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Introduction: The Second Expert Report, Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective from World Cancer Research Fund/ American Institute for Cancer Research (WCRF/AICR), features general and special recommendations for cancer prevention. Objective: To evaluate nutritional and lifestyle characteristics of newly diagnosed women with breast cancer according to WCRF/AICR Second Report recommendations. Methods: This is a cross-sectional study with a sample of 133 women. Diet data were obtained from a food frequency questionnaire and anthropometric data by standard procedures. The characteristics of study population were evaluated in comparison with the recommendations of the WCRF/AICR Second Report. Results: Mean age of participants was 51.6 ± 10.98 (range 28-78) years; 35% was obese and 51% had waist circumference higher than the maximum cut-off value. Regarding life style, 80% of participants were sedentary, 89% reported diet presenting energy density higher than 125 kcal/100 g, 51% reported consumption of fruits and vegetables lower than 400 g/day, and 47% reported high consumption of red or processed meat (>= 500 g per week). Just 3% related consumption of alcoholic beverages above the recommendation (15 g/day), 82% presented the intake of sodium lower than the limit recommended (2.4 g/day), and the use of dietary supplements was reported by 11% of the subjects. Finally 51% of women reported breast feeding for less than 6 months. Conclusion: Inadequacies were observed related to behavior factors that can result in weight gain, such as inadequate physical activity and high energy density diet. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate changes in dietary intake, anthropometric parameters and markers of oxidative stress in 40 women who underwent surgery, chemotherapy or radiation therapy for breast cancer.Methods: Pretreatment and post-treatment measurements included data collected through a food frequency questionnaire, weight and height to calculate the body mass index (BMI) and oxidative stress markers assessed from blood reduced glutathione (GSH), serum antioxidant capacity (AC), plasma thiobarbituric acid reactive substances (TBARS), serum lipid hydroperoxides (LH) and plasma carbonyls. Differences were compared using paired Student's t-test or paired Wilcoxon's test.Results: A significant increase (P < 0.05) in the intake of the food groups: meat and eggs, dairy products, beans, oils and fats, as well as food from the subgroups: red meat, milk and other dairy products rich in fat, fruit rich in vitamin C and vegetable fats was found after treatments. There was a significant increase in body weight (P < 0.05), BMI (P < 0.05), levels of TBARS (P < 0.0001), LH (P < 0.005) and carbonyls (P < 0.0001) and a significant decrease of levels of AC (P < 0.005) and GSH (P < 0.0001).Conclusion: Breast cancer diagnosis and treatments were associated with dietary intake changes and increased body weight, BMI and oxidative stress. These potential changes have important implications for preventive nutrition counseling. [ABSTRACT FROM AUTHOR]

Escherichia coli can harbor a broad repertoire of virulence and antimicrobial resistance (AMR) genes, which can be exchanged across the human gastrointestinal microflora, thus posing a public health risk. In this study, 6 batches of artisanal soft cheese and a 6-month ripened fermented dried sausage were investigated to assess the occurrence, phylogeny, and genomic traits (AMR, virulence, and mobilome) of E. coli . 30 and 3 strains isolated from salami and cheese food chains, respectively, were confirmed as E. coli by whole genome sequencing. The accumulation of single nucleotide polymorphism differences within small clusters of strains encompassing batches or processing stages, combined with high serotype and phylogroup diversity, suggested the occurrence of different contamination phenomena among the facilities. A total of 8 isolates harbored plasmid-mediated resistance genes, including one cheese strain that carried an IncQ1 plasmid carrying AMR determinants to macrolides [ mph (B)], sulfonamides ( sul1 , sul2 ), trimethoprim (dfrA1) , and aminoglycosides [ aph (3")-Ib and aph (6)-Id]. A pool of virulence-associated genes in the class of adhesion, colonization, iron uptake, and toxins, putative ColV -positive iron uptake systems sit , iro , or iuc (8 salami and 2 cheese), plasmid-encoded hemolysin operon hly ABCD (one salami), and potential atypical enteropathogenic E. coli (3 salami environment) were reported. Overall, our findings underscore the importance of routine surveillance of E. coli in the artisanal food chain to prevent the dissemination of AMR and virulence., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (Copyright © 2024, the Author(s).)

Autologous peripheral blood stem cell transplantation (aPBSCT) provides optimal outcomes in POEMS syndrome but the definition of the best treatment before aPBSCT remains to be defined because of the rarity of the disease and the heterogeneity of published case series. We collected clinical and laboratory data of patients with POEMS syndrome undergoing aPBSCT from 1998 to 2020 in ten Italian centers. The primary endpoint of the study was to evaluate the impact of prior therapies and mobilization regimen on outcome. We divided the patients into three groups: patients who did not receive any treatment before transplant (15 patients, group A: front-line), patients pre-treated with other agents (14 patients, group B) and patients treated with cyclophosphamide as their mobilizing regimen (16 patients, group C). The three groups did not show differences in terms of demographic and clinical characteristics. All 45 patients underwent aPBSCT after a high-dose melphalan conditioning regimen, with a median follow-up of 77 months (range, 37-169 months). The responses were not statistically different between the three groups (P=0.38). Progression-free and overall survival rates at 6 years were: 70% (95% confidence interval: 55-85%) and 91% (95% confidence interval: 82-99) 65%, respectively, and did not differ between the three groups. The cumulative incidence of transplant-related mortality and relapse was 4% and 36%, respectively. In conclusion, in a relatively large number of patients with POEMS syndrome, undergoing an autologous transplant, pre-treatment and disease status at transplant did not appear to have an impact on major transplant outcomes.

