Aortoiliac occlusive disease - a novel classification system based on anatomical segments and disease severity for management planning.

AIMS: The aim of this classification system is to provide vascular surgeons with a simple tool that categorises disease severity by anatomical segment in aortoiliac occlusive disease and thus guide decision making and management strategies. Disease of the common femoral arteries is included as the distal extent of disease with respect to access for both open and endovascular intervention is essential to management planning. METHODS: The classification system designates diseased segment letters and numbers to guide treatment planning. The degree of disease other than stenotic or occluded is not required. In a similar manner to the TNM classification, anatomy and disease severity - based on angiography, CTA, and MRA - are categorised using a simple, user-friendly method. Two clinical cases are presented to exemplify the clinical application of this classification system. RESULTS: A simple and useful classification system is presented and ease of use exemplified by two clinical cases. CONCLUSIONS: Management strategies for peripheral artery disease in general, aortoiliac occlusive disease specifically, have evolved rapidly in recent years. Existing classification systems, such as TASC II, steer the clinician towards specific treatment approaches. However, the first step in the management decision-making process is the accurate identification of the arterial segments that require treatment. None of the existing classification systems specifically address anatomy as an entity in itself. This classification system provides an intuitive framework, based on letters and numbers, that provides specific information on arterial segments and disease severity in aortoiliac occlusive disease on which clinicians can base management decisions. It has been developed to bolster this aspect of the vascular surgery armamentarium; to be used as a decision making and management planning tool, in partnership with, not instead of, existing classification systems.

Low muscle mass determined by psoas muscle area does not correlate with dual-energy x-ray absorptiometry or total lumbar muscle mass scores: A prospective cohort study of patients undergoing vascular surgery.

Background/Objective: Low muscle mass and sarcopenia have been explored as risk factors for poor outcomes following vascular surgery. The findings have been variable. The use of a diverse range of techniques to identify low muscle mass is a confounder in establishing the true relationship between low muscle mass, sarcopenia and outcomes. Our aim was to establish if different scoring methods identified the same patients as sarcopenic. We also explored which method best predicted outcomes. Method: 70 patients undergoing vascular surgery were prospectively assessed for sarcopenia using dual-energy x-ray absorptiometry (DEXA) scan, grip strength and gait speed. These patients underwent abdominal CT imaging as routine care. The muscle mass of each patient was determined using DEXA and by both psoas muscle and total skeletal muscle area on CT, normalised for patient height (PMI and CT-SMI, respectively). Low muscle mass was defined by published age- and sex-specific cut-offs. Grip strength data was combined with muscle mass to define sarcopenic patients. One- and 3-year mortality and time to readmission was recorded. Conclusion and Results: 10-22% of patients had low muscle mass and 4-10% of patients were sarcopenic, depending on the method employed. PMI did not correlate with DEXA or CT-SMI for low muscle mass, but CT-SMI correlated with DEXA (p = 0.0007). For sarcopenia, CT-SMI and DEXA scoring correlated (p = 0.002); PMI correlated with CT-SMI (p = 0.0006) but not DEXA. Low muscle mass by PMI predicted 1-year mortality (p = 0.02, X2 = 5.34, Effect size = 1.04) but the applicability of this finding is limited by the diverse pathologies explored. No other method predicted 1- or 3-year mortality or readmissions in this heterogenous cohort. The psoas area did not correlate with muscle mass defined by DEXA or total lumbar skeletal muscle area. Low psoas muscle index may be an independent marker of poor outcome, unrelated to generalised sarcopenia, and this warrants investigation in specific pathologies. A lower total number of patients were sarcopenic than had been expected, emphasising the need to use population-based pre-defined cut-offs.

Increasing Stormwater Capture and Recharge Using Forecast Informed Reservoir Operations, Prado Dam.

