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Background: Atrial fibrillation (AF) is common in cardiac resynchronization therapy (CRT) recipients. It is a marker of impaired CRT response mainly mediated by the reduction of effectively captured biventricular paced beats (BiVp). There are no randomized trials comparing strategies to maintain high BiVp percentage., Objective: To compare the efficacy of rhythm vs rate control strategies in CRT recipients with long-standing persistent AF., Methods: We performed a randomized trial including CRT recipients with persistent AF resulting in low BiVp%. All patients received amiodarone, the rhythm control group received external electrical cardioversion (EC), and the rate control group received atrioventricular node ablation, if needed. The primary end-point was 12-month BiVp% (NCT)., Results: 43 patients were included in the analysis. The mean age was 68.4 (SD: ± 8.3) years and the mean BiVp% 82.4% ± 9.7%. AF lasted 25 ± 19 months. The mean baseline left ventricular ejection fraction (LVEF), left atrium area, and the maximal oxygen uptake (VO2max) were: 30 ± 8%, 33 ± 7 cm 2 , and 14 ± 5 mL/(kg*min), respectively. The EC success rate was 58%. 38% patients remained in sinus rhythm (SR) after 12 months. BiVp% increased similarly in both arms reaching 99% [95% CI 97.3-99.8] and 98% [94.0-99.0], P = 0.14 in rhythm and rate control groups, respectively. LVEF raised significantly only in the rhythm control group (ΔLVEF 4.1 (± 7.3), P = 0,018) which was driven by the patients who maintained SR. No differences in VO2max, QoL, clinical and safety end-points were observed., Conclusion: Despite comparable BiVp% in both groups, only restoration of SR led to improved left ventricular ejection fraction in CRT patients with long-standing AF., Trial Registration: NCT01850277 registered on 22/04/2013., (© 2024. The Author(s).)

Navigation lies at the core of social robotics, enabling robots to navigate and interact seamlessly in human environments. The primary focus of human-aware robot navigation is minimizing discomfort among surrounding humans. Our review explores user studies, examining factors that cause human discomfort, to perform the grounding of social robot navigation requirements and to form a taxonomy of elementary necessities that should be implemented by comprehensive algorithms. This survey also discusses human-aware navigation from an algorithmic perspective, reviewing the perception and motion planning methods integral to social navigation. Additionally, the review investigates different types of studies and tools facilitating the evaluation of social robot navigation approaches, namely datasets, simulators, and benchmarks. Our survey also identifies the main challenges of human-aware navigation, highlighting the essential future work perspectives. This work stands out from other review papers, as it not only investigates the variety of methods for implementing human awareness in robot control systems but also classifies the approaches according to the grounded requirements regarded in their objectives.

Introduction: Antazoline is a frequently used antiarrhythmic drug (AAD); however, to date, no randomized controlled trial has evaluated its efficacy and safety for cardioversion of recent‑onset atrial fibrillation (AF) in comparison with other approved AADs., Objectives: This study aimed to compare clinical efficacy and safety of antazoline and propafenone for a rapid conversion of nonvalvular paroxysmal AF to sinus rhythm in patients without heart failure., Patients and Methods: This was a single‑center, randomized, double‑blind study. It included patients with AF (lasting <48 hours) who were in a stable cardiopulmonary condition and eligible for cardioversion. The individuals who fulfilled the inclusion criteria were randomly assigned to receive either antazoline (up to 300 mg) or propafenone (up to 140 mg) intravenously. The primary end point was conversion of AF to sinus rhythm confirmed on electrocardiography., Results: Overall, 94 participants (46 [48.9%] in the antazoline group and 48 [51.1%] in the propafenone group) were included. The mean (SD) age was 67.5 (14) years, and 40 participants (42.5%) were men. Successful AF conversion was observed in 29 patients (63%) from the antazoline group and 25 individuals (52.1%) from the propafenone group (P = 0.39). The median time to conversion was 10 minutes in the antazoline group and 30 minutes in the propafenone group (P = 0.03). Severe adverse events were observed in 5 patients (10.8%) treated with antazoline and 5 individuals (10.4%) who received propafenone., Conclusions: Intravenous antazoline demonstrated efficacy and safety comparable to those of intravenous propafenone for acute conversion of nonvalvular paroxysmal AF to sinus rhythm in patients without heart failure.

Background: Knowledge of thrombosis (T) risk predictors and transesophageal echocardiography (TEE) are important tools in appropriate qualification of patients for safe electrical cardioversion., Aims: We aimed to investigate predictors of T and spontaneous echocardiographic contrast (SEC) with sludge in the left atrium (LA) and appendage (LAA) in atrial fibrillation (AF) patients on oral anticoagulation., Methods: The study included 300 patients with AF lasting >48 hours. Two hundred and nineteen patients were treated with oral anticoagulants (OACs) (study group, rivaroxaban: 104 [47.5%], apixaban: 52 [23.7%], dabigatran: 23 [11.5%], VKAs: 40 [18.3%]). Eighty-one consecutive patients with AF lasting >48 hours and not treated with OACs constituted the control group. Before electrical cardioversion, all patients underwent transthoracic echocardiography and TEE., Results: TEE revealed T in the LAA in 4.7% of cases. The number of patients with T or SEC4+ with sludge in the OAC and control groups was similar, 5.9% vs. 1.2% and 16.4% vs. 16.0%, respectively. The risk of SEC4+/T in patients treated with OACs was lowest in those taking rivaroxaban (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.21-0.87; P = 0.027) and highest in those receiving VKAs (OR, 2.49; 95% CI, 1.15-5.39; P = 0.018). Multivariable analysis showed independent prognostic factors for SEC 4+/T: female sex (OR, 3.800; 95% CI, 1.592-9.072; P = 0.003), left ventricular ejection fraction (OR, 0.932; 95% CI, 0.890-0.957; P <0.001), and minimum LAA flow velocity (LAAfly min) (OR, 0.895; 95% CI, 0.841-0.954; P <0.001)., Conclusions: Female sex, transthoracic echocardiography, and TEE results should be taken into account in assessing the risk of T/SEC with sludge in LA/LAA patients with AF.

