Space hierarchy theorem revised

AbstractWe show that, for an arbitrary function h(n) and each recursive function ℓ(n), that are separated by a nondeterministically fully space constructible g(n), such that h(n)∈Ω(g(n)) but ℓ(n)∉Ω(g(n)), there exists a unary language L in NSPACE(h(n)) that is not contained in NSPACE(ℓ(n)). The same holds for the deterministic case.The main contribution to the well-known Space Hierarchy Theorem is that (i) the language L separating the two space classes is unary (tally), (ii) the hierarchy is independent of whether h(n) or ℓ(n) are in Ω(logn) or in o(logn), (iii) the functions h(n) or ℓ(n) themselves need not be space constructible nor monotone increasing, (iv) the hierarchy is established both for strong and weak space complexity classes. This allows us to present unary languages in such complexity classes as, for example, NSPACE(loglogn·log∗n)⧹NSPACE(loglogn), using a plain diagonalization

Thoracoscopic vs. catheter ablation for atrial fibrillation: long-term follow-up of the FAST randomized trial

Aims: Our objectives were to compare effectiveness and long-term prognosis after epicardial thoracoscopic atrial fibrillation (AF) ablation vs. endocardial catheter ablation, in patients with prior failed catheter ablation or high risk of failure. Methods and results: Patients were randomized to thoracoscopic or catheter ablation, consisting of pulmonary vein isolation with optional additional lines (2007–2010). Patients were reassessed in 2016/2017, and those without documented AF recurrence underwent 7-day ambulatory electrocardiography. The primary rhythm outcome was recurrence of any atrial arrhythmia lasting >30 s. The primary clinical endpoint was a composite of death, myocardial infarction, or cerebrovascular event, analysed with adjusted Cox proportional hazard ratios (HRs). One hundred and 24 patients were randomized with 34% persistent AF and mean age 56 years. Arrhythmia recurrence was common at mean follow-up of 7.0 years, but substantially lower with thoracoscopic ablation: 34/61 (56%) compared with 55/63 (87%) with catheter ablation [adjusted HR 0.40, 95% confidence interval (CI) 0.25–0.64; P < 0.001]. Additional ablation procedures were performed in 8 patients (13%) compared with 31 (49%), respectively (P < 0.001). Eleven patients (19%) were on anti-arrhythmic drugs at end of follow-up with thoracoscopy vs. 24 (39%) with catheter ablation (P = 0.012). There was no difference in the composite clinical outcome: 9 patients (15%) in the thoracoscopy arm vs. 10 patients (16%) with catheter ablation (HR 1.11, 95% CI 0.40–3.10; P = 0.84). Pacemaker implantation was required in 6 patients (10%) undergoing thoracoscopy and 3 (5%) in the catheter group (P = 0.27). Conclusion: Thoracoscopic AF ablation demonstrated more consistent maintenance of sinus rhythm than catheter ablation, with similar long-term clinical event rates

Phase II Multicenter Clinical Trial of Pulmonary Metastasectomy and Isolated Lung Perfusion with Melphalan in Patients with Resectable Lung Metastases

IntroductionThe 5-year overall survival rate of patients undergoing complete surgical resection of pulmonary metastases (PM) from colorectal cancer (CRC) and sarcoma remains low (20–50%). Local recurrence rate is high (48–66%). Isolated lung perfusion (ILuP) allows the delivery of high-dose locoregional chemotherapy with minimal systemic leakage to improve local control.MethodsFrom 2006 to 2011, 50 patients, 28 male, median age 57 years (15–76), with PM from CRC (n = 30) or sarcoma (n = 20) were included in a phase II clinical trial conducted in four cardiothoracic surgical centers. In total, 62 ILuP procedures were performed, 12 bilaterally, with 45 mg of melphalan at 37°C, followed by resection of all palpable PM. Survival was calculated according to the Kaplan–Meier method.ResultsOperative mortality was 0%, and 90-day morbidity was mainly respiratory (grade 3: 42%, grade 4: 2%). After a median follow-up of 24 months (3–63 mo), 18 patients died, two without recurrence. Thirty patients had recurrent disease. Median time to local pulmonary progression was not reached. The 3-year overall survival and disease-free survival were 57% ± 9% and 36% ± 8%, respectively. Lung function data showed a decrease in forced expiratory volume in 1 second and diffusing capacity of the alveolocapillary membrane of 21.6% and 25.8% after 1 month, and 10.4% and 11.3% after 12 months, compared with preoperative values.ConclusionCompared with historical series of PM resection without ILuP, favorable results are obtained in terms of local control without long-term adverse effects. These data support the further investigation of ILuP as additional treatment in patients with resectable PM from CRC or sarcoma