Hospital malnutrition is especially common among elderly patients with neurological deficits or dementia. These conditions can be exacerbated by unpalatable diets and issues such as dysphagia and presbyphagia. Our study aimed to investigate the prevalence of malnutrition in patients on a homogenized diet and to identify potential correlations with specific clinical variables. We conducted a retrospective observational study in compliance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. The study encompassed 82 patients, mainly elderly and diagnosed with neurodegenerative diseases. Upon initial assessment, 46.34% of the sample displayed a risk of malnutrition based on the Malnutrition Universal Screening Tool (MUST), and 62.20% were classified as malnourished based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Only 45.12% retained autonomy in food intake. Weight loss identified prior to the study was closely tied to malnutrition and influenced BMI. Moreover, autonomy in food intake was strongly associated with a prolonged hospital stay (LOS), and a similar trend was observed for water intake. Our findings emphasize the importance of promptly recognizing patients at risk of malnutrition, especially within such a vulnerable population. Autonomy in food intake and hydration emerge as critical indicators in the clinical management of hospitalized patients.

Artisanal salami is produced in small-scale production plants, where the lack of full automation might result in higher variability in food intrinsic properties. The aim of the present study was to evaluate the inter- and intra-batch variability in physicochemical parameters and its impact on microbial quality and occurrence of foodborne pathogens on 480 samples collected from six batches of an artisanal Italian production of organic salami. Relatively high total bacterial counts (TBC) were found on the surface of the table in the stuffing room (4.29 ± 0.40 log cfu/cm 2 ). High loads of Enterobacteriaceae in the meat mixture of batch 2 and TBC in batch 5 were associated with a higher occurrence of bacterial pathogens. During ripening, water activity (a w ) and pH failed to reach values lower than 0.86 and 5.3, respectively. Six Staphylococcus aureus and four Listeria monocytogenes isolates were collected from the salami meat mixture during ripening and the processing environment. A total of 126 isolates of Enterobacteriaceae were characterized at a species level, with Escherichia coli , Klebsiella pneumoniae , Enterobacter cloacae , and Citrobacter freundii isolated from the final products. Results suggest the relevance of first steps of production in terms of the hygiene of raw materials and handling during stuffing procedures, especially when the physicochemical parameters of the final products do not reach values that represent hurdles for foodborne pathogens.

The prevalence of malnutrition is increasing globally due to factors such as age-related pathological conditions and diseases that impact food and beverage intake. In hospital settings, older adult patients often require homogenised diets, which can lead to malnutrition due to poor palatability and limited variety. This study compared the Standard Homogenised Diet (HSD) and a Modified Homogenized Diet (HMD) proposed in a tertiary hospital in Northern Italy. A retrospective and observational design was used to analyse data from 86 adult patients with various conditions requiring a homogenised diet. The primary goal was to compare food intake, rheological characteristics, and palatability of the two diets. The secondary objective was to evaluate the economic impact by comparing costs and quantifying food waste from unused meals. Patients on HMD had a median daily caloric intake of 852 kcal (IQR 787-926 kcal) compared to 631 kcal (IQR 506-797 kcal) in the HSD group. Taste, texture, palatability, and ease of intake for HMD outperformed HSD with scores such as 3.7 ± 0.6 vs. 2.5 ± 0.4 for taste. Economically, HMD was EUR 0.53 less expensive per day than HSD, and food wastage costs were significantly lower for HMD (EUR 2.66 ± 0.81) than HSD (EUR 4.66 ± 1.27). Overall, HMD presented substantial benefits in patient satisfaction and cost-efficiency. This insight may aid diverse care settings to enhance meal acceptance and nutritional intake for patients needing homogenised diets.

The aim of the present study was to investigate the genetic diversity and antimicrobial resistance (AMR) of E. coli during enrofloxacin therapy in broilers affected by colisepticemia. Three unrelated farms with ongoing colibacillosis outbreaks were sampled at day 1 before treatment and at days 5, 10 and 24 post-treatment. A total of 179 E. coli isolates were collected from extraintestinal organs and submitted to serotyping, PFGE and the minimum inhibitory concentration (MIC) against enrofloxacin. PFGE clusters shifted from 3-6 at D1 to 10-16 at D5, D10 and D24, suggesting an increased population diversity after the treatment. The majority of strains belonged to NT or O78 and to ST117 or ST23. PFGE results were confirmed with SNP calling: no persistent isolates were identified. An increase in resistance to fluoroquinolones in E. coli isolates was observed along the treatment. Resistome analyses revealed qnrB19 and qnrS1 genes along with mutations in the gyrA , parC and parE genes. Interestingly, despite a fluoroquinolone selective pressure, qnr -carrying plasmids did not persist. On the contrary, two conjugative AMR plasmid clusters (AB233 and AA474) harboring AMR genes other than qnr were persistent since they were identified in both D1 and D10 genomes in two farms. Further studies should be performed in order to confirm plasmid persistence not associated (in vivo) to antimicrobial selective pressure.

Increasing reports on K. pneumoniae strains with antimicrobial resistance and virulence traits from food and farm animals are raising concerns about the potential role of Klebsiella spp. as a foodborne pathogen. This study aimed to report and characterize Klebsiella spp. isolates from two artisanal ready-to-eat food (soft cheese and salami) producing facilities, and to track similar genotypes in different ecological niches. Over 1170 samples were collected during the whole production chain of different food batches. The overall Klebsiella prevalence was 6%. Strains were classified into the three Klebsiella species complexes: K. pneumoniae (KpSC, n = 17), K. oxytoca (KoSC, n = 38) and K. planticola (KplaSC, n = 18). Despite high genetic diversity we found in terms of known and new sequence types (STs), core genome phylogeny revealed clonal strains persisting in the same processing setting for over 14 months, isolated from the environment, raw materials and end-products. Strains showed a natural antimicrobial resistance phenotype-genotype. K. pneumoniae strains showed the highest virulence potential, with sequence types ST4242 and ST107 strains carrying yersiniabactin ybt16 and aerobactin iuc3. The latter was detected in all K. pneumoniae from salami and was located on a large conjugative plasmid highly similar (97% identity) to iuc3 + plasmids from human and pig strains circulating in nearby regions of Italy. While identical genotypes may persist along the whole food production process, different genotypes from distinct sources in the same facility shared an iuc3-plasmid. Surveillance in the food chain will be crucial to obtain a more comprehensive picture of the circulation of Klebsiella strains with pathogenic potential., (© 2023. The Author(s).)

