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Herpesviridae infection in COVID-19 patients has been reported, particularly muco-cutaneous lesions. Little is known about Herpesviridae lung infection in critically ill COVID-19 patients. Typical scattered lesions seen through fiberoptic bronchoscopy in these patients should raise the question as to whether to start empirically acyclovir treatment while a Herpesviridae diagnostics result becomes available.

Objective: To evaluate the incidence of postoperative complications arising within 30 days of minimally invasive esophagectomy in the prone position with total lung ventilation and their relationship with 30-day and 1-year mortality. Secondary outcomes included possible anesthesia-related factors linked to the development of complications., Methods: The study is a retrospective single-center observational study at the Anesthesia and Surgical Department of a tertiary care center in the northeast of Italy. Patients underwent cancer resection through esophagectomy in the prone position without one-lung ventilation., Results: We included 110 patients from January 2010 to December 2017. A total of 54% of patients developed postoperative complications that increased mortality risk at 1 year of follow-up. Complications postponed first oral intake and delayed patient discharge to home. Positive intraoperative fluid balance was related to increased mortality and the risk to develop postoperative complications. C-reactive protein at third postoperative day may help detect complication onset., Conclusions: Complication onset has a great impact on mortality after esophagectomy. Some anesthesia-related factors, mainly fluid balance, may be associated with postoperative mortality and morbidity. These factors should be carefully taken into account to obtain better outcomes after esophagectomy in the prone position without one-lung ventilation.

Objective: This review summarizes the peri-operative anesthesiological approaches to esophagectomy considering the best up-to-date, evidence-based medicine, discussed from the anesthesiologist's standpoint., Background: Esophagectomy is the only curative therapy for esophageal cancer. Despite the many advancements made in the surgical treatment of this tumour, esophagectomy still carries a morbidity rate reaching 60%. Patients undergoing esophagectomy should be referred to high volume centres where they can receive a multidisciplinary approach to treatment, associated with better outcomes. The anesthesiologist is the key figure who should guide the peri-operative phase, from diagnosis through to post-surgery rehabilitation. We performed an updated narrative review devoted to the study of anesthesia management for esophagectomy in cancer patients., Methods: We searched MEDLINE, Scopus and Google Scholar databases from inception to May 2021. We used the following terms: "esophagectomy", "esophagectomy AND pre-operative evaluation", "esophagectomy AND protective lung ventilation", "esophagectomy AND hemodynamic monitoring" and "esophagectomy AND analgesia". We considered only articles with abstract written in English and available to the reader. We excluded single case-reports., Conclusions: Pre-operative anesthesiological evaluation is mandatory in order to stratify and optimize any medical condition. During surgery, protective ventilation and judicious fluid management are the cornerstones of intraoperative "protective anesthesia". Post-operative care should be provided by an intensive care unit or high-dependency unit depending on the patient's condition, the type of surgery endured and the availability of local resources. The provision of adequate post-operative analgesia favours early mobilization and rapid recovery. Anesthesiologist has an important role during the peri-operative care for esophagectomy. However, there are still some topics that need to be further studied to improve the outcome of these patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-21-940). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Background: Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia., Methods: The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT)., Results: A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0-1] in the SoC arm vs. 2 [1-3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed., Conclusion: In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To explore the true short esophagus (TSE) frequency and long-term results of patients undergoing gastroesophageal reflux disease (GERD) or hiatus hernia (HH) surgery., Background: The existence and treatment of TSE during GERD/HH surgery is controversial. Satisfactory long-term results have been achieved with and without surgical techniques dedicated to TSE., Methods: In 311 consecutive patients undergoing minimally invasive surgery for GERD/HH, the distance between the endoscopically-localized gastroesophageal junction (GEJ) and the apex of the diaphragmatic hiatus after maximal thoracic esophagus mobilization was measured. A standard Nissen fundoplication (SN) was performed in cases with an abdominal length >1.5 cm; in cases of TSE (abdominal length <1.5 cm), a Collis-Nissen (CN) or stomach around the stomach fundoplication (SASF) in elderly patients was performed. The fundoplication superior margin was fixed below the hiatus, but over the GEJ. The patients' symptoms, and radiological and endoscopic data were pre/postoperatively recorded., Results: After intrathoracic esophageal mobilization (median 9 cm), TSE was diagnosed in 31.8% of 311 cases. With a median follow-up of 96 months (309 patients), HH relapse was radiologically diagnosed in 3.2% of patients, with excellent, good, fair, and poor outcomes in 45.6%, 44.3%, 6.2%, and 3.9% of cases, respectively, and no significant differences among SN (68.5%), CN (26.4%), and SASF (5.2%)., Conclusions: TSE was present in 31.8% of patients routinely submitted to GERD/HH surgery. In the presence of TSE, CN and SASF performed according to determined surgical principles may achieve similar satisfactory results. This finding warrants confirmation with a prospective multicenter study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aim: Diaphragmatic dysfunction is seen in up to 60% of critically ill patients with respiratory failure, and it is associated with worse outcomes. The functionality of the diaphragm can be studied with simple and codified bedside ultrasound evaluation. Diaphragm excursion is one of the most studied parameters. The aim of this study was to assess the prevalence of diaphragmatic dysfunction in critically ill non-intubated patients admitted to a general intensive care unit with acute respiratory failure., Methods: We collected data, including ultrasound diaphragm excursion, at 2 time points: at T0 (at the time of recruitment, just before starting NIV) and at T1 (after one hour of NIV)., Results: A total of 47 patients were enrolled. The prevalence of diaphragm dysfunction was 42.5% (95% CI 28, 3 - 57,8). Surgical patients showed a higher incidence (relative risk of 1.97) than medical patients. Mean DE was not significantly different between NIV responders (1,35 ± 0.78 cm) and non-responders (1.21 ± 0.85 cm, p 0,6). Patients with diaphragmatic dysfunction responded positively to NIV in 60% (95% CI 36.0 - 80.9%) of cases, while patients without diaphragmatic dysfunction responded positively to the NIV trial in 70.4% (95% CI 49.8 - 86.2%) of cases (p = 0.54). Taking the use of ultrasound diaphragm excursion as a potential predictor of NIV response, the corresponding ROC curve had an area under the curve of 0.53; the best balance between sensitivity (58.1%) and specificity (62.5%) was obtained with a cut-off diaphragm excursion of 1.37 cm., Conclusions: Diaphragm dysfunction is particularly frequent in critically ill patients with respiratory failure. The functionality of the diaphragm can be effectively and easily tested by bedside ultrasound examination. Overall, our results point towards tentative evidence of a trend of a different response to NIV in patients with vs without diaphragmatic dysfunction.

