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Objective: The current work was designed to evaluate whether robotic-assisted mitral valve surgery is associated with a different incidence of early postoperative complications compared with the traditional minimally invasive approach., Design: A retrospective monocentric cohort study was conducted., Setting: The study was performed in an academic hospital., Participants: A total of 375 patients who underwent standard thoracoscopic minimally invasive mitral valve surgery and robotic-assisted mitral valve surgery between April 2014 and November 2022 were enrolled., Intervention: None., Measurements and Main Results: After adjustment using propensity score analysis, 98 patients from each group were identified. Patients who underwent robotic surgery presented a similar rate of early complications to patients undergoing minimally invasive surgery. Nevertheless, they showed shorter intensive care unit and postoperative hospital stays. Finally, patients undergoing robotic-assisted surgery were more frequently discharged home., Conclusions: This study identified a similar incidence of early complications in robotic-assisted mitral valve surgery compared with minimally invasive mitral valve surgery; conversely, patients receiving robotic-assisted surgery were discharged earlier, and more frequently discharged home., 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 © 2024 Elsevier Inc. All rights reserved.)

Background and objective Renewed interest in robot-assisted cardiac procedures has been demonstrated by several studies. However, concerns have been raised about the need for a long and complex learning curve. In addition, the COVID-19 pandemic in 2020 might have affected the learning curve of these procedures. In this study, we investigated the impact of COVID-19 on the learning curve of robotic-assisted mitral valve surgery (RAMVS). The aim was to understand whether or not the benefits of RAMVS are compromised by its learning curve. Materials and Methods Between May 2019 and March 2023, 149 patients underwent RAMVS using the Da Vinci ® X Surgical System at the Humanitas Gavazzeni Hospital, Bergamo, Italy. The selection of patients enrolled in the study was not influenced by case complexity. Regression models were used to formalize the learning curves, where preoperative data along with date of surgery and presence of COVID-19 were treated as the input covariates, while intraoperative and postoperative data were analyzed as output variables. Results The age of patients was 59.1 ± 13.3 years, and 70.5% were male. In total, 38.2% of the patients were operated on during the COVID-19 pandemic. The statistical analysis showed the positive impact of the learning curve on the trend of postoperative parameters, progressively reducing times and other key indicators. Focusing on the COVID-19 pandemic, statistical analysis did not recognize an impact on postoperative outcomes, although it became clear that variables not directly related to the intervention, especially ICU hours, were strongly influenced by hospital logistics during COVID-19. Conclusions Understanding the learning curve of robotic surgical procedures is essential to ensure their effectiveness and benefits. The learning curve involves not only surgeons but also other health care providers, and establishing a stable team in the early stage, as in our case, is important to shorten the duration. In fact, an exogenous factor such as the COVID-19 pandemic did not affect the robotic program despite the fact that the pandemic occurred early in the program.

Aims: Minimally invasive mitral valve surgery leads to shorter postoperative recovery time, cosmetic advantages and significant pain reduction compared with the standard sternotomy approach. Both an external aortic clamp and an endoaortic balloon occlusion can be used to manage the ascending aorta and the myocardial protection. In this study, we aimed to compare these two strategies in terms of effectiveness of myocardial protection and associated early postoperative outcomes., Methods: We investigated the retrospective records of prospectively collected data of patients treated by minimally invasive mitral valve surgery from March 2014 to June 2019. A total of 180 cases (78 in the external aortic clamp group and 102 in the endoaortic balloon clamp group) were collected. A propensity weighting analysis was adopted to adjust for baseline variables., Results: The endoaortic balloon clamp presented higher EuroSCORE II (higher reoperative surgery rate). The intra- and postoperative data were similar between the two groups: the postoperative troponin-I levels, peak of serum lactates and rate of myocardial infarction were also comparable. The endoaortic clamp group recorded longer operative, cardiopulmonary bypass and cross-clamp times. The external clamp group showed a higher rate of postoperative atrial fibrillation and conduction block., Conclusions: In experienced centers, the use of the endoaortic balloon clamp is safe, reproducible and comparable to the external aortic clamp regarding the effectiveness of myocardial protection: its employment might facilitate minimally invasive mitral valve surgery., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Objective: To analyze Italian Cardiac Surgery experience during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identifying risk factors for overall mortality according to coronavirus disease 2019 (COVID-19) status., Methods: From February 20 to May 31, 2020, 1354 consecutive adult patients underwent cardiac surgery at 22 Italian Centers; 589 (43.5%), patients came from the red zone. Based on COVID-19 status, 1306 (96.5%) were negative to SARS-CoV-2 (COVID-N), and 48 (3.5%) were positive to SARS-CoV-2 (COVID-P); among the COVID-P 11 (22.9%) and 37 (77.1%) become positive, before and after surgery, respectively. Surgical procedures were as follows: 396 (29.2%) isolated coronary artery bypass grafting (CABG), 714 (52.7%) isolated non-CABG procedures, 207 (15.3%) two associate procedures, and three or more procedures in 37 (2.7%). Heart failure was significantly predominant in group COVID-N (10.4% vs. 2.5%, p = .01)., Results: Overall in-hospital mortality was 1.6% (22 cases), being significantly higher in COVID-P group (10 cases, 20.8% vs. 12, 0.9%, p < .001). Multivariable analysis identified COVID-P condition as a predictor of in-hospital mortality together with emergency status. In the COVID-P subgroup, the multivariable analysis identified increasing age and low oxygen saturation at admission as risk factors for in-hospital mortality., Conclusion: As expected, SARS-CoV-2 infection, either before or soon after cardiac surgery significantly increases in-hospital mortality. Moreover, among COVID-19-positive patients, older age and poor oxygenation upon admission seem to be associated with worse outcomes., (© 2021 Wiley Periodicals LLC.)

