Predictive risk factors of adverse mental health outcomes in the facial trauma patient.

Patients with facial trauma often experience a psychological burden from their injuries. This study aimed to identify risk factors for adverse mental health outcomes in patients affected by facial trauma, using the 'Integrating Mental and Physical Healthcare: Research, Training and Services' (IMPARTS) screening tool. All patients >18 years of age who completed more than one IMPARTS screening tool in the Oral and Maxillofacial Trauma Clinic between 2019 and 2021 were included in this study. This tool was used to assess the risk of post-traumatic stress disorder (PTSD), generalized anxiety disorder, and depression. Included patients completed the IMPARTS questionnaire at initial follow-up (mean 18 days post-trauma) and one subsequent time point (mean 82 days). 167 patients were included in the study. On multivariable analysis, a history of psychiatric illness (P = 0.015) and interpersonal violence as the mechanism of injury (P = 0.010) were identified as predictive of risk of PTSD. Risk of PTSD was lower in zygomatic injuries (P = 0.001), while nasal involvement increased at-risk status for depression (P = 0.009). 47.3% of patients screened positive on initial IMPARTS assessment, while 35.3% screened positive on follow-up IMPARTS assessment. This study supports the IMPARTS tool in allowing the prompt identification of mental health adversity in facial trauma.

Review of the national usage of antibiotics in arthroplasty surgery: a need for evidence-based prescribing.

INTRODUCTION: Surgical site infections (SSI) remain one of the most serious complications of arthroplasty surgery. The role of antibiotic prophylaxis in preventing SSI post-arthroplasty is well established. However, there is considerable heterogeneity in prophylactic prescribing across the United Kingdom (UK), which is contradicted by the contemporaneous evidence. This descriptive study aimed to compare the current first-line antibiotic recommendations across hospitals in the UK and The Republic of Ireland for elective arthroplasty procedures. METHODS: The MicroGuide mobile phone application was used to access hospital antibiotic guidelines. First-line antibiotic recommendation and dosing regimen for primary elective arthroplasties were recorded. FINDINGS: A total of nine distinct antibiotic regimens were identified through our search. The most frequently used first-line antibiotic was cefuroxime. This was recommended by 30 of the 83 (36.1%) hospitals in the study. This was followed by a combination of flucloxacillin and gentamicin, which was used by 38 of 124 (31%) hospitals. There was also significant heterogeneity in dosing regimens. A single prophylactic dose was most commonly recommended (52%); 4% of hospitals recommended two prophylactic doses, 19% three doses and 23% four doses. CONCLUSIONS: Single-dose prophylaxis is recognised as at least noninferior to multiple-dose prophylaxis in primary arthroplasty. There is considerable variation in the local antibiotic recommendations for surgical site prophylaxis post-primary arthroplasty surgery, with respect to both recommended first-line antibiotic and dosing regimens. With increasing emphasis on the importance of antibiotic stewardship and the emergence of antibiotic resistance, this study highlights the need for an evidence-based approach to prophylactic dosing across the UK.

A predictive model for swallowing dysfunction after oral cancer resection.

Aggressive therapy of oral cancers is associated with significant postoperative morbidity. Patients with feeding issues may require nutritional support. In our unit, patients identified as developing feeding issues are reactively referred for specialist input through a feeding issues multidisciplinary team meeting (FiMDT). Reactive feeding increases length of patient stay (LOS) and may contribute to patient morbidity. We aimed to develop a model to pre-emptively identify patients likely to develop feeding issues postoperatively, to facilitate the establishment of a preoperative referral pathway to increase patient flow. All referrals to a Head and Neck multidisciplinary team meeting over a five-year period were identified and preoperative factors were extracted. Linear regression was used to confirm that FiMDT was an independent predictor of LOS. Logistic regression was used to determine if referral to FiMDT could be predicted based on preoperative factors only. A total of 203 patients met inclusion criteria for analysis. Inpatient referral to FiMDT was an independent predictor of LOS. Significant predictors of inpatient FiMDT referral included tracheostomy, patient age, and alcohol intake. The resulting model was 90% sensitive and 93.8% specific with a threshold of 0.2. We have shown that inpatient FiMDT referral is an independent predictor of patient length of stay, and that the odds of referral can be robustly predicted. We aim to use this model in redirecting emphasis to a preoperative referral pathway for improved patient flow.

