Review of Lyric Opera Production of Show Boat

The premiere effort of the Renée Fleming Initiative brought Jerome Kern and Oscar Hammerstein’s masterpiece Show Boat to the Lyric Opera stage, demonstrating an annual commitment to producing works of the American musical theatre. As Lyric’s general director Anthony Freud asserted in an open letter to patrons, “great works of musical theatre profit enormously from the resources of a major opera company.” While Francesca Zambello’s lavish production may have affirmed that statement within the context of the opera house, little attention was paid to the elements that make American musical theatre generically different from opera, most notably book scenes with storytelling and narrative expressed through realistic spoken dialogue. Such scenes often require a style of acting that conveys relationship and emotional content through nuance and subtlety, rather than through size and scale. Some elements of Zambello’s production served the scope and scale of the musical very well, while others robbed it of a sense of realism or fluidity. Indeed, the Lyric production conjured ghosts from what one might imagine to be the original Ziegfeld production of 1927, evident in static stage pictures of massive ensembles framed by elaborate scenography. The Lyric production may have revived the work and injected it with fresh color and sound, but it neither reinvented it nor provided any new illumination to the eighty-five-year-old piece. If this is to be an ongoing tradition, the Lyric will need to find a way to adequately address those generic differences between opera and musical theatre, especially if it intends to produce more contemporary works

PARP-1 modulates amyloid beta peptide-induced neuronal damage.

Amyloid beta peptide (A beta) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with A beta(25-35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. A beta(25-35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following A beta(25-35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that A beta(25-35) induces DNA damage which in turn activates PARP-1. Challenge with A beta(25-35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, A beta(25-35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by A beta and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed

Surgical treatment in patient with non-small-cell lung cancer with fissure involvement: Anatomical versus nonanatomical resection

OBJECTIVE: Despite the intense debate concerning the prognostic impact of fissure involvement (FI) in patients with non-small-cell lung cancer, no specific surgical strategies have been yet recommended when this condition occurs. In this setting, we report our monocentric 10-years experience to investigate this issue. METHODS: From January 2000 to January 2010, the clinical data of 40 non-small-cell lung cancer patients with FI undergoing curative resection were retrospectively reviewed. The sample was stratified according to the type of resection: group A (28 patients): anatomical resection (bilobectomy [21 patients], pneumonectomy [7 patients]); group B (12 patients): nonanatomical resection (lobectomy plus wedge resection [LWR]). The end-points were (1) impact of different surgical approach on the pulmonary function (measured before surgery and 1 month after discharge); (2) disease-specific survival; and (3) tumor recurrence.The t test, χ, and log-rank tests, Kaplan-Meier method, and Cox and logistic regression analyses were used for the statistical analysis. RESULTS: No differences between the two groups were found when comparing the clinical characteristics, histology, pN or pT status, p-stage, residual (R1) disease, tumor grading, or tumor size. Similarly, the baseline preoperative function (tested as forced expiratory volume in 1 second-%-predicted, FEV1%) was likewise comparable (92.5% ± 21.0% in group A versus 85.2% ± 20.0% in group B; p = not significant). The decline of FEV1% after surgery was slightly higher in group A (-24.9% ± 13.5%) when compared with that in group B (-19.5% ± 13.3%), but this difference was not statistically significant (p = ns). Nevertheless, the 5-year disease-specific survival was 56% for group A and 47% for group B (p = ns). The recurrence rate did not differ between the patients undergoing a LWR (3 of 12 patients) and those undergoing a bilobectomy or pneumonectomy (9 of 28 patients) (p = ns). The presence of FI extended for more than 3 cm was found to be the most significant prognostic factor when analyzing survival (p = 0.002) and recurrence rate (p< 0.001). CONCLUSIONS: Our results suggest that nonanatomical resection (LWR) could be considered as a feasible surgical option (especially in "frail" patients with an extent of FI less than 3 cm) in the light of the similar oncological and functional outcome compared with anatomical resection. Further studies based on larger series are needed to confirm these preliminary data and also to investigate the impact on the postoperative quality of life