In the present study, the occurrence of Listeria monocytogenes , Staphylococcus aureus , Salmonella spp . and Escherichia coli VTEC was investigated in two batches of artisanal Italian salami tested in winter and summer. Moreover, enumerations of total bacterial count, lactic acid bacteria and Enterobacteriaceae were performed as well as monitoring of water activity and pH. Samples were taken from raw materials, production process environment, semi-finished product and finished products. The results revealed an overall increase of total bacterial count and lactic acid bacteria during the ripening period, along with a decrease of Enterobacteriaceae , pH and water activity. No significant difference was observed between the two batches. The enterobacterial load appeared to decrease during the maturation period mainly due to a decrease in pH and water activity below the limits that allow the growth of these bacteria. E. coli VTEC, Salmonella spp. or L. monocytogenes were not detected in both winter and summer batches. However, Klebsiella pneumoniae was detected in both summer and winter products. Except for one isolate, no biological hazards were detected in the finished salami, proving the efficacy of the ripening period in controlling the occurrence of microbiological hazard in ripened salami. Further studies are required to assess the virulence potential of the Klebsiella pneumoniae isolates., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

The aim of the present study was to investigate the resistome and virulome diversity of 43 isolates of Listeria monocytogenes , Salmonella enterica and S. aureus collected from artisanal fermented meat and dairy products and their production environments in Portugal, Spain, Italy and Morocco. After DNA extraction, genomes were sequenced, and de novo assembled. Genetic relationships among genomes were investigated by SNP calling and in silico 7- loci MLST. Genomes of the same species belonged to different ST-types demonstrating the circulation of different clones in in the same artisanal production plant. One specific clone included genomes of S . Paratyphi B belonging to ST43 and repeatedly isolated for more than a year in an artisanal sausage production plant. No genomes but three (belonging to Salmonella enterica ), were predicted as multiresistant to different antimicrobials classes. Regarding virulence, genomes of L. monocytogenes belonging to ST1, ST3 and ST489, as well as genomes of S.enterica enterica (ST43, ST33, ST314, ST3667, ST1818, ST198) and ST121 S. aureus were predicted as virulent and hypervirulent. The occurrence of virulent and hypervirulent L. monocytogenes, Salmonella enterica and S. aureus strains in artisanal fermented meat and dairy productions as well as in their finished products suggests the need for a specific focus on prevention and control measures able to reduce the risk of these biological hazards in artisanal food productions., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

Artisanal cheeses are produced in small-scale production plants, where the lack of full automation and control of environmental and processing parameters suggests a potential risk of microbial contamination. The aim of this study was to perform a longitudinal survey in an Italian artisanal factory producing a spreadable soft cheese with no rind to evaluate the inter- and intra-batch variability of physicochemical and microbial parameters on a total of 720 environmental and cheese samples. Specifically on cheese samples, the evaluation was additionally performed on physicochemical parameters. Cheese samples were additionally collected during 15 days of storage at constant temperatures of 2 and 8°C, as well as a dynamic profile of 2°C for 5 days and 8°C for 10 days. Furthermore, Enterobacteriaceae isolates were identified at species level to have a better knowledge of the environmental and cheese microbiota potentially harboring human pathogens. High inter-batch variability was observed for lactic acid bacteria (LAB) and total bacteria count (TBC) in cheese at the end of production but not for pH and water activity. A temperature of 8°C was associated with a significantly higher load of Enterobacteriaceae in cheeses belonging to batch 6 at the end of storage, and this temperature also corresponded with the highest increase in LAB and TBC loads over cheese shelf life. Results from generalized linear mixed models (GLMMs) indicated that drains in the warm room and the packaging area were associated with higher levels of TBC and Enterobacteriaceae in cheese. Regarding foodborne pathogens, no sample was positive for verotoxigenic Escherichia coli (VTEC) or Listeria monocytogenes , whereas six Staphylococcus aureus and one Salmonella pullorum isolates were collected in cheese samples during storage and processing, respectively. Regarding Enterobacteriaceae, 166 isolates were identified at species level from all batches, with most isolates belonging to Klebsiella oxytoca and pneumoniae , Enterobacter cloacae , Hafnia alvei , and Citrobacter freundii evidencing the need to focus on standardizing the microbial quality of cow milk and on hygienic procedures for cleaning and disinfection especially in warm and maturation rooms. Further studies should be performed to investigate the potential pathogenicity and antimicrobial resistance of the identified Enterobacteriaceae species in artisanal cheeses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pasquali, Valero, Possas, Lucchi, Crippa, Gambi, Manfreda and De Cesare.)

