Temporal evolution of quality of life in patients endoscopically treated for sinonasal malignant tumors.

BACKGROUND: The aim of our study is to assess which factors may affect the quality of life (QoL) and its fluctuation over time in adult patients who received endonasal endoscopic oncologic sinus surgery (EOSS) for sinonasal malignancies (SNM) in our center. METHODOLOGY: We analyzed EOSS cases for primary SNM from January 2015 to June 2020. For each patient, we have recorded the age at treatment, gender, smoking habits, use of psychotropic drugs for mood disorders, stage, histotype, type of surgical resection, need for skull-base reconstruction, development of postoperative major complications, and the use of adjuvant intensity-modulated radiotherapy (IMRT). We evaluated the patient's performance status pre-treatment using the ECOG scale. Quality of life was measured using three questionnaires (SNOT-22; ASK-9; EORTC QLQ-C30 version 3). RESULTS: Fifty-five patients were enrolled in our study, of whom thirty-two (58.18%) received adjuvant IMRT. Overall, a significant improvement in all QoL outcomes was observed at eighteen months, while, female sex, higher ECOG scores, advanced stage of disease, and adjuvant IMRT were associated with worse QoL. After 18 months the delta in QoL between women and men worsened (in SNOT-22 and EORTC QLQ-GLOBAL) while if only the most fragile patients according to ECOG are considered, this difference was reduced for both tools. CONCLUSION: Our analysis revealed that IMRT is the element that has the greatest impact on patient's quality of life, in association with the female sex, ECOG >2, and advanced stage of the disease.

Toxicity after moderately hypofractionated versus conventionally fractionated prostate radiotherapy: A systematic review and meta-analysis of the current literature.

BACKGROUND: Moderately hypofractionated radiotherapy (RT) currently represents the standard RT approach for all prostate cancer (PCa) risk categories. We performed a systematic review and meta-analysis of available literature, focusing on acute and late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) of moderate hypofractionation for localized PCa. MATERIALS AND METHODS: Literature search was performed and two independent reviewers selected the records according to the following Population (P) Intervention (I) Comparator (C) and Outcomes (O) (PICO) question: "In patients affected by localized PCa (P), moderately hypofractionated RT (defined as a treatment schedule providing a single dose per fraction of 3-4.5 Gy) (I) can be considered equivalent to conventionally fractionated RT (C) in terms of G > 2 GI and GU acute and late adverse events (O)?". Bias assessment was performed using Cochrane Cochrane Collaboration's Tool for Assessing Risk of Bias. RESULTS: Thirteen records were identified and a meta-analysis was performed. Risk of acute GI and GU > 2 adverse events in the moderately hypofractionated arm was increased by 9.8 % (95 %CI 4.8 %-14.7 %; I2 = 57 %) and 1.5 % (95 % CI -1.5 %-4.4 %; I2 = 0%), respectively. DISCUSSION: Overall, majority of trials included in our meta-analysis suggested that moderately hypofractionated RT is equivalent, in terms of GI and GU adverse events, to conventional fractionation. Pooled analysis showed a trend to increased GI toxicity after hypofractionated treatment, but this might be related to dose escalation rather than hypofractionation.

Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy

Objectives To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line treatment with androgen receptor-targeted therapy (ARTT). Patients and methods Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan–Meier method, univariate and multivariate analysis (MVA) were performed. Results Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio [HR] 3.66, p = 0.009; HR 3.03, p = 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23, p = 0.017; HR 0.19, p = 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39, p = 0.026; HR 2.79, p = 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity. Conclusion Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed (AU)

Evaluation of a standardised protocol to measure the disease burden of respiratory syncytial virus infection in young children in primary care.