Aims: This study aimed to assess the safety of electric cardioversion in the absence of anesthetists assistance. We also evaluated the efficacy and safety of this procedure in older adults (≥80 years) compared to younger populations. Methods: We retrospectively analyzed the data of patients who underwent electric cardioversion at our cardiology department. Patients were divided into 2 groups according to age: ≥ 80 years and <80 years old. Results: The study included 218 participants, 73 were aged 80 years or more (mean age: 84.8 years), and 145 were younger than 80 years (mean age: 66.7 years). Electric cardioversion was effective in 97.3% of older patients and 96.5% of younger patients ( P  = 1.00). No thromboembolic complications were observed in either of the groups. Asystole >5 s occurred immediately after shock in 4.1% of older and 2.1% of younger patients ( P  = .405). Propofol was used as a sedative, with a mean dose of 0.83 mg/kg versus 0.93 mg/kg, in older and younger patients, respectively. Intubation, medical intervention, or other advanced resuscitation techniques were not required. During hospitalization, arrhythmia recurred in 9.6% and 12.4% of the older and younger patients, respectively ( P  = .537). Conclusions: Electrical cardioversion is an effective and safe procedure regardless of patient age. Sedation with propofol administered by cardiologists was safe. Adverse events were not considered serious or reversible., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Electric cardioversion of atrial fibrillation (AF) is associated with an increased risk of embolism, with embolic material existing in the heart cavities. The initiation of oral anticoagulation therapy reduces the risk of thromboembolic events. The aims of this study were to evaluate the prevalence of left atrial appendage (LAA) thrombi in non-valvular AF, to compare vitamin K antagonists (VKAs) and non-vitamin K oral anticoagulants (NOACs) with respect to thrombus prevalence, and to evaluate the rate of LAA thrombus persistence on repeat transesophageal echocardiography (TEE) after treatment change., Methods: We enrolled 160 consecutive AF patients who presented with an AF duration > 48 h and had undergone TEE before cardioversion., Results: Left atrial appendage thrombus was observed in 12 (7.5%) patients, and spontaneous echo contrast 4 was observed in 19 (11.8%) patients; the incidence was similar between the NOAC and VKA groups (8.9% vs. 3.6% and 12.4% vs. 18.5 %, respectively). Among patients on NOAC, thrombus prevalence was detected in 8.4% of users of rivaroxaban, 8% of users of dabigatran, and 12.5% of users of apixaban., Conclusions: The LAA thrombus developed in 7.5% of patients despite anticoagulation therapy, demonstrating similar prevalence rates among patients either on NOAC or VKA. Lower mean LAA flow velocity and a history of vascular disease were independent predictors of embolic material in the LAA. It seems that in the case of embolic materials in LAA under NOAC treatment, switching to VKA provides additional clinical benefit to the patients.

The adiabatic connection formalism, usually based on the first-order perturbation theory, has been generalized to an arbitrary order. The generalization stems from the observation that the formalism can be derived from a properly arranged Taylor expansion. The second-order theory is developed in detail and applied to the description of two electrons in a parabolic confinement (harmonium). A significant improvement relative to the first-order theory has been obtained., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Atrial fibrillation (AF) remains the most common arrhythmia. The sinus rhythm restoration procedure without adequate anticoagulant preparation may lead to a thromboembolic event in approximately 5-7% of patients. The initiation of oral anticoagulation significantly reduces this risk by inhibiting formation of embolic material in the heart cavities, especially in the left atrial appendage (LAA). However, there is a group of patients who develop embolic material in the LAA despite oral anticoagulation treatment. The best treatment method to dissolve thrombus in the LAA is not clear, due to the lack of studies with adequate power and endpoints that can determine the best management strategy. We present clinical trials comparing the efficacy and safety of oral anticoagulants in patients undergoing AF cardioversion. We evaluate the frequency of LAA thrombus formation in patients with AF on treatment with oral anticoagulants. Furthermore, we discuss the effectiveness of various treatment strategies on LAA thrombus resolution.

Introduction: Targeted false lumen management has been described for complex presentations of aortic dissection. The "Knickerbocker" technique is often referenced and includes dilating a focal portion of an oversized endograft in the true lumen to purposefully rupture the false lumen septum, but at the expense of increased risk for visceral propagation and malperfusion. This case series describes a novel modification of the Knickerbocker technique by caging the distal end of the endograft prior to focal dilation., Methods: A retrospective chart review was conducted at a tertiary academic center from 2018-2020. Patients were included if they had a history or current presentation of aortic dissection and underwent a Caged Knickerbocker (CKB) repair. Data were collected to include demographics, indications for repair, technical success, perioperative outcomes, hospital course, mortality, and further aortic interventions., Results: Five patients were included in our evaluation. Four patients (80%) presented with chronic Type B aortic dissection (cTBAD) and concomitant aneurysmal degeneration of the thoracic aorta; 1 patient (20%) presented with an acute rupture secondary to cTBAD. Three patients (60%) had previous aortic repairs, 2 of which were for Type A Aortic Dissection that additionally required redo sternotomy and total arch replacement prior to CKB. CKB was technically successful in all cases with no peri-operative complications. Two (40%) patients required further aortic intervention due to aneurysmal degeneration., Conclusion: Achieving complete false lumen thrombosis is a considerable challenge when managing complex aortic dissections. Our data demonstrate the technical feasibly and early successful outcomes with the CKB approach. Importantly, CKB facilitates future distal extension into the para-visceral aorta in cases of complex thoracoabdominal aortic aneurysms. Further research should focus on discerning individual patients who will benefit from targeted false lumen management and compare outcomes between different approaches.

Sources of energy errors resulting from the replacement of the physical Coulomb interaction by its long-range erfc(μ r )/ r approximation are explored. It is demonstrated that the results can be dramatically improved and the range of μ giving energies within chemical accuracy limits significantly extended if the generalized cusp conditions are used to represent the wave function at small r . The numerical results for two-electron harmonium are presented and discussed.

Atrial fibrillation (AF) remains the most common arrhythmia. The sinus rhythm restoration procedure without adequate anticoagulant preparation may lead to a thromboembolic event in approximately 5-7% of patients. The initiation of oral anticoagulation significantly reduces this risk by inhibiting formation of embolic material in the heart cavities, especially in the left atrial appendage (LAA). However, there is a group of patients who develop embolic material in the LAA despite oral anticoagulation treatment. The best treatment method to dissolve thrombus in the LAA is not clear, due to the lack of studies with adequate power and endpoints that can determine the best management strategy. We present clinical trials comparing the efficacy and safety of oral anticoagulants in patients undergoing AF cardioversion. We evaluate the frequency of LAA thrombus formation in patients with AF on treatment with oral anticoagulants. Furthermore, we discuss the effectiveness of various treatment strategies on LAA thrombus resolution.

