Staphylococcus aureus AbcA transporter enhances persister formation under ß-lactam exposure.

We evaluated the role of Staphylococcus aureus AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6-14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy increased sixfold as cell viability reporters decreased. Similarly, single-cell analysis in a high-throughput microfluidic system found a strong correspondence between antibiotic exposure and AbcA reporter expression. Persister cells grown in the absence of antibiotics showed neither an increase in nafcillin MIC nor in abcA transcript levels, indicating that survival was not associated with stable mutational resistance or abcA overexpression. Furthermore, persister cell levels on exposure to 1×MIC and 25×MIC of nafcillin decreased in an abcA knockout mutant. Survivors of nafcillin and oxacillin treatment overexpressed transporter AbcA, contributing to an enrichment of the number of persisters during treatment with pump-substrate nafcillin but not with pump-non-substrate oxacillin, indicating that efflux pump expression can contribute selectively to the survival of a persister population.

Staphylococcus aureus Efflux Pumps and Tolerance to Ciprofloxacin and Chlorhexidine following Induction by Mupirocin.

Mupirocin induced expression of genes encoding efflux pumps NorA and MepA as well as a yellow fluorescent protein (YFP) fluorescence reporter of NorA. Mupirocin exposure also produced reduced susceptibility to pump substrates ciprofloxacin and chlorhexidine, a change that was dependent on intact norA and mepA, respectively.

Index-based dietary patterns and risk of lung cancer in the NIH-AARP diet and health study.

BACKGROUND/OBJECTIVES: Dietary pattern analysis considers combinations of food intake and may offer a better measure to assess diet-cancer associations than examining individual foods or nutrients. Although tobacco exposure is the major risk factor for lung cancer, few studies have examined whether dietary patterns, based on preexisting dietary guidelines, influence lung cancer risk. After controlling for smoking, we examined associations between four diet quality indices-Healthy Eating Index-2010 (HEI-2010), Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension (DASH)-and lung cancer risk in the NIH-AARP (National Institutes of Health-American Association of Retired Persons) Diet and Health study. SUBJECTS/METHODS: Baseline dietary intake was assessed in 460 770 participants. Over a median of 10.5 years of follow-up, 9272 incident lung cancer cases occurred. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and confidence intervals (CIs). RESULTS: Comparing highest to lowest quintiles, HRs (95% CIs) for lung cancer were as follows: HEI-2010=0.83 (0.77-0.89), AHEI-2010=0.86 (0.80-0.92), aMED=0.85 (0.79-0.91) and DASH=0.84 (0.78-0.90). Among the individual components of the dietary indices, higher consumption of whole grains and fruits was significantly inversely associated with lung cancer risk for several of the diet indices. Total index score analyses stratified by smoking status showed inverse associations with lung cancer for former smokers; however, only HEI-2010 was inversely associated in current smokers and no index score was inversely associated among never smokers. CONCLUSIONS: Although smoking is the factor most strongly associated with lung cancer, this study adds to a growing body of evidence that diet may have a modest role in reducing lung cancer risk, especially among former smokers.

Associations between food patterns defined by cluster analysis and colorectal cancer incidence in the NIH-AARP diet and health study.

BACKGROUND/OBJECTIVES: To examine associations between food patterns, constructed with cluster analysis, and colorectal cancer incidence within the National Institutes of Health-AARP Diet and Health Study. SUBJECTS/METHODS: A prospective cohort, aged 50-71 years at baseline in 1995-1996, followed until the end of 2000. Food patterns were constructed, separately in men (n=293,576) and women (n=198,730), with 181 food variables (daily intake frequency per 1000 kcal) from a food frequency questionnaire. Four large clusters were identified in men and three in women. Cox proportional hazards regression examined associations between patterns and cancer incidence. RESULTS: In men, a vegetable and fruit pattern was associated with reduced colorectal cancer incidence (multivariate hazard ratio, HR: 0.85; 95% confidence interval, CI: 0.76, 0.94), when compared to less salutary food choices. Both the vegetable and fruit pattern and a fat-reduced foods pattern were associated with reduced rectal cancer incidence in men. In women, a similar vegetable and fruit pattern was associated with colorectal cancer protection (age-adjusted HR: 0.82; 95% CI: 0.70, 0.95), but the association was not statistically significant in multivariate analysis. CONCLUSIONS: These results, together with findings from previous studies support the hypothesis that micronutrient dense, low-fat, high-fiber food patterns protect against colorectal cancer.