BACKGROUND: A better understanding of the burden of respiratory syncytial virus (RSV) infections in primary care is needed for policymakers to make informed decisions regarding new preventive measures and treatments. The aim of this study was to develop and evaluate a protocol for the standardised measurement of the disease burden of RSV infection in primary care in children aged < 5 years. METHODS: The standardised protocol was evaluated in Italy and the Netherlands during the 2019/20 winter. Children aged < 5 years who consulted their primary care physician, met the WHO acute respiratory infections (ARI) case definition, and had a laboratory confirmed positive test for RSV (RT-PCR) were included. RSV symptoms were collected at the time of swabbing. Health care use, duration of symptoms and socio-economic impact was measured 14 days after swabbing. Health related Quality of life (HRQoL) was measured using the parent-proxy report of the PedsQL™4.0 generic core scales (2-4 years) and PedsQL™4.0 infant scales (0-2 years) 30 days after swabbing. The standardised protocol was evaluated in terms of the feasibility of patient recruitment, data collection procedures and whether parents understood the questions. RESULTS: Children were recruited via a network of paediatricians in Italy and a sentinel influenza surveillance network of general practitioners in the Netherlands. In Italy and the Netherlands, 293 and 152 children were swabbed respectively, 119 and 32 tested RSV positive; for 119 and 12 children the Day-14 questionnaire was completed and for 116 and 11 the Day-30 questionnaire. In Italy, 33% of the children had persistent symptoms after 14 days and in the Netherlands this figure was 67%. Parents had no problems completing questions concerning health care use, duration of symptoms and socio-economic impact, however, they had some difficulties scoring the HRQoL of their young children. CONCLUSION: RSV symptoms are common after 14 days, and therefore, measuring disease burden outcomes like health care use, duration of symptoms, and socio-economic impact is also recommended at Day-30. The standardised protocol is suitable to measure the clinical and socio-economic disease burden of RSV in young children in primary care.

Palliative radiotherapy in older adults with head and neck squamous cell carcinoma: A systematic review.

Locally advanced Head and neck squamous cell carcinoma (SCCHN) represents a common oncologic pathology in older adults (OA). While radiotherapy represents a cornerstone in this context, it is unclear what is the optimal radiation regimen for SCCHN in the palliative setting, especially for OA. This article addresses issues related to palliative radiotherapy (PRT) in this setting with a focus on treatment modalities and toxicity. We also explore the use of quality of life and geriatric assessment in this setting. Medline, Scopus and Embase databases were queried for articles in this setting. We included studies published from January 1, 2000 through June 1, 2020, that were independently evaluated by two authors. Analyzed endpoints were progression free survival (PFS), overall survival (OS) and PRT toxicities. The meta-analysis was performed using Stata v.14. A total of 33 studies were included in this meta-analysis. The pooled median OS is 7.7 months, 2-years OS was worse for higher radiation dose (p = 0.02). The pooled median PFS was 5.4 months, PFS was influenced by EQD2 (p = 0.01), with patients receiving an EQD2 < 40 Gy that presented a poorer outcome. Regarding acute toxicities, most common pooled G3 toxicities were mucositis (7%) and dysphagia (15%). Among late toxicity, most common G3 toxicity was dysphagia in 7% of patients. Radiotherapy should be the most effective palliative treatment in symptomatic SCCHN OA. A tailored approach, guided by geriatric tools, would be indicated to choose the right therapy.

Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy.

OBJECTIVES: To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line treatment with androgen receptor-targeted therapy (ARTT). PATIENTS AND METHODS: Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analysis (MVA) were performed. RESULTS: Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio [HR] 3.66, p = 0.009; HR 3.03, p = 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23, p = 0.017; HR 0.19, p = 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39, p = 0.026; HR 2.79, p = 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity. CONCLUSION: Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed.

Inflammatory marker changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women.