Objectives: To report our experience and compare the results of percutaneous endovascular aortic aneurysm repair (PEVAR) performed under monitored anesthesia care (MAC) to PEVAR under general anesthesia (GA)., Methods: A retrospective review of patients who underwent non-emergency endovascular abdominal aortic aneurysm repair (EVAR) was completed. Patients were excluded if they had a complex repair, including fenestrated, branched, or parallel endografting. Demographics, operative data, 30-day mortality/morbidity and postoperative outcomes were analyzed., Results: A total of 159 patients were identified with a median age of 69. 115 patients had PEVAR, 45 (39.1%) PEVAR MAC and 70 (60.9%) PEVAR GA. PEVAR MAC compared to PEVAR GA had decreased operative time (106 vs. 134 min, P  < 0.001), time in the operating room (163 vs. 245 min, P  = 0.016), and estimated blood loss (EBL) (115 vs. 176 mL P  = 0.012). There was no statistically significant difference in the hospital length of stay (LOS) (1.9 vs. 2.7 days, P  = 0.133), and post-operative complications including pulmonary (2.2 vs. 2.9%, P  = 0.835). Forty-four patients had EVAR with a femoral cutdown (FC), including 14 PEVAR conversions. PEVAR conversion was associated with higher EBL (543 vs. 323 mL, P  = 0.03), operative time (230 vs. 178 min, P  = 0.01), and operating room time (307 vs. 275 min, P  = 0.01) compared to planned EVAR with FC., Conclusions: PEVAR under MAC is associated with shorter time in the operating room compared to PEVAR under GA. PEVAR under MAC does however not decrease overall morbidities, including postoperative pulmonary complications.

Objective: We sought to detail the process of establishing a surgical aortic telehealth program and report the outcomes of a 5-year experience., Methods: A telehealth program was established between two regional Veterans Affairs hospitals, one of which was without a comprehensive aortic surgical program, until such a program was established at the referring institution. A retrospective review was performed of all patients who underwent aortic surgery from 2014 to 2019. The operative data, demographics, perioperative complications, and follow-up data were reviewed., Results: From 2014 to 2019, 109 patients underwent aortic surgery for occlusive and aneurysmal disease. Preoperative evaluation and postoperative follow-up were done remotely via telehealth. The median age of the patients was 68 years, 107 were men (98.2%), 28 (25.7%) underwent open aortic repair, and 81 (74.3%) underwent endovascular repair. Of the 109 patients, 101 (92.7%) had a median follow-up of 24.3 months, 5 (4.6%) were lost to follow-up or were noncompliant, 2 (1.8%) were noncompliant with their follow-up imaging studies but responded to telephone interviews, and 1 (0.9%) moved to another state. At the 30-day follow-up, eight patients (7.3%) required readmission. Four complications were managed locally, and four patients (3.6%) required transfer back to the operative hospital for additional care., Conclusions: Telehealth is a great tool to provide perioperative care and long-term follow-up for patients with aortic pathologies in remote locations. Most postoperative care and complications can be managed remotely, and patient compliance for long-term follow-up is high., (Published by Elsevier Inc.)

Background Groin reconstruction with muscle flap coverage is associated with high wound complication rates. Incisional vacuum-assisted closure (iVAC) therapy may lower wound complications. We evaluated the impact of iVAC on postoperative outcomes in patients following groin reconstruction with muscle flap coverage. Methods We conducted a retrospective review of patients who underwent groin reconstruction with muscle flap coverage in 2012-2018. Patients were divided into those who received iVAC therapy and those who received standard sterile dressings (SSD). Results Of the 57 patients included, most received iVAC therapy (71%, n  = 41) and the rest received SSD (28%, n  = 16). The iVAC group had higher rates of diabetes, hypertension, coronary artery disease, and peripheral artery disease ( p  < 0.05). However, iVAC patients had comparable length of hospital stay (12 vs 8.5 days p =  0.0735), reoperations (34% vs 31%, p  = 0.8415), and readmissions (32% vs 37%, p  = 0.6801) with SSD patients. iVAC placement was less likely in prophylactic flaps (odds ratio 0.08, p  = 0.0049). Conclusion Patients with a prophylactic flap were less likely to receive vacuum therapy, which may highlight a selection bias where surgeons pre-emptively use iVAC therapy in surgical candidates identified as high risk. The pre-emptive use of iVAC may minimize adverse postoperative outcomes in high-risk patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Taylor et al.)

Acute coronary syndromes (ACS) in young people are rare. The data regarding differences in symptoms in relation to age are scarce, which may have an influence on outcomes. The aim of this study was to evaluate the differences in the clinical course of ACS between younger women (≤45 years old) and older women (63-64 years old). We compared 7481 women with ACS from the Polish Registry of ACS between 2007 and 2014 (1834 women aged ≤45 years and 5647 women aged 63-64 years). The predominant symptom of ACS in both groups was chest pain, with a higher incidence occurring in younger women (90.4% vs 88.5%, P = 0.025). Prehospital cardiac arrest occurred more often in younger women (2.1% vs 0.8%, P < 0.001), and onset-to-balloon time was shorter (8.9 vs 15.2 hours, P < 0.0001) in this group. Younger women presented with a lower Killip class at admission (class I at admission: 92.7% vs 86.2%, P < 0.001). The dominant type of ACS in the younger cohort was ST-segment elevation myocardial infarction (STEMI) (42% vs 26.1%), localized mainly in the anterior wall (47.7% vs 36.1%, P < 0.001), with a higher percentage of total occlusion of infarct-related artery (TIMI 0, 45.2% vs 36.1%) and left anterior descending artery engagement for all (33.5% vs 26.5%, P < 0.001). Drug-eluting stents were often used in the younger patients (43.3% vs 38.2%, P = 0.003) without significant differences in percutaneous coronary intervention numbers. Pharmacotherapy was used less in younger women. The 30-day and 2-year mortality in young women was lower than in the older cohort. The clinical course of ACS in younger women differed in comparison to older women. Younger women had a higher occurrence of typical chest pain, STEMI, and left anterior descending artery engagement. Except STEMI patients young women received faster revascularization, however with no significant differences in invasive treatment. Pharmacotherapy was inadequate in younger women and that resulted in a lower usage of the beta-blockers, angiotensin-converting enzyme inhibitors, and statins in that group. Short- and long-term mortality was low, regardless of the type of ACS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Given that up to 2% of patients with myocardial infarction (MI) are young women, the purpose of this study was to evaluate factors affecting outcomes in young women with ST-segment-elevation myocardial infarction (STEMI) aged less than or equal to 45 years. We evaluated 796 women with STEMI aged less than or equal to 45 years between 2007 and 2014, and mortality was 4.0%. Death occurred more often in women with prehospital sudden cardiac arrest, and severe symptoms of heart failure; less commonly, the women were subjected to percutaneous coronary intervention (PCI), with a higher rate of incomplete revascularization. Beta blockers (BB) and angiotensin converting enzyme inhibitors were frequently used in the survivor group. The independent predictor of 30-day mortality was as follows: inability to undergo PCI (odds ratio [OR] 4.6, 95% confidence interval [CI] 1.45-14.76, P = 0.009), sudden cardiac arrest (OR 4.5, 95% CI 1.5-18.3, P = 0.04). An increase in systolic blood pressure for every 5 mm Hg was associated with lower mortality, OR 0.90, 95% CI 0.76-0.97 in patients without cardiogenic shock (CS) and OR 0.69, 95% CI 0.61-0.78, P < 0.0001 in the group with CS. Predictors for 1-year mortality were the inability to undergo PCI (hazard ratio [HR] 84, 95% CI 1.6-43.1, P = 0.01) and CS (HR 6.97, 95% CI 1.39-34.7, P = 0.01). An increase of 5% in left ventricular ejection fraction reduced the mortality rate for 60% (HR 0.40, 95% CI 0.26-0.63, P < 0.0001) and an increase in systolic blood pressure for every 5 mm Hg reduced mortality for 34% (HR 0.66, 95% CI 0.52-0.84, P = 0.02). Both short- and long-term outcomes in young women aged less than or equal to 45 years with STEMI are good. The strongest predictor for both 30-day and 1-year mortality was the inability to undergo PCI. Suboptimal use of beta blockers and angiotensin converting enzyme inhibitors affect the outcomes in young women. Hypotension in the acute phase of MI increased mortality in young women, independent of coexisting CS., (Copyright © 2019. Published by Elsevier Inc.)