The United States Army Corps of Engineers (USACE) operates Prado Dam in southern California for flood risk management and to capture stormwater for groundwater recharge. USACE and the Orange County Water District (OCWD) have collaborated for over 30 years to temporarily store Santa Ana River (SAR) stormflow at Prado Dam for groundwater recharge in the Orange County Groundwater Basin (Basin). USACE, OCWD, and other stakeholders are assessing Forecast Informed Reservoir Operations (FIRO) at Prado Dam as a new operational approach to capture additional supplies of SAR water for groundwater recharge without affecting Prado Dam's primary flood risk management purpose. Many dams, including Prado Dam, do not directly incorporate precipitation and streamflow forecasting in their operations. FIRO is an innovative research and operations partnership that uses weather forecasting, streamflow modeling, and watershed monitoring to help water managers selectively retain or release water from reservoirs in a manner that reflects current and forecasted conditions. A recently completed study, called a Preliminary Viability Assessment of FIRO at Prado Dam, determined that increased stormwater capture, beyond the current program, is viable subject to completion of additional studies. The ultimate increase in stormwater capture is anticipated to largely be a function of community and environmental tolerance for more frequent inundation rather than operational constraints of the dam. FIRO is a promising approach to operating Prado Dam that can increase SAR stormwater capture for recharge to the Basin, reducing the need for imported water and contributing to sustainable groundwater management.

Chitosan Ameliorates Candida auris Virulence in a Galleria mellonella Infection Model.

Candida auris has emerged as a multidrug-resistant nosocomial pathogen over the last decade. Outbreaks of the organism in health care facilities have resulted in life-threatening invasive candidiasis in over 40 countries worldwide. Resistance by C. auris to conventional antifungal drugs such as fluconazole and amphotericin B means that alternative therapeutics must be explored. As such, this study served to investigate the efficacy of a naturally derived polysaccharide called chitosan against aggregative (Agg) and nonaggregative (non-Agg) isolates of C. aurisin vitro and in vivo. In vitro results indicated that chitosan was effective against planktonic and sessile forms of Agg and non-Agg C. auris In a Galleria mellonella model to assess C. auris virulence, chitosan treatment was shown to ameliorate killing effects of both C. auris phenotypes (NCPF 8973 and NCPF 8978, respectively) in vivo Specifically, chitosan reduced the fungal load and increased survival rates of infected Galleria, while treatment alone was nontoxic to the larvae. Finally, chitosan treatment appeared to induce a stress-like gene expression response in NCPF 8973 in the larvae likely arising from a protective response by the organism to resist antifungal activity of the compound. Taken together, results from this study demonstrate that naturally derived compounds such as chitosan may be useful alternatives to conventional antifungals against C. auris.

Candida auris Phenotypic Heterogeneity Determines Pathogenicity In Vitro.

Candida auris is an enigmatic yeast that provides substantial global risk in health care facilities and intensive care units. A unique phenotype exhibited by certain isolates of C. auris is their ability to form small clusters of cells known as aggregates, which have been to a limited extent described in the context of pathogenic traits. In this study, we screened several nonaggregative and aggregative C. auris isolates for biofilm formation, where we observed a level of heterogeneity among the different phenotypes. Next, we utilized an RNA sequencing approach to investigate the transcriptional responses during biofilm formation of a nonaggregative and aggregative isolate of the initial pool. Observations from these analyses indicate unique transcriptional profiles in the two isolates, with several genes identified relating to proteins involved in adhesion and invasion of the host in other fungal species. From these findings, we investigated for the first time the fungal recognition and inflammatory responses of a three-dimensional skin epithelial model to these isolates. In these models, a wound was induced to mimic a portal of entry for C. auris We show that both phenotypes elicited minimal response in the model minus induction of the wound, yet in the wounded tissue, both phenotypes induced a greater response, with the aggregative isolate more proinflammatory. This capacity of aggregative C. auris biofilms to generate such responses in the wounded skin highlights how this opportunistic yeast is a high risk within the intensive care environment where susceptible patients have multiple indwelling lines.IMPORTANCECandida auris has recently emerged as an important cause of concern within health care environments due to its ability to persist and tolerate commonly used antiseptics and disinfectants, particularly when attached to a surface (biofilms). This yeast is able to colonize and subsequently infect patients, particularly those that are critically ill or immunosuppressed, which may result in death. We have undertaken analysis on two different phenotypic types of this yeast, using molecular and immunological tools to determine whether either of these has a greater ability to cause serious infections. We describe that both isolates exhibit largely different transcriptional profiles during biofilm development. Finally, we show that the inability to form small aggregates (or clusters) of cells has an adverse effect on the organism's immunostimulatory properties, suggesting that the nonaggregative phenotype may exhibit a certain level of immune evasion.