COVID-19 pandemic has rapidly spread worldwide causing a serious challenge to the global medical community. Italy was struck hard during the first wave earlier this year and several weaknesses as well as general unpreparedness of the national healthcare system were acknowledged. Learning essential lessons from the past, we realized how implementing contingency response measures, human resources and social dynamics could have changed the outcome if promptly adopted. This review translates the previous experience into strategic actions that has to be considered when developing appropriate national and regional operational plans to respond to a pandemic.

Background: Pharmacological treatments for critical processes in patients need to be initiated as rapidly as possible; for this reason, it is a standard of care to prepare the main anesthesia and emergency drugs in advance. As a result, 20%-50% of the prepared drugs remain unused and are then discarded. Decreasing waste by optimizing drug use is an attractive strategy for meeting both cost containment and environmental sustainability. The primary end point of this study was to measure the actual amount of drug wastage in the operating rooms (ORs) and intensive care units (ICUs) of a Regional Health Service (RHS). The secondary end point was to analyze and estimate the economic implications of this waste for the Health Service and to suggest possible measures to reduce it., Methods: This prospective observational multicenter study was conducted across 12 hospitals, all of which belong to the same RHS in the north-east of Italy. Data collection took place in March 2018 and included patients admitted to ICUs, emergency areas, and ORs of the participating hospitals. Data concerning drug preparation and administration were collected for all consecutive patients, independent of case types and of whether operations were scheduled or unscheduled. Drug wastage was defined as follows: drugs prepared in ready-to-use syringes but not administered at all and discarded untouched. We then estimated the costs of wasted drugs for a 1-year period using the data from this study and the yearly regional pharmacy orders of drugs provided to the ORs and ICUs. We also performed a sensitivity analysis to validate the robustness of our assumptions and qualitative conclusions., Results: We collected data for a total of 13,078 prepared drug syringes. Drug wastage varied from 7.8% (Urapidil, an alpha-1 antagonist antihypertensive) to 85.7% (epinephrine) of prepared syringes, with an overall mean wastage rate of 38%. The estimated yearly waste was 139,531 syringes, for a total estimated financial cost of €78,060 ($92,569), and an additional quantity of medical waste amounting to 4968 kg per year. The total provider time dedicated to the preparation of unused drugs was predicted to be 1512 working hours per year., Conclusions: The overall extent of drug wastage in ORs and ICUs is concerning. Interventions aimed at minimizing waste-related costs and improving the environmental sustainability of our practice are paramount. Effort should be put into designing a more efficient workflow that reduces this waste while providing for the emergency availability of these medications in the OR and ICU., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

During the Covid-19 pandemic in Italy, official data are collected with medical swabs following a pure convenience criterion which, at least in an early phase, has privileged the exam of patients showing evident symptoms. However, there are evidences of a very high proportion of asymptomatic patients. In this situation, in order to estimate the real number of infected (and to estimate the lethality rate), it should be necessary to run a properly designed sample survey through which it would be possible to calculate the probability of inclusion and hence draw sound probabilistic inference. Unfortunately, the survey run by the Italian Statistical Institute encountered many field difficulties. Some researchers proposed estimates of the total prevalence based on various approaches, including epidemiologic models, time series and the analysis of data collected in countries that faced the epidemic in earlier times. In this paper, we propose to estimate the prevalence of Covid-19 in Italy by reweighting the available official data published by the Istituto Superiore di Sanità so as to obtain a more representative sample of the Italian population. Reweighting is a procedure commonly used to artificially modify the sample composition so as to obtain a distribution which is more similar to the population. In this paper, we will use post-stratification of the official data, in order to derive the weights necessary for reweighting the sample results, using age and gender as post-stratification variables, thus obtaining more reliable estimation of prevalence and lethality. Specifically, for Italy, we obtain a prevalence of 9%. The proposed methodology represents a reasonable approximation while waiting for more reliable data obtained with a properly designed national sample survey and that it could be further improved if more data were made available., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The incidence of cerebral fat embolism (CFE) ranges from 0.9-11%, with a mean mortality rate of around 10%. Although no univocal explanation has been identified for the resulting fat embolism syndrome (FES), two hypotheses are widely thought: the 'mechanical theory', and the 'chemical theory'. The present article provides a systematic review of published case reports of FES following a bone fracture., Methods: We searched MEDLINE, Web of Science and Scopus to find any article related to FES. Inclusion criteria were: trauma patients; age ≥ 18 years; and the clinical diagnosis of CFE or FES. Studies were excluded if the bone fracture site was not specified., Results: One hundred and seventy studies were included (268 cases). The male gender was most prominent (81.6% vs. 18.4%). The average age was 33 years (±18). The mean age for males (29 ± 14) was significantly lower than for females (51 ± 26) (p < 0.001). The femur was the most common fracture site (71% of cases). PFO was found in 12% of all cases. Univariate and multivariate regression analyses showed the male gender to be a risk factor for FES: RR 1.87 and 1.41, respectively (95%CI 1.27-2.48, p < 0.001; 95%CI 0.48-2.34, p < 0.001)., Conclusions: FES is most frequent in young men in the third decades of life following multiple leg fractures. FES may be more frequent after a burst fracture. The presence of PFO may be responsible for the acute presentation of cerebral embolisms, whereas FES is mostly delayed by 48-72 h.

Mid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893-11.413], together with increased neutrophil count (OR = 1.029 [1.011-1.049]) and WHO disease severity class (OR = 7.632 [5.871-19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771-0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728-0.987] and a specificity of 0.687 [95% Cl 0.587-0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.