Background: Acute coronary syndromes (ACS) are rare in young women. The purpose of this study was to characterize risk factors (RF) predisposing to ACS in young women and evaluate possible age-related differences., Methods and Results: We studied 1941 young women with ACS aged ≤45 years (≤45ACS) from the PL-ACS registry and compared them with two control groups: 4275 women aged 63-64 years with ACS (63-64ACS) from the PL-ACS registry and 1170 young healthy women aged ≤45 years (≤45H) without confirmed coronary artery disease (CAD), from two national, representative, cross-sectional population health surveys, NATPOL 2011 and WOBASZ. The prevalence of major RF in these three groups was as follows, respectively: (≤45 ACS vs. 63-64ACS vs. ≤45H, for all P < 0.0001): hypertension 49.8% vs. 78.1% vs. 16.8%; hypercholesterolemia 36.1% vs. 44.3% vs. 12.9%; obesity 22.3% vs. 28.1% vs. 15.6%; diabetes 10.6% vs. 29.9% vs. 1.8% and smoking 48.7% vs. 22.2% vs. 39%. Healthy women had the lowest number of major RF (1.7 ± 1.2 vs. 2.0 ± 1.1 vs. 1.1 ± 1.0). No RF was found in 16.7% vs. 8.2% vs. 34.4% women, respectively. Independent predictors of ACS in the ≤45ACS group included diabetes [odds ratio (OR) 6.66, 95% confidence interval (CI) 3.47-12.74]*, hypertension (OR 4.30, 95% CI 3.42-5.38)*, hypercholesterolemia (OR 3.45; 95% CI 2.60-4.29)*, and smoking (OR 1.63, 95% CI 1.34-1.98)*, *(P < 0.0001 for all)., Conclusions: The prevalence of risk factors for acute coronary syndromes in young women with ACS is different to those in healthy women and to those in older women. The prevalence of smoking was higher. The strongest predictor of ACS in women ≤45 years of age was diabetes, with a 6-fold increase in risk. There is still need to improve the cardio-vascular primary prevention and health promotion in the population of young women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: This study examines the outcome of hybrid revascularization combining iliofemoral endarterectomy and iliac artery stenting using covered stents in TransAtlantic Inter-Society Consensus (TASC) C and D aortoiliac occlusive disease (AIOD) involving the common femoral artery (CFA)., Methods: A retrospective review was conducted in patients with TASC C and D AIOD involving the CFA and undergoing hybrid revascularization. Covered stents were used primarily. Demographics, indications for surgery, lesion classification, hospital length of stay (LOS), 30-day morbidity/mortality, hemodynamic and clinical success, and patency were assessed., Results: Thirty-six male patients (41 limbs), mean age 63.9 ± 6 years, were identified (TASC C = 39%, D = 61%). Indications for surgery were claudication (27%), rest pain (44%), and tissue loss (29%). A simultaneous adjunctive procedure (5 infrainguinal bypass, 3 superficial femoral artery stents) was performed in 22%. Thirty-day outcomes included 1 mortality (2.7%) and 2 reoperation (5.5%), 1 for femoral artery pseudoaneurysm and 1 for bilateral groin seroma. LOS was 4 days (interquartile range 3-6). All patients with available data experienced 30-day clinical and hemodynamic success. Mean follow-up was 23 months (range 1-79 months) with a primary patency of 85.4%. Cumulative primary assisted and secondary patency was 92.6%. The femoral patch repair was the most frequent site of reintervention (3/3). Mortality was 34% during the study period, and it was significantly higher in patients with tissue loss (57.1% vs. 14.8%, P = 0.01)., Conclusions: The hybrid approach has low morbidity, mortality, and fast recovery. The use of covered stents/stent grafts provides good mid-term patency. Close follow-up with noninvasive imaging is paramount to avoid repair failure, in particular at the femoral patch repair site., (Published by Elsevier Inc.)

Treatment of chronic peripheral ischemic wounds in patients with spinal cord injury (SCI) can be technically challenging, especially if they have significant hip contracture. This article describes the endovascular aortoiliac revascularization of a paraplegic patient with hip contracture and a hostile abdomen. It also reviews the particularity of the peripheral arterial system in SCI patients., (Published by Elsevier Inc.)

Introduction: The prevalence of total coronary occlusion of an infarct‑related artery (IRA) and its impact on the outcome can differ between patients with non‑ST‑elevation myocardial infarction (NSTEMI) and those with ST‑segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI)., Objectives: We evaluated the impact of IRA occlusion on the outcome of myocardial infarction according to the presence or absence of ST‑segment elevation and the location of the culprit lesion., Patients and Methods: We analyzed 4581 patients with STEMI and 2717 patients with NSTEMI who underwent PCI and were enrolled in the Polish Registry of Acute Coronary Syndromes. Patients were divided into 3 cohorts depending on the IRA: left anterior descending artery (LAD), left circumflex artery (LCx), or right coronary artery (RCA). Patients were further divided according to preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow to either a subgroup with total occlusion (TO; TIMI flow grade, 0) or a subgroup with incomplete occlusion (nTO; TIMI flow grade ≥1)., Results: TO was observed in 2949 patients (64.4%) with STEMI and 723 patients (26.6%) with NSTEMI. The most common IRAs were the RCA (49.4%) and LCx (48.4%) in the STEMI and NSTEMI groups, respectively. STEMI patients with TO of the LAD showed higher mortality during the 36‑month follow‑up; mortality in the NSTEMI group was comparable between patients with TO and nTO. STEMI and NSTEMI groups with TO of the LCx showed higher in‑hospital mortality. No differences were observed between patients with TO and nTO of the RCA., Conclusions: Totally occluded IRA (TIMI flow grade 0) on baseline angiogram was not associated with higher 36‑month mortality rates after both NSTEMI and STEMI treated with PCI in comparison with patients with patent IRA except for totally occluded LAD in STEMI.

