BackgroundPatients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient.AimThe aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future.MethodsThis study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992–2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT] ± positron emission tomography [PET], or PET − low-dose CT).ResultsMedian age was 57 years, 54 % of patients were female, and median follow-up was 21 months (interquartile range [IQR] 11–46 months). Median Breslow thickness was 2.10 mm (IQR 1.40–3.40 mm), and 26 % of all primary melanomas were ulcerated. Positive deep pelvic nodes occurred in 35 % of CGDs. Significantly fewer inguinal nodes were positive in case of negative deep pelvic nodes (median 1 [IQR 1–2] vs. 3 [IQR 1–4] for positive deep pelvic nodes; p < 0.001), and LNR was significantly lower for negative versus positive deep pelvic nodes [median 0.15 (IQR 0.10–0.25) vs. 0.33 (IQR 0.14–0.54); p < 0.001]. A combination of negative imaging, low LNR, low number of positive inguinal nodes, and no extracapsular extension (ECE) could accurately predict the absence of pelvic nodal involvement in 84 % of patients.ConclusionsPatients with negative imaging, few positive inguinal nodes, no ECE, and low LNR have a low risk of positive deep pelvic nodes and may safely undergo SGD alone.

BackgroundNicorandil, as a selective potassium channel opener, has dual action including coronary and peripheral vasodilatation and cardioprotective effect through ischemic preconditioning. Considering those characteristics, nicorandil was suggested to reduce the degree of microvascular dysfunction.MethodsThirty-two patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI) were included in the study. Index of microvascular resistance (IMR) was measured in all patients immediatelly after pPCI before the after administration of Nicorandil. ST segment resolution was monitored before intervention and 60 min after terminating the procedure. Echocardiographic evaluation of myocardial function and transthoracic Doppler derived Coronary flow reserve (CFR) of infarct related artery (IRA) was performed during hospitalization and 3 months later.ResultsIMR was significantly lower after administration of Nicorandil (9.9 ± 3.7 vs. 14.1 ± 5.1, p < 0.001). There was significant difference in ST segment elevation before and after primary PCI with administration of Nicorandil (6.9 ± 3.7 mm vs. 1.6 ± 1.6 mm, p < 0.001). Transthoracic Doppler CFR measurement improved after 3 months (2.69 ± 0.38 vs. 2.92 ± 0.54, p = 0.021), as well as WMSI (1.14 ± 0.17 vs. 1.07 ± 0.09, p = 0.004).ConclusionIntracoronary Nicorandil administration after primary PCI significantly decreases IMR, resulting in improved CFR and ventricular function in patients with STEMI undergoing primary PCI.

We present a new method for enhanced sampling for constant-pH simulations in explicit water based on a two-dimensional (2D) replica exchange scheme. The new method is a significant extension of our previously developed constant-pH simulation method, which is based on enveloping distribution sampling (EDS) coupled with a one-dimensional (1D) Hamiltonian exchange method (HREM). EDS constructs a hybrid Hamiltonian from multiple discrete end state Hamiltonians that, in this case, represent different protonation states of the system. The ruggedness and heights of the hybrid Hamiltonian's energy barriers can be tuned by the smoothness parameter. Within the context of the 1D EDS-HREM method, exchanges are performed between replicas with different smoothness parameters, allowing frequent protonation-state transitions and sampling of conformations that are favored by the end-state Hamiltonians. In this work, the 1D method is extended to 2D with an additional dimension, external pH. Within the context of the 2D method (2D EDS-HREM), exchanges are performed on a lattice of Hamiltonians with different pH conditions and smoothness parameters. We demonstrate that both the 1D and 2D methods exactly reproduce the thermodynamic properties of the semigrand canonical (SGC) ensemble of a system at a given pH. We have tested our new 2D method on aspartic acid, glutamic acid, lysine, a four residue peptide (sequence KAAE), and snake cardiotoxin. In all cases, the 2D method converges faster and without loss of precision; the only limitation is a loss of flexibility in how CPU time is employed. The results for snake cardiotoxin demonstrate that the 2D method enhances protonation-state transitions, samples a wider conformational space with the same amount of computational resources, and converges significantly faster overall than the original 1D method.