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We have previously shown in a phase 3 trial that tamoxifen 5 mg/day for 3 years decreased by 52% the incidence of recurrence of invasive breast cancer or DCIS after a median follow-up of 5.1 years in women with excised non invasive breast disease, including atypical ductal hyperplasia, DCIS or LCIS (DeCensi et al. JCO 2019; 37:1629). Toxicity was negligible with only an extra hot flash per day in the tamoxifen arm compared with the placebo arm. These findings were incorporated into the ASCO clinical practice guidelines for breast cancer risk reduction as an alternative option to standard doses and duration of tamoxifen or aromatase inhibitors in women with non-invasive disease (Visvanathan et al. JCO 2019; 37:3152). In the present study we update the findings on breast cancer recurrence after a median of 9.14 years (interquartile range, IQR, 7.16-10.73) and a total of 10.57 person years of follow up to see if the treatment effect is retained with more events and after a median of approximately 6 years from treatment cessation. We conducted a national multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. Between November 1, 2008, and March 31, 2015, 1,160 women were screened and 500 aged 75 years of age or younger were included in the study. Women with high-grade or comedo/necrotic DCIS received adjuvant radiotherapy of 50 Gy in 25 courses. The mean age was 54 years (standard deviation, 9 years), and 55% of participants were postmenopausal. The mean (SD) body mass index, kg/m2, was 25.7 (4.8) on tamoxifen and 25.3 (4.2) on placebo. Twenty percent had ADH, 11% had LCIS, and the remaining 69% had DCIS. After a median follow-up of 9.14 years, there were 22 neoplastic events (invasive breast cancer or DCIS) with tamoxifen and 37 with placebo (annual rate 11.09, 95% CI, 7-30-16.84 on T vs 19.71, 95% CI, 14.28-27.21 on P per 1,000 person-years; hazard ratio, 0.56; 95% CI, 0.33 to 0.95; P = .03), which resulted in a 5-year number needed to treat of 18. Overall, 71% of the recurrences were invasive breast cancer. The follow-up was updated with the most recent visit within 12 months in two thirds of the participants, so an update of all participants will be performed by Sept 30th with full analysis of neoplastic events, annual risk rate ratio, serious adverse events and deaths. Moreover, an updated analysis of potential effect modifiers will be conducted, including menopausal status, baseline estradiol levels, menopausal symptoms, BMI, smoking status and Ki-67 of the primary lesion. In conclusion, our findings indicate that low dose tamoxifen given for 3 years still significantly prevents recurrences from non-invasive breast cancer after a median of 6 years from treatment cessation, providing a valid prevention/interception option in this disease group. Supported by Ente Ospedaliero Ospedali Galliera, Genova, Italy, the Italian Ministry of Health (RFPS-2006-1-339898), the Italian Association for Cancer Research (IG 2008 Grant No. 5611), and the Italian League against Cancer (LILT 7-08). Citation Format: Andrea De Censi, Matteo Lazzeroni, Matteo Puntoni, Luca Boni, Aliana Guerrieri Gonzaga, Tania Buttiron Webber, Marianna Fava, Irene Maria Briata, Livia Giordano, Maria Digennaro, Laura Cortesi, Fabio Falcini, Franca Avino, Francesco Millo, Katia Cagossi, Elisa Gallerani, Alessia De Simone, Anna Cariello, Giuseppe Aprile, Maria Renne, Bernardo Bonanni. 10-year results of a phase 3 trial of low-dose tamoxifen in non-invasive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-08.

