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Objective: To evaluate the diagnostic accuracy of anticarbamylated protein antibodies (CarP), alone and in combination with traditional biomarkers (rheumatoid factor [RF] and anticitrullinated peptide antibodies [ACPA]), in established rheumatoid arthritis (RA). Methods: A commercially available enzyme‐linked immunosorbent assay (ELISA) kit was used to assess CarP concentrations in serum samples of 200 established RA and 206 controls (115 healthy donors and 55 patients with other rheumatic diseases). Main outcome measures were sensitivity, specificity, and area under the curve (AUC; 95% confidence interval [CI]). Difference in accuracy was evaluated by comparison of the respective AUCs. Results: A serum CarP cut‐off of 1.47 ng/ml or more differentiated patients with RA from controls with 30% sensitivity, 97.1% specificity, and good accuracy (AUC[95%CI] = 0.83[0.79‐0.86], P < 0.0001). However, it showed moderate diagnostic accuracy in seronegative RA patients: sensitivity 17.9%, specificity 96.9%, and AUC (95% CI) = 0.69 (0.63‐0.75). The diagnostic accuracy of CarP_ACPA and CarP_RF combinations was significantly superior to that of ACPA and RF alone (P < 0.0001 and P = 0.015, respectively), but not to that of ACPA_RF combination (P = 0.089) In addition, the CarP_ACPA_RF combination did not improve the diagnostic accuracy of the ACPA_RF combination (AUC mean difference [95% CI] = 0.006 [−0.001 to 0.015], P = 0.10). The number of positive autoantibodies (0, 1, 2, or 3) was not significantly associated with moderate‐severe disease (Disease Activity Score‐28 [DAS‐28] > 3.2) in adjusted multiple regression analysis. Conclusion: CarP has good diagnostic accuracy in established RA but not in seronegative RA. The addition of CarP to ACPA and RF alone or in combination does not significantly enhance the diagnostic accuracy of ACPA_RF combination. [ABSTRACT FROM AUTHOR]

Sleeve lobectomy or resection with pulmonary artery reconstruction is a technique that allows for resection of locally advanced central lung carcinoma, preserving lung function, and is associated with lower morbidity and mortality than pneumonectomy. This survey aimed to assess the long-term survival comparing different types of sleeve lobectomy and identify risk factors affecting survival.All consecutive patients who underwent anatomical resection for primary non-small cell lung cancer with bronchial sleeve or pulmonary artery reconstruction in our department between September 2003 and September 2021 were included in this study. Cases with carinal sleeve pneumonectomy were excluded. Data were evaluated retrospectively.Bronchial sleeve resection was performed in 227 patients, double sleeve resection in 67 patients, and 45 cases underwent isolated lobectomy with pulmonary artery reconstruction. The mean follow-up was 33.5 months. The 5-year survival was 58.5% for patients after bronchial sleeve, 43.2% after double sleeve, and 36.8% after resection with vascular reconstruction. The difference in overall survival of these three groups was statistically significant (p = 0.012). However, the UICC stage was higher in cases with double sleeve resection or resection with vascular reconstruction (p = 0.016). Patients with lymph node metastases showed shorter overall survival (p = 0.033). The 5-year survival rate was 60.1% for patients with N0 and 47% for patients with N1 and N2 status. Induction therapy, vascular sleeve resection, and double sleeve resection were independent adverse predictors for overall survival in multivariate analysis.Sleeve lobectomy and resection with vascular reconstruction are safe procedures with good long-term survival. However, double sleeve resection and vascular sleeve resection were adverse predictors of survival, possibly due to a higher UICC stage in these patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background:  Carinal sleeve resection with pneumonectomy is one of the rarest procedures in thoracic surgery, but for locally advanced central lung cancer with infiltration of the carina, it is an option to achieve complete resection. Additionally, it might be the method of choice for patients with stump insufficiency after pneumonectomy or in the cases with anastomosis dehiscence after sleeve lobectomy. The aim of this study was to evaluate the morbidity and long-term survival of patients with non-small-cell lung cancer (NSCLC) who underwent sleeve pneumonectomy, either for curative intent or as an option to treat postoperative complications., Methods:  All consecutive patients with NSCLC who underwent carinal sleeve pneumonectomy for the aforementioned indications in our department between December 2021 and September 2003 were included in this study. An analysis of demographic characteristics, perioperative variables, and long-term survival was carried out. Data were evaluated retrospectively., Results:  Fifty patients underwent pneumonectomy with carina sleeve resection. Thirty-one cases for curative treatment of NSCLC (primary sleeve pneumonectomy [pSP]) and 19 patients were treated because of postpneumonectomy bronchial stump insufficiency or bronchial anastomosis dehiscence (secondary sleeve pneumonectomy [sSP]). Complications occurred in 30 patients (60%) and the 90-day mortality was 18% ( n  = 9). Patients with pSP had an estimated overall survival of 39.6 months, compared to estimated overall survival for patients after sSP of 24.5 months ( p  = 0.01). The N status did not appear to affect outcomes., Conclusion:  Carinal sleeve resection with pneumonectomy is a feasible procedure with limited morbidity and mortality. This procedure is a reasonable therapeutic option for patients with locally advanced central NSCLC after mandatory patient selection., Competing Interests: None declared., (Thieme. All rights reserved.)