The present study aimed at assessing the occurrence of microbiological hazards ( Listeria monocytogenes , Staphylococcus aureus , Salmonella spp . and Escherichia coli O157) in an artisanal soft cheese produced in northern Italy. In the same product total bacterial count, lactic acid bacteria and Enterobacteriaceae were enumerated, and pH and water activity measured in two batches sampled in summer and winter. Samples of raw materials, environmental swabs from the production processes and cheese during 15 days of storage at 2 and 8°C as well as dynamic temperature of 2°C for 5 days and 8°C for 10 days were collected and tested. The load of total bacterial count was significantly higher in the winter batch in comparison to the summer one, with a significant increase at the end of the storage period also noticed for lactic acid bacteria. Statistical higher values of pH were registered in raw materials and end of storage in winter batch. S. aureus was confirmed only in the winter batch within samples (n=4) of stored cheese. On plates used for E. coli O157 detection, colonies of Klebsiella pneumoniae and Klebsiella oxytoca were isolated. The results suggest that the highest bacterial population in the winter batch was associated to a higher pH in stored cheese and a higher number of biological hazards identified. Their isolation started in the maturation room suggesting this step as relevant for possible cheese contamination., Competing Interests: Conflict of interest: The authors declare no potential conflict of interest., (©Copyright: the Author(s).)

This study is focused on resistance to carbapenems and third-generation cephalosporins in Gram-negative microorganisms isolated from swine, whose transmission to humans via pork consumption cannot be excluded. In addition, the common carriage of carbapenem-resistant (CR) bacteria between humans and pigs was evaluated. Sampling involved 300 faecal samples collected from slaughtered pigs and 300 urine samples collected from 187 hospitalised patients in Parma Province (Italy). In swine, MIC testing confirmed resistance to meropenem for isolates of Pseudomonas aeruginosa and Pseudomonas oryzihabitans and resistance to cefotaxime and ceftazidime for Escherichia coli , Ewingella americana , Enterobacter agglomerans , and Citrobacter freundii . For Acinetobacter lwoffii , Aeromonas hydrofila, Burkolderia cepacia , Corynebacterium indologenes , Flavobacterium odoratum , and Stenotrophomonas maltophilia , no EUCAST MIC breakpoints were available. However, ESBL genes ( bla CTXM-1 , bla CTX-M-2 , bla TEM-1 , and bla SHV ) and AmpC genes ( bla CIT , bla ACC , and bla EBC ) were found in 38 and 16 isolates, respectively. P. aeruginosa was the only CR species shared by pigs (4/300 pigs; 1.3%) and patients (2/187; 1.1%). P. aeruginosa ST938 carrying bla PAO and bla OXA396 was detected in one pig as well as an 83-year-old patient. Although no direct epidemiological link was demonstrable, SNP calling and cgMLST showed a genetic relationship of the isolates (86 SNPs and 661 allele difference), thus suggesting possible circulation of CR bacteria between swine and humans.

Several strategies have been in place in food animal production to reduce the unnecessary use of antimicrobial agents. Beyond the monitoring of their use, the evaluation of the effect of these strategies on the occurrence and types of antimicrobial resistance (AMR) associated genes is crucial to untangle the potential emergence and spread of AMR to humans through the food chain. In the present study, the occurrence of these genes was evaluated in commensal Escherichia coli isolated from broiler carcasses "produced without the use of antibiotics" in 3 antibiotic-free (AB-free) farms in Italy in 2019. Sequenced data were analyzed along with publicly available genomes of E. coli collected in Italy from the broiler food chain from previous years (2017-2018). The genetic relationships among all 93 genomes were assessed on de novo assemblies by in silico MLST and SNP calling. Moreover, the resistomes of all genomes were investigated. According to SNP calling, genomes were gathered in three clades. Clade A encompassed, among others, ST117, ST8070, and ST1011 genomes. ST10 belonged to clade B, whereas Clade C included ST58, ST297, ST1101, and ST23 among others. Regarding the occurrence of AMR genes, a statistically significant lower occurrence of these genes in the genomes of this study in comparison to the public genomes was observed considering the whole group of genes as well as genes specifically conferring resistance to aminoglycosides, β-lactams, phenicols, trimethoprim, and lincosamides. Moreover, significant reductions were observed by comparing the whole group of AMR associated mutations, as well as those specifically for fluoroquinolones and fosfomycin resistance. Although the identification of 3° generation cephalosporin resistance associated genes in AB-free E. coli is a concern, this study provides a first indication of the impact of a more prudent use of antimicrobial agents on the occurrence of AMR genes in Italian broiler production chain. More studies are needed in next years on a higher number of genomes to confirm this preliminary observation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (-0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19., (© 2021. The Author(s).)