Objectives: The study objective was to determine the impact on outcome associated with using the second internal thoracic artery as a free compared with an in situ graft among patients who received the first internal thoracic artery as an in situ internal thoracic artery to the left anterior descending artery., Methods: Among 2600 patients who underwent bilateral internal thoracic artery with an in situ internal thoracic artery to the left anterior descending artery, the second internal thoracic artery was used as a free graft bilateral internal thoracic artery in 136 patients and as an in situ graft (in situ bilateral internal thoracic artery) in 2464 patients. One-to-many propensity score matching was performed to produce a cohort of 134 patients with a second free graft internal thoracic artery matched to 2359 patients with a second in situ internal thoracic artery. Early and long-term outcomes including survival, hospital readmission, and repeat revascularization up to a maximum of 25.8 years were compared., Results: There were no differences between the 2 matched groups' preoperative baseline characteristics and early adverse events. Long-term survival at 5, 10, and 15 years was significantly higher among patients with an in situ bilateral internal thoracic artery compared with patients with a free graft bilateral internal thoracic artery (hazard ratio free graft bilateral internal thoracic artery vs in situ bilateral internal thoracic artery, 1.53; 95% confidence interval, 1.14-2.10; P = .004). However, the long-term risk of readmission to the hospital for cardiovascular reasons and need for repeat revascularization were not significantly different between the 2 matched groups., Conclusions: In a small, propensity-matched cohort of patients undergoing coronary artery bypass grafting, the use of a second in situ internal thoracic artery was associated with an increase in late survival compared with the use of a second internal thoracic artery as a free graft. However, the risk of late hospital readmission and the need for repeat revascularization were similar., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: During the Italian Phase-2 of the coronavirus pandemic, it was possible to restart elective surgeries. Because hospitals were still burdened with coronavirus disease 2019 (COVID-19) patients, it was focal to design a separate "clean path" for the surgical candidates and determine the possible effects of major surgery on previously infected patients., Methods: From May to July 2020 (postpandemic peak), 259 consecutive patients were scheduled for elective cardiac surgery in three different centers. Our original roadmap with four screening steps included: a short item questionnaire (STEP-1), nasopharyngeal swab (NP) (STEP-2), computed tomography (CT)-scan using COVID-19 reporting and data system (CO-RADS) scoring (STEP-3), and final NP swab before discharge (STEP-4)., Results: Two patients (0.8%) resulted positive at STEP-2: one patient was discharged home for quarantine, the other performed a CT-scan (CO-RADS: <2), and underwent surgery for unstable angina. Chest-CT was positive in 6.3% (15/237) with mean CO-RADS of 2.93 ± 0.8. Mild-moderate lung inflammation (CO-RADS: 2-4) did not delay surgery. Perioperative mortality was 1.15% (3/259), and cumulative incidence of pulmonary complications was 14.6%. At multivariable analysis, only age and cardiopulmonary bypass (CPB) time were independently related to pulmonary complications composite outcome (age >75 years: odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.25-5.57; p = 0.011; CPB >90 min. OR: 4.3; 95% CI: 1.84-10.16; p = 0.001). At 30 days, no periprocedural contagion and rehospitalization for COVID-19 infections were reported., Conclusions: Our structured roadmap supports the safe restarting of an elective cardiac surgery list after a peak of a still ongoing COVID-19 pandemic in an epicenter area. Mild to moderate CT residuals of coronavirus pneumonia do not justify elective cardiac surgery procrastination., (© 2021 The Authors. Journal of Cardiac Surgery Published by Wiley Periodicals LLC.)

Aims: Aim of the study was to verify the feasibility, safety and efficacy of pulmonary endarterectomy (PEA) in octogenarian patients with chronic thromboembolic pulmonary hypertension., Methods: We retrospectively analyzed 635 chronic thromboembolic pulmonary hypertension patients who underwent PEA at our center and were followed-up for at least 1 year. The end-points of the study were in-hospital mortality, hemodynamic results at 1 year and long-term survival., Results: In-hospital mortality was 4, 10 and 17%, respectively, for 259 patients under the age of 60 years, 352 aged between 60 and 79 years and 24 octogenarians (P = 0.006 octogenarians vs. <60 years). At multivariable analysis, age and pulmonary vascular resistances were independent risk factors for mortality (P = 0.021 and P < 0.001, respectively). At 1 year, the improvement in cardiac index was lower and the distance walked in 6 min was poorer for octogenarians than for the other two groups (both P = 0.001). Survival after hospital discharge was similar over a median follow-up period of 59 months (P = 0.113). Although in-hospital mortality and long-term survival are similar in octogenarians as compared with patients aged between 60 and 79, the improvement in cardiac index and in functional capacity at 1 year are lower in this very elderly population., Conclusion: Age over 80 years should not be a contraindication to PEA surgery in selected patients operated on in referral centers., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background The impact of the coronary artery bypass grafting (CABG) technique (on- versus off-pump, single versus multiple aortic clamping) on postoperative neurological outcome remains a matter of controversy. The aim of this study was to assess the association between the incidence of postoperative stroke and the degree of aortic manipulation in one of the largest contemporary CABG series. Methods and Results A retrospective, multicenter, international study was conducted in 25 388 patients undergoing isolated CABG procedures with on-pump CABG (ONCAB) or off-pump CABG (OPCAB) technique including single or multiple aortic clamping. Postoperative stroke was defined as a postoperative neurological deficit lasting more than 24 hours and associated with evidence of a brain lesion on computed tomography. The degree of aortic manipulation was assumed to be higher for on-pump versus off-pump surgery and for multiple versus single or no aortic clamping. Logistic regression and propensity matching were used. ONCAB procedures were performed in 17 231 cases and OPCAB in 8157. The incidence of postoperative stroke was significantly lower in the OPCAB group even after propensity matching (0.4% OPCAB versus 1.2% ONCAB, P =0.02). In the ONCAB group (but not in the OPCAB arm) the use of single aortic clamping was associated with significantly reduced postoperative stroke rate (odds ratio, 0.05; 95% CI, 0.008 to 0.07 [ P <0.001]). Conclusions OPCAB and the use of single aortic clamping in the ONCAB arm were associated with a reduced incidence of postoperative stroke. Our data confirm a strong association between aortic manipulation and neurological outcome after CABG surgery.