Index-based dietary patterns and risk of colorectal cancer: the NIH-AARP Diet and Health Study.

The authors compared how four indexes-the Healthy Eating Index-2005, Alternate Healthy Eating Index, Mediterranean Diet Score, and Recommended Food Score-are associated with colorectal cancer in the National Institutes of Health-AARP Diet and Health Study (n = 492,382). To calculate each score, they merged data from a 124-item food frequency questionnaire completed at study entry (1995-1996) with the MyPyramid Equivalents Database (version 1.0). Other variables included energy, nutrients, multivitamins, and alcohol. Models were stratified by sex and adjusted for age, ethnicity, education, body mass index, smoking, physical activity, and menopausal hormone therapy (in women). During 5 years of follow-up, 3,110 incident colorectal cancer cases were ascertained. Although the indexes differ in design, a similarly decreased risk of colorectal cancer was observed across all indexes for men when comparing the highest scores with the lowest: Healthy Eating Index-2005 (relative risk (RR) = 0.72, 95% confidence interval (CI): 0.62, 0.83); Alternate Healthy Eating Index (RR = 0.70, 95% CI: 0.61, 0.81); Mediterranean Diet Score (RR = 0.72, 95% CI: 0.63, 0.83); and Recommended Food Score (RR = 0.75, 95% CI: 0.65, 0.87). For women, a significantly decreased risk was found with the Healthy Eating Index-2005, although Alternate Healthy Eating Index results were similar. Index-based dietary patterns that are consistent with given dietary guidelines are associated with reduced risk.

Health behavior changes after colon cancer: a comparison of findings from face-to-face and on-line focus groups.

This qualitative study assessed the feasibility and comparability of findings from face-to-face versus on-line chat focus groups including 12 individuals affected by colon cancer. Discussion questions focused on issues of lifestyle (nutrition and exercise), cancer screening, and treatment. Despite demographic differences, the themes that emerged from the two types of groups were similar. On-line participants generally talked more about cancer treatment and advocacy issues and used support groups more frequently. The anonymity of on-line chat groups appeared to provide a more comfortable forum for some people to discuss sensitive personal health issues. As both methods provided similar results, researchers may wish to consider circumstances in which using chat-based focus groups may provide a feasible alternative to traditional face-to-face groups.

Endogenous Pseudomonas aeruginosa endophthalmitis: a case report and literature review.

Endogenous endophthalmitis is a vision-threatening condition that results from the hematogenous spread of infection to the eye that originated in a distant primary focus. Although it has long been recognized that bloodborne organisms can infect the eye, endogenous bacterial endophthalmitis is considered a rare entity. We present a unique case of a critically ill patient with a cholangiocarcinoma complicated by ascending cholangitis who developed endogenous Pseudomonas aeruginosa endophthalmitis. An awareness of the risk factors predisposing to endogenous endophthalmitis and a high clinical suspicion are necessary to make an early diagnosis in the intensive care unit. Management involves an aggressive combined medical and surgical approach in an effort to prevent ocular morbidity and vision loss.

Phlegmasia cerulea dolens with compartment syndrome: a complication of femoral vein catheterization.

OBJECTIVE: Central venous catheterization is commonly performed in the critically ill. The femoral vein is widely accepted as an insertion site with complications thought to be comparable to other central access sites. We used serial ultrasound examinations with Doppler to examine the evolution of a heretofore undescribed complication of femoral vein catheterization, phlegmasia cerulea dolens with compartment syndrome. DESIGN: Serial ultrasounds were performed in patients before the insertion of femoral venous catheters and sequentially every 48 hrs while the catheters were in place. The noncatheterized leg served as a control. SETTING: A trauma and life support center of a tertiary multidisciplinary critical care unit. PATIENT: A 32-yr-old man with respiratory failure as a consequence of a severe community-acquired pneumonia that required central venous access for antibiotics because no peripheral sites could be obtained. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The initial ultrasound examination of both legs before femoral catheter insertion revealed no sign of venous thrombosis. Ultrasound of the catheterized leg at 48 hrs revealed a small nonocclusive thrombosis, whereas the opposite leg remained normal. At 72 hrs, the catheterized leg had clinical and ultrasonographic evidence of a massive thrombosis. A compartment syndrome defined by pressure measurements soon ensued and required emergent surgical release. CONCLUSIONS: This case report and a review of the available literature suggest that thrombosis associated with femoral vein catheterization should be considered when clinicians decide where to obtain central venous access when multiple sites are available. This report also suggests the utility of serial ultrasound examinations to define clinically nonapparent thrombosis as an early indicator of a potentially catastrophic complication.