Survival analysis in single N2 station lung adenocarcinoma: The prognostic role of involved lymph nodes and adjuvant therapy

Background: Prognostic factors in patients with single mediastinal station (sN2) involvement continues to be a debated issue. Methods: Data on 213 adenocarcinoma patients with sN2 involvement and who had undergone complete anatomical lung resection and lymphadenectomy, were retrospectively reviewed. Clinical and pathological characteristics together with adjuvant therapy (AD) and node (N) status classifications (number of resected nodes (#RN), number of metastatic nodes (#MN), and node ratio (#MN/#RN = NR) were analyzed. Results: Univariable analysis confirmed that age (0.009), #MN (0.009), NR (0.003), #N1 involved stations (p = 0.003), and skip metastases (p = 0.005) were related to overall survival (OS). Multivariable analysis confirmed, as independent prognostic factors, age <66 years and NR with a three-year OS (3YOS) of 78.7% in NR < 10% vs. 46.6% in NR > 10%. In skip metastases, NR (HR 2.734, 95% CI 1.417–5.277, p = 0.003) and pT stage (HR2.136, 95% CI 1.001–4.557, p = 0.050) were confirmed as independent prognostic factors. AD did not influence the OS of patients with singular positive lymph nodes (p = 0.41), while in patients with multiple lymph nodes and AD, a significantly better 3YOS was demonstrated, i.e., 49.1% vs. 30% (p = 0.004). In patients with N2 + N1 involvement, age (p = 0.002) and AD (p = 0.022) were favorable prognostic factors. Conclusions: Adenocarcinoma patients with single N2 station involvement had a favorable outcome in the case of skip metastases and low NR. Adjuvant therapy improves survival with multiple nodal involvement, while its role in single node involvement should be clarified

Rate and predictors of unforeseen PN1/PN2-disease in surgically treated cN0 NSCLC-patients with primary tumor > 3 cm: nationwide results from Italian VATS-group database

Background. Since no robust data are available on the real rate of unforeseen N1-N2 disease (uN) and the relative predictive factors in clinical-N0 NSCLC with peripheral tumours > 3 cm, the usefulness of performing a (mini)invasive mediastinal staging in this setting is debated. Herein, we investigated these issues in a nationwide database. Methods. From 01/2014 to 06/2020, 15,784 thoracoscopic major lung resections were prospectively recorded in the “Italian VATS-Group” database. Among them, 1982 clinical-N0 peripheral solid-type NSCLC > 3 cm were identified, and information was retrospectively reviewed. A mean comparison of more than two groups was made by ANOVA (Bonferroni correction for multiple comparisons), while associations between the categorical variables were estimated with a Chi-square test. The multivariate logistic regression model and Kaplan–Meyer method were used to identify the independent predictors of nodal upstaging and survival results, respectively. Results. At pathological staging, 229 patients had N1-involvement (11.6%), and 169 had uN2 disease (8.5%). Independent predictors of uN1 were SUVmax (OR: 1.98; CI 95: 1.44–2.73, p = 0.0001) and tumour-size (OR: 1.52; CI: 1.11–2.10, p = 0.01), while independent predictors of uN2 were age (OR: 0.98; CI 95: 0.96–0.99, p = 0.039), histology (OR: 0.48; CI 95: 0.30–0.78, p = 0.003), SUVmax (OR: 2.07; CI 95: 1.15–3.72, p = 0.015), and the number of resected lymph nodes (OR: 1.03; CI 95: 1.01–1.05, p = 0.002). Conclusions. The unforeseen N1-N2 disease in cN0/NSCLCs > 3 cm undergoing VATS resection is observable in between 12 and 8% of all cases. We have identified predictors that could guide physicians in selecting the best candidate for (mini)invasive mediastinal staging

Which are the limiting factors in lung tissue sampling and diagnostic accuracy for a new Interventional Pulmonology Unit? From expert consensus-based evidence to results of a new-born Unit