Tocilizumab is widely being used to treat COVID-19. Although reducing systemic inflammation, it also increases the risk for secondary infections as a result of the immunosuppression produced. We report the case of a 69-year-old patient admitted to the ICU with severe respiratory distress caused by COVID-19 pneumonia who developed pulmonary aspergillosis. On the basis of these findings, we suggest early testing for pulmonary aspergillosis in COVID-19 patients treated with tocilizumab., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 The Authors.)

An 84-year-old woman, who had been admitted to the emergency department (ED) several times because of dyspnoea, was treated for acute exacerbation of chronic respiratory failure without satisfactory clinical improvement. According to her medical history, 8 years earlier, she underwent a complicated cardiosurgical procedure that required tracheostomy and mechanical ventilation in the post-operative period for 45 days. Traditional X-Ray did not show any abnormal findings; however, high resolution thorax computed tomography (HRCT) scan revealed a severe tracheal stenosis, which was confirmed with bronchoscopy, and required immediate tracheostomy. Tracheal stenosis is a rare but severe complication that should be suspected when a patient with previous tracheostomy presents to the ED with dyspnoea even if tracheostomy had been closed many years before, because adaptive mechanism results in asymptomatic life for a long period., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (© Copyright 2020 by Turkish Anaesthesiology and Intensive Care Society.)

Objective: Cardiac surgery patients have a high risk of postoperative bleeding. Historically, the platelet count has been one of the main parameters used to establish the need for platelet transfusions, and the recent introduction of point-of-care tests for platelet function has allowed clinicians to rationalize platelet transfusion needs by assessing the platelet (dys-)function of the patient. For the present study, the authors evaluated how the introduction of one of these systems-the adenosine diphosphate (ADP) test, performed using a Multiplate electrode analyzer (Roche Diagnostics, Basel, Switzerland)-into their clinical practice had modified their platelet transfusion practice. The relationship between the platelet count and the functional evaluation of platelet aggregation (via the ADP test) also was examined., Design: This was a retrospective, single-center, observational study., Setting: Cardiac surgery department of a tertiary care center in North-east Italy., Participants: Cardiac surgery patients requiring cardiac bypass in 2017 and 2019., Interventions: The primary outcome was to compare platelet transfusion practice before and after the implementation of a platelet function test (the ADP test) into the institution's transfusion algorithm, which replaced the platelet count as the trigger. Secondary outcomes were assessing whether the incorporation of the ADP test into their transfusion algorithm brought about a reduction in the frequency of platelet transfusions compared with previous rates (when only platelets counts were used); assessing patient blood loss in the first 12 postoperative hours; and ascertaining the percentage of patients requiring surgical reexplorations., Measurements and Main Results: The study comprised 110 patients undergoing cardiac surgery from the platelet count period (2017) and 110 patients from the ADP test period (2019). Agreement between platelet counts versus ADP tests in determining the need for platelet transfusion was moderate (κ = 0.483; 95% confidence interval [CI] 0.239-0.728), and the general linear regression relationship between platelet counts and the ADP test (Akaike information criterion = 2536; p < 0.001) was determined. Since the introduction of ADP testing, a highly significant reduction in platelet transfusions has occurred: 41.82% (platelet count period) versus 13.64% (ADP test period) (p < 0.001); average blood loss in the 12 hours postsurgery also was less in the ADP test period (p < 0.001) at 300 mL (95% CI 150-730) compared with 440 mL in the platelet count period (95% CI 135-900). Furthermore, a decreasing trend was observed in the number of patients requiring reexploration to optimize hemostasis in the first 12 hours postsurgery (6.36% v 2.73%); however, this trend did not achieve statistical significance (p = 0.195)., Conclusion: The application of new Multiplate analyzer technologies, like the ADP test, have the potential to reduce platelet transfusion rates in cardiac surgery patients compared with the use of platelet counts alone; this point-of-care test may constitute an important strategy to help spare the use of allogeneic blood products. Additional studies are needed to confirm this trend and establish the best cutoff values to apply., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: Aim of this retrospective cohort study was to assess the frequency and severity of dental caries (DC) among foster care children in the city of Turin, in North West Italy, and to compare these data with those of a general paediatric population., Materials and Methods: From May 2016 to September 2018, 75 paediatric subjects between the age of 4 and 12, located in 11 residential child care communities were recruited. Instructions were provided concerning oral health, caries and correlation with dietary habits. Oral and dental examination were carried out to establish frequency and severity of caries (not-penetrating, nPC, corresponding to the International Caries Detection and Assessment System (ICDAS) codes: 1-4, vs. penetrating, PC, corresponding to ICDAS codes: 5-6). Decayed, missed, filled teeth (DMFT) index was used. Data for comparison were acquired from the WHO Collaboration Center For Epidemiology and Community Dentistry of Milan (WHO-CCOMS), belonging to a nationwide sample of 2,141 Italian children., Results: Only 13 subjects (17%) were caries-free; 187 caries were identified: 133 were PC, whereas 54 were nPC. Overall, 76% of the caries were found in deciduous teeth. Mean DMFT was 3.43 (D = 2.97; M = 0.24; F = 0.22). When the study data were compared to those from WHO-CCOMS, a significantly higher DMFT (3.43 vs 0.96; p <0.00001) and D (2.97 vs 0.62; p <0.00001) was detected., Conclusion: A significant higher frequency of caries in foster care children in Turin, Italy compared to the general population was detected.

Competing Interests: The authors declare that they have no conflict of interest.

Objective: Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or "cytokine storm". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point., Methods: Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC)., Results: In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were three deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and one serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients., Conclusion: Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lung ultrasound (LU) has rapidly become a tool for assessment of patients stricken by the novel coronavirus 2019 (COVID-19). Over the past two and a half months (January, February, and first half of March 2020) we have used this modality for identification of lung involvement along with pulmonary severity in patients with suspected or documented COVID-19 infection. Use of LU has helped us in clinical decision making and reduced the use of both chest x-rays and computed tomography (CT)., (© 2020 Wiley Periodicals, Inc.)