Microvascular pulmonary emboli secondary to precipitated crystals in a patient receiving total parenteral nutrition: a case report and description of the high-resolution CT findings.

A patient with a history of a small-bowel transplant that was subsequently resected required total parenteral nutrition for nutritional supplementation. While receiving therapy, he developed chest tightness, shortness of breath, and fever. The chest radiograph showed bilateral reticulonodular opacities, and the high-resolution CT scan demonstrated diffuse, poorly marginated micronodular opacities in a miliary pattern. Pathology specimens obtained by transbronchial biopsy revealed amorphous material obstructing the pulmonary microvasculature. Microvascular emboli secondary to precipitated crystals is a potential complication of total parenteral nutrition. An awareness of the factors that influence crystal solubility may prevent adverse interactions in patients who require parenteral nutrition.

Heart transplantation charges: status 1 versus status 2 patients.

BACKGROUND: The current health care environment mandates closer scrutiny of health care dollar allocation. To better understand the distribution of heart transplantation costs, we reviewed hospital and physician billing of patients who underwent orthotopic heart transplantation between August 1988 and September 1993. METHODS: This study is a retrospective review of 107 consecutive cases. Charges and clinical results of United Network for Organ Sharing status 1 patients (n = 46), including 17 bridge to transplantation patients, were compared with those of United Network for Organ Sharing status 2 patients (n = 57). Charges were converted to 1992 dollars. RESULTS: During the first 12 months of the study, 77% of heart transplantations were performed in United Network for Organ Sharing status 2 patients, whereas over the last 12-month period, 25% of the transplantations were performed in status 2 patients. No significant differences were found in age, gender, type of cardiomyopathy, or survival between the status 1 and status 2 groups. The length of hospitalization for the status 1 group ranged from 8 to 138 days (mean 49 days) as opposed to 5 to 82 days (mean 17.5 days) for the status 2 group (p < 0.0001). Pretransplantation hospital charges were significantly higher for the status 1 group ($47,917 to $341,215, mean $109,116) when compared with status 2 ($0 to $10,035, mean $250) (p < 0.0001). No significant difference was found in posttransplantation hospital charges between status 1 ($47,917 to $210,027, mean $95,379) and status 2 patients ($48,093 to $380,745, mean $102,265). Total charges were significantly higher (p < 0.0001) for the status 1 group ($89,910 to $512,331, mean $239,375) when compared with the status 2 group ($63,885 to $455,680, mean $128,594). Total transplantation charges for the study period were $18,341,108. This amount could have paid for 77 status 1 transplantations or 143 status 2 transplantations. CONCLUSIONS: If current trends continue and the donor pool remains the same, most transplant recipients will be status 1, resulting in a comparable number of transplantations performed at twice the charges.

Evaluation of an implantable ventricular assist system for humans with chronic refractory heart failure. Measuring quality of life.

The development of a multidimensional quality of life protocol to be used in a clinical trial of an LVAS was presented. The complexity of the new LVAS technology being evaluated added a unique dimension for HQL assessment. The rationale and procedures used in developing this protocol were described. Although we have elucidated the development of a protocol for a specific clinical trial, the principles and procedures employed are widely applicable. To summarize, these procedures are as follows: 1. Determine what quality of life domains are important to measure. This decision should be based upon the domains expected to be affected by treatment, those expected to change as a result of the natural course of the disease or condition, and those that may be affected by changes in the primary domains. 2. Once the domains are selected, identify specific measures for these domains. Where possible, the measures chosen should be standardized, well validated, and appropriate to the study population. Instrument length and mode of administration are additional considerations. 3. Consider any unique aspects of the study population or intervention and develop specific questions to address them. 4. Identify and measure important variables that may moderate or influence quality of life. 5. Test the protocol on an appropriate population for length, flow, and ease of administration. Copies of the complete HQL protocol are available by writing to: Dr. Nancy Avis, New England Research Institute, 9 Galen Street, Watertown, MA 02172.