Totally thoracoscopic ablation for atrial fibrillation:a systematic safety analysis

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Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer:A Randomized Clinical Trial

PURPOSE:Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking.METHODS:Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior &lt;.0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality.RESULTS:Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior =.0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior =.0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P =.4940).CONCLUSION:On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.</p

Impact of different surgical strategies on perioperative protein s100β release in elderly patients undergoing coronary artery bypass grafting

This study was designed to compare neurological injury-associated protein S100β release during three different treatment modalities, minimized closed circuit coronary artery bypass grafting (CABG) (MCABG), off-pump CABG (OPCAB), and conventional CABG (CCABG), comprising high-volume prime and cold crystalloid cardioplegia. Our working hypothesis was that fluid restriction as provided by MCABG may decrease neurological injury-associated protein S100β release. In this prospective trial, in a tertiary center, 30 surgical patients (aged >70 years, 25 men and 5 women) undergoing first-time elective CABG were enrolled. The inclusion criteria were three-vessel disease and elective surgery. The exclusion criteria were left ventricular ejection fraction of less than 30%, use of clopidogrel, carotid disease, or needing fewer than three distal anastomoses. Protein S100β concentrations, hematocrit (Ht) levels, and PO2 levels were measured after induction of anesthesia, 10 minutes after reperfusion, upon arrival at the intensive care unit, 3 hours postoperatively at the intensive care unit, and the next morning. Statistics consisted of areas under the curve, peak levels, and correlation and variance tests. A significant negative correlation was found indicating higher S100β release at lower Ht levels and at lower PO2 levels in all study groups. The lowest S100β variance was measured during MCABG (Wilks Λ P = 0.052). The perioperative Ht was significantly higher in the MCABG group and in the OPCAB group compared with the CCABG group (P = 0.04 vs P < 0.01). At all time points, the S100β protein concentration showed no significant differences between the different surgical techniques. The mean (95% confidence interval) values of S100 area under the curve were the following: CCABG, 2.3 (1.06-3.5); MCABG, 1.44 (0.6-2.21); and OPCAB, 1.87 (1.5-2.19) [independent nonparametric Kruskal-Wallis test (P = 0.13)]. The mean (95% confidence interval) peak S100 values (calculated as the maximum value seen in a patient during the research period) were the following: CCABG, 1.07 (0.4-1.68); MCABG, 0.59 (0.28-0.90); and OPCAB, 0.83 (0.59-1.06) [independent nonparametric Kruskal-Wallis test (P = 0.22)]. Despite similar perioperative S100β protein release for all techniques studied, higher Ht and PO2 levels correlated with lower S100β release within all study groups. The low S100β variance during the fluid restrictive MCABG technique may be due to more efficient oxygen transport to the brain provided by significantly higher perioperative Ht levels. Further prospective data are required to better understand this complex issu

Selective pulmonary artery perfusion for the treatment of primary lung cancer:Improved drug exposure of the lung