We report the case of a woman with pulmonary embolism due to a cardiac mass. Echocardiography, computed tomography scan, and cardiac magnetic resonance raised the suspicion of right atrial myxoma and confirmed the presence of pulmonary embolism. The patient was sent to the University of Pavia School of Medicine, where the atrial myxoma was excised, and, using interrupted periods of circulatory arrest, extraction of the myxoma emboli from the pulmonary arteries was performed. No adjuvant chemotherapy was required as surgical treatment is an effective therapy in cases of pulmonary embolism of a benign neoplastic mass., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: After successful pulmonary endoarterectomy (PEA), patients may still suffer from exercise limitation, despite normal pulmonary vascular resistance. We sought to assess the proportion of these patients after the extension of PEA to frail patients, and the determinants of exercise limitation., Methods: Out of 553 patients treated with PEA from 2008 to 2016 at our institution, a cohort of 261 patients was followed up at 12 months. They underwent clinical, haemodynamic, echocardiographic, respiratory function tests and treadmill exercise testing. A reduced exercise capacity was defined as Bruce test distance < 400 m., Results: Eighty patients did not had exercise testing because of inability to walk on treadmill and/or ECG abnormalities Exercise limitation 12 months after PEA was present in 74/181 patients (41, 95%CI 34 to 48%). The presence of COPD was more than double in patients with exercise limitation than in the others. Patients with persistent exercise limitation had significantly higher mPAP, PVR, HR and significantly lower RVEF, PCa, CI, VC, TLC, FEV 1 , FEV 1 /VC, D LCO , HbSaO 2 than patients without. The multivariable model shows that PCa at rest and TAPSE are important predictors of exercise capacity. Age, COPD, respiratory function parameters and unilateral surgery were also retained., Conclusions: After successful PEA, most of the patients recovered good exercise tolerance. However, about 40% continues to suffer from limitation to a moderate intensity exercise. Besides parameters of right ventricular function, useful information are provided by respiratory function parameters and COPD diagnosis. This could be useful to better address the appropriate therapeutic approach.

Objectives: The only curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). PEA requires cardiopulmonary bypass (CPB) which is associated with a high acute kidney injury (AKI) risk. Circulating endothelin-1 (ET-1) levels are elevated in CTEPH, and ET-1 plays a pivotal role in AKI. Because AKI is burdened by high morbidity and mortality, we aimed to evaluate the association between preoperative ET-1 and the risk to develop AKI in CTEPH individuals who undergo PEA. We also evaluated the association of AKI and ET-1 with kidney function and mortality at 1 year after PEA., Methods: In 385 consecutive patients diagnosed with CTEPH who underwent PEA at the Foundation IRCC Policlinico San Matteo (Pavia, Italy) from January 2009 to April 2015, we assessed preoperative circulating ET-1 by ELISA and identified presence of AKI based on 2012 KDIGO criteria., Results: AKI occurred in 26.5% of the 347 patients included in the analysis, and was independently associated with preoperative ET-1 (p = 0.008), body mass index (BMI) (p = 0.022), male gender (p = 0.005) and duration of CPB (p = 0.002). At 1-year post PEA, estimated glomerular filtration rate (eGFR) significantly improved in patients who did not develop AKI [ΔeGFR 5.6 ml/min/1.73 m 2 (95% CI 3.6-7.6), p < 0.001] but not in those with perioperative AKI. AKI (p < 0.001), age (p < 0.001), preoperative eGFR (p < 0.001) and systemic hypertension diagnosis (p = 0.015) were independently associated with 1-year ΔeGFR. Neither perioperative AKI nor preoperative ET-1 was associated with 1-year survival., Conclusion: Perioperative AKI is associated with higher preoperative circulating ET-1 and it negatively influences long-term kidney function in patients with CTEPH who undergo PEA.

Background: In this prospective, single-center, observational study, we investigated the association between repeated short periods of circulatory arrest with moderate hypothermia during pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and different neuropsychological dimensions., Methods: We examined 70 patients with CTEPH, >18 to 80 years of age, who had been treated with PEA. Neuropsychological testing was performed., Results: Learning ability and delayed memory remained well within the normal range for patients' age. We found a statistically significant post-surgical improvement in motor speed, which was accompanied by a better quality of life and reduced symptoms of depression and anxiety., Conclusion: PEA with repeated short periods of circulatory arrest in CTEPH did not result in any neuropsychological complications and may even lead to post-surgical psychological improvements., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

In our experience, we reperformed pulmonary endarterectomy (PEA) in 10 patients who previously underwent a first PEA. We analyzed this cohort of patients to investigate the main causes of recurrence of symptomatic pathology and the clinical and hemodynamic results of redo surgery. Between 1994 and April 2016, 10 of 716 patients were reoperated at our institution. Available postoperative data were analyzed, and a comparison between first and second PEA hemodynamic and clinical results was carried out. In-hospital mortality rate was also evaluated. After reoperation, mean pulmonary arterial pressure decreased from 45?±?9 to 34?±?10?mm Hg, and pulmonary vascular resistance reduced from 932?±?346?dyne*s*cm ?5 to 428?±?207?dyne*s*cm ?5 . Hemodynamic data revealed worthy results of redo PEA, although they are less important than after first PEA. The World Health Organization (WHO) functional class improvement demonstrated satisfactory clinical results. In-hospital mortality of repeat PEA is 40%. Reoperative PEA operative candidacy should be assessed in case of young patients, no other risk factor, and recent medical history of pulmonary hypertension. In the other cases, in-hospital mortality rate is very high and pulmonary hypertension-specific drug therapy or interventional approach should be previously considered., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, is the third most common cause of cardiovascular death. The management of the acute phase of VTE has already been described in several guidelines. However, the management of the follow-up (FU) of these patients has been poorly defined. This consensus document, created by the Italian cardiologists, wants to clarify this issue using the currently available evidence in VTE. Clinical and instrumental data acquired during the acute phase of the disease are the cornerstone for planning the FU. Acquired or congenital thrombophilic disorders could be identified in apparently unprovoked VTE during the FU. In other cases, an occult cancer could be discovered after a VTE. The main targets of the post-acute management are to prevent recurrence of VTE and to identify the patients who can develop a chronic thromboembolic pulmonary hypertension. Knowledge of pathophysiology and therapeutic approaches is fundamental to decide the most appropriate long-term treatment. Moreover, prognostic stratification during the FU should be constantly updated on the basis of the new evidence acquired. Currently, the cornerstone of VTE treatment is represented by both the oral and the parenteral anticoagulation. Novel oral anticoagulants should be an interesting alternative in the long-term treatment.

Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism, is the third most common cause of cardiovascular death. The management of the acute phase of VTE is well described in several papers and guidelines, whereas the management of the follow-up of the patients affected from VTE is less defined. This position paper of the Italian Association of Hospital Cardiologists (ANMCO) tries to fill the gap using currently available evidence and the opinion of the experts to suggest the most useful way to manage patients in the chronic phase.The clinical and laboratory tests acquired during the acute phase of the disease drives the decision of the following period. Acquired or congenital thrombophilic factors may be identified to explain an apparently not provoked VTE. In some patients, a not yet clinically evident cancer could be the trigger of VTE and this could lead to a different strategy. The main target of the post-acute management is to prevent relapse of the disease and to identify those patients who could worsen or develop chronic thromboembolic pulmonary hypertension. The knowledge of the etiopathogenetic ground is important to address the therapeutic approach, choosing the best antithrombotic strategy and deciding how long therapy should last. During the follow-up period, prognostic stratification should be updated on the basis of new evidences eventually acquired.Treatment of VTE is mainly based on oral or parenteral anticoagulation. Oral direct inhibitors of coagulation represent an interesting new therapy for the acute and extended period of treatment.

Copper (Cu) and azadirachtin (AZA-A+B) are pesticides allowed in organic agriculture whose environmental risk and toxicity for aquatic wildlife is only partially known. Reverse Transcription Polymerase Chain Reaction was used to assess the molecular effect of acute and short-term exposure (3, 24h) of Cu (0.01, 0.05, 1, 10, 25mgl(-1)) and AZA-A+B (0.2, 0.3, 0.4, 0.5, 1mgl(-1)) on the expression of five candidate genes (hsp70, hsc70, hsp40, hsp10 and cyP450) in a non-target species, Chironomus riparius. Fourth-instar larvae were collected from a mountain stream polluted by agricultural land run-off. All genes were responsive to both pesticides but each gene had a specific response to the different experimental concentrations and exposure times. A few similarities in transcriptional profiling were observed, such as a linear concentration-dependent response of hsp70 after 24h of exposure (at ≥1mgl(-1) of Cu and ≥0.2mgl(-1) of AZA-A+B) and an up-regulation regardless of the concentration of hsc70 after 24h of exposure (at ≥0mgl(-1) of Cu and ≥0.2mgl(-1) of AZA-A+B and the up-regulation of hsp70 after 3h of exposure at ~LC50 (Cu-LC50=26.1±2.5mgl(-1), AZA-A+B-LC50=1.1±0.2mgl(-1)). According to the results, hsp40, hsp10 and cyP450 may be defined as pesticide-dependent (i.e., hsp40 and hsp10 seemed to responded mainly to AZA-A+B and cyP450 to Cu), while hsc70 as time-dependent regardless of the pesticide (i.e., hsc70 responded only after 24h of treatment with Cu and AZA-A+B). This study gives new insights on the potential role of the C. riparius's hsps and cyP450 genes as sensitive biomarkers for freshwater monitoring., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The aim of the present study was to evaluate the changes of electrocardiographic (ECG) markers of right ventricular (RV) hypertrophy/overload in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA)., Methods and Results: We evaluated 99 CTEPH patients who underwent PEA. P wave amplitude in DII, R wave amplitude in V1 and the number of patients with negative T wave in V1-V3 decreased significantly at 1month after surgery with no further change at 1year, in parallel with the rapid improvement in right heart hemodynamics. S wave amplitude in V1, R:S wave ratio in lead V6 and prevalence of SIQIII pattern improved significantly at 1year, in parallel with the progressive reverse remodeling of the right ventricle at echocardiography., Conclusions: The study shows that some of the ECG markers of RV hypertrophy/overload better reflect RV hemodynamic overload while others better reflect the pathologic remodeling of the right ventricle., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension, but there are few data in the literature about the results of this procedure in the elderly. In this study, we aimed to assess whether this type of surgery is effective and well tolerated for the elderly., Methods: A total of 264 consecutive patients who underwent PEA between January 2008 and December 2012 were reviewed. PEA was performed under cardiopulmonary bypass and hypothermic ventricular fibrillation, with the aorta left unclamped. The population was dichotomized according to age into the following two groups: below 70 years (n = 176, younger patients) and at least 70-year-olds (n = 88, elderly patients). Regression models were used to identify predictors of hospital mortality and postoperative adverse events, and their interaction with age was tested., Results: Hospital mortality was slightly, but not significantly higher in elderly patients (9.1 vs. 5.1%; P = 0.22). Effect modification by history of smoking and preoperative O2 therapy was present. The cumulative survival at 1, 2, and 4 years was 93, 92, and 91% among younger patients; and 88, 86, and 86% among older patients (P = 0.19). Clinical and hemodynamic improvement was similar in the two groups., Conclusion: Despite a slightly higher short-term mortality, PEA is feasible and well tolerated for the vast majority of the elderly patients. Clinical and hemodynamic improvements are outstanding, with satisfactory long-term survival rates.