Purpose: To evaluate whether the use of piezoelectric bone surgery (PBS) for implant site preparation reduces surgical time, improves implant stability, preserves marginal bone level and improves the survival rate of oral implants compared with conventional drilling techniques., Materials and Methods: This meta-analysis followed the PRISMA (preferred reporting items for systematic review and meta-analysis) guidelines and was registered in the PROSPERO (international prospective register of systematic reviews) database (CRD42019142749). The PubMed, Embase, Scopus and Open Grey databases were screened for articles published from 1 January 1990 to 31 December 2018. The selection criteria included randomised controlled trials (RCTs) and case-control studies (CCTs) comparing the PBS with conventional rotary instruments for implant site preparation, and reporting any of the selected clinical outcomes (surgical time, implant stability, marginal bone variations and implant failure rate) for both groups. The risk of bias assessment was performed using the Cochrane Collaboration tool for RCTs and the Newcastle-Ottawa scale (NOS) for CCTs. A meta-analysis was performed, and the power of the meta-analytic findings was assessed by trial sequential analysis (TSA)., Results: Eight RCTs and one CCT met the inclusion criteria and were included in the review. The meta-analysis and the TSA showed moderate evidence suggesting that the PBS prolongs surgery duration and improves secondary stability 12 weeks after implant placement compared with conventional drilling techniques. Insufficient data are available in literature to assess if the PBS reduces marginal bone loss and/or improves the implant survival rate compared with conventional drilling techniques., Conclusions: Adequately powered randomised clinical trials are needed to confirm the PBS positive effect on the secondary stability and to draw conclusions about the influence of PBS on marginal bone stability and implant survival., Competing Interests: Conflict-of-interest statement: The authors report no conflicts of interest related to this study. The present study received no external funding.

In this paper, we study the problem of heterogeneity in cervical mucus hydration at different times relative to the mucus peak both between cycles and women, specifying and estimating appropriate multilevel latent class models for longitudinal data. We estimate multilevel and growth latent class models which classify women on the basis of the evolution of cervical mucus characteristics observed over the fertile period of each menstrual cycle taking into account that we observe a different number of cycles per woman and correlation over time between consecutive observations. The effect of potential covariates on mucus evolution patterns is as well evaluated. Results confirm the existence of heterogeneity in mucus evolution between cycles and women. Moreover, an important significant effect of a woman's age is found.

Purpose: To prospectively evaluate the survival at 1 and 4 years of short implants retaining removable partial dentures (RPDs) in Kennedy Class I and II edentulism., Materials and Methods: Twenty patients (Kennedy Class I and II) rehabilitated with RPDs were selected for the insertion of one short implant in the distal edentulous ridge, connected to the RPD with a Locator attachment after osseointegration. The following data were recorded at the 1- and 4-year follow-up: bone loss, bleeding on probing (BOP), probing depth (PD), implant mobility, and survival., Results: Thirty-five implants were placed from September 2012 to April 2014. At the 4-year follow-up, 12 implants showed BOP, and for PD, 15 implants showed 2 mm, 16 implants showed 3 mm, and 2 implants showed 4 mm. One implant showed mobility, and two were lost (survival rate: 94.3%; 95% CI: 80.84 to 99.30). The mean bone loss was 1.04 ± 1.88 mm., Conclusion: Within the limitations of this study, the implant survival rate and the mean bone loss values reported are comparable with those reported by other authors. The use of short implants for retaining RPDs may be considered a viable treatment option for patients with distal edentulism and contraindications for more complex implant rehabilitation.

Purpose: Piezoelectric bone surgery was introduced into clinical practice almost 20 years ago as an alternative method for cutting bone in dental surgical procedures, in an attempt to reduce the disadvantages of using conventional rotary instruments. The aim of this Consensus Conference was to evaluate the current evidence concerning the use of piezoelectric surgery in oral surgery and implantology., Materials and Methods: Three working groups conducted three meta-analyses with trial sequential analysis, focusing on the use of piezoelectric surgery in impacted mandibular third molar extraction, lateral sinus floor elevation and implant site preparation. The method of preparation of the systematic reviews, based on comprehensive search strategies and following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, was discussed and standardised., Results: Moderate/low evidence suggests that piezoelectric surgery is significantly associated with a more favourable postoperative course (less pain, less trismus) after impacted mandibular third molar extraction than conventional rotary instruments. Moderate evidence suggests that implants inserted with piezoelectric surgery showed improved secondary stability during the early phases of healing compared with those inserted using a drilling technique. Strong/moderate evidence suggests that piezoelectric surgery prolongs the duration of surgery in impacted mandibular third molar extraction, sinus floor elevation and implant site preparation, but it is unclear whether the slight differences in duration of surgery, even if statistically significant, represent a real clinical advantage for either operator or patient. Weak evidence or insufficient data are present to draw definitive conclusions on the other investigated outcomes., Conclusions: Further well-designed trials are needed to fully evaluate the effects of piezoelectric surgery, especially in implant site preparation and sinus floor elevation.

Purpose: To verify whether single-implant-supported mandibular overdentures improve thickness discrimination., Materials and Methods: A selection of edentulous patients treated with single-implant-supported overdentures underwent interocclusal thickness discrimination tests using dedicated metal strips. Fifteen patients were included, and recordings were repeated five times: with complete dentures in place before placement of implants, the day of the prosthetic connection, and 1 month, 1 year, and 6 years after the connection., Results and Conclusion: Thickness discrimination improved at the 1-month recall recording, while after 1 year, it remained stable at low levels.