Chronic low-grade inflammation plays a role in the pathogenesis of several chronic diseases including cancer. Physical activity (PA) and diet have been supposed to modulate inflammatory markers. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of pro-inflammatory cytokines, a secondary analysis in the DAMA factorial trial. The 234 study participants (healthy postmenopausal women with high breast density, 50-69 years, non smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Interleukins (IL)-1α, -1ß, -6, tumor necrosis factor-α and C-reactive protein were measured at baseline and at the end of the intervention. Intention-to-treat-analyses were carried out using Tobit regression. Although all cytokines tended to increase over time, after 24 months women in the PA intervention (arms 2 + 3) showed lower levels of IL-1α (exp(ß) = 0.66; p = 0.04) and IL-6 (exp(ß) = 0.70; p = 0.01) in comparison with women in the control group (arms 1 + 4). No effects of the dietary intervention emerged. In healthy postmenopausal women with high breast density a moderate-intensity PA appears to slow the age-related increase of pro-inflammatory cytokines.

The association between pesticide use and cutaneous melanoma: a systematic review and meta-analysis.

BACKGROUND: The incidence of cutaneous melanoma (CM), the deadliest form of skin cancer, has gradually increased in the last decades among populations of European origin. Epidemiological studies suggested that farmers and agricultural workers are at an increased risk of CM because they were exposed to pesticides. However, little is known about the relationship between pesticides and CM. OBJECTIVES: To investigate the association between exposure to pesticides and CM by systematically reviewing the literature. Secondary aim was to determine the categories of pesticides mainly involved in CM development. METHODS: A systematic review of the literature was performed up to September 2018 using MEDLINE, Embase and Web of Science. Studies assessing CM risk in licensed pesticide applicators were considered. Strict criteria were established to select independent studies and risk estimates; random effect models, taking into account heterogeneity, were applied. A pooled risk estimate for CM was calculated for the use of each type of pesticide and type of exposure. Between-study and estimate heterogeneity was assessed and publication bias investigated. RESULTS: A total of nine studies (two case-controls and seven cohorts) comprising 184 389 unique subjects were included. The summary relative risks for the categories 'herbicides - ever exposure', 'insecticides - ever exposure', 'any pesticide - ever exposure' and 'any pesticide - high exposure' resulted 1.85 [95% confidence interval (CI): 1.01, 3.36], 1.57 (95% CI: 0.58, 4.25), 1.31 (95% CI: 0.85, 2.04) and 2.17 (95% CI: 0.45, 10.36), respectively. Herbicides and insecticides had no between-study heterogeneity (I2  = 0%), while a significant heterogeneity (I2  > 50%) was detected for the high exposure to any pesticide. No indication for publication bias was found. CONCLUSIONS: Individuals exposed to herbicides are at an increased risk of CM. Future properly designed observational studies are required to confirm this finding.

The risk of extra-ovarian malignancies among women with endometriosis: A systematic literature review and meta-analysis.

We conducted a meta-analysis of studies reporting on the risk of extra-ovarian malignancies among women with endometriosis. Summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We explored causes of between-studies heterogeneity and assessed the presence of publication bias. We included 32 studies published between 1989 and 2018. We found an increased risk of endometrial (SRR 1.38, 95%CI 1.10-1.74) and thyroid cancer (SRR 1.38, 95%CI 1.17-1.63), and inverse association with cervical cancer (SRR 0.78, 95%CI 0.60-0.95). No association emerged for breast cancer (SRR 1.04, 95%CI 0.99-1.09) and melanoma (SRR 1.31, 95%CI 0.86-1.96). Between-study heterogeneity was large for breast and endometrial cancer and melanoma. Associations were generally stronger in case-control, cross-sectional, and cohort studies with internal control group, compared to cohort studies with external control group. No indication for publication bias was found. Our conclusions need to be confirmed in properly designed cohort studies with clinical confirmation of endometriosis.

Prevalence and co-occurrence of unhealthy lifestyle habits and behaviours among secondary school students in Tuscany, central Italy.

