighted the need for the development of stratification techniques to identify at-risk patients who might benefit from thromboprophylaxis. Clinical risk models were developed and validated, in order to assign high-risk patients to a proper thromboprophylaxis regimen that, however, might not be justified in all clusters. Besides, efforts have been devoted to identify candidate biomarkers that may be used in VTE risk assessment, although none has been recognized, so far, as a predictor for VTE in lung cancer patients. In this review, we will summarize the latest information concerning this very controversial topic, with focus on some of the proposed strategies to select the appropriate patients for prophylaxis.

A prospective observational study to evaluate G-CSF usage in patients with solid tumors receiving myelosuppressive chemotherapy in Italian clinical oncology practice.

Febrile neutropenia (FN) is a severe dose-limiting side effect of myelosuppressive chemotherapy in patients with solid tumors. Clinical practice guidelines recommend primary prophylaxis with G-CSF in patients with an overall ≥ 20 % risk of FN. AIOM Italian guidelines recommend starting G-CSF within 24-72 h after chemotherapy; for daily G-CSF, administration should continue until the absolute neutrophil count (ANC) is 1 × 10(9)/L post-nadir and should not be terminated after ANC increase in the early days of administration. The aim of this study was to assess guideline adherence in oncology practice in Italy. In this multicenter, prospective, observational study, patients were enrolled at the first G-CSF use in any cycle and were followed for two subsequent cycles (or until the end of chemotherapy if less than two additional cycles). Primary objective was to explore G-CSF use in Italian clinical practice; therefore, data were collected on the G-CSF type, timing of administration, and number of doses. 512 eligible patients were enrolled (median age, 62). The most common tumor types were breast (36 %), lung (18 %), and colorectal (13 %). A total of 1,164 G-CSF cycles (daily G-CSF, 718; pegfilgrastim, 446) were observed. Daily G-CSF was administered later than 72 h after chemotherapy in 42 % of cycles, and the median [range] number of doses was four [1, 10]. Pegfilgrastim was administered later than 72 h in 8 % of cycles. G-CSF prophylaxis in Italy is frequently administered in a manner which is not supported by evidence-based guidelines. As this practice may lead to poor outcomes, educational initiatives are recommended.

TNF-α gene promoter polymorphisms and risk of venous thromboembolism in gastrointestinal cancer patients undergoing chemotherapy.

BACKGROUND: TNF-α has been proposed as a predictive factor for venous thromboembolism (VTE). Genetic polymorphisms could regulate TNF-α production. However, the relationship between TNFA gene variants and VTE is not clarified. This study aims to investigate the predictive role of five different TNFA gene promoter SNPs, or their haplotype combination(s), for a first VTE episode in gastrointestinal cancer out-patients treated with chemotherapy. PATIENTS AND METHODS: Serum TNF-α levels and TNFA -863C/A, -857C/T, -376G/A, -308G/A and -238G/A gene promoter polymorphisms were retrospectively evaluated in 314 subjects, including 157 controls and 157 Caucasian patients with histologically diagnosed GI cancers beginning chemotherapy delivery (5-fluorouracil either as monotherapy or in combination with platinum compounds or irinotecan). RESULTS: Haplotype analysis showed that a five-loci haplotype (CTGGG haplotype) has higher frequency in GI cancer patients who developed VTE (n = 15) during chemotherapy [odds ratio = 2.7, 95% confidence interval (CI) 1.04-7.11, P = 0.04]. GI patients who remained VTE-free did not differ in CTGGG haplotype frequency from controls. No association was observed between serum TNF-α levels and TNFA haplotype, but both were independent predictors of VTE. Approximately 20% of GI cancer patients carrying the CTGGG haplotype developed VTE compared with 4% of the remaining 101 patients (hazard ratio = 5.6, 95% CI 1.8-17.6, P = 0.003). CONCLUSION: These results suggest that TNFA might represent a candidate gene contributing to VTE pathogenesis in GI cancer patients and suggest that VTE risk during chemotherapy might be genetically identified. Validation studies are needed for translation into clinical practice.

A probiotics-containing biscuit modulates the intestinal microbiota in the elderly.

OBJECTIVES: Evaluation of the impact of a biscuit containing the probiotics Bifidobacterium longum Bar33 and Lactobacillus helveticus Bar13 on the intestinal microbiota in the elderly. DESIGN: Randomized double-blind placebo-controlled trial. PARTICIPANTS: Thirty-two elderly volunteers living in Italy. The group was composed of 19 women and 13 men aged between 71 and 88 years (mean 76). INTERVENTION: Subjects were randomized in two groups consuming one dose of the probiotics-containing biscuit or placebo once a day for 30 days. MEASUREMENTS: For each subject the intestinal microbiota was characterized using the phylogenetic microarray platform HTF-Microbi.Array before and after intervention. RESULTS: Our data demonstrated that one-month consumption of a probiotics-containing biscuit was effective in redressing some of the age-related dysbioses of the intestinal microbiota. In particular, the probiotic treatment reverted the age-related increase of the opportunistic pathogens Clostridium cluster XI, Clostridium difficile, Clostridium perfringens, Enterococcus faecium and the enteropathogenic genus Campylobacter. CONCLUSION: The present study opens the way to the development of elderly-tailored probiotic-based functional foods to counteract the age-related dysbioses of the intestinal microbiota.