In mammalians, social life and circadian rhythms find their neurobiological basis in a network that includes the dopaminergic system. The malfunctioning of dopamine pathways can lead to various disorders such as Attention-Deficit/Hyperactivity and Obsessive/compulsive disorders. A useful research approach is to exploit animal models that carry a functional silencing of SLC6A3 gene, encoding the dopamine transporter (DAT). Hyperactivity, working memory deficits, and asocial tendencies are core features in truncated-DAT rats, for example. We investigated how inheritance and maternal caring style influence circadian rhythms and social behaviours in DAT heterozygous (HET) rats, belonging to four groups: Mat-P, Mat-M, Mix-P, and Mix-M (Mat label stands for care from wild-type dam, Mix label stands for care by heterozygous dam; M label stands for maternal wild-DAT and P label stands for paternal wild-DAT). In Experiment 1, we monitored 24/7 the spontaneous locomotor activity of peri-adolescent subjects. Hyperactivity occurred only in P-asset subjects (with maternal-origin truncated-DAT allele) at specific bins of the day. In Experiment 2, we observed social interactions of the same rats. Mix-M subjects (raised by HET dams and/or inheriting the wild-DAT allele from mothers) tend to interact with all rats; Mat-P (cared by WT dams and/or inheriting the truncated-DAT allele from mothers) seem to be ignored, when acting as stimulus subjects. Overall, results confirm complex modulations for circadian cycle and social life: flexible DAT expression in HET subjects depends on epigenetic combinations of parental inheritance and early experiential factors. Once confirmed, these data could shed light on trans-generational contributions to dopaminergic-related disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dopamine is essential to many functions like reward, motivation, and attention; when its neural pathways do not function properly, various disorders (e.g., anxiety, depression, hyperactivity, compulsions) can arise. Truncated-DAT rats display persistent stereotypies and aggressiveness; hence they are a new valuable animal model to study the pathogenesis of these disorders. The focus of research is often on the individual epigenetic determinants and much less on the impact of social experiences. Here, we investigate the developmental impact of the social environment on adolescent wild type (WT) rats. We divided subjects at weaning into three groups: living with another adolescent (WT Peer), with a WT adult, or with a truncated-DAT one, and we observed homecage social behavior of these pairs (play, jump, victory, and "bullying") during whole adolescence. When adult, we observed the same subjects in plus maze, forced swim, and social preference tests to measure levels of anxiety, depression, and quality of social interactions. Compared to the other groups, WT rats that had spent their adolescence with a truncated-DAT adult as companion show more anxious, depressive, hyperactive, impulsive, and compulsive behaviours. Results confirm that social interactions and healthy play (i.e., when play has behavioural, social, and psychomotor rewards that support the cognitive, emotional and physical development of the individual) are essential to neurobehavioral maturation. Conversely, anomalous interactions like poor play and "bullying" in developing rats may impact onto their dopaminergic system. Consequently, an impoverished social play could be one of the factors contributing to the appearance of putative indexes of attention deficit hyperactivity disorder (ADHD) and\or obsessive-compulsive disorder (OCD)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: Bronchopleural fistula after pneumonectomy and dehiscence of an anastomosis after sleeve lobectomy are severe complications. Several established therapeutic options are available. Conservative treatment is recommended for a small fistula without pleural infection. In patients with a bronchopleural fistula and subsequent pleural empyema, surgical management is the mainstay. Overall, the associated morbidity and mortality are high. Carinal sleeve resection is the last resort for patients with a short stump after pneumonectomy or anastomotic dehiscence after sleeve resection near the carina., Methods: All patients with bronchopleural fistula after pneumonectomy or sleeve resection who underwent secondary carinal sleeve resection between 2003 and 2019 in our institution were evaluated retrospectively. Patients with anastomotic dehiscence after sleeve lobectomy underwent a completion pneumonectomy. The surgical approach was an anterolateral thoracotomy; the anastomosis was covered with muscle flap, pericardial fat or omentum majus. In case of empyema, povidone-iodine-soaked towels were introduced into the cavity and changed at least twice., Results: A total of 17 patients with an initial sleeve lobectomy in 12 patients and pneumonectomy in 5 patients were treated with carinal sleeve resection in our department. Morbidity was 64.7% and 30-day survival was 82.4% (n = 14). A total of 70.6% of the patients survived 90 days (n = 12). Median hospitalization was 17 days and the median stay in the intensive care unit was 12 days., Conclusions: Carinal sleeve resection is a feasible option in patients with a post-pneumonectomy fistula or anastomotic insufficiency following sleeve lobectomy in the absence of alternative therapeutic strategies. Nevertheless, postoperative morbidity is high, including prolonged intensive care unit stay., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

While both risk-taking and avoidant behaviors are necessary for survival, their imbalanced expression can lead to impulse-control and anxiety disorders, respectively. In laboratory rodents, the conflict between risk proneness and anxiety can be studied by using their innate fear of heights. To explore this aspect in detail and investigate venturesome behavior, here we used a "Himalayan Bridge," a rat-adapted version of the suspended wire bridge protocol originally developed for mice. The apparatus is composed of two elevated scaffolds connected by bridges of different lengths and stability at 1 m above a foam rubber-covered floor. Rats were allowed to cross the bridge to reach food, and crossings, pawslips, turnabouts, and latencies to cross were measured. Given the link between risky behavior and adolescence, we used this apparatus to investigate the different responses elicited by a homecage mate on the adolescent development of risk-taking behavior. Thus, 24 wild-type (WT) subjects were divided into three different housing groups: WT rats grown up with WT adult rats; control WT adolescent rats (grown up with WT adolescents), which showed a proclivity to risk; and WT rats grown up with an adult rat harboring a truncated mutation for their dopamine transporter (DAT). This latter group exhibited risk-averse responses reminiscent of lower venturesomeness. Our results suggest that the Himalayan Bridge may be useful to investigate risk perception and seeking; thus, it should be included in the behavioral phenotyping of rat models of psychiatric disorders and cognitive dysfunctions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Festucci, Buccheri, Parvopassu, Oggiano, Bortolato, Laviola, Curcio and Adriani.)

A patient with simultaneous bilateral non-small-cell lung cancer underwent a thoracoscopic sleeve segmentectomy on the right side to avoid lobectomy in curative approach. The patient also had a second, left-sided tumour requiring at least a left-sided sleeve upper lobectomy for complete resection. In anticipation of the second pulmonary resection in a patient whose lung function was already impaired by the first operation, we opted for a thoracoscopic approach with fast recovery. The left-sided operation was performed 60 days after the right-sided sleeve segmentectomy without any complications., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

To evaluate the performance of different blood cells-derived indexes in the diagnosis of rheumatoid arthritis (RA).Neutrophil-to-lymphocyte ratio (NLR), lymphocyte to monocyte ratio, platelet to lymphocyte ratio (PLR), systemic inflammation response index (SIRI), and aggregate inflammation systemic index were calculated in 199 consecutive RA patients and 283 sex and age-matched controls (147 healthy donors and 136 patients with other rheumatic diseases). Area under the curve (AUCs), sensitivity and specificity were calculated to evaluate the accuracy of indexes in discriminating between RA and controls. Association between indexes and RA variables was explored by multiple linear regression analyses.Blood cells-derived indexes did not demonstrate good accuracy in differentiating RA from controls with lymphocyte to monocyte ratio, the index with the best diagnostic performance, having 63.6% of sensitivity and 65.3% specificity [AUC (95%CI) = 0.67 (0.62-0.72]. The accuracy of the indexes in differentiating RA from healthy donors was significantly higher than that (AUCs < 0.6 for all comparisons) differentiating RA from rheumatic diseases. In RA, SIRI and aggregate inflammation systemic index showed significant association with C-reactive protein and erythrocyte sedimentation rate.Our results do not support the use of blood cells-derived indexes for the diagnosis of RA, suggesting that they might reflect chronic inflammatory burden in rheumatic diseases rather than, specifically, in RA.

The Naples High-Excitability (NHE) is a validated rat strain to model for a mesocortical variant of Attention Deficit Hyperactivity Disorder (ADHD). NHE rats' brains have a tuned-down cortical and a potentiated limbic loop (Zoratto et al., 2017). ADHD and comorbid pathological gambling (PG) involve similar deficits of prefrontal-striatal dialogue. This work aimed to understand if NHE rats (compared to normal random-bred rats, NRB) can be a useful model for gambling vulnerability in ADHD. Experiment 1 evaluated gambling proneness in NHE rats, namely attraction/avoidance in nose-poking for a "Large & Luck-Linked" (LLL) reward (versus a "Small & Sure" one, SS), when the probability of LLL delivery was progressively reduced. Experiment 2 assessed (by phMRI) differential responsivity of ventral (vStr) versus dorsal (dStr) striatum following a methylphenidate (MPH, 4 mg/kg I.P.) challenge. In NHE rats, reduced attraction by secondary cues (associated with uncertain, rarefying LLL delivery) comes along with little or no activation of dStr and enhanced activation of vStr by MPH. Together, such evidences from NHE rats indicate distinctive roles of ventral (enhanced value given to actual primary reward) and dorsal (lower encoding of repeated stimulus-reward associations into a habit) striatum. In conclusion, the dynamics of reward systems could link an attention deficit with a decreased vulnerability to pathological gambling., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background & Objectives: One of the most important problems in Mediterranean regions is finding blood donors to overcome the high need of its population. Understanding the health benefits of blood donation frequency will activate more volunteers to donate. The aim of this study variations of hematological and biochemical indices in regular male and female donors from Greece and Italy METHODS: A cross-sectional study consisted of 350 voluntary blood donors (VDs)was conducted in two mediterranean Blood Banks, Greece and Italy. The first one from the General Hospital of Naousa, Greece on samples of 90 regular and 60 first-time blood donors. The second one from AOU Sassari, Sardinia, Italy on convenient samples of 100 first-time samples and 100 regular blood donors. Donors' particulars were obtained from blood bank records. The hematological and biochemical parameters were determined for all donors and Total Antioxidant Status (TAS) only for greek VDs., Results: High frequency blood donation of Greek VDs could be associated with evidence of reduction of body iron stores, reduced oxidative stress and improvement of liver function biomarkers in regular groups. Interestingly, Sardinian regular male VDs presented increased iron stores in compare with the first time VDs. In both Mediterranean populations (Greeks and Italians) the lipid profile of the female regular blood donors has been improved in compare with the first timers., Conclusion: Regular blood donation increases antioxidant capacity and affects positively the hematological parameters and biochemical biomarkers in donors. Gender plays an important role in relation to all hematological and biochemical parameters. Further studies in larger population should evaluate the beneficial-effect of blood donation and promote people to donate more frequent., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: An adequate perioperative analgesia reduces neuroendocrine stress response and postoperative complica-tions. Opioids are the most effective parenteral drugs to control pain and stress response., Design: This is a prospective randomized double-blinded controlled study., Setting: Institutional tertiary level., Patients, Participants: Fifty patients underwent general anesthesia with desflurane for laparoscopic cholecystectomy., Main Outcome Measures: To compare two different doses of remifentanil (0.15 mcg/kg/min or 0.3 mcg/kg/min) in reducing markers of stress. Perioperative stress was assessed through the dosage of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), and prolactin (PRL). Three venous blood samples were collected from patients: before transferring the patient to the operating room (Time 0), at the trocar insertion (Time 1), and 1 hour after the end of the surgery (Time 2)., Results: Hemodynamic parameters showed no differences between the two groups. The authors observed an increase of GH and PRL in both groups at trocar insertion (Time 1) ( p = 0.473 and 0.754, respectively). ACTH and cortisol showed a decrease at Time 1 and an increase after surgery (p = 0.586). The modification of stress parameters levels showed no significant differences between the two groups., Conclusions: The results of our study showed that a lower dose of remifentanil is equally effective in controlling stress hormones during laparoscopic cholecystectomy.