Background: Diffusion-weighted whole-body MRI (DW-MRI) is increasingly used in the management of multiple myeloma (MM) patients, but data regarding the prognostic role of DW-MRI imaging response after treatment are lacking. The Myeloma Response Assessment and Diagnosis System (MY-RADS) imaging recommendations recently proposed the criteria for response assessment category (RAC) with a 5-point scale in order to standardize response assessment after therapy, but this score still needs to be validated., Methods: We investigated the prognostic role of RAC criteria in 64 newly diagnosed MM patients after autologous stem cell transplantation (ASCT), and we combined the results of MY-RADS with those of minimal residual disease (MRD) assessment by multiparametric flow cytometry (MFC)., Results: Superior post-ASCT PFS and OS were observed in patients with complete imaging response (RAC1), with respect to patients with imaging residual disease (RAC≥2): median PFS not reached (NR) versus 26.5 months, p = 0.0047, HR 0.28 (95% CI: 0.12-0.68); 3-year post-ASCT OS 92% versus 69% for RAC1 versus RAC ≥2, respectively, p = 0.047, HR 0.24 (95% CI: 0.06-0.99). Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively (PFS NR vs. 10.6 months); p = 0.001, HR 0.07 (95%CI: 0.01-0.36)., Conclusion: The present study supports the applicability of MY-RADS recommendations after ASCT; RAC criteria were able to independently stratify patients and to better predict their prognosis and the combined use of DW-MRI with MFC allowed a more precise evaluation of MRD., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The phase 3 GIMEMA-MMY-3006 trial, which compared bortezomib, thalidomide, and dexamethasone (VTD) combination therapy with thalidomide and dexamethasone (TD) as induction therapy before and consolidation therapy after double autologous haematopoietic stem-cell transplantation (HSCT) for newly diagnosed multiple myeloma, showed the superiority of the triplet regimen over the doublet in terms of increased complete response rate and improved progression-free survival. We report the results from the final analysis of the study., Methods: In this randomised, open-label, phase 3 study, patients aged 18-65 years with previously untreated symptomatic multiple myeloma and a Karnofsky Performance Status of 60% or higher were enrolled at 73 centres in Italy. Patients were randomised (1:1) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily orally for the first 14 days and 200 mg daily thereafter) plus dexamethasone (total 320 mg per cycle; 40 mg on days 1-2, 4-5, 8-9, and 11-12 in the VTD regimen, and 40 mg on days 1-4 and 9-12 in the TD regimen), either alone (TD group) or with bortezomib (1·3 mg/m 2 intravenously on days 1, 4, 8, and 11; VTD group). After double autologous HSCT, patients received two 35-day cycles of either the VTD or TD regimen, according to random assignment, as consolidation therapy. The primary outcome was the rate of complete response and near complete response after induction (already reported). In this updated analysis we assessed long-term progression-free survival and overall survival (secondary endpoints of the study) with an extended 10-year median follow-up, and analysed the variables influencing survival. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, NCT01134484., Findings: Between May 10, 2006, and April 30, 2008, 480 patients were enrolled and randomly assigned to receive VTD (241 patients) or TD (239 patients). Six patients withdrew consent before start of treatment. 236 (99 [42%] women) in the VTD group and 238 (102 [43%] women) in the TD group were included in the intention-to-treat analysis. The data cutoff date for this analysis was May 31, 2018. Median follow-up for surviving patients was 124·1 months (IQR 117·2-131·7). The 10-year progression-free survival estimate for patients in the VTD group was 34% (95% CI 28-41) compared with 17% (13-23) for the TD group (hazard ratio [HR] 0·62 [95% CI 0·50-0·77]; p<0·0001). 60% (95% CI 54-67) of patients in the VTD group were alive at 10 years versus 46% (40-54) of patients in the TD group (HR 0·68 [95% CI 0·51-0·90]; p=0·0068). VTD was an independent predictor of improved progression-free survival (HR 0·60 [95% CI 0·48-0·76]; p<0·0001) and overall survival (HR 0·68 [0·50-0·91]; p=0·010). The incidence of second primary malignancies per 100 person-years was 0·87 (95% CI 0·49-1·44) in the VTD group compared with 1·41 (0·88-2·13) in the TD group., Interpretation: Incorporation of VTD into double autologous HSCT resulted in clinically meaningful improvements in long-term progression-free survival and overall survival, confirming that a regimen including bortezomib and an immunomodulatory drug is the gold standard treatment for patients with newly diagnosed myeloma who are fit for high-dose chemotherapy., Funding: Seràgnoli Institute of Haematology, University of Bologna, and BolognAIL., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Consolidation treatment in acute myeloid leukemia (AML) patients achieving complete remission (CR) is warranted. High-dose cytarabine (HDAC) is considered first choice in favorable risk and an option in intermediate-risk AML. However, its optimal dose and schedule, as well as the benefit of additional chemotherapy agents remain controversial. Herein, we report on the long-term outcome of consecutive unselected AML patients treated with repeated courses of HDAC, with the addition of idarubicin, followed by autologous peripheral blood stem cell (PBSC) support, in order to limit toxicity, according to Northern Italy Leukemia Group (NILG) AML-01/00 study (EUDRACT number 00400673). Among 338 patients consecutively diagnosed from 2001 to 2017 at our center, 148 with high-risk AML (adverse cytogenetic, isolated FLT3-internal tandem duplication mutation, refractory to first induction) were addressed to allogeneic stem cell transplant. All other cases, 186 patients (55%), median age 53 (range 19-75), were considered standard-risk and received the NILG AML-01/00 program. After achieving CR, patients were mobilized with cytarabine 8 g/sqm to collect autologous CD34+-PBSC and received three consolidation cycles with HDAC (20 g/sqm) plus idarubicin (20 mg/sqm) per cycle, followed by reinfusion of limited doses of CD34+ PBSC (1-2x106/kg). The program was completed by 160 (86%) patients. Toxicity was acceptable. Neutrophils recovered a median of 10 days. Treatment-related mortality was 3/160 (1.8%). After a median follow-up of 66.4 months, overall survival (OS) and relapse-free survival (RFS) at 5-years were 61.4% and 52.4%, respectively. Twenty-eight selected patients aged >65 had similar outcomes. According to European leukemia net-2010 classification, the OS and RFS at 5-years were 76.4% and 65% in favorable risk, without differences between molecular subgroups, 52.3% and 47.2% in Intermediate-I, 45.2% and 36.5% in Intermediate-II risk patients, respectively. In conclusion, consolidation including repeated courses of high dose cytarabine and idarubicin, with limited PBSC support, proved feasible and very effective in nonhigh risk patients. The incorporation of novel agents in its backbone may be tested to further improve patient's prognosis., (© 2020 John Wiley & Sons Ltd.)