Whereas the 18 F-FDG PET/CT pattern of malignant thyroid neoplasia is known, the glucose uptake of autonomously functioning thyroid nodules (AFTNs) has not been fully investigated. We aimed to analyze the FDG uptake of AFTNs and its correlation with clinical, laboratory, ultrasonography, and histological features.We retrospectively analyzed the records of all AFTN patients from 2 centers, in which an 18 F-FDG PET/CT, thyroid function tests, and neck ultrasound were available within a 3-month window from the thyroid scintigraphy. Forty-five patients (35 female patients; median age, 65 years) were retrospectively included. The presence of FDG uptake was compared with the laboratory data and, whenever available, the histology.Over a 36-month follow-up, 20 patients underwent surgery; 4 cancers, 10 follicular adenomas, and 6 follicular hyperplasias were found. Twenty-two AFTNs (48.9%) were FDG-positive, whereas the remaining 23 (51.1%) were not. Thyroid-stimulating hormone (TSH) was significantly lower in FDG-positive AFTNs than in negative ones (0.055 [0.02-0.42] vs 0.65 [0.2-0.96] mIU/L, P = 0.0018). On multivariate analysis, only TSH was independently associated with FDG uptake ( P = 0.008). On receiver operating characteristic curve analysis, TSH0.08 mIU/L indicated FDG-positive AFTNs, with 64% sensitivity, 87% specificity, 4.88 positive likelihood ratio, and 0.42 negative likelihood ratio. In histologically proven benign lesions, TSH was significantly lower in follicular adenomas than in follicular hyperplasias ( P0.001). Patients with cancer had TSH in the low-normal range.Autonomously functioning thyroid nodules show heterogeneous uptake FDG pattern, which depends on histopathology and thyroid function. Particularly, follicular adenomas tend to display increased glucose uptake and suppressed TSH.

Identifying factors predisposing individuals to post-acute sequelae of COVID-19 (PASC) would allow for the timely treatment of those vulnerable. Attention on the role of sex and age is growing, but published studies have shown mixed results. Our objective was to estimate the effect modification of age on sex as a risk factor for PASC. We analyzed data from two longitudinal prospective cohort studies on adult and pediatric subjects positive to SARS-CoV-2 infection that were enrolled between May 2021 and September 2022. Age classes (≤5, 6–11, 12–50, >50 years) were based on the potential role of sex hormones on inflammatory/immune and autoimmune processes. A total of 452 adults and 925 children were analyzed: 46% were female and 42% were adults. After a median follow-up of 7.8 months (IQR: 5.0 to 9.0), 62% of children and 85% of adults reported at least one symptom. Sex and age alone were not significantly associated to PASC, but their interaction was statistically significant (p-value = 0.024): the risk was higher for males aged 0–5 (females vs. males HR: 0.64, 95% CI: 0.45–0.91, p = 0.012) and for females aged 12–50 (HR: 1.39, 95% CI: 1.04–1.86, p = 0.025), especially those in the cardiovascular, neurological, gastrointestinal and sleep categories. Further research on PASC with regard to sex and age is warranted.

Metformin is associated with lower breast cancer risk in epidemiologic studies and showed decreased proliferation in HER2-positive breast cancer in a presurgical trial. To provide insight into its preventive potential, we measured proliferation by Ki-67 labeling index (LI) of intraepithelial lesions surrounding breast cancer. We randomly assigned 200 nondiabetic patients diagnosed with invasive breast cancer in core biopsies to metformin, 1,700 mg or placebo once daily for 28 days before surgery. Upon surgery, five to seven specimens of cancer adjacent (≤1 cm) and distant (>1 cm) tissue were screened for LCIS, ductal carcinoma in situ (DCIS), and ductal hyperplasia (DH). The prevalence of LCIS, DCIS, and DH was 4.5% (9/200), 67% (133/200), and 35% (69/200), respectively. Overall, metformin did not affect Ki-67 LI in premalignant disorders. The median posttreatment Ki-67 LI (IQR) in the metformin and placebo arm was, respectively, 15% (5–15) versus 5% (4–6) in LCIS (P = 0.1), 12% (8–20) versus 10% (7–24) in DCIS (P = 0.9), and 3% (1–4) versus 3% (1–4) in DH (P = 0.5). However, posttreatment Ki-67 in HER2-positive DCIS lesions was significantly lower in women randomized to metformin especially when ER was coexpressed: 22% (11–32) versus 35% (30–40) in HER2-positive DCIS (n = 22, P = .06); 12% (7–18) versus 32% (27–42) in ER-positive/HER2-positive DCIS (n = 15, P = .004). Eight of 22 (36%) HER2-positive DCIS were adjacent to HER2-negative invasive breast cancer. In tissue samples obtained following 4 weeks of study drug, proliferation was lower in HER2-positive DCIS for women randomized to metformin versus placebo. An adjuvant trial incorporating metformin in HER2-positive DCIS is warranted. Cancer Prev Res; 8(10); 888–94. ©2015 AACR.