OBJECTIVES: Unhealthy habits acquired during adolescence may persist in adulthood and eventually increase the risk of chronic illnesses. STUDY DESIGN: We reported on a survey conducted in 2013-2015 among secondary school students in Tuscany, central Italy. METHODS: We compared the prevalence of self-reported lifestyle characteristics and overweight/obesity between genders and age groups (14-16 vs 17-21 years). We partitioned each gender- and age-specific stratum into groups based on cigarette smoking and engagement in sport activities, and compared the prevalence of other unhealthy lifestyles across groups using Poisson regression. RESULTS: Overall, 2167 students (53.3% males, mean age 16.8 years) were included. Males were more frequently overweight/obese than females. Cigarette smoking increased with age and did not differ by gender. Males were more likely to engage in sport activities, drink alcoholic beverages and adopt other unhealthy lifestyle habits, whereas females reported a more frequent use of painkillers. Cigarette smoking was the single lifestyle characteristic most consistently associated with other unhealthy habits. CONCLUSIONS: The prevalence and patterns of co-occurrence of unhealthy lifestyle habits varied by gender and age group among secondary school students in Italy. Our findings should be taken into account when planning public health initiatives aiming to combat obesity and tackle unhealthy lifestyles among secondary school students in Italy.

Correction to: A priori dietary patterns and blood pressure in the EPIC Florence cohort: a cross-sectional study.

In the original publication of the article have been published in an incorrect form. The correct form is given below.

A priori dietary patterns and blood pressure in the EPIC Florence cohort: a cross-sectional study.

PURPOSE: Several foods and nutrients have been independently associated with systolic (SBP) and diastolic (DBP) blood pressure values. This study aimed to evaluate the effects of combined dietary habits on SBP and DBP values in a large cohort of healthy adults, with a cross-sectional design. Adherence of participants to four a priori dietary patterns was considered: the Healthy Eating Index 2010 (HEI-2010); the Dietary Approaches to Stop Hypertension (DASH); the Greek Mediterranean Diet Score (MDS); and the Italian Mediterranean Index (IMI). METHODS: Overall, 13,597 volunteers (35-64 years) were enrolled in 1993-1998 in the EPIC-Florence cohort. Information on dietary habits, anthropometry, smoking status, education, physical activity habits, previous diagnosis of hypertension and SBP and DBP measurements were collected at baseline. Multivariate regression models were performed on 10,163 individuals (7551 women) after excluding subjects with prevalent hypertension. RESULTS: IMI, DASH and HEI-2010 were significantly and inversely associated with SBP and DBP values in the total population. The strongest association emerged between IMI and SBP (ß - 1.80 excellent adherence vs low adherence, 95% CI - 2.99; - 0.61, p trend 0.001) and DBP (ß - 1.12, 95% CI - 1.869; - 0.39, p trend 0.001) values. In sub-group analyses, an inverse association also emerged between IMI and SBP and DBP values among females and between DASH and DBP among males. MDS was not associated with SBP or DBP. CONCLUSION: Overall, this study, carried out in a large cohort of healthy adults from Tuscany (Central Italy), showed inverse significant associations between specific a priori dietary patterns, identifying general models of health-conscious diet, and blood pressure values.

What is the prognostic impact of FDG PET in locally advanced head and neck squamous cell carcinoma treated with concomitant chemo-radiotherapy? A systematic review and meta-analysis.

PURPOSE: Evidence is conflicting on the prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in head and neck squamous cell carcinoma. The aim of our study was to determine the impact of semiquantitative and qualitative metabolic parameters on the outcome in patients managed with standard treatment for locally advanced disease. METHODS: A systematic review of the literature was conducted. A meta-analysis was performed of studies providing estimates of relative risk (RR) for the association between semiquantitative metabolic parameters and efficacy outcome measures. RESULTS: The analysis included 25 studies, for a total of 2,223 subjects. The most frequent primary tumour site was the oropharynx (1,150/2,223 patients, 51.7%). According to the available data, the majority of patients had stage III/IV disease (1,709/1,799, 94.9%; no information available in four studies) and were treated with standard concurrent chemoradiotherapy (1,562/2,009 patients, 77.7%; only one study without available information). A total of 11, 8 and 4 independent studies provided RR estimates for the association between baseline FDG PET metrics and overall survival (OS), progression-free survival (PFS) and locoregional control (LRC), respectively. High pretreatment metabolic tumour volume (MTV) was significantly associated with a worse OS (summary RR 1.86, 95% CI 1.08-3.21), PFS (summary RR 1.81, 95% CI 1.14-2.89) and LRC (summary RR 3.49, 95% CI 1.65-7.35). Given the large heterogeneity (I2 > 50%) affecting the summary measures, no cumulative threshold for an unfavourable prognosis could be defined. No statistically significant association was found between SUVmax and any of the outcome measures. CONCLUSION: FDG PET has prognostic relevance in the context of locally advanced head and neck squamous cell carcinoma. Pretreatment MTV is the only metabolic variable with a significant impact on patient outcome. Because of the heterogeneity and the lack of standardized methodology, no definitive conclusions on optimal cut-off values can be drawn.