Understanding ventricular assist devices: a self-study guide.

Considerable progress has been made over the past several decades in development of ventricular assist device (VAD) technology. Initially, failure to wean from cardiopulmonary bypass was the primary indication for VAD support. However, VAD role has expanded to include patients with ventricular failure due to myocardial infarction and patients awaiting cardiac transplantation. A greater number of nurses, both in the intensive care and general floors, are required to care for patients supported with VADs. Therefore, a self-study guide was developed to facilitate learning. Heart failure physiology, mechanical device descriptions, patient selection, potential complications, and nursing care of patients who require VAD support are reviewed.

Nursing care of the patient with an intravascular oxygenator.

Conventional therapy in the management of adult respiratory distress syndrome is often associated with an increased mortality rate. Several methods to improve survival in patients with severe respiratory insufficiency are under evaluation. One recently developed method of treatment is an implantable intravascular oxygenator, which provides supplemental gas exchange for failing lungs. This device can provide temporary ventilatory support in patients with acute, potentially reversible respiratory insufficiency. Reduction in ventilator settings such as airway pressure, oxygen concentration, positive end-expiratory pressure and minute volume can be achieved, decreasing the likelihood of oxygen toxicity and barotrauma. Success of the intravascular oxygenator in adult respiratory distress syndrome is dependent in part on critical care staff expertise. Therefore, a thorough understanding of the operation of this device and its role in acute respiratory failure is necessary for optimal care.

Bridging to cardiac transplantation with mechanical circulatory support.

During the last decade, it has been clearly demonstrated that mechanical assist devices are capable of supporting patients in the interim before cardiac transplantation. The use of these devices prior to transplantation has provided an important window of opportunity to evaluate critically the devices and their potential for adaptation to permanent systems. The overall survival rates in the bridge-to-transplant patient population have improved. This is in part due to lessons learned in the past several years with regard to better patient selection and applicability of the devices. This review focuses on selected papers published in the past year that have made significant contributions to the evolution of mechanical support.

Transfer of a patient with a ventricular assist device to a non-critical care area.

Ventricular assist device (VAD) support has traditionally been associated with critically ill patients. Indeed, a VAD is inserted as the last hope for patients with cardiogenic shock who are unresponsive to conventional therapy. However, many patients bridged to potential cardiac transplantation are no longer critically ill after hemodynamic stabilization is achieved with VAD support. The focus of this article is to provide guidelines established for the transfer and provision of quality nursing care for patients with a VAD on a general cardiothoracic nursing floor.

The importance of patient mobility with ventricular assist device support.

Patients bridged to transplantation with ventricular assist devices (VADs) often require prolonged support. To reduce complications associated with bed rest, the authors developed a program to mobilize patients with VADs. Between August 1986 and May 1992, 25 men and 7 women aged 12-65 years (mean: 42.4 years) were bridged for possible transplantation. The 32 patients were supported with either a Novacor (n = 9) or a Thoratec (n = 23) VAD. Thirty-one patients were turned within 2-12 hr of VAD insertion and received range of motion therapy. Twenty-six patients sat in a chair 2-16 days (mean: 5 days) after VAD insertion. Twenty-one patients used a stationary bicycle, and 23 patients were ambulatory 3-57 days (mean: 11 days) after VAD insertion. Two patients were transplanted within 72 hr of device insertion. Twenty-one of the 23 ambulatory patients were successfully transplanted or weaned from the VAD and discharged from the hospital. Two ambulatory patients who were difficult to rehabilitate (ambulatory 22 and 57 days, respectively, after VAD insertion) died before transplantation. In conclusion, VAD patients should be mobilized early because the VAD can improve exercise capability and survival rate.