Table showing the studies that were excluded from analysis and reasons why.

Supplementary Figure Legend from Effect of Metformin on Breast Ductal Carcinoma In Situ Proliferation in a Randomized Presurgical Trial

Ki-67 values in pre- and post-treatment invasive cancer and post-treatment adjacent DCIS tissue in patients with HER2+ve adjacent DCIS and HER2+ve or HER2-ve invasive breast cancer

Dotplot of Ki-67 labeling index by LCIS and DCIS grade in all subjects.

Epidemiological studies of metformin and cancer risk with BMI adjustment

Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis.After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, β-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue.Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of −10.6%, 95% confidence interval (CI), −20.5 to −0.7, and −8.1%, 95% CI, −22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (−16.4%; 95% CI, −29.0 to −3.8). No dose–response relationship was noted, except for NF-κB expression in normal tissue.Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity. Cancer Prev Res; 6(2); 74–81. ©2012 AACR.

Commentary on This Article from A Randomized, Placebo-Controlled, Preoperative Trial of Allopurinol in Subjects with Colorectal Adenoma

Previous meta-analyses have shown that the antidiabetic agent metformin is associated with reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models and recent epidemiologic studies. We performed a meta-analysis with a focus on confounders and biases, including body mass index (BMI), study type, and time-related biases. We identified 71 articles published between January 1, 1966, and May 31, 2013, through Pubmed, ISI Web of Science (Science Citation Index Expanded), Embase, and the Cochrane library that were related to metformin and cancer incidence or mortality. Study characteristics and outcomes were abstracted for each study that met inclusion criteria. We included estimates from 47 independent studies and 65,540 cancer cases in patients with diabetes. Overall cancer incidence was reduced by 31% [summary relative risk (SRR), 0.69; 95% confidence interval (CI), 0.52–0.90], although between-study heterogeneity was considerable (I2 = 88%). Cancer mortality was reduced by 34% (SRR, 0.66; 95% CI, 0.54–0.81; I2 = 21%). BMI-adjusted studies and studies without time-related biases also showed significant reduction in cancer incidence (SRR, 0.82; 95% CI, 0.70–0.96 with I2 = 76% and SRR, 0.90; 95% CI, 0.89–0.91 with I2 = 56%, respectively), albeit with lesser magnitude (18% and 10% reduction, respectively). However, studies of cancer mortality and individual organ sites did not consistently show significant reductions across all types of analyses. Although these associations may not be causal, our results show that metformin may reduce cancer incidence and mortality in patients with diabetes However, the reduction seems to be of modest magnitude and not affecting all populations equally. Clinical trials are needed to determine if these observations apply to nondiabetic populations and to specific organ sites. Cancer Prev Res; 7(9); 867–85. ©2014 AACR.

CONSORT Checklist

Supplementary Table S1. Results of the summary evaluation on the risk of bias assessment, using the domain-based evaluation of the Cochrane risk of bias tool: low, unclear, and high risk of bias are the 3 possible judgments for each item considered of each of the study assessed. Supplementary Table S2. Detailed results of the risk of bias assessment on the NEOALTTO study (ref. 39). Supplementary Table S3. Detailed results of the risk of bias assessment on the CALGB 40601 study (ref. 40). Supplementary Table S4. Detailed results of the risk of bias assessment on the NSABP B-41 study (ref. 41). Supplementary Table S5. Detailed results of the risk of bias assessment on the EORTC 10054 study (ref. 42). Supplementary Table S6. Detailed results of the risk of bias assessment on the TRIO-US B07 study (ref. 43). Supplementary Table S7. Detailed results of the risk of bias assessment on the CHERLOB study (ref. 44).