Objectives: The risk factors for oesophageal achalasia, a precancerous condition that can lead to epidermoid carcinoma, are unknown. The aim of this study was to determine these factors., Methods: Beginning in 1973, patients presenting with achalasia from 1955 to 2016 periodically underwent clinical assessment, the barium swallow test (the oesophageal diameter and residual barium column were measured) and endoscopy according to a prospective protocol. We included patients with the minimum follow-up duration of 12 months., Results: Of 681 cases, 583 patients were considered. The median follow-up time was 147.13 months (interquartile range 70.42-257.82 months), and 17 epidermoid carcinomas and 1 carcinosarcoma were diagnosed. After excluding 4 achalasia patients admitted with a cancer diagnosis, the incidence rate of epidermoid carcinomas was 1.61/1000 persons-year, and the cumulative probability of developing cancer at 56.34 years of follow-up was 13%. Risk factors for cancer were a sigmoid oesophagus [risk ratio (RR) = 17.64, 95% confidence interval (CI) 4.13-75.43], duration of achalasia symptoms >280 months (RR = 19.62, 95% CI 4.59-83.80), duration of follow-up >353 months (RR = 5.96, 95% CI 2.50-14.18), oesophageal diameter at diagnosis >71 mm (RR = 21.07, 95% CI 9.29-47.82), residual barium column at diagnosis >23 cm (RR = 24.27, 95% CI 6.93-85.01) and residual barium column at the last follow-up >10 cm (RR = 8.15, 95% CI 2.40-27.62). Conversely, the risk of epidermoid carcinoma was lower when the residual barium swallow decreased by >57% (RR = 0.10, 95% CI 0.03-0.34)., Conclusions: Patients with achalasia carry a substantial risk of developing epidermoid carcinoma. Several factors, such as sigmoid achalasia and dysphagia lasting more than 23 years, are associated with an increased risk of cancer. An effective Heller myotomy may positively influence the carcinogenetic process., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The presence of an unknown intracardiac shunt due to a patent foramen ovale may be an unusual cause of hypoxemia. We report the case of a patient who presented persistent hypoxemia after an adequate treatment for a severe asthma attack requiring intensive care unit admission. The patient underwent a transthoracic microbubbles contrast echocardiography that showed a massive patent foramen ovale. The favorable clinical course and the absence of major signs and symptoms related to patent foramen ovale allowed a conservative approach with a follow-up program. Patent foramen ovale should be suspected in case of persistent hypoxemia after a severe asthma attack had resolved.

Tunisia, being part of the secondary center of diversity for durum wheat, has rich unexploited landraces that are being continuously lost and replaced by high yielding modern cultivars. This study aimed to investigate the genetic diversity and population structure of 196 durum wheat lines issued from landraces collected from Tunisia using Diversity Array Technology sequencing (DArTseq) and to understand possible ways of introduction in comparing them to landraces from surrounding countries. A total of 16,148 polymorphic DArTseq markers covering equally the A and B genomes were effective to assess the genetic diversity and to classify the accessions. Cluster analysis and discriminant analysis of principal components (DAPC) allowed us to distinguish five distinct groups that matched well with the farmer's variety nomenclature. Interestingly, Mahmoudi and Biskri landraces constitute the same gene pool while Jenah Zarzoura constitutes a completely different group. Analysis of molecular variance (AMOVA) showed that the genetic variation was among rather than within the landraces. DAPC analysis of the Tunisian, Mediterranean and West Asian landraces confirmed our previous population structure and showed a genetic similarity between the Tunisian and the North African landraces with the exception of Jenah Zarzoura being the most distant. The genomic characterization of the Tunisian collection will enhance their conservation and sustainable use.

Background: Cats are susceptible to feline panleukopenia virus (FPV) and canine parvovirus (CPV) variants 2a, 2b and 2c. Detection of FPV and CPV variants in apparently healthy cats and their persistence in white blood cells (WBC) and other tissues when neutralising antibodies are simultaneously present, suggest that parvovirus may persist long-term in the tissues of cats post-infection without causing clinical signs. The aim of this study was to screen a population of 54 cats from Sardinia (Italy) for the presence of both FPV and CPV DNA within buffy coat samples using polymerase chain reaction (PCR). The DNA viral load, genetic diversity, phylogeny and antibody titres against parvoviruses were investigated in the positive cats., Results: Carnivore protoparvovirus 1 DNA was detected in nine cats (16.7%). Viral DNA was reassembled to FPV in four cats and to CPV (CPV-2b and 2c) in four cats; one subject showed an unusually high genetic complexity with mixed infection involving FPV and CPV-2c. Antibodies against parvovirus were detected in all subjects which tested positive to DNA parvoviruses., Conclusions: The identification of FPV and CPV DNA in the WBC of asymptomatic cats, despite the presence of specific antibodies against parvoviruses, and the high genetic heterogeneity detected in one sample, confirmed the relevant epidemiological role of cats in parvovirus infection.

Pharmacologic challenge with sodium channel blockers is part of the diagnostic workout in patients with suspected Brugada syndrome. The test is overall considered safe but both ajmaline and flecainide detain well known pro-arrhythmic properties. Moreover, the treatment of patients with life-threatening arrhythmias during these diagnostic procedures is not well defined. Current consensus guidelines suggest to adopt cautious protocols interrupting the sodium channel blockers as soon as any ECG alteration appears. Nevertheless, the risk of life-threatening arrhythmias persists, even adopting a safe and cautious protocol and in absence of major arrhythmic risk factors. The authors revise the main published case studies of sodium channel blockers challenge in adults and in children, and summarize three cases of untreatable ventricular arrhythmias discussing their management. In particular, the role of advanced cardiopulmonary resuscitation with extra-corporeal membrane oxygenation is stressed as it can reveal to be the only reliable lifesaving facility in prolonged cardiac arrest., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained., Patients and Methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive., Results: Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95-0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767)., Conclusion: TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To identify and critically appraise scientific publications evaluating the possible effect of implant design on treatment outcomes in the rehabilitation of patients with a fully edentulous maxilla., Materials and Methods: Scientific reports were sought in three electronic bibliographic databases, combined with searches for meeting abstracts, and in the grey literature. English, German, or Scandinavian scientific publications on prospective or retrospective longitudinal studies with effects of an implant design or feature on the treatment outcomes were eligible. Minimum requirement for inclusion was at least 10 study participants who were followed up for at least 2 years after implant loading. The PRISMA guidelines were followed for selecting data to extract from the individual studies. These were characteristics of the individual studies, risk of bias within individual studies, and the results of individual studies. Three editorial teams independently identified and extracted the data., Results: The search resulted in 998 primary studies, of which 525 met the inclusion criteria and were read in full text. Of these, 105 studies were included in qualitative syntheses. Seventeen studies were designed with an objective to assess effects of implant design or feature on outcomes, 23 studies described tilted implants to enable placement of longer implants, 30 studies reported effects of implants placed in zygomatic bone with or without additional alveolar implants, and 9 studies reported effects of implants placed in pterygoid bone or other bony buttresses with or without additional alveolar implants. Sixteen articles reported bone augmentation with simultaneous or delayed implant placement in patients with a predominantly Cawood-Howell bone class V and VI maxilla. Ten papers reported effects of implant design on outcomes, despite the lack of an a priori stated objective to assess a particular implant design or feature. There is a lack of compelling data to state that one particular implant system or design feature stands out amidst others, when applied to restoring the fully edentulous maxilla with implant-retained prostheses., Conclusion: This systematic review failed to identify compelling evidence to conclude that any particular implant or feature affects the treatment outcome in patients with a fully edentulous maxilla.