Obesity-driven inflammation and colorectal cancer.

Visceral obesity is characterized by increased risk of cardiovascular disease as well as higher incidence of malignancies, including colorectal cancer (CRC), although the mechanisms linking excess adiposity with cancer are only partly characterized. Visceral obesity is currently acknowledged as a chronic inflammatory disorder and a growing body of evidence demonstrates the interconnections between obesity-related secretion pattern of adipo/cytokines and CRC. Specific molecules derived from the visceral adipose tissue (VAT), including adiponectin, leptin and resistin, are able to establish a positive feedback loop, thus increasing the proinflammatory and insulin resistant state and promoting tumorigenesis. Interestingly, these molecules have emerged as novel prognostic factors and therapeutic targets. This review will focus on current molecular and clinical evidence linking VAT-related inflammation to CRC initiation and progression, and summarize the role of dietary factors and lifestyle interventions aimed at promoting weight control and physical activity on CRC prevention and prognosis.

Insulinemia and the risk of breast cancer and its relapse.

A fairly large body of evidence has shown that insulin is a tumour-promoting agent, especially for breast cancer. High circulating and microenvironmental levels of insulin may directly increase the risk of breast cancer via the activation of cognate receptors expressed on normal and cancer cells and indirectly be associated with other known metabolic risk factors of cancer that usually are present in conjunction with the hyperinsulinic state. The focus of this review is to analyse and discuss available data in the literature on the possible causative/prognostic role of insulin resistance/hyperinsulinemia in breast cancer development and progression.

[Assessment of urinary cotinine in a group occupationally exposed to nicotine]. / Valutazione della cotinina urinaria in un gruppo di esposti professionalmente alla nicotina.

In a Tobacco processing company, located in central Italy, both air nicotine and, one of its metabolites, the urinary cotinine were assessed, as part of the evaluation of the effectiveness of recently implemented technical preventive controls. Urinary cotinine measurements ranged from 9,63 to 234,09 microg/gr creat. in non-smokers and from 178,79 to 2476,19 microg/gr creat. in smokers. Urinary cotinine proved useful as an exposure biological index especially in terms of population monitoring. On the contrary, the meaning of the measured values were less clear in single workers, because of significant both intra- and inter-individual variability.

Determinants of homocysteine levels in colorectal and breast cancer patients.

BACKGROUND: Homocysteinemia has been associated with oncogenic risk. This study was designed to investigate the homocysteine (Hcy) genotype/phenotype interactions together with the inflammatory and nutritional status of cancer patients. PATIENTS AND METHODS: The Hcy levels were analyzed in 47 cancer patients in association with methylenetetrahydrofolate reductase (MTHFR) polymorphisms, folate and inflammatory markers. RESULTS: The MTHFR C677T and A1298C genotype distributions did not differ from those predicted by the Hardy-Weinberg distribution. Conversely, the Hcy levels were higher in the cancer patients (p=0.04), who were also characterized by low-grade inflammation. The Hcy levels correlated with the interleukin-6 (IL-6) (p=0.001), tumor necrosis factor-alpha (TNF-alpha) (p=0.042) and folate (p<0.0001) levels of the patients. Multivariate analysis showed that TNF-alpha (p=0.014) and folate (p=0.019) were independent predictors of elevated Hcy levels in the cancer patients. CONCLUSION: The MTHFR polymorphisms do not significantly contribute to tHcy (total Hcy) levels in cancer patients, and cancer-related inflammation may be associated with elevated tHcy levels, possibly involving a TNF-alpha mediated pathway.

Role of CA19.9 in predicting bevacizumab efficacy for metastatic colorectal cancer patients.

CEA and CA19.9 are biomarkers routinely measured for monitoring treatment response in metastatic colorectal cancer (MCRC) patients, yet their predictive value during therapies containing new antineoplastic drugs (i.e. FOLFIRI/OLFOX/Bevacizumab) has not yet been investigated. Consecutive chemotherapy-naive MCRC patients treated with either standard chemotherapy-alone (FOLFIRI/FOLFOX) or chemotherapy+bevacizumab (FOLFIRI+bevacizumab) were included in the analysis. Patients had to have serial biweekly measurement of CEA and CA19.9 available for at least three months of treatment. Primary study endpoint was Progression Free Survival (PFS). Biomarker levels and type of treatment as well as major demographic and clinical factors were analyzed for their impact on PFS. Out of 243 evaluated MCRC patients, 87 had biomarkers available as per inclusion criteria. Among all evaluated factors only type of treatment (chemotherapy-alone vs chemotherapy+bevacizumab) and baseline CA19.9 (> vs < normal) were independently associated with PFS, whilst neither baseline CEA nor biomarker reduction during therapy reached statistical significance. When patients with different baseline CA19.9 levels were analysed separately, only patients with abnormal CA19.9 benefited significantly from the administration of bevacizumab.The current study demonstrated a significant predictive value of CA19.9, but not of CEA and biomarker reduction, for MCRC patients treated with new antineoplastic drugs. Moreover, only patients with abnormal baseline CA19.9 levels benefited significantly from bevacizumab.