Autologous stem cell transplantation (ASCT) is feasible and effective in selected older patients with Multiple Myeloma, but specific criteria for evaluating ASCT eligibility in elderly patients are lacking. We evaluated 131 patients aged 65-75 considered for ASCT at our center: The Charlson Comorbidity Index (CCI), Hematopoietic cell transplantation comorbidity index (HCT-CI) and IMWG frailty score were obtained at diagnosis, but the intensity of treatment was left to physician's choice. The scores and age's impact on outcome was analyzed: 85 patients were judged transplant eligible, whereas 46 patients received a less intensive treatment (median follow up 27 months). No patients classified as frail had been considered eligible to ASCT with a worse outcome compared to fit and unfit patients (median PFS (progression free survival): 7.9 vs 32.9 and 29.6 months; P < .001). PFS was superior in the ASCT group (35.6 vs 19.9 months, P .013). In the ASCT group, PFS was better in patients aged 65-69 years than in patients ≥70 (51.5 vs 27.7 months, P.004). Indeed, in unfit patients aged ≥70 the PFS of the ASCT group was comparable to NO ASCT group (18 vs 27 months, P = .33) whereas in unfit patients aged 65-69 PFS was superior in the ASCT group: 43.3 vs 18.4 months, P .01. ISS III and impaired functional status independently affected PFS in a multivariate analysis (P .011 and P .006). While CCI and HCT-CI did not predict different outcome in ASCT patients, the IMWG frailty score would be of help in identifying unfit patients aged 70-75, whose outcome with ASCT selected by clinical judgment was no better than with less intensive treatments., (© 2020 Wiley Periodicals, Inc.)

Bortezomib- and lenalidomide-containing regimens are well-established therapies in multiple myeloma (MM). However, despite their extensive use, head-to-head comparisons have never been performed. Therefore, we compared bortezomib and lenalidomide in fixed-duration therapies. In this open-label, phase III study, we randomized MM patients at first relapse to receive either nine cycles of bortezomib plus cyclophosphamide plus dexamethasone (VCD) or lenalidomide plus cyclophosphamide plus dexamethasone (RCD). The primary endpoint was achievement of a very good partial response (VGPR) or better at six weeks after nine treatment cycles. From March 2011 to February 2015, 155 patients were randomized. VGPR or better was achieved by 12 patients (15%) in the VCD arm and 14 patients (18%) in the RCD arm (P = 0·70). Median progression-free survival (PFS) was 16·3 (95% CI: 12·1-22·4) with VCD and 18·6 months (95% CI: 14·7-25·5) with RCD, and the two-year overall survival (OS) was 75% (95% CI: 66-86%) and 74% (95% CI: 64-85%) respectively. In subgroup analyses, no differences in PFS were observed in bortezomib- and lenalidomide-naïve patients, nor in patients who received a bortezomib-based regimen in first line. Adverse events were consistent with the well-established safety profiles of both drugs. Bortezomib and lenalidomide treatments were equally effective in terms of depth of response, PFS, and OS in MM patients at first relapse., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

The purpose of this retrospective study was to evaluate the short and midterm radiological outcome with regards to bone healing, correlated with humeral shaft fractures treated with anterograde intramedullary nailing, when interfragmentary gap was significant. Here, we critically review our experience of short and midterm term results in over 65 year-old patients. Inclusion criteria in the study were: (1) patients over 65 years old (2) patients with displaced humeral mid shaft fractures (AO/OTA 12 A B C type fractures); (3) patients treated with closed reduction and internal fixation with intramedullary nail (Trigen Humeral Nail® Smith and Nephew) with at least two screws for proximal locking and one screw for distal locking; (4) residual interfragmentary gap, being considered significant any gap >6 mm (being 7 mm the minimum nail diameter available in our facility). Various factors were considered in our analysis: the size of the interfragmentary gap in both projections (also the mean of the measured gaps was calculated), the relationship between the greater and the mean interfragmentary gap and the second diameter measurement of the nail in the half distal part, the number of the screws in distal locking procedure, the use of a reaming procedure or not, the AO classification, the actual age at the time of surgery, the operating time, the nail second diameter as described before and its ratio with the measured residual gap. At 3 months follow-up, 4 patients showed radiographic healing (26,67%), 9 patients showed a visible callus (60%), with a total of 13 patients (86,67%) showing signs of normal recovery, the remaining 2 patient had insufficient callus formation (13,3%). At 6 months follow-up, 1 patient was missing (6,67%), although radiographic healing was already evident during the previous follow-up check, another one showed incomplete callus formation, the remaining 13 patients showed radiographic healing (86,67%), with a total of 14 patient considered healed at 6 months follow-up (93,33%). In conclusion, osteosynthesis with anterograde nail in geriatric patients appears to be a quite safe approach despite a great interfragmentary gap. After 6 months of treatment, callus formation and the overall clinical outcome were proven to be above satisfaction. (www.actabiomedica.it).

We evaluated the impact of invasive pulmonary aspergillosis (IPA) on epidemiology and outcome in acute leukemia (AL), analyzing all acute myeloid (AML) and acute lymphoblastic leukemia (ALL) consecutively admitted to our Institution during a 5-year period of observation. Only AML patients received anti-mold prophylaxis. Among 175 AL patients (136 AML/39 ALL), possible and proven/probable IPA were diagnosed in 28 (16%). Frequency of IPA was similar in AML (16.2%) and in ALL (15.4%). Two-year overall survival (OS) was significantly affected by IPA (no IPA: 69.8% vs IPA: 31.7% p  = .002). OS was similar in patients with proven/probable (28.2%) and possible IPA (36.4%) ( p  = .003 and .065, respectively). When censoring patients at transplant, IPA still affected 2-year survival (49.6% vs 79.2%, p  = .02), but only proven/probable IPA was associated with lower survival (34.7%, p  = .0003). IPA negatively impacts on long-term survival of leukemia patients; antifungal prophylaxis should be adopted also during induction in ALL and in AML beyond induction therapy.