Purpose: (Neo)adjuvant treatment with chemotherapy plus trastuzumab reduces recurrence and death risk in HER2-positive (HER2+) breast cancer. Randomized trials assessed HER2 dual block by adding lapatinib to trastuzumab and chemotherapy in the neoadjuvant setting using pathologic complete response (pCR) as the outcome measure. We conducted a meta-analysis of randomized trials testing neoadjuvant dual block with lapatinib and trastuzumab versus trastuzumab alone in HER2+ breast cancer.Experimental Design: Trials were identified by Medline (PubMed), ISI Web of Science (Science Citation Index Expanded), Embase, Cochrane library, and reference lists of published studies, review articles, editorials, and by hand-searched reports from major cancer meeting reports.Results: Six randomized trials including 1,155 patients were identified, of whom 483 (41.8%) were hormone receptor–negative, 672 (58.2%) hormone receptor–positive, 534 (46.2%) received taxanes alone, and 621 (53.8%) anthracyclines plus taxanes or the docetaxel–carboplatin regimen. Overall, the dual block was associated with a significant 13% absolute improvement in pCR rate compared with single-agent trastuzumab (summary risk difference, SRD 0.13; 95% CI, 0.08–0.19). The activity was greater in hormone receptor–negative patients who received chemotherapy with taxanes alone (SRD 0.25; 95% CI, 0.13–0.37), compared to hormone receptor–positive or hormone receptor–negative disease treated with anthracyclines plus taxanes or the docetaxel–carboplatin regimen (SRD 0.09; 95% CI, 0.02–0.15; Pinteraction = 0.05).Conclusions: On the basis of ΔpCR data, the dual block with trastuzumab and lapatinib plus chemotherapy is a very active treatment only in HER2+ and hormone receptor–negative breast cancer treated with taxane monochemotherapy. Clin Cancer Res; 22(18); 4594–603. ©2016 AACR.

Purpose:Low-dose tamoxifen halved recurrence after surgery in a phase III trial in breast noninvasive disease without increasing adverse events. We explored the effect of low-dose tamoxifen in clinically relevant subgroups, including menopausal status, estradiol levels, smoking, body mass index, and proliferation of baseline lesion.Patients and Methods:Incidence of invasive breast cancer or ductal carcinoma in situ was the primary endpoint. HRs and interaction terms were estimated using Cox models.Results:A favorable HR and 95% confidence interval (CI) could be demonstrated for postmenopausal status (HR = 0.30; 95% CI, 0.11–0.82 vs. HR = 0.73; 95% CI, 0.30–1.76 in premenopausal women; Pinteraction = 0.13), women with estradiol less than 15.8 pg/mL, presence of menopausal symptoms at baseline, and never smoking (Pinteraction = 0.07), although the interaction P value was >0.05 for all characteristics. Efficacy was similar in all body mass index categories. Tumors with Ki-67 above the median level of 10% had a greater benefit (HR = 0.27; 95% CI, 0.09–0.81) than those with Ki-67 ≤10% (HR = 1.58; 95% CI, 0.45–5.60; Pinteraction = 0.04).Conclusions:The efficacy of low-dose tamoxifen seems to be greater in postmenopausal women and in women with lower estradiol levels. Benefits appear to be larger also in women with menopausal symptoms, never smokers, and tumors with Ki-67 >10%. Our results by menopausal status provide important insight into low-dose tamoxifen personalized treatment, although caution is necessary given their exploratory nature. Observation of an improved response in tumors with Ki-67 >10% is consistent but the use of the marker in this setting is investigational.See related commentary by Fabian, p. 3510