Background: The prevalence and impact of total coronary occlusion of an infarct-related artery (IRA) on outcomes in patients with non-ST-elevation myocardial infarction (NSTEMI) remain unclear., Aim: We evaluated the clinical significance of total coronary occlusion in NSTEMI patients., Methods: A total of 2767 patients with NSTEMI enrolled in the Polish Registry of Acute Coronary Syndromes, who underwent percutaneous coronary interventions, were analysed. The patients were divided into two groups according to preprocedural culprit vessel thrombolysis in myocardial infarction (TIMI) flows (TIMI flow 0 - total coronary occlusion [TO]: 728, 26.3% of the patients, and TIMI flow 1-3 - non-total occlusion [non-TO]: 2039, 73.7% of the patients)., Results: Patients with total occlusion were younger, were more often current smokers, and had lower incidence of hypertension and diabetes mellitus. The left circumflex artery (LCx) was the major IRA in the TO group (48.1%), whereas the left anterior descending artery (LAD) was more commonly the IRA in the non-TO group (38.8%). Multivariate analysis revealed that LCx as the culprit lesion (OR ± 95 CI 1.54 [1.26-1.89], p < 0.0001) was an independent predictor of TIMI flow 0 in IRA. In-hospital and one-month mortality occurred more frequently in the TO group (4.0% vs. 1.7%, p = 0.0005 and 5.5% vs. 3.5%, p = 0.0175, respectively), no differences in the 12-, 24-, or 36-month mortalities were observed between these groups., Conclusions: Only LCx as a culprit lesion was an independent predictor of total occlusion in IRAs. The NSTEMI patients with TO had higher in-hospital and one-month mortalities, but their long-term outcomes were similar to those of non-TO patients.

Background: The impact of final Thrombolysis in Myocardial Infarction (TIMI) flow in the infarct-related artery (IRA) on outcomes in non-ST-segment elevation myocardial infarc-tion (NSTEMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study aimed to evaluate the impact of post-procedural TIMI flow in IRA on outcomes in NSTEMI patients undergoing percutaneous coronary revascularization., Methods: We analyzed 2,767 patients with first NSTEMI from the Polish Registry of Acute Coronary Syndromes (PL-ACS) who underwent PCI. The patients were divided according to post-procedural culprit vessel TIMI (0-1: 90, 3.26%; 2: 61, 2.20%; 3: 2,616, 94.54%)., Results: The following mortality values were obtained in TIMI 0-1, 2, and 3 groups, respec-tively: in-hospital, 12.22%, 13.11%, 1.72% (p < 0.0001); 1-month, 13.33%, 13.11%, 3.44% (p < 0.0001); 12-month, 15.56%, 16.39%, 6.50% (p < 0.0001); 36-month, 25.56%, 21.31%, 13.91% (p = 0.0007). Mortality rates in patients with final TIMI 0-1 and 2 were not signifi-cantly different. Optimal TIMI 3 was independently associated with baseline TIMI 2-3 (OR ± ± 95% CI: 7.070 [4.35-11.82]), p < 0.0001; higher ejection fraction (1.30 [1.03-1.63]), p = 0.0038; and family history of coronary artery disease (2.83 [1.17-8.11]), p = 0.0294. Type C lesion, previous heart failure, and PCI without stenting independently predicted suboptimal TIMI 0-2., Conclusions: Only achieving final TIMI 3 in IRA improves outcomes in NSTEMI patients treated with percutaneous coronary revascularization. The mortality rate of near-normal TIMI 2 is comparable to that of TIMI 0-1 after PCI. (.

A 66-year-old male with lower extremity ischemia underwent femoral-posterior tibial bypass with composite vein graft from the arm. Ten days later, he presented to the emergency department with pain, wound erythema, and drainage. Despite a prolonged course of intravenous antibiotics and serial operative debridements, the wound edges repeatedly necrosed after each procedure. The vein graft remained viable. Punch biopsies of wound edges were consistent with pyoderma gangrenosum (PG). The patient's condition improved on immunosuppressive therapy. Although a rare clinical entity, postsurgical PG is a well-described phenomenon whose diagnosis is often delayed. Clinical suspicion is imperative to ensure timely treatment and minimize morbidity.

Objectives: Experience with open surgical bypass suggests similar overall outcomes in women compared with men, but significantly increased risk of wound complications. Percutaneous treatment of lower extremity occlusive disease is therefore an attractive alternative in women, although it is not clear whether there is a difference in outcomes between women and men treated with this technique. We sought to determine the results and predictors of failure in women treated by percutaneous intervention., Methods: Percutaneous infrainguinal revascularization was performed on 309 women between 2001 and 2006. Procedures, complications, demographics, comorbidities, and follow-up data were entered into a prospective database for review. Patency was assessed primarily by duplex ultrasonography. Outcomes were expressed by Kaplan-Meier curves and compared by log-rank analysis., Results: A total of 447 percutaneous interventions performed in 309 women were analyzed and compared with 553 interventions in men. Mean age in women was 73.2 years; comorbidities included hypertension (HTN) (86%), diabetes melitus (DM) (58%), chronic renal insufficiency (CRI) (15%), hemodialysis (7%), hypercholesterolemia (52%), coronary artery disease (CAD) (42%), and tobacco use (47%). Indications in women included claudication (38.0%), rest pain (18.8%), and tissue loss (43.2%). Overall primary & secondary patency and limb-salvage rates for women were 38% +/- 4%, 66% +/- 3%, and 80% +/- 4% at 24 months. In this patient sample, women were significantly more likely than men to present with limb-threatening ischemia (61.6% vs 47.3%, P < 0.001) and have lesions of TASC C and D severity (71.4% vs 61.7%, P < .005). However, there were no significant differences in primary and secondary patency rates or limb-salvage rates between genders. Furthermore, while women with limb-threat, diabetes, and advanced TASC severity lesions were at increased risk of failure overall, there were no differences between women and men with these characteristics., Conclusions: Percutaneous infrainguinal revascularization is a very effective modality in women with lower extremity occlusive disease. Although women in this sample were more likely to present with limb-threat than men, patency and limb-salvage rates were equivalent between genders, even in high-risk subsets such as diabetics or those with lesions of increased TASC severity.