Purpose  The aim of this study is to present clinical results of a retrospective case series that includes patients treated with an extensive modification of the Kocher lateral approach to the elbow with surgical detachment of the anterior branches of the radial collateral ligament. Methods  From January 2016 to January 2018, nine patients with closed isolated displaced or multifragmentary radial head fractures (Mason type II, III, or IV) who underwent osteosynthesis or arthroplasty through a modified Kocher lateral elbow approach were available for follow-up. Results  There were six female and three male patients. The median age at the time of surgery was 52 years old (range: 26-70). The dominant upper limb was injured in 22.2% of patients. After a median follow-up of 8 (range: 6-27) months, all patients regained completely all their daily activities and no cases of infections were recorded. Conclusion  We believe that the approach proposed can be a useful choice to deal with these challenging injuries. Our strategy may represent a valid alternative to more popular approaches as the use of anchors decreases the risk of instability that is the major danger considered in the past when soft tissues as tendons and ligaments are detached. Level of Evidence  This is a level IV study (therapeutic case series)., Competing Interests: Conflict of Interest None declared.

Bicondylar plateau fractures are complex injuries often requiring a challenging treatment. We report a case of a 68 year-old-male patient with a complicated tibial plateau bicondylar fracture. The fracture of the tibial plateau involved all columns (lateral, medial, posterior). The fracture pattern of the proximal tibia managed by triple plating through dual posteromedial and anterolateral incisions. Posterior-medial and the medial plating result in increased stability. The posteromedial approach to the knee that we used in our case, offers various advantages. We recommend the option of the posteromedial access, as an approach that allows excellent control of the posterior involvement of this pattern of tibial plateau fracture.

he goal of our preliminary report is to investigate hip stem stability and intra-operative cement mantle integrity after screw insertion in plate fixation of periprosthetic Vancouver B1 femur fractures. From a cohort of 50 patients with a periprosthetic femur fracture treated in our department from February 2012 until February 2017, we included in our study patients with a periprostethic Vancouver B1 femoral fracture in cemented hip arthroplasty and hemiarthroplasty, operated with ORIF using a 4.5/5.0 LCP Proximal Femoral Hook Plate ® (Synthes, Switzerland) with at least one screw perforating the cement mantle. Anteroposterior and lateral femur views and pelvis X-rays were performed preoperatively. The stability of the hip implant and the cemented mantle integrity was evaluated intra-operatively in a macroscopic way and with a post-operative X-ray in anteroposterior and lateral views. Only 7 patients satisfied the inclusion criteria; no lesion/break of the cement mantle occurred intra-operatively at any step during drilling or screw insertion, also confirmed with C-arm assessment. No cases of stem mobilization were found and cement mantle integrity was maintained in every case. Insertion of screws around a cemented stem for plate fixation in periprosthetic femur fractures Vancouver type B1 could be considered a safe procedure. However, further and more extended studies are necessary for proving additional knowledge at the evaluation of the cement mantle in osteosynthesis procedures.

The MIPO (Minimally Invasive Plate Osteosynthesis) technique for treating metadiaphyseal fractures of the proximal humerus has gained great attention during the past years. The purpose of this retrospective study was to underline all the important difficulties when the MIPO technique is applied, to propose practical solutions and to evaluate the overall clinical outcome of our patients treated with this technique. A total of 14 patients had been operated in two different surgical units, at San Carlo Borromeo Hospital (Milan, Italy - 11 patients) and in Policlinico Umberto I Hospital (Rome, Italy - 3 patients), between June 2013 and November 2016. The humeral fractures were divided according to the Maresca et al. classification system. A lateral deltoid-split or an anterolateral deltopectoral approach was performed in the proximal humerus. In distal approach, an anterior or a lateral window was performed for plate fixation. After a follow-up of 17,4 (range 3-31) months all patients showed fracture healing and there were no non-unions or infected cases. MIPO of the humerus is a tissue sparing technique and in expert hands can improve healing rates and can also reduce complications like nerve damages and infections. In conclusion, we would like to highlight the importance of the MIPO technique as a possible alternative option to the traditional ORIF technique.

The purpose of this study was to observe, in a rat animal model, the short and medium term effects of vegan (VEG) or omnivorous (OMNI) diets with different energy partition between nutrients (zone or classic). Six different diets were administered, for 72 days to 120 growing male Sprague-Dawley rats: (i) VEG zone diet; (ii) VEG classic diet; (iii) OMNI zone diet; (iv) OMNI classic diet; (v) OMNI zone diet with added fibre and (vi) OMNI classic diet with added fibre. Zone diets (high protein and low carbohydrates), resulted in better growth , feed efficiency, lower blood glucose and insulin responses. VEG diets have lowered cholesterol blood level. Histopathological analysis evidenced no damage to liver and kidney tissue by the intake of any of the diet types. Further longer animal and human duration studies should be performed to exclude detrimental effect of higher protein diet.