Oral squamous cell carcinoma (OSCC) is the most common oral cancer, and major efforts is being made to identify molecular markers capable to differentiate oral potentially malignant lesions (OPMLs) with indolent course from lesions with aggressive behavior. We undertook a study to evaluate if gain of the human telomerase RNA component (hTERC) gene in OPMLs could indicate lesions at high risk of developing OSCC. The study was performed on 30 OPMLs with long-term follow-up using a dual-color interphase fluorescence in situ hybridization (FISH) for hTERC status. Progression to malignancy was observed in 9 of 10 cases harboring hTERC gain and in 1 of 20 cases retaining a normal copy number of hTERC (P < .0001). Combining morphological grading and FISH analysis, all the cases with high-grade squamous intraepithelial lesion or carcinoma in situ harboring hTERC amplification progressed to OSCC, whereas none of the low-grade squamous intraepithelial lesions without hTERC gain progressed. Intermediate situations occurred. The data suggest that precise morphological evaluation together with FISH assessment for hTERC gain might pave the way to stratify OPMLs into high-risk and low-risk categories and could be helpful in selecting the most appropriate treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Chromosome 3q gain has been consistently observed in cervical intraepithelial neoplasia grades 2 and 3 (CIN 2,3) and squamous cell carcinomas of the cervix. There are a number of potential clinical uses of testing for 3q gain in liquid cytology specimens, including the identification of subsets of women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology who are at greatest risk of having CIN 2,3 and would thus benefit most from immediate colposcopy. The objective of this study was to establish the sensitivity and specificity of 3q gain for discriminating between CIN 2,3 and normal., Study Design: Residual cytology specimens were collected from 199 women. Liquid-based cytology (LBC) was used for the selection of subjects, with women with high-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion who had colposcopy and adjudicated biopsy-confirmed CIN 2,3 forming the disease-positive group (n = 28) and women doubly negative for both cytology and high-risk human papillomavirus (hrHPV) testing forming the disease-negative group (n = 171). A single slide was prepared from each residual LBC specimen and analyzed for 3q gain by fluorescent in situ hybridization, using a probe specific for the 3q26 region and a control probe for the chromosome 7 centromere. Two approaches were compared for the determination of 3q gain. The first was based on the analysis of an entire cervical cytology slide for the presence of rare cells with a high copy number (>4 copies) for the 3q locus. The second approach was based on the analysis of 400 cells to determine the percentage with 3 or more copies of the 3q locus., Results: Using the approach based on the detection of rare cells with a high copy number (>4 copies) for the 3q locus, 26 of the specimens from women with CIN 2,3 and none of the 171 specimens from women who were both hrHPV and cytology negative was positive for 3q gain. This translates to a sensitivity of 92.9% (95% confidence interval [CI], 76.5-98.9%), a specificity of 100% (95% CI, 97.8-100%), a positive predictive value of 100% (95% CI, 86.7-100%), and a negative predictive value of 98.8% (95% CI, 95.9-99.8), for distinguishing CIN 2,3 from normal., Conclusion: These data support the potential clinical use of 3q gain for the evaluation of women in a number of clinical situations, including women with atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, and those who are hrHPV positive., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In the past several years we have observed a significant increase in our understanding of molecular mechanisms that drive lung cancer. Specifically in the non-small cell lung cancer sub-types, ALK gene rearrangements represent a sub-group of tumors that are targetable by the tyrosine kinase inhibitor Crizotinib, resulting in significant reductions in tumor burden. Phase II and III clinical trials were performed using an ALK break-apart FISH probe kit, making FISH the gold standard for identifying ALK rearrangements in patients. FISH is often considered a labor and cost intensive molecular technique, and in this study we aimed to demonstrate feasibility for automation of ALK FISH testing, to improve laboratory workflow and ease of testing. This involved automation of the pre-treatment steps of the ALK assay using various protocols on the VP 2000 instrument, and facilitating automated scanning of the fluorescent FISH specimens for simplified enumeration on various backend scanning and analysis systems. The results indicated that ALK FISH can be automated. Significantly, both the Ikoniscope and BioView system of automated FISH scanning and analysis systems provided a robust analysis algorithm to define ALK rearrangements. In addition, the BioView system facilitated consultation of difficult cases via the internet., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The decisional balance worksheet (DBW), an open-ended measure of motivation to change, may be used to record the perceived advantages and disadvantages of substance use as well as alternative behaviors. Recent findings have indicated that the open-ended DBW can be quantified to validly reflect college students' level of motivation to reduce their drinking (Collins, Carey, & Otto, 2009). The goal of the current study was to enhance our understanding of college students' perceived advantages and disadvantages of drinking by qualitatively examining the content of their decisional balance. Participants were undergraduate college students at a 4-year university (N = 760) who participated in a randomized controlled trial of online brief motivational interventions. Using the DBW, participants recorded the advantages and disadvantages of their current drinking. Conventional content analysis methods were used to extract common themes. Social, enjoyment, and psychological reasons were the most commonly mentioned advantages of drinking, whereas physical side effects, expense and interference with goals were the most commonly mentioned disadvantages of drinking. These findings show that college students primarily use alcohol for enjoyment, particularly in social situations, as well as for coping with stress and social anxiety. On the other hand, many college students report having physical side effects from drinking as well as other kinds of concerns (e.g., expense, calories). Findings suggest that using the open-ended DBW may result in a more client-centered and accurate representation of what college students perceive as advantages and disadvantages to drinking than established, Likert-scale measures of decisional balance.