Patients with neurologic symptoms who undergo carotid endarterectomy (CEA) have a higher incidence of stroke and death in the perioperative period than those with asymptomatic carotid disease. This study examines the outcomes of symptomatic and asymptomatic patients undergoing carotid stenting (CAS). From 2002 to 2006, 201 CAS procedures were performed in 193 patients (117 men, mean age 73 +/- 10 years), of whom 142 were for asymptomatic (AS) and 59 for symptomatic (S) disease. Preoperative neurologic symptoms included recent ipsilateral cerebrovascular accident (CVA, 29%), transient ischemic attack (50%), and amaurosis fugax (22%). There were 201 carotid stents placed (107 Acculink, 43 Wallstent, 23 Precise, 21 NexStent, 3 Exponent, 3 Xact, 1 Herculink) and 198 protection devices used (79 Accunet, 53 EPI Filterwire, 43 PercuSurge, 20 Angiogard, 3 EmboShield). Mean follow-up was 41 weeks. The groups were matched in terms of demographics and comorbidities (carotid artery disease, hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular disease, smoking, and chronic obstructive pulmonary disease; p = nonsignificant [NS]). There was no significant difference in anatomic risk factors (neck irradiation, S 3%, AS 6%; prior CEA, S 14%, AS 14%; bovine arch, S 22%, AS 16%; p = NS), and the types of embolic protection devices and stents used were similar between groups. The mean percentages of preintervention carotid stenosis were equal (S 88%, AS 88%), and the technical success rate was 99%. Incidence rates of CVA (S 3.4%, AS 1.4%), myocardial infarction (S 1.7%, AS 1.4%), and death (S 0, AS 0.7%) were equivalent between groups (p = NS). CAS with cerebral protection can be performed safely in both symptomatic and asymptomatic patients. The presence of preoperative neurologic symptoms does not significantly increase the risk of adverse events in the perioperative period in this study.

Ischemic preconditioning (IP) uses transient ischemia to render tissues tolerant to subsequent, prolonged ischemia. This study sought to evaluate factors that contributed to the development of cerebral ischemia during PercuSurge balloon (Medtronic, Santa Rosa, CA) occlusion in patients undergoing carotid angioplasty and stenting (CAS). The PercuSurge occlusion balloon was used in 43 of 165 patients treated with CAS for high-grade stenosis; 20% were symptomatic. Symptoms of cerebral hypoperfusion during temporary occlusion of the internal carotid artery occurred in 10 of 43 patients and included dysarthria, agitation, decreased level of consciousness, and focal hemispheric deficit. The development of neurologic symptoms after initial PercuSurge balloon inflation and occluded internal carotid artery flow was associated with a decrease in the mean Glasgow Coma Scale (GCS) from 15 to 10 (range 9-14); the GCS returned to normal after occlusion balloon deflation. The mean time to spontaneous recovery of full neurologic function was 8 minutes (range 4-15 minutes). The mean subsequent procedure duration was 11.9 minutes (range 6-21 minutes). No recurrence of neurologic symptoms occurred when the occlusion balloon was reinflated. All 10 patients underwent successful CAS without occlusion, dissection, cerebrovascular accident, or death. Ischemic preconditioning can be used to enable CAS with embolic protection in patients who cannot tolerate initial interruption of antegrade cerebral perfusion by PercuSurge occlusion.

Objectives: Catheter-based revascularization has emerged as an alternative to surgical bypass for lower extremity vascular disease and is a frequently used tool in the armamentarium of the vascular surgeon. In this study we report contemporary outcomes of 1000 percutaneous infra-inguinal interventions performed by a single vascular surgery division., Methods: We evaluated a prospectively maintained database of 1000 consecutive percutaneous infra-inguinal interventions between 2001 and 2006 performed for claudication (46.3%) or limb-threatening ischemia (52.7%; rest pain in 27.7% and tissue loss in 72.3%). Treatments included angioplasty with or without stenting, laser angioplasty, and atherectomy of the femoral, popliteal, and tibial vessels., Results: Mean age was 71.4 years and 57.3% were male; comorbidities included hypertension (84%), coronary artery disease (51%), diabetes (58%), tobacco use (52%), and chronic renal insufficiency (39%). Overall 30-day mortality was 0.5%. Two-year primary and secondary patencies and rate of amputation were 62.4%, 79.3%, and 0.5%, respectively, for patients with claudication. Two-year primary and secondary patencies and limb salvage rates were 37.4%, 55.4%, and 79.3% for patients with limb-threatening ischemia. By multivariable Cox PH modeling, limb-threat as procedural indication (P < 0.0001), diabetes (P = 0.003), hypercholesterolemia (P = 0.001), coronary artery disease (P = 0.047), and Transatlantic Inter-Society Consensus D lesion complexity (P = 0.050) were independent predictors of recurrent disease. For patients that developed recurrent disease, 7.5% required no further intervention, 60.3% underwent successful percutaneous reintervention, 11.7% underwent bypass and 20.5% underwent amputation. Patency rates were identical for the initial procedure and subsequent reinterventions (P = 0.97)., Conclusion: Percutaneous therapy for peripheral vascular disease is associated with minimal mortality and can achieve 2-year secondary patency rates of nearly 80% in patients with claudication. Although patency is diminished in patients with limb-threat, limb-salvage rates remain reasonable at close to 80% at 2 years. Percutaneous infra-inguinal revascularization carries a low risk of morbidity and mortality, and should be considered first-line therapy in patients with chronic lower extremity ischemia.

Objectives: Carotid artery angioplasty and stenting (CAS) is now routinely performed with embolic protection devices, yet little is known about the compositional characteristics of the captured embolic debris and whether the type or quantity of debris correlates with patient, lesion, or operator characteristics. This study examined the embolic debris generated during CAS using electron microscopy and energy dispersive spectroscopy (EDS) for symptomatic and asymptomatic patients., Methods: Between 2003 and 2005, CAS for carotid stenosis was performed in 175 patients. Cerebral protection devices were used in all but three cases. Sixty-four consecutive unselected microporous filters from procedures performed by a single vascular surgeon were obtained for analysis. Captured particulate debris within the protection devices was quantified (number and mean size of particles) by light microscopy for all filters. Twenty protection devices (9 symptomatic, 11 asymptomatic patients) were processed for electron microscopy and EDS to assess morphology, cellular composition, and calcium content of debris., Results: Captured particulate matter was present in 49 filters (77%) and included particles measuring 200 to 500 mum in 72%, 500 to 1000 mum in 53%, and >1000 mum in 33%. The mean number of captured particles was 6.9, and mean size was 248 +/- 150 mum. Univariate analysis revealed that sequential patient cohort and filter type were correlated with the number (but not size) of captured particles. The number of particles significantly decreased after the first cohort of 20 patients (11.5 particles) compared with the second (5.0 particles, P = .023) and third (5.2 particles, P = .029) cohorts. The type of captured debris ranged from sheets of damaged red blood cells without other components to clumps of recently activated platelets with early fibrin crosslinking to plaque debris coated with well-organized coalescing areas of platelet thrombus. Platelet activation was more common in symptomatic patients (78%) than asymptomatic patients (27%; P < .05). Despite the presence of calcified lesions in six patients whose filters were analyzed by EDS, <1% of energy emission on EDS of scanned particulate debris fell within the emission range of calcium, indicating the presence of minimal calcium in the embolic particles., Conclusions: Particulate embolic debris is released in most patients during CAS and can measure >1000 mum in one third of patients. The number of particles may decrease with increasing operator experience with CAS. Debris captured during CAS with embolic protection exhibits a range of cellular and acellular components on electron microscopy, with a higher prevalence of platelet activation evident in symptomatic patients.