Physical activity and blood pressure in 10,000 Mediterranean adults: The EPIC-Florence cohort.

BACKGROUND AND AIMS: The relevant role of physical activity (PA) in cardiovascular risk prevention is widely agreed. We aimed to evaluate, in a large Mediterranean population, the influence of PA on systolic (SBP) and diastolic blood pressure (DBP), taking into account individual characteristics and lifestyle habits. METHODS AND RESULTS: In the Florence section of the European Prospective Investigation into Cancer and Nutrition 10,163 individuals, 35-64 years, without a previous diagnosis of hypertension were recruited. Information on occupational and leisure-time PA and blood pressure were collected at recruitment, together with data on lifestyle, dietary habits and anthropometry. Multivariate regression models were applied to evaluate the effect of total, occupational and leisure-time PA on SBP and DBP. Mean values of SBP and DBP in the study subjects were 124.4 (SD 15.6) and 79.7 mmHg (SD 9.4), respectively. Overall, a total PA index and an index including cycling, fitness and occupational PA (Cambridge index) were inversely associated with DBP (beta -0.87, p-value 0.02 actives vs inactives, p for trend 0.02 and beta -0.84, p value 0.003 actives vs inactives, p for trend 0.002, respectively), while SBP was associated only with the latter index (beta -1.14, p-value 0.01 actives vs inactives, p for trend 0.006). An inverse association emerged between manual/heavy manual occupation and DBP (p 0.02, ref sedentary/standing occupation) and between increasing cycling activity and SBP (p for trend 0.04). CONCLUSIONS: In this large cohort of Mediterranean adults without a diagnosis of hypertension we confirm the role of overall PA in modulating SBP and DBP values. Cycling and manual occupations were associated with lower DBP values.

Correction: Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

[This corrects the article DOI: 10.1371/journal.pone.0152310.].

Risk of second primary malignancies among 1537 melanoma patients and risk of second primary melanoma among 52 354 cancer patients in Northern Italy.

BACKGROUND: The number of melanoma survivors has been increasing for decades due to early diagnosis and improved survival. These patients have an increased risk of developing a second primary cancer (SPC); also, melanoma is frequently diagnosed among patients firstly diagnosed with an extracutaneous malignancy. OBJECTIVE: We evaluated the risk of developing a SPC among 1537 melanoma patients, and the risk of second primary melanoma (SPM) in 52 354 extracutaneous cancer patients, who were treated at the European Institute of Oncology in Milan, Italy, during 2000-2010. MATERIAL AND METHODS: We calculated standardized incidence ratios (SIR) by applying gender-, age-, year- and region-specific reference rates to the follow-up time accrued between the diagnosis of the first and the second primary malignancies. RESULTS: Seventy-six SPC were diagnosed during a median follow-up of 4 years, of which 49 (64%) during the first 2 years upon melanoma diagnosis. The SIR was increased for cancer of breast (4.10, 95% CI 2.79-6.03), thyroid (4.67, 95% CI 1.94-11.22), brain (6.13, 95% CI 2.30-16.33) and for non-Hodgkin lymphoma (3.12, 95% CI 1.30-7.50). During a median follow-up of 4 years, 127 SPM were diagnosed: thick lesions were less frequent than for melanoma diagnosed as first cancer. The SIR was increased for cancer of breast (5.13, 95%CI 3.91-6.73), thyroid (16.2, 95%CI: 5.22-50.2), head and neck (5.62, 95%CI 1.41-22.50), soft tissue (8.68, 95%CI 2.17-34.70), cervix (12.5, 95% CI 3.14-50.20), kidney (3.19, 95%CI 1.52-6.68), prostate (4.36, 95%CI 2.63-7.24) and acute myeloid leukaemia (6.44, 95%CI 2.42-17.20). CONCLUSIONS: The most likely causes of these associations are the clustering of lifestyle risk factors in the same subgroups of population, mainly on a sociocultural basis and surveillance bias. This raises important questions about how to best follow cancer survivors by avoiding an inefficient use of resources and an excessive medicalization of these patients' lives.