Objectives: Chronic thromboembolic pulmonary hypertension can be cured by pulmonary endarterectomy. Operability assessment remains a major concern, because there are no well-defined criteria to discriminate proximal from distal obstructions, and surgical candidacy depends mostly on the surgeon's experience. The intraoperative classification of chronic thromboembolic pulmonary hypertension describes 4 types of lesions, based on anatomy and location. We describe our recent experience with the more distal (type 3) disease., Methods: More than 500 pulmonary endarterectomies were performed at Foundation I.R.C.C.S. Policlinico San Matteo (Pavia, Italy). Because of recent changes in the patient population, 331 endarterectomies performed from January 2008 to December 2013 were analyzed. Two groups of patients were identified according to the intraoperative classification: proximal (type 1 and type 2 lesions, 221 patients) and distal (type 3 lesions, 110 patients)., Results: The number of endarterectomies for distal chronic thromboembolic pulmonary hypertension increased significantly over time (currently ∼37%). Deep venous thrombosis was confirmed as a risk factor for proximal disease, whereas patients with distal obstruction had a higher prevalence of indwelling intravascular devices. Overall hospital mortality was 6.9%, with no difference in the 2 groups. Postoperative survival was excellent. In all patients, surgery was followed by a significant and sustained improvement in hemodynamic, echocardiographic, and functional parameters, with no difference between proximal and distal cases., Conclusions: Although distal chronic thromboembolic pulmonary hypertension represents the most challenging situation, the postoperative outcomes of both proximal and distal cases are excellent. The diagnosis of inoperable chronic thromboembolic pulmonary hypertension should be achieved only in experienced centers, because many patients who have been deemed inoperable might benefit from favorable surgical outcomes., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objective: Primary pulmonary artery sarcoma is a severe and underdiagnosed disease, with the clinical and surgical approach not clearly established. Only a few individual case reports or small series on this topic have been published. The aim of the present study was to report our surgical experience in this field., Methods: From March 2004 to December 2012, 13 patients underwent surgery for pulmonary artery sarcoma at our institution. In 7 patients, the sarcoma was unilateral (53.8%), and in 6 (46.2%), the tumor had already extended to both lungs. The surgical strategy evolved over the years, but the 2 techniques used were always the same: pneumonectomy in 5 patients and pulmonary endarterectomy in 8., Results: Two patients died in-hospital, both in the pneumonectomy group. The median length of the intensive care unit and hospital stay was 1 day (range, 1-10) and 14 days (range, 11-17) for the pneumonectomy group and 6 days (range, 3-23) and 19 days (range, 10-32) fort the pulmonary endarterectomy group, respectively. The median survival was 26.8 months after pneumonectomy and 6.6 months after pulmonary endarterectomy., Conclusions: Primary pulmonary artery sarcoma has a poor prognosis. The surgical strategy at our institution included pneumonectomy, for possible radical resection, and palliative endarterectomy, to reduce symptoms and increase the life expectancy. The correct surgical approach must be evaluated individually, according to the tumor presentation, the presence of pulmonary hypertension, and the patient's clinical condition., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Specific bacterial infections or alterations of the gut microbiota likely trigger immuno-pathological phenomena associated with Crohn's disease and ulcerative colitis. Mycobacterium avium subspecies paratuberculosis is a candidate etiological agent of Crohn's disease. Definitive causal connection between Mycobacterium avium subspecies paratuberculosis infection and Crohn's disease has not been demonstrated., Aims: To determine the circulation of Mycobacterium avium subspecies paratuberculosis in Crohn's disease patients and water supplies in an Italian region where this bacterium is endemic in cattle farms., Methods: Mycobacterium avium subspecies paratuberculosis screening was performed on biopsies from human patients, and from water samples, using two different PCR procedures., Results: In hospitals where multiple specimens were obtained from different sites in the intestine, the prevalence of Mycobacterium avium subspecies paratuberculosis infection was 82.1% and 40% respectively in Crohn's disease and ulcerative colitis patients; in another hospital, where single specimens were obtained from patients, the bacterium was not detected. Control subjects also harboured Mycobacterium avium subspecies paratuberculosis, but at a lower prevalence. Tap water samples collected in the study area contained Mycobacterium avium subspecies paratuberculosis DNA., Discussion: The results of screenings for Mycobacterium avium subspecies paratuberculosis in humans are deeply influenced by both the number and location of the collected biopsies. There is a wide circulation of the organism in the study area, considering the prevalence in humans and its presence in drinking water., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Urinary tract infections (UTIs) are among the most frequent community-acquired infections worldwide. Escherichia coli is the most common UTI pathogen although underlying host factors such as patients' age and gender may influence prevalence of causative agents. In this study, 61 273 consecutive urine samples received over a 22-month period from outpatients clinics of an urban area of north Italy underwent microbiological culture with subsequent bacterial identification and antimicrobial susceptibility testing of positive samples. A total of 13 820 uropathogens were isolated and their prevalence analyzed according to patient's gender and age group. Overall Escherichia coli accounted for 67.6% of all isolates, followed by Klebsiella pneumoniae (8.8%), Enterococcus faecalis (6.3%), Proteus mirabilis (5.2%), and Pseudomonas aeruginosa (2.5%). Data stratification according to both age and gender showed E. coli isolation rates to be lower in both males aged ≥60 years (52.2%), E. faecalis and P. aeruginosa being more prevalent in this group (11.6% and 7.8%, resp.), as well as in those aged ≤14 years (51.3%) in whom P. mirabilis prevalence was found to be as high as 21.2%. Streptococcus agalactiae overall prevalence was found to be 2.3% although it was shown to occur most frequently in women aged between 15 and 59 years (4.1%). Susceptibility of E. coli to oral antimicrobial agents was demonstrated to be as follows: fosfomycin (72.9%), trimethoprim/sulfamethoxazole (72.9%), ciprofloxacin (76.8%), ampicillin (48.0%), and amoxicillin/clavulanate (77.5%). In conclusion, both patients' age and gender are significant factors in determining UTIs etiology; they can increase accuracy in defining the causative uropathogen as well as providing useful guidance to empiric treatment.