The purpose of the present case report was to describe the surgical treatment of a peri-implantitis lesion associated with a regenerative approach. A 48-year-old patient came to authors' attention 36 months after the placement of a dental implant (ITI-Bonefit Straumann, Waldenburg, Switzerland) in position 46. A swelling of the peri-implant soft tissues was observed, associated with bleeding on probing and probing depth > 10 mm. A significant peri-implant bone loss was clearly visible on the periapical radiograph. A nonsurgical periodontal supportive therapy was firstly conducted to reduce the inflammation, followed by the surgical treatment of the defect. After mechanical and chemical decontamination with tetracycline solution, a regenerative approach consisting in the application of deproteinized bovine bone mineral (Bio-Oss, Geistlich Pharma AG, Wolhusen, Switzerland) and a collagen membrane (Bio-Gide, Geistlich Pharma AG, Wolhusen, Switzerland) was performed. An antibiotic therapy was associated with the treatment. The 17-year follow-up showed a physiological probing depth with no clinical signs of peri-implant inflammation and bleeding on probing. No further radiographic bone loss was observed. The treatment described in the present case report seemed to show improved clinical results up to a relevant follow-up period.

Treatment of diabetics with metformin is associated with decreased breast cancer risk in observational studies, but it remains unclear if this drug has clinical antineoplastic activity. In a recent presurgical trial, we found a heterogeneous effect of metformin on breast cancer proliferation (ki-67) depending upon insulin resistance (HOMA index). Here, we determined the associations of additional serum biomarkers of insulin resistance, tumor subtype, and drug concentration with ki-67 response to metformin. Two-hundred non-diabetic women were randomly allocated to metformin (850 mg/bid) or placebo for 4 weeks prior to breast cancer surgery. The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery. For patients with a blood sample taken within 24 h from last drug intake, metformin level was measured. Compared with placebo, metformin significantly decreased ki-67 in women with HOMA > 2.8, those in the lowest IGFBP-1 quintile, those in the highest IGFBP-3 quartile, those with low free IGF-I, those in the top hs-CRP tertile, and those with HER2-positive tumors. In women with HOMA index > 2.8, drug levels were positively correlated with the ki-67 decrease, whereas no trend was noted in women with HOMA < 2.8 (p-interaction = 0.07). At conventional antidiabetic doses, the effect of metformin on tumor ki-67 of non-diabetic breast cancer patients varies with host and tumor characteristics. These findings are relevant to design breast cancer prevention and treatment trials with metformin.

Introduction: The St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 recognized substantial progress in the pathological characterization of breast cancer subtypes. A useful surrogate definition was developed to distinguish luminal A-like breast cancer from luminal B-like disease based on a combination of estrogen receptor (ER), progesterone receptor (PgR) and Ki-67 status, without a requirement for molecular diagnostics. Differences depend upon the choice of the threshold value for Ki-67 and the requirement for substantial PgR positivity. We aimed to verify the suitability of the new surrogate definitions of luminal subtypes in terms of distant disease control in a large series of patients., Methods: We studied 9,415 women with a median follow-up of 8.1 years who (1) had ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer and (2) had undergone surgery at the European Institute of Oncology between 1994 and 2006. We evaluated distant disease-free survival of patients with "low" (<14%), "intermediate" (14% to 19%) or "high" (≥20%) Ki-67 positivity stratified by PgR expression (negative or low versus high). We calculated the cumulative incidence of distant events, considered competing events and performed multivariable analysis adjusted for pathologic tumor stage, pathologic node stage, tumor grade, peritumoral vascular invasion and menopausal status., Results: Lack of substantial PgR positivity was associated with poorer outcomes only for patients with an intermediate Ki-67 level (P<0.001). The 4,890 patients (51.9%) with low Ki-67 level (any PgR expression level) or with intermediate Ki-67 level but substantial PgR positivity had comparably good outcomes and thus may represent a most advantageous grouping of those with luminal A-like disease., Conclusions: The updated pathological definition of intrinsic molecular subtypes may maximize the number of patients classified as having the luminal A-like intrinsic subtype of breast cancer and for whom the use of cytotoxic drugs could mostly be avoided.

The functional outcomes related to treating patients afflicted with tooth loss are an important hallmark in substantiating prosthodontic intervention. The Oral Rehabilitation Outcomes Network (ORONet) conducted two international workshops to develop a core set of outcome measures, including a functional domain. The process followed the general format used in the Outcome Measures in Rheumatology (OMERACT) workshops to develop consensus for clinical outcome measures in arthritis research, which included: developing a comprehensive list of potential outcomes in the literature; submitting them to a filter for validity, clinical discrimination, and feasibility; and ranking those measures meeting all the filter criteria for relative value. The search was conducted to include functional assessments of speech, swallowing, mastication, nutrition, sensation, and motor function as they relate to dental implant therapies. This literature review surveyed 173 papers that produced some result of these descriptors in the functional domain. Of these, 67 papers reported on functional assessments and further defined objective and subjective outcomes. Many of these results were patient-perceived improvements in function, while others were objective assessments based on established methodologies and instruments. Objective evaluations of masticatory function and speech may meet criteria for validity and discriminability for selected interventions, but are generally not feasible for routine use in clinical care settings. The current recommendation is to employ a well-validated survey instrument that covers mastication and speech, such as the Oral Health Impact Profile (OHIP-14, short form), recognizing that patient perceptions of function may differ from objective ability.