Introduction: Selective pulmonary artery perfusion (SPAP) is an experimental drug infusion method for the treatment of lung cancer that aims to achieve more effective T(umour) and lymph N(ode) down-staging. The aim of this experiment was to compare drug uptake of gemcitabine and carboplatin during SPAP and intravenous infusion (IV). Material and methods: SPAP was performed in 12 pigs using clinically applied doses of gemcitabine (1.25 g/m(2), n = 4) and carboplatin (AUC 5, n = 4) and a combination of both (n = 4). All animals underwent catheterisation of the left pulmonary artery and furthermore a left thoracotomy and lumbotomy for tissue sampling. After 2 min of SPAP, 30 min of blood flow occlusion was performed in order to delay drug washout from the lung. Two additional groups were infused intravenously (IV) using the same dose of gemcitabine (n = 4) and carboplatin (n = 4). Peak concentrations and area under the curve (AUC) were compared with t-tests. Results: Significantly higher pulmonary gemcitabine peak concentrations (p Conclusion: SPAP with gemcitabine and carboplatin resulted in significantly improved drug exposure of the lung compared to IV. Equivalent serum concentrations and a trend towards higher mediastinal lymph node concentrations were achieved for carboplatin. Summery: Selective pulmonary artery perfusion (SPAP) is an experimental drug infusion method for the treatment of lung cancer that aims to achieve more effective T(umour) and lymph N(ode) down-staging. The aim of this experiment was to compare drug uptake of gemcitabine and carboplatin during SPAP and intravenous infusion (IV). In conclusion, SPAP with carboplatin and gemcitabine or the combination of both showed a superior uptake profile into the lung while systemic exposure was equivalent compared to IV. Mediastinal lymph node concentrations are comparable with IV or tended to be higher after SPAP with carboplatin. (C) 2008 Elsevier Ireland Ltd. All rights reserved

"AF HeartTeam" guided indication for stand-alone thoracoscopic left atrial ablation and left atrial appendage closure

Background:Traditional surgical treatment for patients with atrial fibrillation (AF) is performed via sternotomy and on cardiopulmonary bypass. It is very effective in regard to rhythm control, but remains unpopular due to its invasiveness. Truly endoscopic AF treatments have decreased the threshold for electrophysiologists (and cardiologists) to refer, and the reluctance of patients to accept a standalone surgical approach. Practice guidelines from around the world have recognized this as an acceptable therapeutic approach. Current guidelines recommend the HeartTeam approach in treating these complex AF cases. In this study we report our experience with AF HeartTeam approach for surgical stand-alone AF ablation. Methods: The AF HeartTeam Program began in 2013, patients qualified for inclusion if either of the following was present: failed catheter ablation and/or medication, not suitable for catheter ablation, contraindication to anticoagulation, or patients preferring such an approach. All patients with a complex AF history were assessed by the AF HeartTeam, from which 42 patients were deemed suitable for a totally endoscopic AF procedure (epicardial ablation and LAA closure). Endpoints were intraoperative bidirectional block of the pulmonary veins and closure of left atrial appendage confirmed by transesophageal echocardiography (TEE). Post discharge rhythm follow-up was performed after 3 and 12, 24 and 36 months. Anticoagulation was discontinued 6 weeks after the procedure in patients after documented LAA closure. Results: In total 42 patients underwent the endoscopic procedure (Median CHA2DS2-VASC=3 (1-6), HAS-BLED=2 (1-6)) for paroxysmal (15/42) and non-paroxysmal AF (27/42) respectively. Bidirectional block was obtained in all patients and complete LAA closure was obtained in all but one Patient on TEE (41/42). In one patient the LAA was not addressed due to extensive adhesions. Two patients underwent median sternotomy because of bleeding during the endoscopic surgery early in the series. There were no deaths. Procedure duration was a median of 124min (Range 83-211) and duration of hospitalization was median of 5 days (Range 3-12). During 36 months follow-up survival free of mortality, thromboembolic events or strokes was 100%. Twelve month freedom from atrial arrhythmia off anti-arrhythmic medication was 93% and 89% for paroxysmal and non-paroxysmal patients respectively. 6/42 patients who had an AF recurrence during the follow-up underwent touch-up catheter ablation. Conclusions: Atrial fibrillation heart team approach provides excellent outcomes for patients with AF. This approach is beneficial for patients after failed catheter ablation or not candidates for such and offers a very effective mid-term outcome data. In addition to effective rhythm control the protective effect of epicardial LAA closure may play an important role in effectively reducing stroke. The creation of an AF HeartTeam as recommended by the guidelines insures unbiased therapies and provides access to this minimally invasive but effective therapeutic option for AF patients