Background: There is a gap of knowledge about the factors that may determine the quality and the accuracy of diagnostic bronchoscopic procedures when setting up a new Interventional Pulmonology Unit. As little evidence-based medicine is available on this matter, an online consensus opinion of experts was gathered and compared with real-life data coming from a new Interventional Pulmonology (IP) Unit. Methods: A survey was emailed to the heads of all Italian IP Units to investigate the factors influencing the success of the diagnostic yield of a new IP Unit. The survey consisted of 24 items grouped by topic; the level of agreement ranged from 1 (no influence) to 7 (strong influence). After responses were collected, we submitted the data on the accuracy of the endoscopic procedures performed during the first two years of our new IP Unit to the attention of the participants for a second round of survey; the level of consistency between the first and second round of responses was assessed. Results: After having been shown the results of the first two years of activity of our Unit, in the second round of the survey the responders indicated the personal skills of the Interventional Pulmonologist, the availability of echoendoscopic technology and the expertise in evaluating cytological samples as the factors able to positively influence the performance of a newly established IP Unit. Neither the role of dedicated nursing assistance, the availability of a rapid on-site evaluation, nor the presence of anesthesiology assistance were considered to be limiting factors for the final accuracy results. Conclusions: A consensus of opinion of a group of expert interventional pulmonologists highlighted the factors that may be responsible for the diagnostic success of a newly established Italian IP Unit. These factors are mainly three: personal skills of the interventional pulmonologist, the availability of echoendoscopic technology, and the expertise in reading cytological samples

The International Thymic Malignancy Interest Group Classification of Thymoma Recurrence: Survival Analysis and Perspectives

Introduction: The International Thymic Malignancy Interest Group (ITMIG) classifies thymoma recurrences on the basis of the topographic location, but its effectiveness in prognosis prediction has not been well investigated yet. Aims of this study are to analyze survival outcome of patients surgically treated for thymoma recurrence according to the ITMIG recurrence classification and to investigate possible alternatives. Methods: From January 1, 1990, to January 7, 2017, data on 135 surgically treated patients for thymoma recurrence from three high-volume centers were collected and retrospectively analyzed. Patients were classified according to the ITMIG classification as local, regional, and distant. The ITMIG classification and alternative classifications were correlated to overall survival (OS). Results: According to the ITMIG classification, recurrence was local in 17 (12.5%), regional in 97 (71.8%), and distant in 21 (15.7%) patients, with single localization in 38 (28.2%) and multiple localizations in 97 (71.8%). The 5- and 10-year OS were 79.9% and 49.7% in local, 68.3% and 52.6% in regional, and 66.3% and 35.4% in distant recurrences, respectively, but differences were not statistically significant (p = 0.625). A significant difference in survival was present considering single versus multiple localizations: 5- and 10-year OS of 86.2% and 81.2% versus 61.3% and 31.5% (p = 0.005, hazard ratio = 7.22, 95% confidence interval: 0.147–0.740), respectively. Combining the localization number with the recurrence site, ITMIG locoregional single recurrence had a statistically significant better survival compared with patients with ITMIG locoregional multiple recurrence or ITMIG distant recurrence (p = 0.028). Similarly, a significant difference was present considering intrathoracic single versus intrathoracic multiple versus distant recurrence (p = 0.024). Conclusions: The ITMIG classification for thymoma recurrence did not have significant survival differences comparing local, regional, and distant recurrences. Integrating this classification with the number of the localizations may improve its effectiveness in prognosis prediction

Uniportal-VATS vs. open McKeown esophagectomy: Surgical and long-term oncological outcomes

Background: Till now there are very few reports about surgical results of Uniportal-VATS esophagectomy and no one about long-term outcomes. This study is the first comparing surgical and oncological outcomes of Uniportal-VATS with open McKeown esophagectomy, with the largest reported series and longest oncological follow-up. Methods: The prospectively collected clinical, surgical and oncological data of 75 patients, undergone McKeown esophagectomy at our Thoracic Surgery Department, from January 2012 to August 2022, were retrospectively analyzed. Nineteen patients underwent esophagectomy by thoracotomy and reconstruction according to McKeown technique while 56 by Uniportal-VATS approach. Gastric tubulization was performed totally laparoscopic or through a mini-laparatomic access and cervical anastomosis was made according to Orringer's technique. Results: The mean operative thoracic time was similar in both accesses (102.34 ± 15.21 min in Uniportal-VATS vs. 115.56 ± 23.12 min in open, p: 0.646), with a comparable number of mediastinal nodes retrieved (Uniportal-VATS:13.40 ± 8.12 vs. open:15.00 ± 6.86, p: 0.275). No case needed conversion from VATS to open. The learning curve in Uniportal-VATS was completed after 34 cases, while the Mastery was reached after 40. Both approaches were comparable in terms of minor post-operative complications (like pneumonia, lung atelectasis, anemization, atrial fibrillation, anastomotic-leak, left vocal cord palsy, chylothorax), while the number of re-operation for major complications (bleeding or mediastinitis) was higher in open group (21.0% vs. 3.6%, p: 0.04). Both techniques were also effective in terms of surgical radicality and local recurrence but VATS approach allowed a significantly lower chest tube length (11.89 ± 9.55 vs. 25.82 ± 24.37 days, p: 0.003) and post-operative stay (15.63 ± 11.69 vs. 25.53 ± 23.33, p: 0.018). The 30-day mortality for complications related to surgery was higher in open group (p: 0.002). The 2-, 5- and 8-year survival of the whole series was 72%, 50% and 33%, respectively. Combined 2- and 5-year OS in Uniportal-VATS group was 76% and 47% vs. 62% and 62% in open group, respectively (Log-rank, p: 0.286; Breslow-Wilcoxon: p: 0.036). No difference in DFS was recorded between the two approaches (5 year-DFS in Uniportal-VATS: 86% vs. 72%, p: 0.298). At multivariate analysis, only pathological stage independently affected OS (p: 0.02), not the surgical approach (p: 0.276). Conclusions: Uniportal-VATS seems to be a safe, feasible and effective technique for performing McKeown esophagectomy, with equivalent surgical and long-term oncological results to standard thoracotomy, but with a faster and unharmed recovery, and a quite short learning curve

Distinct monocyte subset phenotypes in patients with different clinical forms of chronic Chagas disease and seronegative dilated cardiomyopathy

BACKGROUND: Chronic infection with Trypanosoma cruzi leads to a constant stimulation of the host immune system. Monocytes, which are recruited in response to inflammatory signals, are divided into classical CD14hiCD16-, non-classical CD14loCD16+ and intermediate CD14hiCD16+ subsets. In this study, we evaluated the frequencies of monocyte subsets in the different clinical stages of chronic Chagas disease in comparison with the monocyte profile of seronegative heart failure subjects and seronegative healthy controls. The effect of the anti-parasite drug therapy benznidazole on monocyte subsets was also explored. METHODOLOGY/PRINCIPAL FINDINGS: The frequencies of the different monocyte subsets and their phenotypes were measured by flow cytometry. Trypanosoma cruzi-specific antibodies were quantified by conventional serological tests. T. cruzi-infected subjects with mild or no signs of cardiac disease and patients suffering from dilated cardiomyopathy unrelated to T. cruzi infection showed increased levels of non-classical CD14loCD16+ monocytes compared with healthy controls. In contrast, the monocyte profile in T. cruzi-infected subjects with severe cardiomyopathy was skewed towards the classical and intermediate subsets. After benznidazole treatment, non-classical monocytes CD14loCD16+ decreased while classical monocytes CD14hiCD16-increased. CONCLUSIONS/SIGNIFICANCE: The different clinical stages of chronic Chagas disease display distinct monocyte profiles that are restored after anti-parasite drug therapy. T. cruzi-infected subjects with severe cardiac disease displayed a profile of monocytes subsets suggestive of a more pronounced inflammatory environment compared with subjects suffering from heart failure not related to T. cruzi infection, supporting that parasite persistence might also alter cell components of the innate immune system