Microalbuminuria and hypertension are risk factors for diabetic nephropathy in Type 2 diabetic patients. Recent data suggest that blockade of the renin-angiotensin system slows the progression of diabetic nephropathy; in contrast, the results on the renoprotective effect of calcium channel antagonists are conflicting. We evaluated the effectiveness of lercanidipine, in comparison with ramipril, on the reduction in albumin excretion rate (AER) and blood pressure in mild-to-moderate hypertensive patients with Type 2 diabetes and persistent microalbuminuria. A total of 277 patients were enrolled in a multicentric, randomized, double-blind, active-controlled, parallel-group trial; 180 were randomized to receive 10-20 mg/day of lercanidipine or 5-10 mg/day of ramipril and followed up for 9-12 months. The primary outcome was the change in AER from baseline. After 9-12 months of follow-up, a reduction in AER of -17.4+/-65 microg/min (p<0.05) and -19.7+/-52.5 (p<0.05) in the lercanidipine and ramipril group, respectively, was observed, without differences between the groups. A significant reduction in systolic and diastolic blood pressure was observed in both the lercanidipine and ramipril-based treatment groups (p<0.0001 for both). This study demonstrated that treatment with lercanidipine 10-20 mg/day does not worsen albuminuria in microalbuminuric Type 2 diabetic patients with hypertension. Indeed, both lercanidipine and ramipril treatments resulted in a significant reduction in AER without a statistically significant difference between the two groups.

This study was undertaken to evaluate the feasibility of using commercial control materials in a regional external quality assessment scheme (EQAS) for serum carcinoembryonic antigen (CEA) measurement. We have assessed the commutability of 12 commercial control materials using five automated immunochemical systems. We compared the intermethod behavior of the materials with that of 12-14 patient serum pools. In a total of 48 comparisons (12 materials x 4 pairs of analytical systems), seven instances of non-commutability were apparent, as shown by normalized residuals falling outside the +/-3 interval. The use of non-commutable materials generates two negative effects. In EQAS, the interlaboratory variation recorded is not representative of the variation expected in the assay of patient sera; in interlaboratory harmonization programs, recalibration with non-commutable materials increases, instead of decreasing, the interlaboratory variation. Both these effects were shown to occur in CEA measurement with the tested materials and systems. The materials planned to be used in our EQAS turned out to be commutable: this gave us the guarantee of measuring realistic interlaboratory variation values, although the check for commutability should be extended to all the analytical systems used by the participants in the scheme.

Chondrocytes may play an important role in the inflammatory reactions involving intervertebral discs: the role of metalloproteases (MMP) and the imbalance between proteases and their inhibitors seems to play a crucial role in the disc degenerative process. In the present study we have analysed the production of collagenase-1 and stromelysin in different parts of herniated intervertebral discs. Ten samples of herniated lumbar discs were obtained from adult patients operated on for primary microdiscectomy because of persistent radicular symptoms and subdivided into three samples: 1. The nearest to the nerve root in close contact with it, 2. the sample obtained from the intervertebral space, and 3. the sample obtained from the vertebral plates. The DNA content of each specimen was measured in order to obtain the best estimate of the cell content as well as to normalise the content of collagenase-1 and stromelysin found in the same tissues with respect to the number of cells. In 9 out of the 10 cases the DNA content was significantly higher in samples obtained from the intervertebral plates than in samples obtained near the nerve root or the intervertebral space. DNA content did not show any significant difference considering disc samples contiguous to the nerve root and samples obtained from the intervertebral space. The production of collagenase-1 did not show a specific pattern, being produced in similar quantities in the three disc compartments. The production of stromelysin was significantly lower in disc samples obtained from the intervertebral plates. In conclusion the results of the present study suggest firstly that in the herniated lumbar disc the reactivity and the production of pro-inflammatory agents is independent of DNA content, i.e. the cellularity of the sample, and secondly that activated cells in the intervertebral space and in the part of the disc in contact with the nerve root, even if scarce in number, are able to synthesise a proportionally higher quantity of MMP than the high-cellular disc fragments from the intervertebral plates, potentially playing a specific role in the inflammatory reactions.

Chondrocytes may play an Important role in the inflammatory reactions involving intervertebral discs: the role of metalloproteases (MMP.) and the imbalance between proteases and their inhibitors seems to play a crucial role in the disc degenerative process. In the present study we have analysed the production of collagenase-1 and stromelysin in different parts of herniated intervertebral discs. Ten samples of herniated lumbar discs were obtained from adult patients operated on for primary microdiscectomy because of persistent radicular symptoms and subdivided into three samples: 1. The nearest to the nerve root in close contact with it, 2. the sample obtained from the intervertebral space, and 3. the sample obtained from the vertebral plates. The DNA content of each specimen was measured in order to obtain the best estimate of the cell content as well as to normalise the content of collagenase-1 and stromelysin found in the same tissues with respect to the number of cells. In 9 out of the 7 0 cases the DNA content was significantly higher in samples obtained from the intervertebral plates than in samples obtained near the nerve root or the intervertebral space. DNA content did not show any significant difference considering disc samples contiguous to the nerve root and samples obtained from the intervertebral space. The production of collagenase-1 did not show a specific pattern, being produced in similar quantities in the three disc compartments. The production of stromelysin was significantly lower in disc samples obtained from the intervertebral plates. In conclusion the results of the present study suggest firstly that in the herniated lumbar disc the reactivity and the production of pro-inflammatory agents is independent of DNA content, i.e. the cellularity of the sample, and secondly that activated cells in the intervertebral space and in the part of the disc in contact with the nerve root, even if scarce in number, are able to synthesise a proportionally higher quantity of MMP than the high-cellular disc fragments from the intervertebral plates, potentially playing a specific role in the inflammatory reactions. [Neurol Res 1999; 21: 677-681].

Recent studies have suggested that metalloproteinases (MMP) might be involved in the pathogenesis of cerebral aneurysm formation and rupture and that elevated serum levels of MMP may effectively be considered as possible markers of cerebrovascular malformations. The present study was planned in order to verify if serum levels of MMPs may be the mirror of the MMP activity in the wall of intracranial aneurysms, reflecting the predisposition to aneurysm development and/or rupture. A series of 84 patients operated for intracranial cerebrovascular lesions (63 aneurysms and 21 arterovenous malformations (AVM)) and 20 controls entered the study. Among the 63 cases of intracranial aneurysms, nine were discovered before rupture, while 54 patients were included after subarachnoid hemorrhage (SAH). Using radioimmunoassay, plasma elastase levels were measured in all cases, while in 25 cases, when aneurysmectomy was possible, the activity of elastase and collagenase were measured in aneurysm samples. Mean plasma elastase level in patients bearing both an intracranial aneurysm or an intracranial AVM was significantly higher than in controls, while there was no significant difference between plasmatic level of elastase in patients with aneurysms when compared with patients bearing an intracranial AVM; there was no significant difference between mean elastase level in patients who suffered SAH and patients bearing an intracranial unruptured aneurysm. The activity of elastase and collagenase measured in the aneurysm wall were significantly higher in cases of ruptured than in unruptured aneurysms. The present results show that plasmatic level of elastase does not reflect the activity of MMP as measured in the aneurysm wall and that the patterns of MMP activities measured in the aneurysm wall differ considerably at different stages of SAH. This suggests that local rather than systemic changes in metalloproteases activity might be involved in cerebral aneurysm formation and rupture.

The tissue contents of total collagen and of 3-hydroxypyridinium cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), were measured in 15 samples of human aneurysms of Willis' Circle obtained at surgery and in 25 autopsy control samples of intracranial arteries of Willis' Circle obtained from 6 subjects who died of other causes than cerebral hemorrhage. PYD and DPD were detected fluorimetrically after HPLC separation. Total collagen content was significantly lower (P < 0.001) in aneurysm samples (mean +/- S.E.M. 2.50 +/- 0.33 nmol of alpha 1(I) collagen chain per mg of delipidated and dried material) than in controls (mean +/- S.E.M. 3.86 +/- 0.14). DPD, but not PYD, content appears to be lower in aneurysm walls. In the aneurysms, the tissue contents of PYD ranged from 212 to 587 pmol/nmol of alpha 1(I) collagen chain (mean +/- S.E.M. 430 +/- 31) while in control samples the values observed ranged from 292 to 642 (mean +/- S.E.M. 471 +/- 21). The tissue content of DPD was measurable only in 6 aneurysm samples (60%), ranging from 12 to 60 pmol/nmol of alpha 1(I) collagen chain (mean +/- S.E.M. 33 +/- 9), while in control samples, DPD content ranged from 30 to 123 (mean +/- S.E.M. 75 +/- 5).

The collagen of tissues submitted to mechanical load (i.e. arterial wall) is characterised by the presence of intermolecular covalent cross-links (hydroxylysyl pyridinoline or pyridinoline: PYD; and lysyl-pyridinoline or deoxypyridinoline: DPD) which stabilise the molecular structure. In this preliminary study we look for quantitative or qualitative alterations of collagen cross-linkage in intracranial aneurysms of posterior communicating artery (PCoA) which may be considered a site of elective weakening in the intracranial arterial circulation, being one of the most frequent locations of intracranial aneurysms and of so called "infundibular widening'. We analysed the collagen cross-linkage in 6 autopsy samples of intracranial arterial segments of the Circle of Willis which were removed from patients whose cause of death was other than cerebral hemorrhage, and in 6 samples of intracranial PCoA aneurysms obtained at surgery. The analysis of cross-links showed that there was no significant difference in collagen and cross-link content between autopic and aneurysmatic samples except for PCoA. In autoptic nonaneurysmatic samples of PCoA a lower content of PYD than in internal carotid artery (ICA) and a lower content of DPD than in all other arterial segments has been demonstrated; moreover a lower content of cross-links (DPD + PYD/ Collagen) was evident in nonaneurysmatic PCoA samples when compared to other segments (ICA and Anterior Communicating Artery). On the other hand, the mean content of DPD was significantly lower in PCoA aneurysms than in nonaneurysmatic samples of the artery and moreover, a significantly low content of cross-links (DPD + PYD/Collagen) is overemphasised in PCoA aneurysms, suggesting that the peculiar lower content of DPD in PCoA arteries may be considered the expression of minor resistance of the arterial wall at this site, and may be related to the higher incidence of aneurysms or infundibular widening of this arterial segment.

Transrectal microwave hyperthermia of the prostate was administered to 191 patients with bladder outlet obstruction due to benign prostatic hyperplasia who were either at poor operative risk or who refused surgery. Patients were divided in 2 groups according to age and they underwent either 5 or 10, 60-minute sessions of hyperthermia, with a calculated intraprostatic temperature of 42.5 plus or minus 0.5C. Light and electron microscopy showed no irreversible damage at the glandular epithelium but did demonstrate a significant increase in neoformed intraprostatic capillary-like vessels. At 1, 12 and 24 months residual urine volume was significantly decreased in the majority of patients but only a minor amelioration of urinary flow rates and subjective symptoms was observed. According to maximum flow nomograms all patients were still obstructed postoperatively. Transrectal hyperthermia cannot be considered a genuine alternative to surgery for patients with bladder outlet obstruction due to benign prostatic hyperplasia.

An epidemiological investigation was carried out in Northern Italian spa to detect presence and incidence of free-living amoebae, mostly belonging to amphizoic species Acanthamoeba and Naegleria. Seven pathogenic strains of Naegleria spp. were isolated. Morpho-biological characterization and indirect immunofluorescence assays showed that all these strains belong to N. australiensis, a new pathogenic species. Such a species could induce, along with N. fowleri and Acanthamoeba spp., fatal meningo-encephalitis in man and other mammals.