CONSORT Diagram

Adherence by smoking status.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE Five-year data of the phase III trial TAM-01 showed that low-dose tamoxifen at 5 mg once daily administered for 3 years in women with intraepithelial neoplasia (IEN) reduced by 52% the recurrence of invasive breast cancer or ductal carcinoma in situ (DCIS), without additional adverse events over placebo. Here, we present the 10-year results. METHODS We randomly assigned 500 women with breast IEN (atypical ductal hyperplasia, lobular carcinoma in situ [LCIS], or hormone-sensitive or unknown DCIS) to low-dose tamoxifen or placebo after surgery with or without irradiation. The primary end point was the incidence of invasive breast cancer or DCIS. RESULTS The TAM-01 population included 500 women (20% atypical ductal hyperplasia, 11% LCIS, and 69% DCIS). The mean (±SD) age at the start of treatment was 54 ± 9 years, and 58% of participants were postmenopausal. After a median follow-up of 9.7 years (IQR, 8.3-10.9 years), 66 breast cancers (15 in situ; 51 invasive) were diagnosed: 25 in the tamoxifen group and 41 in the placebo group (annual rate per 1,000 person-years, 11.3 with tamoxifen v 19.5 with placebo; hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.95; log-rank P = .03). Most recurrences were invasive (77%) and ipsilateral (59%). Regarding contralateral breast cancer incidence, there were six events in the tamoxifen arm and 16 in the placebo arm (HR, 0.36; 95% CI, 0.14 to 0.92; P = .025). The number needed to be treated to prevent one case of breast event with tamoxifen therapy was 22 in 5 years and 14 in 10 years. The benefit was seen across all patient subgroups. There was a significant 50% reduction of recurrence with tamoxifen in the DCIS cohort, which represents 70% of the overall population (HR, 0.50; 95% CI, 0.28 to 0.91; P = .02). No between-group difference in the incidence of serious adverse events was reported during the prolonged follow-up period. CONCLUSION Tamoxifen 5 mg once daily for 3 years significantly prevents recurrence from noninvasive breast cancer after 7 years from treatment cessation without long-term adverse events.

This study examined the effects of the routine assessment of patient-reported outcomes (PROs) on the overall survival of adult patients with cancer. We included clinical trials and observational studies with a control group that compared PRO monitoring interventions in cancer clinical practice to usual care. The Cochrane risk-of-bias tools were used. In total, six studies were included in the systematic review: two randomized trials, one population-based retrospectively matched cohort study, two pre–post with historical control studies and one non-randomized controlled trial. Half were multicenter, two were conducted in Europe, three were conducted in the USA and was conducted in Canada. Two studies considered any type of cancer, two were restricted to lung cancer and two were restricted to advanced forms of cancer. PRO screening was electronic in four of the six studies. The meta-analysis included all six studies (intervention = 130.094; control = 129.903). The pooled mortality outcome at 1 year was RR = 0.77 (95%CI 0.76–0.78) as determined by the common effect model and RR = 0.82 (95%CI 0.60–1.12; p = 0.16) as determined by the random-effects model. Heterogeneity was statistically significant (I2 = 73%; p < 0.01). The overall risk of bias was rated as moderate in five studies and serious in one study. This meta-analysis seemed to indicate the survival benefits of PRO screening. As routine PRO monitoring is often challenging, more robust evidence regarding the effects of PROs on mortality would support systematic applications.

Il fenomeno del re-ricovero impatta fortemente sulla sanita pubblica e ha subito un sempre maggiore interesse da parte della comunita scientifica. E stato dimostrato che diversi parametri possano influenzare tale fenomeno. L'educazione terapeutica e uno di questi. Obiettivo del presente lavoro e analizzare come un reparto a conduzione infermieristica caratterizzato da un'importate educazione terapeutica possa impattare sulla riduzione di tale fenomeno. A tal fine, sono stati estratti i dati relativi a un anno di attivita del reparto a conduzione infermieristica che sono stati confrontati con un gruppo di controllo di pazienti ricoverati nel medesimo ospedale con analoghe caratteristiche in rapporto 1:2. Sono stati calcolati indicatori di "controllo" rispetto al fenomeno del re-ricovero (numero re-ricovero e durata della loro degenza). I risultati dello studio sono stati: 1 episodio di re-ricovero, con una durata di 15 giorni, in ACI a fronte dei 22 episodi di re-ricovero del gruppo di controllo con 188 giornate di degenza complessivi. Sono stati inoltre monitorati ulteriori parametri relativi al benessere organizzativo degli infermieri che hanno riportato risultati quali la diminuzione della % di attivita omesse e l'azzeramento di giornate di assenza. Anche l'efficacia del riconoscimento tempestivo di 5 eventi critici clinici ha impedito che la situazione evolvesse negativamente. In questo lavoro e stato quindi dimostrato come una gestione prettamente infermieristica e l'educazione terapeutica possano impattare positivamente sul re-ricovero e sono state fatte considerazioni che possono essere estese anche ad altri contesti.