Consensus regarding outcomes of the treatment of tooth loss, especially the psychologic outcomes, is needed to guide discovery of best practices and enable a better understanding of patient management for this chronic condition. This paper presents the findings of the ORONet Psychological Working Group for prosthodontics and aims to identify psychologic outcomes with properties deemed critical to meet clinical trial and clinical practice needs for the future. References obtained using a PubMed/Medline search were reviewed for clinical outcomes measures of interest. Clinical outcomes measures were judged relative to the criteria of truth, discrimination, and feasibility. Of the psychologic outcome measures identified in this systematic review, only the OHIP-14 was thought to be suitable for use in general practice and multi-institutional outcome registries and clinical trials. Development of clinically useful psychologic outcomes for future use could benefit from developmental methods and tools outlined in the patient-related outcomes field of clinical care.

Purpose: A systematic literature review was conducted to identify the types of economic measures currently used in implant prosthodontics and determine the degree to which cost of care is considered in the context of any positive outcome of the care provided., Materials and Methods: A literature search was conducted using the following set of terms plus some additional hand searching: "dental implants" (Mesh) AND ("cost") OR "maintenance" OR "healthcare policy" OR "access to care" OR "third party" OR "economic") AND (("1995/01/01"[PDat]:'2009/12/31"[PDat]) AND (Humans[Mesh]) AND (English[lang]))., Results: After a review of the 466 titles and abstracts identified by the search, 18 articles were accepted for further consideration, as some attempt at economic outcome measures was made. An additional four articles were identified by hand searching. The 22 accepted articles were grouped into four basic categories: (1) measure of costs of treatment (direct, indirect, and maintenance costs), (2) cost-effectiveness mathematical modeling applied to simulate the lifetime paths and cost of treatment, (3) cost-effectiveness analysis/cost minimization, and (4) willingness-to-pay, willingness-to-accept. Attempts at determining the costs of treatment varied widely. When the OMERACT filters were applied to the various measures it was felt that discrimination and/or feasibility was a problem for most of the current economic outcome measures., Conclusions: Measures of cost-benefit, cost-effectiveness, and cost-utility are currently the gold standard; however, feasibility of such analyses is an issue. Collaboration with health economists to guide future research is highly recommended.

The Oral Rehabilitation Outcomes Network (ORONet) Longevity Working Group undertook a search of the literature from 1995 to 2009 on randomized controlled trials related to longevity of osseointegrated implants. Outcomes measures used in these studies were identified and subjected to the OMERACT component criteria of truth, validity, and feasibility. Through this process, it was a challenge to identify clinical outcomes measures that fully met the criteria. An attenuated version of the component criteria was applied, and clinical measures were identified for implant outcomes, prosthetic outcomes, and indices. A recommendation on standardized reporting periods was also presented for future consideration. The endpoint of the evaluation process is to develop consensus on clinical outcomes measures that can be applied across broad populations for osseointegrated implant care. The present ORONet initiative represents a beginning toward continual improvement and consensus development for clinical outcomes measures for osseointegrated implants.

The published literature describing clinical evidence used in treatment decisionmaking for the management of tooth loss continues to be characterized by a lack of consistent outcome measures reflecting not only clinical performance but also a range of patient concerns. Recognizing this problem, an international group of clinicians, educators, and scientists with a focus on prosthodontics formed the Oral Rehabilitation Outcomes Network (ORONet) to promote strategies for improving health based on comprehensive, patient-centered evaluations of comparative effectiveness of therapies for oral rehabilitation. An initial goal of ORONet is to identify outcome measures for prosthodontic therapies that represent multiple domains with patient relevance, are amenable to utilization in both institutional and practice-based environments, and have established validity. Following a model used in rheumatology, the group assessed the prosthodontic literature, with an emphasis on implantbased therapies, for outcomes related to longevity and functional, psychologic, and economic domains. These systematic reviews highlight a need for further development of standardized outcomes that can be integrated across clinical and research environments.

Introduction: We previously demonstrated that 1 or 5 mg per day of tamoxifen (T) given for four weeks before surgery reduces Ki-67 in breast cancer (BC) patients to the same extent as the standard 20 mg/d. Given the long half-life of T, a weekly dose (10 mg per week (w)) may be worth testing. Also, raloxifene (R) has shown Ki-67 reduction in postmenopausal patients in a preoperative setting, but data in premenopausal women are limited. We conducted a randomized trial testing T 10 mg/w vs. R 60 mg/d vs. placebo in a presurgical model., Methods: Out of 204 screened subjects, 57 were not eligible, 22 refused to participate and 125 were included in the study. The participants were all premenopausal women with estrogen receptor-positive BC. They were randomly assigned to either T 10mg/w or R 60 mg/d or placebo for six weeks before surgery. The primary endpoint was tissue change of Ki-67. Secondary endpoints were modulation of estrogen and progesterone receptors and several other circulating biomarkers., Results: Ki-67 was not significantly modulated by either treatment. In contrast, both selective estrogen receptor modulators (SERMs) significantly modulated circulating IGF-I/IGFBP-3 ratio, cholesterol, fibrinogen and antithrombin III. Estradiol was increased with both SERMs. Within the tamoxifen arm, CYP2D6 polymorphism analysis showed a higher concentration of N-desTamoxifen, one of the tamoxifen metabolites, in subjects with reduced CYP2D6 activity. Moreover, a reduction of Ki-67 and a marked increase of sex hormone-binding globulin (SHBG) were observed in the active phenotype., Conclusions: A weekly dose of tamoxifen and a standard dose of raloxifene did not inhibit tumor cell proliferation, measured as Ki-67 expression, in premenopausal BC patients. However, in the tamoxifen arm women with an extensive phenotype for CYP2D6 reached a significant Ki-67 modulation.

Background: The post-surgical management of ductal intraepithelial neoplasia (DIN) of the breast is still a dilemma. Ki-67 labelling index (LI) has been proposed as an independent predictive and prognostic factor in early breast cancer., Methods: The prognostic and predictive roles of Ki-67 LI were evaluated with a multivariable Cox regression model in a cohort of 1171 consecutive patients operated for DIN in a single institution from 1997 to 2007., Results: Radiotherapy (RT) was protective in subjects with DIN with Ki-67 LI ≥ 14%, whereas no evidence of benefit was seen for Ki-67 LI <14%, irrespective of nuclear grade and presence of necrosis. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-interaction <0.01). Hormonal therapy (HT) was effective in both Luminal A (adjusted hazard ratio (HR)=0.56 (95% CI, 0.33-0.97)) and Luminal B/Her2neg DIN (HR 0.51 (95% CI, 0.27-0.95))., Conclusion: Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. The Ki-67 LI of 14% could be a potential cutoff for better categorising this population of women at increased risk for breast cancer and in which adjuvant treatment (RT, HT) should be differently addressed, independent of histological grade and presence of necrosis.