Accuracy and Reproducibility of HER2 Status in Breast Cancer Using Immunohistochemistry: A Quality Control Study in Tuscany Evaluating the Impact of Updated 2013 ASCO/CAP Recommendations.

The correct identification of HER2-positive cases is a key point to provide the most appropriate therapy to breast cancer (BC) patients. We aimed at investigating the reproducibility and accuracy of HER2 expression by immunohistochemistry (IHC) in a selected series of 35 invasive BC cases across the pathological anatomy laboratories in Tuscany, Italy. Unstained sections of each BC case were sent to 12 participating laboratories. Pathologists were required to score according to the Food and Drug Administration (FDA) four-tier scoring system (0, 1+, 2+, 3+). Sixteen and nineteen cases were HER2 non-amplified and amplified respectively on fluorescence in situ hybridization. Among 192 readings of the 16 HER2 non-amplified samples, 153 (79.7%) were coded as 0 or 1+, 39 (20.3%) were 2+, and none was 3+ (false positive rate 0%). Among 228 readings of the 19 HER2 amplified samples, 56 (24.6%) were scored 0 or 1+, 79 (34.6%) were 2+, and 93 (40.8%) were 3+. The average sensitivity was 75.4%, ranging between 47% and 100%, and the overall false negative rate was 24.6%. Participation of pathological anatomy laboratories performing HER2 testing by IHC in external quality assurance programs should be made mandatory, as the system is able to identify laboratories with suboptimal performance that may need technical advice. Updated 2013 ASCO/CAP recommendations should be adopted as the widening of IHC 2+ "equivocal" category would improve overall accuracy of HER2 testing, as more cases would be classified in this category and, consequently, tested with an in situ hybridisation method.

Hospital-acquired infections due to multidrug-resistant organisms in Hungary, 2005-2010.

Healthcare-associated infections caused by multidrug-resistant organisms are associated with prolonged medical care, worse outcome and costly therapies. In Hungary, hospital-acquired infections (HAIs) due to epidemiologically important multidrug-resistant organisms are notifiable by law since 2004. Overall, 6,845 case-patients (59.8% men; median age: 65 years) were notified in Hungary from 2005 to 2010. One third of case-patients died in hospital. The overall incidence of infections increased from 5.4 in 2005 to 14.7 per 100,000 patient-days in 2010. Meticillin-resistant Staphylococcus aureus (MRSA) was the most frequently reported pathogen (52.2%), but while its incidence seemed to stabilise after 2007, notifications of multidrug-resistant Gram-negative organisms have significantly increased from 2005 to 2010. Surgical wound and bloodstream were the most frequently reported sites of infection. Although MRSA incidence has seemingly reached a plateau in recent years, actions aiming at reducing the burden of HAIs with special focus on Gram-negative multidrug-resistant organisms are needed in Hungary. Continuing promotion of antimicrobial stewardship, infection control methodologies, reinforced HAI surveillance among healthcare and infection control practitioners, and engagement of stakeholders, hospital managers and public health authorities to facilitate the implementation of existing guidelines and protocols are essential.