Background Variability of parameter measurements in heart failure with reduced ejection fraction (HFrEF) may contribute to reducing the prediction accuracy of available prognostic models. We investigated whether the use of longitudinal versus cross-sectional measurements of established predictors of mortality in patients with HFrEF would increase the accuracy of prognostication. Methods We used longitudinal measurements of systolic blood pressure (SBP), heart rate, hemoglobin, creatinine and uric acid from HFrEF patients enrolled in the GISSI-HF trial. We performed linear mixed models to investigate the difference in first 6-month trajectories of these parameters between patients alive and dead at 4-year follow-up, and examined the change in prediction accuracy by comparing area under the curve (AUC) and net reclassification index (NRI) values obtained using a traditional cross-sectional survival model versus a longitudinal joint model using information up to 6-month follow-up. Results We included 5469 patients with 32,206 repeated visits and measurements. We demonstrated a significant difference in the first 6-month change of each one of the selected parameters between those alive and dead at the end of follow-up (p-value for time∗mortality interaction ≤0.01). The comparison of prediction accuracy of the two models revealed a significant increase of about 2% in the AUCs when using longitudinal values of each parameter of interest up to 6 months, with significant concomitant increase in NRI. The greatest increase in accuracy was noticed when using longitudinal SBP measurements in patients with baseline SBP ≤ 110 mmHg. Conclusions Our findings support the use of longitudinal data to improve prognostication in patients with HFrEF, and warrant validation in external cohorts and creation of new prognostic tools.

Attention is being focused on improving mothers' positive experiences of childbirth while reducing the negative ones. Cesarean section is a known factor able to increase maternal anxiety.To determine whether a new binaural beat-based technique can reduce the preoperative discomfort of the elective surgical patient.Prospective, randomized double-blind controlled study: 60 women scheduled to undergo elective cesarean section. Women with a low risk pregnancy were recruited and enrolled at the time of the "37 weeks" visit. Exclusion criteria were: psychiatric disorders, neurological impairment, epilepsy, deafness, use of drugs/alcohol during pregnancy, insufficient reading level. Participants will be contestually allocated to one of three groups according to a predetermined computer-generated random sequence: (1) "binaural" group, (2) "normal music" group, and (3) "control" group. Participants of groups 1 and 2 will be unaware of the type of audio heard.According to the allocation arm, participants were asked to listen an engineered audio track (binaural beat arm) created with the novel algorithm "Dynamic Spectrum Phase Shift" (DMSPS), or an identical soundtrack without DMSPS in it (music arm), or no specific intervention, representing standard practice. The feeling of anxiety has been measured by the State-Trait Anxiety Inventory (STAI-Y) questionnaire.

Background & aims: The literature regarding enteral nutrition and mortality in older frail people is limited and still conflicting. Moreover, the potential role of comprehensive geriatric assessment is poorly explored. We therefore aimed to investigate whether the Multidimensional Prognostic Index (MPI), an established tool that assesses measures of frailty and predicts mortality, may help physicians in identifying patients in whom ETF (enteral tube feeding) is effective in terms of reduced mortality. Methods: Observational, longitudinal, multicenter study with one year of follow-up. Data regarding ETF were recorded through medical records. A standardized comprehensive geriatric assessment was used to calculate the MPI. Participants were divided in low (MPI-1), moderate (MPI-2) or severe (MPI-3) risk of mortality. Data regarding mortality were recorded through administrative information. Results: 1064 patients were included, with 79 (13 in MPI 1–2 and 66 in MPI-3 class) receiving ETF. In multivariable analysis, patients receiving ETF experienced a higher risk of death (odds ratio, OR = 2.00; 95% confidence intervals, CI: 1.19–3.38). However, after stratifying for their MPI at admission, mortality was higher in MPI-3 class patients (OR = 2.03; 95%CI: 1.09–3.76), but not in MPI 1–2 class patients (OR = 1.51; 95%CI: 0.44–5.25). The use of propensity score confirmed these findings. Conclusions: ETF is associated with a higher risk of death. However, this is limited to more frail patients, suggesting the importance of the MPI in the prognostic evaluation of ETF. © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism

To evaluate the reliability of 18F-FDG PET/CT in distinguishing differentiated thyroid cancers (DTCs) and follicular neoplasms (FNs) from nodular hyperplasias (NH) in thyroid nodules with indeterminate cytology according to the Italian consensus for the classification and reporting of thyroid cytology (ICCRTC). We also tested whether the 18F-FDG PET/CT result was an independent risk factor for DTCs or FNs when sex, age, nodule dimensions, the European Thyroid Imaging and Reporting Data System (EU-TIRADS) and ICCRTC were considered. We evaluated all patients with thyroid nodules and indeterminate cytology from September 2015 to May 2019; nodules were classified as low risk (TIR3A) and high risk (TIR3B) according to the ICCRTC. Neck ultrasonography features according to EU-TIRADS were re-evaluated and 18F-FDG PET/CT performed. All these patients were surgically treated. We included 111 patients; 67 nodules were classified as TIR3A and 44 as TIR3B. Overall, we found 27 DTCs, 57 NHs and 27 FNs. Among 73 FDG-negative nodules, we found four low-risk papillary thyroid cancers. All follicular thyroid cancers were identified by 18F-FDG-PET/CT. All TIR3A with low-risk US and negative 18F-FDG-PET/CT were NH. In TIR3A nodules, the sensitivity, specificity, negative and positive predictive values (NPV, PPV) of 18F-FDG PET/CT and EU-TIRADS for DTCs were 77.8%, 41.4%, 92.3%, 17.1% and 66.7%, 56.9%, 91.7%, 19.4%, respectively. In TIR3B nodules, the sensitivity, specificity, NPV and PPV of 18F-FDG PET/CT and EU-TIRADS for DTCs were 88.9%, 38.5%, 83.3%, 50% and 88.2%, 58.3%, 87.5%, 60%, respectively. On multivariate analysis, 18F-FDG-PET/CT (OR 9.04), ICCRTC (O.R. 7.57) and EU-TIRADS (OR 4.41) were all independent risk factors associated to DTCs and FNs. 18F-FDG-PET/CT is a reliable rule-out test for DTC even in thyroid nodules with indeterminate high-risk results. In this subgroup, PPV also tends to be considerable. 18F-FDG-PET/CT results, ICCRTC and EU-TIRADS proved independent risk factors associated to DTCs and FNs.

Background: We recently showed that low dose (5mg/d) tamoxifen (babytam) for 3 years can halve the incidence of new breast neoplastic events in hormone sensitive or unknown breast pre-invasive neoplasia after surgery with limited toxicity (DeCensi et al JCO 2019; 37:1629-37). Here we report the results of circulating surrogate endpoint biomarkers of breast cancer risk with special attention to the risk of ovarian stimulation observed with the full dose in premenopausal women. Methods: Five hundred women 75 years old or younger were randomized to babytam or placebo (PLA). A subgroup of 406 women consented for collection of morning fasting serum at baseline (0), 1 (1Y) and 3 years (3Y) of treatment. There was a loss of about 25% of blood sampling at 3Y. Serum IGF-I, IGFBP-3, SHBG and C-reactive Protein (CRP) were performed on all available samples. Estradiol and testosterone were determined in a subsample (n=285) to determine the extent of ovarian stimulation by babytam in premenopausal women. We used Mann-Whitney test for univariate comparisons and linear regression modeling for multivariate analyses setting changes from baseline (1Y or 3Y minus baseline values) as dependent variable and treatment arm, age, BMI and baseline biomarkers values as explanatory factors. We tested treatment*menopausal status as interaction term. COX P-H model was used to calculate hazard ratio for CRP increase. Results: At baseline, all biomarkers were evenly balanced between arms (data not shown). IGF-I decreased significantly on babytam as compared to PLA. The difference of the changes between arms was -20 ng/mL after 1Y (p Citation Format: Harriet Johansson, Matteo Puntoni, Debora Macis, Valentina Aristarco, Aliana Guerrieri-Gonzaga, Davide Serrano, Silvia Caviglia, Laura Cortesi, Cristiana Taverniti, Antonio Ponti, Maria Grazia Pacquola, Marcella Gulisano, Fabio Falcini, Maria Digennaro, Anna Carriello, Katia Cagossi, Graziella Pinotti, Tania Buttiron Webber, Matteo Lazzeroni, Bernardo Bonanni, Luca Boni, Andrea DeCensi. Effects of low dose tamoxifen on circulating risk biomarkers in a phase III trial in breast pre-invasive disease [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-08.

Evidence shows that a substantial proportion of patients with COVID-19 experiences long-term consequences of the disease, but the predisposing factors are poorly understood. We conducted a systematic review and meta-analysis to identify factors present during COVID-19 hospitalization associated with an increased risk of exhibiting new or persisting symptoms (Post-COVID-19 Syndrome, PCS). MedLine and WebOfScience were last searched on 30 September 2021. We included English language clinical trials and observational studies investigating prognostic factors for PCS in adults previously hospitalized for COVID-19, reporting at least one individual prospective follow-up of minimum 12 weeks. Two authors independently assessed risk of bias, which was judged generally moderate. Risk factors were included in the analysis if their association with PCS was investigated by at least two studies. To summarize the prognostic effect of each factor (or group of factors), odds ratios were estimated using raw data. Overall, 20 articles met the inclusion criteria, involving 13,340 patients. Associations were statistically significant for two factors: female sex with any symptoms (OR 1.52; 95% CI 1.27–1.82), with mental health symptoms (OR 1.67, 95% CI 1.21–2.29) and with fatigue (OR 1.54, 95% CI 1.32–1.79); acute disease severity with respiratory symptoms (OR 1.66, 95% CI 1.03–2.68). The I² statistics tests were calculated to quantify the degree of study heterogeneity. This is the first meta-analysis measuring the association between factors present during COVID-19 hospitalization and long-term sequelae. The role of female sex and acute disease severity as independent prognostic factors must be confirmed in robust longitudinal studies with longer follow-up. Identifying populations at greatest risk for PCS can enable the development of targeted prevention and management strategies. Systematic review registration: PROSPERO CRD42021253467.

Surgical site infections (SSIs) represent a potential complication of surgical procedures, with a significant impact on mortality, morbidity, and healthcare costs. Patients undergoing cardiac surgery and thoracic surgery are often considered patients at high risk of developing SSIs. This consensus document aims to provide information on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing cardiac and non-cardiac thoracic surgery. The following scenarios were considered: (1) cardiac surgery for the correction of congenital heart disease and/or valve surgery; (2) cardiac catheterization without the placement of prosthetic material; (3) cardiac catheterization with the placement of prosthetic material; (4) implantable cardiac defibrillator or epicardial pacemaker placement; (5) patients undergoing ExtraCorporal Membrane Oxygenation; (6) cardiac tumors and heart transplantation; (7) non-cardiac thoracic surgery with thoracotomy; (8) non-cardiac thoracic surgery using video-assisted thoracoscopy; (9) elective chest drain placement in the pediatric patient; (10) elective chest drain placement in the newborn; (11) thoracic drain placement in the trauma setting. This consensus provides clear and shared indications, representing the most complete and up-to-date collection of practice recommendations in pediatric cardiac and thoracic surgery, in order to guide physicians in the management of the patient, standardizing approaches and avoiding the abuse and misuse of antibiotics.

Pre-operative delirium may cause delay in surgical intervention in older patients hospitalized for hip fracture. Also it has been associated with higher risk of post-surgical complications and worst functional outcomes. Aim of this retrospective cohort study was to evaluate whether the multidimensional prognostic index (MPI) at hospital admission was associated with pre-operative delirium in older individuals with hip fracture who are deemed to require surgical intervention. Consecutive older patients (≥ 65 years) with hip fracture underwent a comprehensive geriatric assessment to calculate the MPI at hospital admission. According to previously established cut-offs, MPI was expressed in three grades, i.e. MPI-1 (low-risk), MPI-2 (moderate-risk) and MPI-3 (high risk of mortality). Pre-operative delirium was assessed using the four ‘A’s Test. Out of 244 older patients who underwent surgery for hip fracture, 104 subjects (43%) received a diagnosis of delirium. Overall, the incidence of delirium before surgery was significantly higher in patients with more severe MPI score at admission. Higher MPI grade (MPI-3) was independently associated with higher risk of pre-operative delirium (OR 2.45, CI 1.21–4.96). Therefore, the MPI at hospital admission might help in early identification of older patients with hip fracture at risk for pre-operative delirium.