Leaf rust (Puccinia triticina Eriks. & Henn.) is a major disease affecting durum wheat production. The Lr14a-resistant gene present in the durum wheat cv. Creso and its derivative cv. Colosseo is one of the best characterized leaf-rust resistance sources deployed in durum wheat breeding. Lr14a has been mapped close to the simple sequence repeat markers gwm146, gwm344 and wmc10 in the distal portion of the chromosome arm 7BL, a gene-dense region. The objectives of this study were: (1) to enrich the Lr14a region with single nucleotide polymorphisms (SNPs) and high-resolution melting (HRM)-based markers developed from conserved ortholog set (COS) genes and from sequenced Diversity Array Technology (DArT(®)) markers; (2) to further investigate the gene content and colinearity of this region with the Brachypodium and rice genomes. Ten new COS-SNP and five HRM markers were mapped within an 8.0 cM interval spanning Lr14a. Two HRM markers pinpointed the locus in an interval of <1.0 cM and eight COS-SNPs were mapped 2.1-4.1 cM distal to Lr14a. Each marker was tested for its capacity to predict the state of Lr14a alleles (in particular, Lr14-Creso associated to resistance) in a panel of durum wheat elite germplasm including 164 accessions. Two of the most informative markers were converted into KASPar(®) markers. Single assay markers ubw14 and wPt-4038-HRM designed for agarose gel electrophoresis/KASPar(®) assays and high-resolution melting analysis, respectively, as well as the double-marker combinations ubw14/ubw18, ubw14/ubw35 and wPt-4038-HRM-ubw35 will be useful for germplasm haplotyping and for molecular-assisted breeding.

Hepatitis C virus (HCV) infection is one of the major causes of hepatocellular carcinoma (HCC). Although predominant in cirrhotic HCV patients, the risk of HCC exists also in case of mere chronic hepatitis C (CHC). Thus the goal of the antiviral therapy is to obtain an early eradication of the HCV infection in order to reduce the risk of hepatocarcinogenesis. We report the case of a 61-year-old Caucasian male with CHC, who developed hemoperitoneum from HCC bleeding after having achieved sustained virological response (SVR). He underwent surgical resection and the histopathological examination showed a moderately-differentiated HCC in a slightly fibrotic liver. The patient has no tumor recurrence and keeps on doing well 18 months after surgery. This report, as many others, proves the existence of a residual risk of hepatocarcinogenesis in spite of obtaining an SVR in the absence of cirrhosis. Therefore, in our opinion, it is of primary importance to understand the underlying mechanisms of hepatocarcinogenesis and the major risk factors for HCC, in order to select those patients who most deserve a follow up. In this regard, we have proposed a different surveillance strategy according to the response to antiviral therapy, hepatic histology and the existence of one or more risk factors for HCC in SVR patients.

Introduction: Surgical resection represents the only therapeutic action having a radical intent for the treatment of resectable esophageal neoplasms. Minimally invasive esophagectomy for esophageal cancer is being more and more frequently performed. Few cases of esophagectomy after pneumonectomy have been described in the literature, and, to our knowledge, none of them was performed by the minimally invasive technique., Subject and Methods: A 77-year-old woman, who had undergone left thoracotomic pneumonectomy due to squamous cell lung cancer 2 years before, underwent minimally invasive esophagectomy because of esophageal cancer at the authors' institution. The intervention was performed by right thoracoscopic esophageal mobilization with the patient in the prone position, followed by the laparoscopic and cervicotomic stages, with cervical anastomosis., Results: Total operative time was 230 minutes. Intensive care unit stay was 1 day, followed by a hospital stay of 13 days. We did not observe any major postoperative complication., Conclusions: Minimally invasive esophagectomy with thoracoscopic esophageal mobilization in the prone position is a valid option in the treatment of esophageal cancer and may be feasible in previously left pneumonectomized patients.

Objectives: The first aim of the present study was to evaluate the pre- and postoperative B-type natriuretic peptide (BNP) levels in patients undergoing surgery for repair of an infrarenal abdominal aortic aneurysm (AAA) and analyze their power as a predictor of in-hospital cardiac events. The second aim was to evaluate the association among pre- and postoperative BNP levels, postoperative patient complications, and length of hospital stay., Design: Prospective observational study., Setting: A university hospital., Participants: Forty-five patients undergoing elective surgery for an abdominal aortic aneurysm., Interventions: The plasma BNP level was assessed just before surgery and then on postoperative day 1. Cardiac troponin I levels were measured postoperatively on arrival to the intensive care unit (time 0) and then 12, 48, and 72 hours later., Measurements and Main Results: The preoperative BNP concentration in patients who developed an acute myocardial infarction was 209 (IQR 84-346) pg/mL compared with 74 (IQR 28-142) pg/mL in those who did not. The difference between groups was statistically significant (p = 0.04). The Spearman correlation showed that postoperative BNP levels correlated significantly with preoperative BNP levels (r = 0.73, p = 0.0001), length of hospital stay (r = 0.35, p = 0.04), and troponin I concentration at 0 hour (r = 0.42, p = 0.02), 12 hours (r = 0.51, p = 0.0052), and 48 hours (r = 0.40, p = 0.033). In contrast, preoperative BNP levels correlated with troponin I at only 12 hours (r = 0.34, p = 0.02). Postoperative BNP levels were influenced significantly by transfusions (p = 0.035) and cross-clamping times (p = 0.038)., Conclusions: The present results confirm the high negative predictive value of preoperative BNP levels; and postoperative BNP levels showed a better correlation with postoperative troponin levels, blood transfusion, and postoperative cardiac events., (Copyright © 2012 Elsevier Inc. All rights reserved.)