Purpose: Maintenance demonstrated to improve survival in newly diagnosed multiple myeloma (NDMM) patients and the achievement of complete response (CR) is a strong predictor of survival. Nevertheless, the role of maintenance according to response after induction/consolidation has not been investigated so far. To evaluate the impact of maintenance according to response, we pooled together and retrospectively analyzed data from 955 NDMM patients enrolled in two trials (GIMEMA-MM-03-05 and RV-MM-PI-209)., Methods: Primary endpoints were progression-free survival (PFS)1, PFS2 and overall survival (OS) of CR patients randomized to maintenance and no maintenance. Secondary endpoints were PFS1, PFS2 and OS in very good partial response/partial response (VGPR/PR) patients., Results: Overall, 213 patients obtained CR after induction/consolidation, 118 received maintenance and 95 no maintenance. In patients achieving CR, maintenance significantly improved PFS1 (HR 0.50, P < 0.001), PFS2 (HR 0.58, P 0.02) and OS (HR 0.51, P 0.02) compared with no maintenance; the advantage was maintained across all the analyzed subgroups according to age, International Staging System (ISS) stage, cytogenetic profile and treatment. Similar features were seen in VGPR/PR patients., Conclusion: Maintenance prolonged survival in CR and in VGPR/PR patients. The benefit in CR patients suggests the importance of continuing treatment in patients with chemo-sensitive disease., Trial Registration: The two source studies are registered at ClinicalTrials.gov: identification numbers NCT01063179 and NCT00551928.

The "heart" of the calcar is the internal cortical septum called "femoral thigh spur". Nevertheless, the integrity of the femoral thigh spur and its extensions in Garden I and II  femoral neck fractures has not been examined in depth, in CT scan-based studies. The aim of this retrospective study is to analyze characteristics as integrity of upper thigh spur area of the intra-capsular femoral neck using precise CT scans, as well as features of the medial cortical bone interruption of orthopedic calcar, in femoral fractures that are radiographically defined as Garden type I-II.A total number of 23 patients was finally included in our study. We called it the "upper thigh spur area" the area around a 360 degree perimeter of the upper thigh spur. The above-mentioned area is a cylindrical intracapsular structure oriented parallel to the intertrocanteric line of the proximal femur . We analyzed the modification of the cortical bone in this specific intra-capsular area of the femoral neck. In all the cases the upper thigh spur area (the internal cortical septum) was intact. The medial cortical (the known "orthopedic calcar") was evaluated by CT scans in coronal views; it was found to be interrupted in 14 patients and intact in 9; among patients of the first group, 50% were classified as Garden I and 50% as Garden II. The cortical integrity on 360° of the upper thigh spur area was evaluated by CT scans in axial views through different cuts, and it was found to be intact in all cases. More extended studies including CT scans of Garden I-II-III and IV fractures are needed so as to obtain more complete results. In conclusion, it seems that the integrity of the upper thigh spur zone is associated with stable fractures.

Background: Pink pulseless hand syndrome is a rare condition of vascular injury due to distal humerus fracture. It is characterized by radial and ulnar pulselessness in a complex of good hand perfusion which can remain pink and warm. The management and treatment of this condition is still very debated., Methods: We report 4 cases of arm traumas which occurred in pediatric patients. In all cases, after the fixation of the fracture by the orthopedic surgeon, the clinical evaluation and duplex ultrasound demonstrated the so called "pink pulseless hand syndrome.", Results: We decided to proceed with an immediate surgical exploration and decompression followed by a prompt recovery of the pulsatility. Postoperative course was uneventful. At 3-year follow-up, the young patients have a normal hand function with no neurovascular damages and regular peripheral signals., Conclusions: Physical and ultrasound examination in cases of pediatric humerus fractures is important to show vascular complications before the orthopedic treatment which is usually privileged. In case of vascular damages, urgent surgical exploration can be the unique choice for a correct treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Radiological evaluation of complex intra-articular fractures of the proximal humerus is still challenging. Here, we describe the post-operative "P" sign as a reproducible radiographical mark of a varus reduction, performed by assembling a head-shaft angulation of less than 130 degrees. Our retrospective study was conducted in a group of subjects who previously suffered from proximal humerus four-part fractures. We evaluated the post-operative evolution of specific radiographical parameters that are of crucial prognostic significance: Cervix-diaphysis angle (HHSA), quality level of the orthopaedic reduction (insufficient, sufficient and good) based on a radiological generalized subjective overview, presence of calcar screws through the Philos plate. The final cohort included a group of 39 patients of 70.76 ± 8.3 years of age and an average follow-up of 7.2 months. The post-operative mean HHSA was 131.5 ± 9.4. Interestingly, a positive correlation was detected between presence of the radiographical "P" sign in the post-operative period and the number of surgical complications coming up in the post-operative period (OR:  3.68 - I.C. 95%: 0.7984255-19.2532430), although not statistically significant. In our study, the high number of complications corresponds to literature database. Presence of the "P" sign could be a useful tool for assessing the quality of reduction during intra and post-operative radiological evaluation. We  underline the importance of the "P" sign as a "quality of reduction" factor and strongly recommend its intra-operative monitoring as an additional tool together with a standard subjective evaluation of the reduction.

Purpose: To describe our clinical experience with a system named SureShot? Distal Targeting (Smith & Nephew, Memphis, USA) based on magnetic field presence and discuss our suggestions on this technique., Methods: We analysed prospectively 47 patients affected by humeral, tibial or femoral fractures, treated in our institution during a 3-year period of time (August 2010 to September 2013). We considered the following parameters: the time to set up, the time to position a single screw, the effectiveness of the system (drilling ad screwing), the irradiation exposure time during distal locking procedure and surgical complications., Results: A total number of 96 screws were inserted. The mean preparation time of the device was 5.1 min ± 2 min (range 3-10 min). The mean time for single screw targeting was 5.8 min ± 2.3 min (range 4-18 min). No major complications occurred. Only a few locking procedures were needed to be practiced in order to obtain the required expertise with this targeting device., Conclusion: According to our results, this device is reliable and valid whenever the correct technique is followed. It is also user friendly, exposes to lower radiation and needs less surgical time compared to relative data from the literature. However, the surgeon should always be aware of how to use the free hand technique in case of malfunctioning of the system.