Despite recent studies highlighting the advantages of endoluminal intervention in the management of chronic limb ischemia (CLI), outcomes following failed peripheral angioplasty remain less well described. We present a retrospective analysis of failed transluminal infrainguinal percutaneous arterial angioplasty with or without stenting (PTA/S) in patients with CLI. A database of patients undergoing infrainguinal PTA/S between 2002 and 2005 was maintained. Patients underwent duplex scanning follow-up at 2 weeks, 3 months, and every 6 months after the intervention. Angiograms were reviewed in all cases to assess lesion characteristics. Results were standardized to current Transatlantic Inter-Society Consensus (TASC) criteria. Kaplan-Meier survival analyses were performed to assess time-dependent outcomes. In total, our analysis involved 246 patients who underwent treatment for CLI using PTA/S. Eighteen percent of procedures (n = 46) were considered an intervention failure secondary to restenosis by duplex ultrasound, returning clinical symptoms, a nonhealing foot lesion, or the absence of a prior palpable pulse. Indications for the original procedure in patients whose PTA/S failed were tissue loss in 44%, claudication in 44%, and rest pain in 12%, while TASC lesion grades were A (0%), B (18%), C (18%), and D (64%). Of patients failing PTA/S, 4% failed in the first 30 days, 78% failed between 1 and 18 months, while 18% failed following 18 months, with a mean time to failure of 8.7 months. Also, 82% of PTA/S failures were candidates for a second endovascular procedure, 11% were suitable for only traditional open bypass, and 4% demonstrated progression of disease necessitating amputation. Of patients undergoing a second endovascular procedure, limb salvage rates were 86% at 12-month follow-up and there was a single periprocedural mortality and complication rate of 6.6%. Of patients requiring open surgical bypass after failed PTA/S, 20% (n = 1) required a major amputation and there were no mortalities. Failure of endoluminal therapy for treatment of lower extremity arterial occlusive disease is amenable to subsequent endovascular intervention for limb salvage with limited morbidity and mortality.

A study was conducted to investigate the effect of selective catalytic reduction (SCR) catalyst on mercury (Hg) speciation in bituminous and subbituminous coal combustion flue gases. Three different Illinois Basin bituminous coals (from high to low sulfur [S] and chlorine [Cl]) and one Powder River Basin (PRB) subbituminous coal with very low S and very low Cl were tested in a pilot-scale combustor equipped with an SCR reactor for controlling nitrogen oxides (NOx) emissions. The SCR catalyst induced high oxidation of elemental Hg (Hg0), decreasing the percentage of Hg0 at the outlet of the SCR to values <12% for the three Illinois coal tests. The PRB coal test indicated a low oxidation of Hg0 by the SCR catalyst, with the percentage of Hg0 decreasing from approximately 96% at the inlet of the reactor to approximately 80% at the outlet. The low Cl content of the PRB coal and corresponding low level of available flue gas Cl species were believed to be responsible for low SCR Hg oxidation for this coal type. The test results indicated a strong effect of coal type on the extent of Hg oxidation.

Angioplasty and stenting of short segment obstructions is highly effective in the treatment of aorto-iliac occlusive disease. However, long-segment, diffuse and calcific aorto-iliac atherosclerosis is most effectively treated with surgical bypass. While aorto-femoral bypass procedures are durable and effective, too often patients are elderly, high risk and poor candidates for open surgery. Endografting of the abdominal aorta and iliac arteries is aimed at improving the short and long-term results of endovascular treatment of extensive, end-stage aorto-iliac disease. Aorto-iliac endografts are widely used in the treatment of aneurysmal disease. Early experiences with endografts in the treatment of occlusive disease are promising. However, evidence that long-term patency of endografts will be substantially better than angioplasty and stenting is not yet available. Prospective clinical trials are needed to determine the role of endografts in the treatment strategy of aorto-iliac occlusive disease.

Objective: To determine the impact on late postoperative renal function of suprarenal and infrarenal fixation of endografts used to treat infrarenal abdominal aortic aneurysm (AAA)., Methods: Retrospective analysis of 277 patients treated from 2000 to 2003 with three different endografts at two clinical centers. Five patients on dialysis for preoperative chronic renal failure were excluded. Group IF of 135 patients treated with an infrarenal device (Medtronic AneuRx) was compared with group SF of 137 patients treated with a suprarenal device (106 Cook Zenith and 31 Medtronic Talent). Renal function was evaluated by calculating preoperative and latest postoperative creatinine clearance (CrCl) using the Cockcroft formula. Patients who developed a >20% decrease in CrCl were considered to have significantly impaired renal function., Results: There were no significant differences in patient age, sex, aneurysm size, preoperative risk factors, dose of intra- and postoperative contrast, or baseline CrCl (IF: 69.3 mL/min, SF: 71.7 mL/min, P = .4). Follow-up time of 12.2 months was the same in both groups. CrCl decreased significantly during the follow-up period in both groups (IF: 69.3 mL/min to 61.7 mL/min, P < .01; SF: 71.7 mL/min to 64.9 mL/min, P < .03). Postoperative CrCl (IF: 61.7 mL/min, SF: 64.9 mL/min, P = .3), and the rate of CrCl decrease during the follow-up period (IF: -10.9%, SF: -9.5%, P = .2) was not different between the two groups. The number of patients with a >20% decrease in CrCl was not different between the two groups (IF: n = 35 [25.9%], SF: n = 41 [29.9%], P = .46). However, the magnitude of decrease in CrCl in patients with renal impairment was greater in patients treated with suprarenal fixation endografts (SF: -39%) compared with those treated with infrarenal endografts (IF: -31%, P = .005). This greater degree of renal impairment was not due to identifiable differences in preoperative risk factors, age, or baseline CrCl. No patients in these series required dialysis., Conclusions: Regardless the type of endograft used, there is a 10% decrease in CrCl in the first year after endovascular aneurysm repair. Suprarenal fixation does not seem to increase the likelihood of postoperative renal impairment. Decline in renal function over time after endovascular aortic repair is probably due to multiple factors, and measures known to be effective in protecting kidneys should be considered for these patients. Long-term follow-up with measurement of CrCl, along with renal imaging and regular blood pressure measurements, should be performed to detect possible late renal dysfunction. Prospective studies comparing suprarenal versus infrarenal fixation are needed to confirm those results.