Sexual dimorphism and geographical variance: their impact on the reliability of the antilingula as a landmark in human mandibular surgery.

The intraoral vertical ramus osteotomy (IVRO) is an orthognathic procedure that is used to correct dentofacial abnormalities, and is performed by approaching the lateral aspect of the mandibular ramus. This approach, however, precludes visualisation of the inferior alveolar nerve (IAN) on the medial side, thereby placing it at risk of iatrogenic damage. The antilingula, a bony prominence on the lateral mandibular ramus, has been proposed as a landmark for prediction of the IAN's location during IVRO. The current study aimed to evaluate the variation in incidence and position of the antilingula, and therefore to determine its suitability as a surgical landmark during IVRO. The study included 480 dry hemimandibles from eight geographical populations from the Duckworth Collection in Cambridge. Skulls were sexed by visual analysis of dimorphic traits. Positional relations were determined through the digitisation of nine anatomical landmarks. The antilingula was identified in all specimens. No significant difference was identified in the positional relation between the antilingula and mandibular foramen between sexes, but multiple differences were identified in this relation between geographical populations. Our data showed that, irrespective of geographical variation, an osteotomy performed 8mm posterior to the antilingula would avoid the mandibular foramen in 98.8% of cases.

Systematic review and meta-analysis of tracheostomy outcomes in COVID-19 patients.

A systematic review and meta-analysis of the entire COVID-19 Tracheostomy cohort was conducted to determine the cumulative incidence of complications, mortality, time to decannulation and ventilatory weaning. Outcomes of surgical versus percutaneous and outcomes relative to tracheostomy timing were also analysed. Studies reporting outcome data on patients with COVID-19 undergoing tracheostomy were identified and screened by 2 independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Outcome data were analysed using a random-effects model. From 1016 unique studies, 39 articles reporting outcomes for a total of 3929 patients were included for meta-analysis. Weighted mean follow-up time was 42.03±26 days post-tracheostomy. Meta-analysis showed that 61.2% of patients were weaned from mechanical ventilation [95%CI 52.6%-69.5%], 44.2% of patients were decannulated [95%CI 33.96%-54.67%], and cumulative mortality was found to be 19.23% [95%CI 15.2%-23.6%] across the entire tracheostomy cohort. The cumulative incidence of complications was 14.24% [95%CI 9.6%-19.6%], with bleeding accounting for 52% of all complications. No difference was found in incidence of mortality (RR1.96; p=0.34), decannulation (RR1.35, p=0.27), complications (RR0.75, p=0.09) and time to decannulation (SMD 0.46, p=0.68) between percutaneous and surgical tracheostomy. Moreover, no difference was found in mortality (RR1.57, p=0.43) between early and late tracheostomy, and timing of tracheostomy did not predict time to decannulation. Ten confirmed nosocomial staff infections were reported from 1398 tracheostomies. This study provides an overview of outcomes of tracheostomy in COVID-19 patients, and contributes to our understanding of tracheostomy decisions in this patient cohort.

The recommended lifetime immunization schedule from the board of vaccination calendar for life in Italy: A continuing example of impact on public health policies.

The Vaccination Calendar for Life is an alliance of scientific and professional societies of public health physicians, paediatricians and general practitioners in Italy which provides a periodical update on the ideal, scientifically driven vaccination calendar throughout lifetime. Since 2012, the Lifetime Immunization Schedule has represented a benchmark for Regional and National Authorities to set up the updated list of vaccines provided actively and free of charge to infants, children, adolescents, adults and the elderly by inclusion in the Triennial National Vaccination Plan (TNVP), and in the Essential Levels of Care (LEA). The impact of the different editions of the Lifetime Immunization Schedule on the TNVP was deep, representing the inspiring source for the present vaccination policy. The 2019 edition called for more attention to pregnant women immunization; risk groups vaccination; uniform high coverage with the MMRV vaccine; extension of Meningococcal B vaccination also at adolescent age; use of quadrivalent conjugate meningococcal vaccine also at 1 year of life; progressive decrease of the age of free-of-charge offer of influenza to ≥ 60 and then to ≥ 50 year-old population; implementation of flu immunization ages 6 months-6 years; HPV vaccination also offered to 25-year old women at the time of the first screening (gender neutral immunization already offered); sequential PCV13-PPV23 pneumococcal vaccination in 65 year-old subjects; increased coverage with rotavirus vaccine in infants and zoster vaccine in the elderly.

Investigating the correlation between bone density and fracture frequency in the mandibular condyle with micro-computed tomography.

Fractures of the mandibular condyle are common and include diacapitular fractures that affect the condylar head. The medial part of the condylar head is least commonly fractured, possibly due to decreased propensity for lines of force to run in the region. Micro-computed tomography (X-ray microtomography) of five temporomandibular joint specimens was conducted to explore whether trabecular bone structure correlates positively with fracture prevalence, which could reflect adaptation in response to lower exposure to physiological loads throughout life. Models of trabecular bone, and graphic representation of bone density indicated least dense bone medially, but a statistically significant ANOVA result was not obtained. Further study is required to verify whether a relationship between bone microstructure and fracture frequency exists, and whether or not this is the product of association between the directions of physiological and traumatic forces.

"Shh-don't say the Q-word" or do you?

We aimed to assess the superstitious belief that saying the word 'quiet' during an on-call period in oral and maxillofacial surgery (OMFS) causes a disproportionate increase in workload. A two-armed, single-centre, randomised trial was performed in a single-blinded fashion within the OMFS department at Addenbrookes Hospital, Cambridge. Duty on-call OMFS SHOs were assigned to a 'quiet group' or 'non-quiet group'. The former group was actively told that the on-call period would be 'quiet' whilst in all contexts in the latter this word was not used. Data were collected from 8am to 7pm from a period that spanned a total of 40 week-day on calls. The total number of bleeps was 491, the mean (SD) bleep count/day irrespective of treatment was 12.3 (4.6). The mean (SD) bleep count was 11.45 (4.15) for the control group and 13.1 (4.9) for the quiet (treatment) group. Welch's independent-sample t test identified no significant difference in the mean number of bleeps encountered between groups. Moreover, ANOVA identified no significant difference in the mean number of bleeps between days (F(4,35)=0.086, p=0.986). Statistical analysis was performed using R package version 3.6.2 (The R Foundation). Our study refutes the central dogma of all of medicine, which suggests that saying the word 'quiet' increases the clinician's workload during the working day. We identified no significant difference in the number of bleeps between different days of the week. OMFS sees a large breadth of presentations within the head and neck that requires a diverse set of skills to manage the varying presentations when on call.

Systematic scoping review of mandibular bone tissue engineering.

Tissue engineering is a promising alternative that may facilitate bony regeneration in small defects in compromised host tissue as well as large mandibular defects. This scoping systematic review was therefore designed to assess in vivo research on its use in the reconstruction of mandibular defects in animal models. A total of 4524 articles were initially retrieved using the search algorithm. After screening of the titles and abstracts, 269 full texts were retrieved, and a total of 72 studies included. Just two of the included studies employed osteonecrosis as the model of mandibular injury. All the rest involved the creation of a critical defect. Calcium phosphates, especially tricalcium phosphate and hydroxyapatite, were the scaffolds most widely used. All the studies that used a scaffold reported increased formation of bone when compared with negative controls. When combined with scaffolds, mesenchymal stem cells (MSC) increased the formation of new bone and improved healing. Various growth factors have been studied for their potential use in the regeneration of the maxillofacial complex. Bone morphogenic proteins (BMP) were the most popular, and all subtypes promoted significant formation of bone compared with controls. Whilst the studies published to date suggest a promising future, our review has shown that several shortfalls must be addressed before the findings can be translated into clinical practice. A greater understanding of the underlying cellular and molecular mechanisms is required to identify the optimal combination of components that are needed for predictable and feasible reconstruction or regeneration of mandibular bone. In particular, a greater understanding of the biological aspects of the regenerative triad is needed before we can to work towards widespread translation into clinical practice.

Endogenous and artificial miRNAs explore a rich variety of conformations: a potential relationship between secondary structure and biological functionality.

Mature microRNAs are short non-coding RNA sequences which upon incorporation into the RISC ribonucleoprotein complex, play a crucial role in regulation of gene expression. However, miRNAs can exist within the cell also as free molecules fulfilling their biological activity. Therefore, it is emerging that in addition to sequence even the structure adopted by mature miRNAs might play an important role to reach the target. Indeed, we analysed by several spectroscopic techniques the secondary structures of two artificial miRNAs selected by computational tool (miR-Synth) as best candidates to silence c-MET and EGFR genes and of two endogenous miRNAs (miR-15a and miR-15b) having the same seed region, but different biological activity. Our results demonstrate that both endogenous and artificial miRNAs can arrange in several 3D-structures which affect their activity and selectivity toward the targets.

Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer.

BACKGROUND: There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. PATIENTS AND METHODS: Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years. RESULTS: Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.89, P = 0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71-1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09-2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05-1.09, P = 0.064), resulting in a significant interaction (P = 0.015). CONCLUSIONS: TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.

Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety. Results: A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001). Conclusions: This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse. Trial Registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

Immediate function dental implants inserted with less than 30N·cm of torque in full-arch maxillary rehabilitations using the All-on-4 concept: retrospective study.

The aim of this retrospective clinical study was to evaluate the short-term implant success rate and marginal bone loss in full-arch fixed prosthetic maxillary rehabilitations supported by implants in immediate function with the All-on-4 treatment concept placed with insertion torque of <30N·cm or ≥30N·cm. This study included 83 patients (69 female, 14 male) with 332 implants placed (120 inserted with <30N·cm and 212 inserted with ≥30N·cm) who were treated between January 2010 and March 2013. Outcome measures were implant success and marginal bone loss at 1year of follow-up. Ten patients (12.0%; 13 implants inserted with <30N·cm and 27 implants with ≥30N·cm) were lost to follow-up. The cumulative implant success rate was 97.5% at the patient level, and 98.3% for implants inserted with <30N·cm and 97.5% for implants inserted with ≥30N·cm. The mean±standard deviation marginal bone loss at 1year was 1.14±0.38mm for implants inserted with <30N·cm and 1.39±0.49mm for implants inserted with ≥30N·cm (significant difference; P<0.001, Wilcoxon signed rank test). These results indicate that implants with insertion torques of <30N·cm may render comparable success rates and marginal bone loss at 1year compared to implants inserted with insertion torques of ≥30N·cm.

The use of breast imaging for predicting response to neoadjuvant lapatinib, trastuzumab and their combination in HER2-positive breast cancer: Results from Neo-ALTTO.

AIM: To determine the value of mammography and breast ultrasound (US) in predicting outcomes in HER2 positive breast cancer patients (pts) within Neo-ALTTO trial. PATIENTS AND METHODS: Mammography and US were required at baseline, week 6 and surgery. Two independent blinded investigators reviewed the measurements and assigned the corresponding response category. Pts showing complete or partial response according to RECIST (v1.1) were classified as responders. The association between imaging response at week 6 or prior to surgery was evaluated with respect to pathological complete response (pCR) and event-free Survival (EFS). RESULTS: Of the 455 pts enrolled in the trial, 267 (61%) and 340 (77%) had evaluable mammography and US at week 6; 248 (56%) and 309 (70%) pts had evaluable mammography and US prior to surgery. At week 6, 32% and 43% of pts were classified as responders by mammography and US, respectively. pCR rates were twice as high for responders than non-responders (week 6: 46% versus 23% by US, p < 0.0001; 41% versus 24% by mammography, p = 0.007). Positive and negative predictive values of mammography and US prior to surgery were 37% and 35%, and 82% and 70%, respectively. No significant correlation was found between response by mammography and/or US at week 6/surgery and EFS. CONCLUSIONS: Mammography and US were underused in Neo-ALTTO although US had the potential to assess early response whereas mammography to detect residual disease prior to surgery. Our data still emphasise the need for further imaging studies on pts treated with neoadjuvant HER2-targeted therapy.

Study of anatomical variations of the zygomaticofacial foramen and calculation of reliable reference points for operation.

Dissection on to the facial aspect of the zygoma is common in procedures of the midface for trauma, craniofacial deformity, and cosmesis. These procedures carry the risk of injury to the neurovascular structures that exit from the zygomaticofacial foramen (ZFF). The purpose of this study was to map the ZFF, and to establish reliable reference points from which to identify it before and during operation. We also aimed to compare the anatomy of the ZFF between sexes and among geographical populations. A total of 429 adult skulls from nine geographical sites were used. A cross-line laser was superimposed on to each zygoma to generate consistent landmarks (lines 1 and 2) from which to measure the ZFF, and the number of ZFF on each zygoma was recorded. The site and incidence of ZFF differed significantly among geographical populations, but not between sexes. Of all 858 sides, no foramina were found in 16.3%, one foramen in 49.8%, two foramina in 29%, three in 3.4% and four in 1.4%. A total of 93% of foramina were within a 25mm diameter zone (ZFF zone) centred 5mm anterior to the intersection of lines 1 and 2 on the right zygoma, and 94% were within equivalent measurements on the left. Using these landmarks, we propose a new method of identifying a ZFF zone that is irrespective of sex or geographical population. This technique may be useful in the prevention of iatrogenic damage to the ZFF neurovascular bundle during procedures on the midface and in local nerve blocks.

Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study.

PURPOSE: This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients. METHODS: Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A-C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination. RESULTS: Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely. CONCLUSIONS: Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab-chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.

Intracellular and extracellular miRNome deregulation in cellular models of NAFLD or NASH: Clinical implications.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers. METHODS AND RESULTS: We profiled the expression of 754 cellular and medium-secreted human miRNAs in HepG2 cells after lipotoxic (Palmitate, model of NASH) or not-lipotoxic stimuli (Oleate-Palmitate, model of NAFLD). Results were validated through Single TaqMan assays. We performed computational analysis of miRNA targets and pathways. Oleate-palmitate treatment induced a variation of 2.8% and 10% of total miRNAs in cells and medium, respectively; palmitate treatment caused 10% and 19% intracellular and extracellular miRNA deregulation, respectively. We validated miR-126, miR-150, miR-223, miR-483-3p, miR-1226*, and miR-1290 deregulation. Through computational analysis, we observed that targets of both intracellular and extracellular DE miRNAs were involved in processes associated with the onset and progression of NAFLD and NASH, such as fatty acid metabolism, apoptosis and inflammation. CONCLUSIONS: These data would be useful to elucidate the role of miRNAs in the pathogenesis and progression of the NAFLD spectrum, but they also allow the identification of novel potential biomarkers for differential diagnosis to be tested in vivo.

Observational study on adjuvant trastuzumab in HER2-positive early breast cancer patients.

AIM: This observational study investigates the use of adjuvant trastuzumab (AT) in HER2-positive breast cancer patients in a real-life setting, focusing on relapse and discontinuation rates. PATIENTS & METHODS: Data on a group of HER2-positive patients collected from 13 oncology centers of northeast Italy were analyzed. RESULTS: In total, 1245 patients were analyzed. 13.1% of patients were excluded from AT because of comorbidities, age, tumor stage, refusal or other reasons; 8.2% of patients who received AT interrupted the therapy, mainly for toxicity. Overall the relapse rate was 10.9% in the AT-treated population versus 22.6% in nontreated patients (follow-up: 37.4 and 62.1 months, respectively). Disease-free survival (DFS) was lower in AT-relapsed patients than in not-relapsed. Statistical analysis showed a correlation between DFS and estrogen receptor status in AT-treated patients. CONCLUSION: Relapse rates are lower in clinical setting compared to clinical trials. Overall, AT is effective in HER2-positive early-stage breast cancer patients.

Self-sampling to increase participation in cervical cancer screening: an RCT comparing home mailing, distribution in pharmacies, and recall letter.

BACKGROUND: We performed a multicentre randomised controlled trial to evaluate the effect on participation in organised screening programmes of a self-sampling device mailed home or picked up at a pharmacy compared with the standard recall letter. METHODS: Women aged 30-64 non-responding to screening invitation were eligible. Response rate to first invitation ranged from 30% to 60% between centres. The control was the standard reminder letter to undergo the test used by the programme (Pap test in three centres and HPV DNA test in three other centres). Home mailing of the self-sampler was preceded by a letter with a leaflet about HPV. The analysis was intention-to-treat. RESULTS: In all, 14 041 women were randomised and recruited: 5012 in the control arm, 4516 to receive the self-sampler at home, and 4513 to pick up the self-sampler at a pharmacy. Participation was 11.9% in the control, 21.6% (relative participation: 1.75; 95% CI 1.60-1.93) in home, and 12.0% (relative participation: 0.96; 95% CI 0.86-1.07) in the pharmacy arms, respectively. The heterogeneity between centres was high (excess heterogeneity of that expected due to chance, i.e., I(2), 94.9% and 94.1% for home and pharmacy arm, respectively). The estimated impact on the overall coverage was +4.3% for home mail self-sampling compared with +2.2% for standard reminder. CONCLUSIONS: Home mailing of self-sampler proved to be an effective way to increase participation in screening programmes, even in those with HPV as primary testing. Picking up at pharmacies showed effects varying from centre to centre.