Pre-diabetes, diabetes and predictors of incident angina among older women and men in the Cardiovascular Health Study.

Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 ± 6.9 years of follow-up. Overall, 39.1% of participants had pre-diabetes mellitus, 14.0% had diabetes mellitus and 532 (11.8%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all p < 0.05 to p < 0.01). In our cohort of older adult participants, while the incidence of AP is greater in those with diabetes mellitus, neither diabetes mellitus nor pre-diabetes mellitus independently predicted incident angina pectoris.

Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells.

The gingival epithelium is a physical and immunological barrier to the microbiota of the oral cavity, which interact through soluble mediators with the immune cells that patrol the tissue at the gingival epithelium. We sought to develop a three-dimensional gingivae-biofilm interface model using a commercially available gingival epithelium to study the tissue inflammatory response to oral biofilms associated with "health", "gingivitis" and "periodontitis". These biofilms were developed by sequential addition of microorganisms to mimic the formation of supra- and sub-gingival plaque in vivo. Secondly, to mimic the interactions between gingival epithelium and immune cells in vivo, we integrated peripheral blood mononuclear cells and CD14+ monocytes into our three-dimensional model and were able to assess the inflammatory response in the immune cells cultured with and without gingival epithelium. We describe a differential inflammatory response in immune cells cultured with epithelial tissue, and more so following incubation with epithelium stimulated by "gingivitis-associated" biofilm. These results suggest that gingival epithelium-derived soluble mediators may control the inflammatory status of immune cells in vitro, and therefore targeting of the epithelial response may offer novel therapies. This multi-cellular interface model, both of microbial and host origin, offers a robust in vitro platform to investigate host-pathogens at the epithelial surface.

Neutrophil-lymphocyte ratio as a prognostic marker of outcome in infrapopliteal percutaneous interventions for critical limb ischemia.

BACKGROUND: Endovascular intervention has become a frequently used treatment of critical limb ischemia (CLI) in recent times. The recent Bypass vs Angioplasty in Severe Ischaemia of the Leg (BASIL) trial consensus recommended endovascular treatment as a first-line treatment in patients who have a life expectancy that was limited to <2 years. Despite these recommendations, there still remains limited data available to clinicians when seeking to risk stratify patients who present with CLI. The neutrophil-lymphocyte ratio (NLR) has been suggested to be a marker for predicting mortality and patency. This study aimed to investigate the use of the NLR as a prognostic marker for primary patency and mortality after an infrapopliteal endovascular intervention in patients with CLI. METHODS: All patients who underwent tibial angioplasty for CLI were retrospectively analyzed. Demographics, degrees of stenosis, vessel patency rates, mortality, and comorbidities were recorded. NLRs were calculated from preoperative blood samples. Primary end points were all-cause mortality, primary patency, and amputation-free survival (AFS) within the follow-up period of 12 months. Multivariate Cox proportional hazard models were used to identify independent predictors. Overall survival, AFS, and the probability of a vessel remaining patent were evaluated by standard Kaplan-Meier survival curves and groups compared by the log-rank test. RESULTS: Eighty-three patients were monitored for 12 months. Ninety limbs were identified, with 104 procedural events and 127 vessels undergoing successful angioplasty. The technical success rate was 86%, and patency at 1 year was 19%. Survival at 1 year was 76% and AFS was 61%. Patients with a NLR ≥5.25 had an increased risk of death (hazard ratio, 1.97; 95% confidence interval, 1.08-3.62; P = .03) compared with those with a NLR of <5.25. Furthermore, those with lymphocytes counts of <1.5 × 10(9)/L had higher mortality (hazard ratio, 1.88; 95% confidence interval, 1.02-3.70; P = .045) than those with lymphocyte counts >1.5 × 10(9)/L. CONCLUSIONS: The NLR and absolute lymphocyte counts are potentially valuable prognostic indicators for risk stratification of patient's presenting with CLI undergoing infrapopliteal angioplasty.