Successful management of acute mesenteric ischemia is predicated on prompt diagnosis, which still remains clinical in nature. No single radiographic test has a sensitivity or specificity reliable enough to supplant frequent and thorough physical examination and clinical judgment. Operative management requires adequate excision of clearly necrotic bowel and a high index of suspicion of borderline segments. Arterial reconstruction is best done with autogenous tissue when possible in the setting of gangrene or spillage. While diagnosis of chronic mesenteric ischemia is far more straightforward, significant controversy still remains regarding operative management with regards to the number of vessels reconstructed, direction of the graft, and choice of conduit.

Spectra of hydrogenlike atoms embedded in a Debye plasma are investigated. The state energies and the transition rates are studied using a fully relativistic formalism based on the Dirac equation. The effect of the plasma is described by introducing an exponential screening to the nuclear Coulomb potential (the Debye screening). Systematic trends with respect to both the nuclear charge and the screening parameter are observed for all calculated quantities. The pattern of splittings of ns(1/2), np(1/2) and np(3/2) is modified in a specific way due to the combined relativity and plasma effect. The transition rates decrease with an increase of the Debye parameter as well as with an increase of Z.

Background: Arterial diameter changes in response to flow. Chronic flow-mediated arterial enlargement may be mediated through metalloproteinase activity in the extracellular matrix of the arterial wall. We examined flow-mediated enlargement in the setting of increasing competitive matrix metalloproteinase (MMP) inhibition and with respect to gelatinase A and B expression and activity., Methods: Left common femoral arteriovenous fistulas (AVFs) were created in dose-response (52) and time course (34) cohorts of rats. Dose-response rats received either vehicle alone or 12.5, 25, or 37. 5 mg/kg b.i.d. RS 113,456, a competitive MMP inhibitor. Heart rate, blood pressure, and weight were measured at intervals following AVF construction. Aortic and common iliac diameters were measured on postoperative day (POD) 21. Untreated time course rats were sacrificed on PODs 0 (no AVF), 3, 7, 14, and 21. Aortic diameter was measured and the vessels were harvested for tissue analysis. Equal amounts of aortic RNA underwent reverse transcription and polymerase chain reaction with primers for MMP-2, MMP-9, and GAPDH. Zymography was performed on iliac artery tissue to measure gelatinolytic activity., Results: A significant, stepwise reduction in flow-mediated aortic and left common iliac enlargement following left femoral AVF creation was noted with progressively higher doses of RS 113,456 without apparent hemodynamic or toxic effects. Right common iliac diameter was unchanged. Over 21 days following AVF creation, there was an upward trend in expression and activity for MMP-2 not evident for MMP-9., Conclusion: Flow-mediated arterial enlargement is limited by competitive MMP inhibition in a dose-dependent fashion. MMP-dependent flow-mediated enlargement may involve differential expression and activity of MMP-2 and MMP-9., (Copyright 1999 Academic Press.)

Two novel triterpene sulfates have been isolated from Fusarium compactum by bioactivity-directed fractionation using an assay which measures the inhibition of proteolytic activity of rhinovirus 3C protease on a fluorogenic peptide substrate. The compounds were purified by countercurrent and reverse phase chromatographies. NMR, MS, UV and IR studies revealed two triterpene sulfates, uncommon metabolites of terrestrial fungi.

A new method is described for the selective isolation of species of Myxococcus directly from soil by dilution plating. The method involves suppression of competing microorganisms with antibiotics combined with air drying and wet heat treatment of soils. Fungi were eliminated by supplementing the plating medium with cycloheximide and nystatin. Non-sporulating bacteria were controlled by air drying soils and then heating aqueous soil dilutions for 10 min at 56 degrees C. The predominant sporulating bacteria in soil, Streptomyces and Bacillus, were suppressed by adding either tiacumicin B, ristocetin or vancomycin to the medium. Swarming of Myxococcus colonies was controlled with a casein digest-yeast extract plating medium (CY-C10 agar). Ultrasound treatment of soil suspensions gave the highest number of Myxococcus colonies in the soils studied, but these cultures could be recovered without ultrasound. Strains of Myxococcus fulvus, M. xanthus, M. coralloides, M. stipitatus and M. virescens were isolated from soil using this technique. Soils examined yielded one or two Myxococcus species per sample.

The novel calcineurin inhibitor, dibefurin, has been isolated from the fungal culture AB 1650I-759. The isolation was bioactivity-directed fractionation using an assay which measures the phosphatase activity of calcineurin. The compound was purified by countercurrent, reverse phase and gel filtration chromatographies. Several studies, including crystallographic, NMR and MS, revealed that dibefurin is a novel dimeric compound of a unique structural type.

The fuscandins, antifungal agents of the papulacandin class, are produced by a strain of Fusarium sambucinum. Fermentation yielded 60 mg/liter of fusacandin A and minor amounts of fusacandin B. As expected, the fusacandins inhibit (1,3)-beta-glucan synthesis. Fusacandin A is slightly less active than papulacandin B against Candida albicans and, like papulacandin, loses activity in the presence of serum.

A novel series of microbial metabolites were discovered in fermentation broths of two soil isolates. Both cultures were identified as strains of Micromonospora chalcea. Production of the metabolites, named macquarimicins, was monitored by an HPLC assay. A seven-day fermentation yielded 27 mg/liter of macquarimicin A. With MICs of 50 to 100 micrograms/ml, macquarimicin A has only very low activity against strains of Bacteroides and other anaerobes. Macquarimicin B has inhibitory activity against the leukemia cell line P-388.

Determination of the mechanism of action of FK506 and cyclosporin A has yielded new molecular targets involved in signal transduction during T cell activation. A common target of FK506 and cyclosporin A is inhibition of activation of the NFAT transcription factor, for which a specific binding region is present in the promoter of the IL-2 gene. A reporter gene assay has been used to screen for agents that interfere with this early step in T cell activation. Simple aromatic compounds that block NFAT-dependent transcription and show in vitro immunosuppressive activity were isolated from the broth and mycelia of two Streptomyces sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic.