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Introduction: Although recent guidelines have recommended monitoring vancomycin (VAN) area under the curve (AUC)/minimum inhibitory concentration (MIC) to ensure clinical efficacy and minimize toxicity in methicillin-resistant Staphylococcus aureus (MRSA) for various infections, there are no recommendations regarding complicated skin and soft tissue infections (cSSTIs). We aimed to evaluate the association between VAN AUC and clinical outcomes in MRSA cSSTIs., Methods: This was a retrospective cohort study of adult patients treated with ≥72 hours of VAN for MRSA cSSTI from 2008 to 2013 at Detroit Medical Center. The primary outcome was timely clinical success (TCS) defined as (1) resolution of signs and symptoms of infection within 72 hours, (2) stabilization and/or reduction in lesion size, (3) alternative agents not required due to VAN failure or toxicity as elected by the prescribing clinician. Classification and regression tree (CART) analysis was performed to determine the AUC associated with TCS in the cohort. Multivariable logistic regression was used to evaluate the association between VAN-AUC and the primary outcome., Results: A total of 154 patients were included in this analysis. CART identifed an AUC ≥435 mg*hr/L for TCS. Overall, 60.9% of patients experienced TCS; 69.7% in the target-AUC group versus 52.5% in the below-target AUC group, (P = .013). Target-AUC attainment was independently associated with increased odds of TCS (adjusted odds ratio [aOR], 2.208; 95% confidence interval [CI], 1.047-4.659)., Conclusions: In adults treated with VAN for MRSA cSSTI, target-AUC attainment was independently associated with improved clinical outcomes and maybe most warranted for patients at high risk of VAN failure or VAN-associated toxicity., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: We sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI)., Methods: Retrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria., Results: In total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929-11.499), no medical insurance (aOR 3.451, 95% CI 1.310-9.090), ICU residence (aOR 4.398, 95% CI 1.676-11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158-7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037-1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p = 0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p < 0.001) and increased all-cause 30-day mortality (5.1 vs. 0.3%, p = 0.024) CONCLUSIONS: V-AKI occurred in approximately one in ten ABSSSI patients and may be largely prevented by preferential use of oral antibiotics whenever possible, using beta-lactams for non-purulent cellulitis and limiting durations of vancomycin therapy.

Introduction: Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection., Methods: Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics., Results: One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%)., Conclusion: Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2-3 days, thus limiting our ability to critically assess clinical outcomes., Trial Registration: ClinicalTrials.gov identifier, NCT02582203., Funding: Allergan plc.

Aim: The Western world has an expanding older population, who are living longer with increasing numbers of comorbidities. In addition, expectations of patients and relatives are increasing. As a general hospital operating in a rural setting, our University Hospital Kerry, Tralee, Ireland, deals with a significant number of emergency presentations to the acute surgical service. The aim of the present study was to examine outcomes for patients in the extremes of age who present requiring emergency surgical procedures., Methods: A retrospective review of theater and admission logs was carried out to identify all emergency surgeries from January 2008 to December 2015. All patients aged >80 years at the time of surgery were identified. Details of surgery were recorded, in addition to biochemical and hematological data, use of intensive care unit, length of stay and mortality., Results: In total, 128 octogenarians underwent an emergency surgery. The average patient age was 84.3 years (range 80-94 years). The commonest procedures were laparotomy (65%, n = 84), repair of strangulated/incarcerated hernia (18%, n = 23) and laparoscopic procedures (16%, n = 21). The 30-day all-cause mortality was 22.6%. On multivariate analysis, American Society of Anesthesia status and intensive care unit utilization predicted mortality (P = 0.04 and 0.05, respectively). A total of 82 patients required intensive care unit admission, with an average length of stay of 4.8 days, using 484 bed days in total., Conclusions: Emergency surgery in octogenarians is a significant part of the workload of general surgeons. Poor baseline status is associated with an increased risk of mortality. Emergency surgery in older adults only utilizes a fraction of available intensive care unit resources. Geriatr Gerontol Int 2018; 18: 1211-1214., (© 2018 Japan Geriatrics Society.)

Objectives: The traditional activation ratio divides contracted muscle thickness by resting muscle thickness while an abdominal draw-in maneuver is performed during hook lying. Ultrasound imaging during function, such as standing or gait, or peak knee flexion in a single-leg squat allows for further visualization of muscle activity. The goal of this study was to examine activation ratio calculations for transverse abdominis function in supine versus loaded conditions to determine the most informative normalization strategy for muscle activity based on thickness values., Methods: Transverse abdominis thickness was measured via ultrasound in 35 healthy participants under 4 different conditions. Comparisons were made between the traditional activation ratio tabletop, standing activation ratio (standing abdominal draw-in maneuver thickness/quiet standing thickness), and functional activation ratio (single-leg squat thickness/quiet standing thickness). Additionally, a cued activation ratio (single-leg squat with cued abdominal draw-in maneuver thickness/single-leg squat thickness) during the single-leg squat was obtained. Activation ratios of greater than 1.0 indicated that participants could activate the muscle during activity, and values were compared by analysis of variance., Results: The participants included 23 women and 12 men with a mean age ± SD of 21.3 ± 2.7 years, mass of 66.1 ± 14.4 kg, and height of 168.5 ± 10.1 cm. Activation ratios exceeded 1.0 in 94.3% for the traditional activation ratio, 85.7% for the standing activation ratio, 82.9% for the cued activation ratio, and 82.9% for the functional activation ratio. With groups defined as tabletop activated or not, the standing, cued, and functional activation ratios were all significantly different (all P < .05)., Conclusions: Normalizing muscle thickness to the corresponding functional position quiet value provides a useful functional activation ratio and may help clinicians better understand the transverse abdominis role during complex functional tasks. Assessment techniques using various formulas for activation ratios reveal that the muscle functions differently during weight bearing compared to traditional measures., (© 2017 by the American Institute of Ultrasound in Medicine.)

Evidence supports vancomycin therapeutic-drug monitoring by area under the concentration-time curve (AUC), but data to establish an AUC upper limit are limited and published nephrotoxicity thresholds range widely. The objective of this analysis was to examine the association between initial vancomycin AUC and nephrotoxicity. This was a multicenter, retrospective cohort study of adult patients receiving intravenous vancomycin from 2014 to 2015. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/liter and 50% from baseline on consecutive measurements. Vancomycin exposure profile during the initial 48 h of therapy was estimated using maximum a posteriori probability Bayesian estimation. Vancomycin AUC and minimum-concentration ( C min ) thresholds most strongly associated with nephrotoxicity were identified via classification and regression tree (CART) analysis. Predictive performances of CART-derived and other candidate AUC thresholds was assessed through positive and negative predictive value and receiver operating characteristic curves. Poisson regression was used to quantify the association between exposure thresholds and nephrotoxicity while adjusting for confounders. Among 323 patients included, nephrotoxicity was significantly higher in patients with AUCs from 0 to 48 h (AUC 0-48 ) of ≥1,218 mg · h/liter, AUC 0-24 of ≥677 mg · h/liter, AUC 24-48 of ≥683 mg · h/liter, and day 1 C min ( C min24 ) of ≥18.8 mg/liter. Vancomycin exposure in excess of these thresholds was associated with a 3- to 4-fold-increased risk of nephrotoxicity in Poisson regression. The predictive performance of AUC for nephrotoxicity was maximized at daily AUC values between 600 and 800 mg · h/liter. Although these data support an AUC range for vancomycin-associated nephrotoxity rather than a single threshold, available evidence suggests that a daily AUC limit of 700 mg · h/liter is reasonable., (Copyright © 2017 American Society for Microbiology.)

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure., (Copyright © 2017 American Society for Microbiology.)

Background: Recent evidence suggests that among patients receiving vancomycin, receipt of concomitant piperacillin-tazobactam increases the risk of nephrotoxicity. Well-controlled, adequately powered studies comparing rates of acute kidney injury (AKI) among patients receiving vancomycin + piperacillin-tazobactam (VPT) compared to similar patients receiving vancomycin + cefepime (VC) are lacking. In this study we compared the incidence of AKI among patients receiving combination therapy with VPT to a matched group receiving VC., Methods: A retrospective, matched, cohort study was performed. Patients were eligible if they received combination therapy for ≥48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dL or they were receiving renal replacement therapy. Patients receiving VC were matched to patients receiving VPT based on severity of illness, intensive care unit status, duration of combination therapy, vancomycin dose, and number of concomitant nephrotoxins. The primary outcome was the incidence of AKI. Multivariate modeling was performed using Cox proportional hazards., Results: A total of 558 patients were included. AKI rates were significantly higher in the VPT group than the VC group (81/279 [29%] vs 31/279 [11%]). In multivariate analysis, therapy with VPT was an independent predictor for AKI (hazard ratio = 4.27; 95% confidence interval, 2.73-6.68). Among patients who developed AKI, the median onset was more rapid in the VPT group compared to the VC group (3 vs 5 days P =< .0001)., Conclusion: The VPT combination was associated with both an increased AKI risk and a more rapid onset of AKI compared to the VC combination., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Despite their common use as an empirical combination therapy for the better part of a decade, there has been a recent association between combination therapy with vancomycin and piperacillin-tazobactam and high rates of acute kidney injury (AKI). The reasons for this increased association are unclear, and this analysis was designed to investigate the association. Retrospective cohort and case-control studies were performed. The primary objective was to assess if there is an association between extended-infusion piperacillin-tazobactam in combination with vancomycin and development of AKI. The secondary objectives were to identify risk factors for AKI in patients on the combination, regardless of infusion strategy, and to evaluate the impact of AKI on clinical outcomes. AKI occurred in 105/320 (33%) patients from the cohort receiving combination therapy with vancomycin and piperacillin-tazobactam, with similar rates seen in those receiving intermittent (53/160 [33.1%]) and extended infusions (52/160 [32.5%]) of piperacillin-tazobactam. Independent risk factors for AKI in the cohort included having a documented Gram-positive infection, the presence of sepsis, receipt of a vancomycin loading dose (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.05 to 4.71), and receipt of any concomitant nephrotoxin (OR, 2.44; 95% CI, 1.41 to 4.22). For at-risk patients remaining on combination therapy, the highest rates of AKI occurred on days 4 (10.7%) and 5 (19.3%). The incidence of AKI in patients on combination therapy with vancomycin and piperacillin-tazobactam is high, occurring in 33% of patients. Receipt of piperacillin-tazobactam as an extended infusion did not increase this risk. Modifiable risk factors for AKI include receipt of a vancomycin loading dose, concomitant nephrotoxins, and longer durations of therapy., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

To date, no comparative clinical studies have investigated the effects of different vancomycin products on nephrotoxicity. The objective of this single-center, retrospective, matched-cohort study was to investigate the impact of two different vancomycin products on the development of nephrotoxicity. The study population included adults receiving a single vancomycin product, from either Pfizer or Hospira, for their entire course of therapy. Patients were matched based on underlying nephrotoxicity risk factors. Secondary outcomes included the need for renal replacement therapy, length of hospital stay, and in-hospital mortality. One-hundred forty-six matched pairs (n = 292) were included, and they had no significant differences in demographics, comorbid conditions, severity of illness, or vancomycin-associated nephrotoxicity risk factors. The frequency of nephrotoxicity was 8.9% in the Pfizer group and 11.0% in the Hospira group as defined by the 2009 consensus vancomycin guidelines (P = 0.56), 17.1% in the Pfizer group and 13.0% in the Hospira group as defined by the Acute Kidney Injury Network (AKIN) (P = 0.33), and 10.3% in the Pfizer group and 11.6% in the Hospira group as defined by RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria (P = 0.71). There were no differences between groups in regard to nephrotoxicity by any definition or in secondary outcomes. In multivariate analysis of overall nephrotoxicity risk factors, the type of vancomycin product was not independently associated with increased odds of developing nephrotoxicity according to the RIFLE criteria. Based on our results, there are no discernible differences between Pfizer and Hospira vancomycin products in the frequency of nephrotoxicity. Confirmation of these results with other types of vancomycin and different patient populations is warranted., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objectives: Prescription errors occur frequently in pediatric emergency departments (PEDs).The effect of computerized physician order entry (CPOE) with electronic medication alert system (EMAS) on these is unknown. The objective was to compare prescription errors rates before and after introduction of CPOE with EMAS in a PED. The hypothesis was that CPOE with EMAS would significantly reduce the rate and severity of prescription errors in the PED., Methods: A prospective comparison of a sample of outpatient, medication prescriptions 5 months before and after CPOE with EMAS implementation (7,268 before and 7,292 after) was performed. Error types and rates, alert types and significance, and physician response were noted. Medication errors were deemed significant if there was a potential to cause life-threatening injury, failure of therapy, or an adverse drug effect., Results: There was a significant reduction in the errors per 100 prescriptions (10.4 before vs. 7.3 after; absolute risk reduction = 3.1, 95% confidence interval [CI] = 2.2 to 4.0). Drug dosing error rates decreased from 8 to 5.4 per 100 (absolute risk reduction = 2.6, 95% CI = 1.8 to 3.4). Alerts were generated for 29.6% of prescriptions, with 45% involving drug dose range checking. The sensitivity of CPOE with EMAS in identifying errors in prescriptions was 45.1% (95% CI = 40.8% to 49.6%), and the specificity was 57% (95% CI = 55.6% to 58.5%). Prescribers modified 20% of the dosing alerts, resulting in the error not reaching the patient. Conversely, 11% of true dosing alerts for medication errors were overridden by the prescribers: 88 (11.3%) resulted in medication errors, and 684 (88.6%) were false-positive alerts., Conclusions: A CPOE with EMAS was associated with a decrease in overall prescription errors in our PED. Further system refinements are required to reduce the high false-positive alert rates., (© 2015 by the Society for Academic Emergency Medicine.)

The cartilaginous columellar strut is a well established, commonly used graft in rhinoplasty which provides support and stability to the nasal base. The risk of such a graft is related to grafts designs, whereby the posterior aspect can cause clicking with movement across the anterior nasal spine. We present an additional unusual complication of ill-fitting maxillary dentures in an edentulous patient, previously not reported in the literature. This unique complication should alert facial plastic surgeons to use additional caution when sculpting columellar grafts in edentulous patients in order to avoid potential post-operative complications in this specific patient population., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Doripenem is the most recently introduced carbapenem, with a broad spectrum of antimicrobial activity. Preliminary data indicated that activity is optimized by maximizing the time that serum concentration remains above the minimum inhibitory concentration; however, limited clinical data are available to support this approach., Objective: To compare clinical outcomes before and after implementation of a hospital-wide initiative extending the duration of infusion for doripenem from 1 hour (standard) to 4 hours (prolonged)., Methods: This retrospective, quasi-experimental study compared clinical outcomes associated with doripenem administered as a 1-hour infusion versus a 4-hour infusion for treatment of suspected or documented infections caused by gram-negative organisms. Outcomes were assessed for the entire cohort, as well as for the subpopulation of patients admitted to the intensive care unit., Results: Two hundred patients were included; 106 patients received doripenem via standard infusion and 94 patients via prolonged infusion. No significant differences were noted between the treatment groups in clinical success, length of stay, or duration of treatment when the entire cohort was evaluated. In the critically ill subgroup, pneumonia, standard-infusion doripenem, and concomitant bacteremia were independent predictors of clinical failure (adjusted odds ratio [95% CI] 7.8 [2.4-25.6], 5.5 [1.6-18.7], and 7.0 [1.6-31.3], respectively). Additionally, critically ill patients who received doripenem via standard infusion were significantly more likely to experience recurrence of infection or death within 90 days. No significant differences were noted in length of stay or duration of bacteremia., Conclusions: The duration of infusion did not significantly impact outcomes when the entire cohort was compared; however, prolonged infusion of doripenem was associated with significantly improved clinical outcomes among critically ill patients. These findings support the use of prolonged infusion of doripenem for critically ill patients.

Background: Recent reports have described decreased effectiveness with vancomycin treatment for methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) when the vancomycin minimum inhibitory concentration (MIC) is >1 µg/mL., Methods: This matched, retrospective cohort study compared the clinical effectiveness of daptomycin with that of vancomycin for the treatment of MRSAB with vancomycin MICs >1 µg/mL. The primary outcome was clinical failure, defined as a composite of 30-day mortality or bacteremia persisting for ≥7 days., Results: One hundred seventy patients were matched 1:1 with respect to the antimicrobial administered. In the daptomycin group, all patients received <72 hours of vancomycin (median, 1.7 days [interquartile range, 1.1-2.3 days]) prior to switching to daptomycin. The rate of clinical failure at 30 days was significantly lower in the daptomycin arm compared to the vancomycin arm (20.0% vs 48.2%; P < 0.001). Both 30-day mortality and persistent bacteremia were significantly lower in the daptomycin group compared to the vancomycin group (3.5% vs 12.9% [P = .047] and 18.8% vs 42.4% [P = .001], respectively). Logistic regression confirmed the association between vancomycin treatment and increased risk of clinical failure (adjusted odds ratio, 4.5; 95% confidence interval, 2.1-9.8)., Conclusions: This is the first matched study comparing early daptomycin versus vancomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL. Treatment with daptomycin resulted in significantly improved outcomes, including decreased 30-day mortality and persistent bacteremia. These results support the practice of switching early from vancomycin to daptomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL.

We demonstrated a significant inverse correlation between vancomycin and beta-lactam susceptibilities in vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) isolates. Using time-kill assays, vancomycin plus oxacillin or ceftaroline was synergistic against 3 of 5 VISA and 1 of 5 hVISA isolates or 5 of 5 VISA and 4 of 5 hVISA isolates, respectively. Beta-lactam exposure reduced overall vancomycin-Bodipy (dipyrromethene boron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding but may have improved vancomycin-cell wall interactions to improve vancomycin activity. Further research is warranted to elucidate the mechanism behind vancomycin and beta-lactam synergy.

Tumors of the orbital apex region are traditionally difficult to approach surgically due to key anatomic structures found in this highly crowded region. We present a case of progressively enlarging orbital apex venous angioma treated with a novel endoscopic transnasal septotomy technique. We highlight the key steps to this approach, as well as specific landmarks necessary to achieve a safe and successful outcome.

Objective: The infratemporal fossa (ITF) has historically been one of the most difficult regions of the skull base to access surgically. Available open approaches are complex, are associated with high morbidity, and do not always afford optimal visualization. Endoscopic access to the ITF improves visualization for management of many sinonasal and lateral skull base lesions involving this region. The purpose of this study is to evaluate a graduated multiangle approach for endoscopic access to this area using a cadaveric model., Study Design and Setting: Cadaveric study at an academic medical center., Methods: Endoscopic dissection was performed on a total of 10 sides of 5 fresh cadaveric heads. Four different approaches to the ITF were studied: ipsilateral endonasal, endoscopically assisted Caldwell-Luc, contralateral endonasal via septotomy, and endoscopically assisted Gillies transtemporal. High-quality endoscopic pictures and high-definition videos of each technique were obtained in order to document the differences in access achieved with each approach., Results: The combination of the 4 different endoscopic techniques allowed complete access to all areas of the ITF. The endoscopically assisted Caldwell-Luc improved anteroposterior access, the contralateral septotomy approach resulted in excellent far lateral access, and the endoscopically assisted Gillies approach allowed posterosuperior visualization and instrumentation., Conclusion: Endoscopic access to the ITF can be accomplished by each of the 4 methods described. A multiangle, graduated approach can provide surgeons the ability to customize surgical access depending on the location of a specific lesion within the ITF.

Objective: The endoscopic modified Lothrop procedure (EMLP) is a relatively safe and efficacious advanced approach to access the frontal sinus for recalcitrant disease. There have been limited data specifically addressing those patients with advanced but unilaterally limited and supraorbitally based frontal sinus disease. In this study, the authors propose a modification of the EMLP technique, titled a modified hemi-Lothrop procedure (MHLP), which would limit the dissection of the EMLP to removal of the frontal sinus floor of the unilaterally diseased frontal sinus, thereby sparing the mucosa and natural drainage pathways of the nondiseased contralateral frontal sinus., Study Design and Setting: Cadaveric study at an academic medical center., Methods: A cadaveric dissection with photodocumentation was performed to demonstrate the MHLP and to quantify the accessibility of this approach to far-laterally based frontal sinus disease., Results: The MHLP dissection was shown to provide adequate access to the most distal supraorbital and laterally based aspects of the frontal sinus. Using 3 cadavers, the authors demonstrated and documented the technique of MHLP to access lateral frontal sinus disease from the contralateral nasal cavity via a superior septectomy window., Conclusion: The MHLP was demonstrated to be a feasible approach and alternative to more traditional endoscopic procedures in addressing unilateral frontal sinus disease. This modification may be useful in addressing difficult to access unilateral disease that may otherwise require more extensive resection. This demonstration helps define the accessibility of the lateral frontal sinus via an MHLP and begins to provide estimates of which patients may benefit from this approach.

Objectives: Based on the reduced morbidity seen in our retrospective study, we undertook a prospective, randomized trial to determine whether transposition of the sartorius muscle improves post-operative morbidity in women with squamous cell carcinoma of the vulva undergoing inguinal-femoral lymphadenectomy., Methods: Patients with squamous carcinoma of the vulva requiring inguinal-femoral lymphadenectomy were randomized to undergo sartorius transposition or not. All patients received perioperative antibiotics, DVT prophylaxis, and closed suction surgical site drainage. Outcomes assessed include wound cellulitis, wound breakdown, lymphocyst formation, lymphedema, and/or rehospitalization. Cohorts were compared using Fisher's exact test. Baseline characteristics were compared using Student's t test or Fischer's exact test as appropriate. Logistic regression was used to assess the impact of sartorius transposition, after adjusting for other factors., Results: From June 1996 to December 2002, 61 patients underwent 99 inguinal-femoral lymphadenectomies, 28 with sartorius transposition, and 33 without. The mean (SD) age for controls and patients undergoing sartorius transposition was 63.5 (15.2) and 73.8 (13.7) years, respectively (P < 0.05). There were no statistically significant differences in BSA, tobacco use, co-morbid medical conditions, past surgical history, medication use, size of incision, duration of surgery, number of positive lymph nodes, pathologic stage, pathologic grade, pre- or postoperative hemoglobin, or length of hospitalization. There were no statistically significant differences in the incidence of wound cellulitis, wound breakdown, lymphedema, or rehospitalization. The incidence of lymphocyst formation was increased in the sartorius transposition group. After adjusting for age, however, the groups appeared similar., Conclusions: Sartorius transposition after inguinal-femoral lymphadenectomy does not reduce postoperative wound morbidity.

Objective: Primary peritoneal carcinosarcomas are similar to ovarian carcinomas in that they can metastasize by intraperitoneal dissemination; therefore, invasion of the submesothelial interstitial (stromal) matrix is an integral part of the pathology. Our objective was to study cell-matrix interactions that may influence invasive behavior of a novel, primary peritoneal carcinosarcoma cell line (PC880), and to assess how these cell-matrix interactions are different from frequently studied cultured ovarian carcinoma cells NIH:OVCAR-3, SKOV-3, and ES-2. We also wanted to determine how the expression of the cell-cell adhesion molecule E-cadherin is related to invasive behavior., Methods: The PC880 cell line was established from ascites fluid of a patient diagnosed with primary peritoneal carcinosarcoma. Adhesion assays were done in titer plates coated with individual matrix components. Cell migration in monolayer cultures was assessed by the scratch wound assay method. Invasion assays were done using a three-dimensional type I collagen gel. Cytokeratin, vimentin, and E-cadherin were detected by Western blotting. E-cadherin mRNA was detected by RT-PCR., Results: PC880 cells adhered well to fibronectin, laminin, and vitronectin in an integrin-dependent manner. The cells also adhered to type I collagen and invaded a three-dimensional type I collagen matrix. The invasiveness of the PC880 cells was moderated by pretreatment of the collagen matrix with heparin or chondroitin sulfate (82 and 63% of control invasiveness, respectively), indicating a role of cell surface proteoglycans in promoting invasive phenotype. Treatment of PC880 cells with sodium chlorate also decreased invasiveness (80% of control), further confirming the role of cell surface proteoglycans. Treatment of PC880 cells with function-blocking antibody to alpha2 integrin decreased invasiveness (57% of control), indicating the role of integrins in promoting the invasive phenotype. The protease inhibitors GM6001, E-64, and AEBSF decreased invasiveness (35, 57, and 37% of control, respectively) of PC880 cells. The ES-2 cells also adhered to type I collagen, and invaded the three-dimensional type I collagen matrix; however, inhibitors such as heparin, chondroitin sulfate, function-blocking antibody to alpha2 integrin, E-64, and AEBSF were less effective in moderating the invasiveness. Inhibition of invasiveness with sodium chlorate was the same as in PC880 cell, while GM6001 did not inhibit invasiveness at all. The NIH:OVCAR-3 and SK-OV-3 cells were previously found to adhere to type I collagen, but these cells did not invade the three-dimensional type I collagen matrix. In a monolayer culture PC880 and ES-2 cells had significantly higher motility than NIH:OVCAR-3 and SK-OV-3 cells. Only these noninvasive cell lines expressed E-cadherin protein or mRNA., Conclusions: PC880 is the first cell line established from primary peritoneal carcinosarcoma, and the cytoskeletal composition indicated that these cells represent the sarcomatous elements of the tumor. PC880 cells, similar to ES-2 cells, adhered to type I collagen, and invaded a three-dimensional collagen matrix. The invasion of the interstitial matrix by both the peritoneal carcinosarcoma and the ovarian carcinoma cell line was mediated by cell surface proteoglycans, alpha2 integrin, and proteases. The invasive cell behavior of PC880 and ES-2 cells correlated with a high degree of motility, and with the lack of expression of the cell-cell adhesion molecule E-cadherin.

Objective: The purpose of this study was to attempt to reduce the small bowel volume in cervical cancer patients undergoing radiation therapy using the belly board device and a four-field technique., Methods: From 1994 through 1997, twenty-one patients with cervical cancer were referred to the University of Minnesota Medical Center and underwent surgical staging with or without radical hysterectomy followed by postoperative external beam radiotherapy for various indications including positive nodal disease (n = 11), lymph-vascular space invasion (n = 2), poor histology (n = 3), parametrial disease (n = 4), and positive vaginal margin (n = 1)., Results: The median age of the 21 patients was 42 years (25-54 years) and a median external beam pelvic radiation dose of 4775 cGy (range, 4200-5075 cGy) was administered. All patients were evaluated for amount of small bowel in the field in both the supine and prone positions, with and without the belly board device (BBD), using a four-field technique. With a full bladder, abdominal radiographs with contrast were obtained to evaluate the volume of small bowel within the radiation fields. In most patients, the BBD was effective at minimizing the amount of small bowel in the lateral fields, whereas a prone position on the treatment table (without the BBD) spared the most small bowel with the AP/PA fields. Therefore over a 2-day cycle, the most small bowel sparing was obtained with the patients treated prone on the BBD for the lateral fields on Day 1 and prone on the table for the AP/PA fields on Day 2. Patients had FIGO stage IB (n = 18), IA2 (n = 1), and IIA (n = 2). The median follow-up was 37 months (24-65 months). No significant acute gastrointestinal or genitourinary toxicity was experienced and no patients have experienced a bowel obstruction to date., Conclusions: The BBD may offer a means for positioning the mobile small intestine out of the radiation field and improving the tolerance of radiotherapy. The BBD provides a noninvasive technique for reduction of acute and chronic gastrointestinal morbidity., (Copyright 2001 Academic Press.)

Objectives: The aim of the study is to determine whether critical pathways can be implemented at an academic institution to limit cost, without compromising patient satisfaction and quality of care., Patients and Methods: Patients undergoing a hysterectomy with either cervical or endometrial cancer were placed on specific critical pathways consecutively for an 18-month study period. Preoperative teaching was intensified to educate the patient regarding expectations during the postoperative period. All patients were started on early feeding and patients were also placed on separate care pathways addressing pain and deep vein thrombosis prophylaxis. Total direct costs and patient satisfaction were obtained throughout the study period. During the year prior to care pathway implementation, patient data and direct costs were obtained for the preintervention group utilized for comparison. Postintervention groups were summarized every 6 months during the study period., Results: From January 1997 through June 1998, 63 patients with cervical carcinoma undergoing a radical hysterectomy (DRG 353) and 21 patients with endometrial cancer who underwent a hysterectomy and lymph node sampling (DRG 355) were utilized as the preintervention group. During the 18-month study period (July 1998-December 1999), 42 patients (DRG 353) and 25 patients (DRG 355) were accrued. The average length of stay was reduced from 5.2 (DRG 353) and 4.7 days (DRG 355) prior to implementation of pathways to 3.4 days in both groups. In addition, total direct costs were reduced by 29 (DRG 353) and 32% (DRG 355) after implementation of care pathways. Patient satisfaction data recorded during the study did not demonstrate any change throughout the study period nor were there any higher rates of readmission after implementation of the care pathways., Conclusions: Critical pathways in gynecologic oncology can be implemented in a managed care environment in order to maintain high quality of care, maintain outcomes, and help reduce costs., (Copyright 2001 Academic Press.)

Ice worms occupy a unique position in metazoan phylogeny in that they are the only known annelid that completes its life cycle in ice. The mechanism(s) associated with this adaptation are likely to occur at different levels, ranging from modification of their metabolism to changes in morphology. In this study, we examined specimens of Mesenchytraeus solifugus by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in an effort to identify morphologic structures that may aid in its glacial habitation. We report that M. solifugus contains an elongated head pore at the tip of its prostomium, numerous sensory structures, and differentially oriented setae that curve abruptly at their distal end.

Objective: Complement system plays an important role in host defense mechanisms against microorganisms and tumor cells. To protect themselves from autologous complement-mediated damage, normal host tissues express cell membrane-associated complement regulatory proteins (CRPs). To investigate whether neoplastic endometrial tissues overexpress these proteins to escape complement damage, we examined the distribution of complement receptor type 1 (CR1, CD35), membrane cofactor protein (MCP, CD46), decay-accelerating factor (DAF, CD55), and protectin (MACIF, CD59) on frozen endometrial tissue samples., Methods: A total of 54 endometrial tissue samples were collected. Cryosections were obtained of 31 benign and 23 malignant tissue specimens. Tissue sections were stained by immunohistochemical staining procedure using specific antibodies and employing the avidin-biotin technique. Quantitation of the protein content of these CRPs was determined using the Samba 4000 image analysis system., Results: For all four of the CRPs studied, a statistically significant difference in protein expression between the benign and malignant endometrial tissue specimens (P < 0.0001) was observed., Conclusions: Overexpression of all the CRPs studied (CD35, CD46, CD55, CD59) was observed in the malignant as compared with the benign endometrial tissues. The upregulation of these CRPs may promote resistance of the endometrial malignant tissue to complement-mediated damage, thereby allowing the tumor cells to escape from cytolysis and thus promoting carcinogenesis., (Copyright 2000 Academic Press.)

Background: Complex biliary surgery is associated with significant morbidity, prolonged hospital stay, and high cost. Clinical pathway implementation has the potential to standardize treatment and improve outcomes. Therefore the aim of this analysis was to determine whether clinical pathway implementation and/or feedback of outcome data would alter hospital stay, charges, and mortality rates for complex biliary surgery at an academic medical center, Methods: Pre- and postoperative length of stay, hospital charges, and mortality rates were monitored for 36 months before (period 1) and for 2 18-month periods (periods 2 and 3) after implementation of a clinical pathway for hepaticojejunostomy. Outcome data were provided to the surgeons 18 months after pathway implementation to determine whether further clinical practice improvement was possible., Results: From 1991 to 1997, 339 patients underwent hepaticojejunostomy at The Johns Hopkins Hospital for malignant and benign biliary obstruction. Total length of stay was 13.3 +/- 0.9 days for period 1 compared with 12.5 +/- 0.8 days for period 2 (not significant) and 10.1 +/- 0.3 days for period 3 (P < .01 vs period 1; P < .03 vs period 2). Hospital charges averaged $24,446 during period 1 compared with $23,338 during period 2 and $20,240 during period 3 (P < .01 vs periods 1 and 2). Hospital mortality rate was 4.5% during period 1 compared with 0.7% during periods 2 and 3 (P < .05)., Conclusions: These data suggest that implementation of a clinical pathway for hepaticojejunostomy reduces hospital mortality rates and that feedback of outcome data to surgeons results in further clinical practice improvement. Thus clinical pathway implementation and feedback are effective methods to control costs at an academic medical center.

Background: Cholesterol gallstones occur most commonly in multiparous women, but the causes for this phenomenon remain unclear. This same patient population is prone to chronic iron deficiency anemia. In addition, iron is known to play an important role in hepatic enzyme metabolism. Therefore, we tested the hypotheses that iron deficiency would alter hepatic cholesterol metabolism and enhance gallstone formation., Methods: Forty adult prairie dogs were fed either a control iron-supplemented (200 ppm), an iron-deficient (8 ppm), a 0.4% cholesterol iron-supplemented (200 ppm), or a 0.4% cholesterol iron-deficient (8 ppm) diet. After 8 weeks gallbladder bile, serum, and liver were harvested. Gallbladder bile was examined for cholesterol crystals and gallstones. Bile lipids and hepatic enzymes were measured, and a cholesterol saturation index (CSI) was calculated., Results: Animals receiving the iron-deficient diet were more likely to have cholesterol crystals in their bile than were animals on the control diet (80% vs. 20%; p < 0.05). Animals on the 0.4% cholesterol iron-deficient diet had more cholesterol crystals per high-powered field (79 +/- 10 vs. 49 +/- 9; p = 0.07), a higher molar % cholesterol (6.0 +/- 0.3 vs 4.4 +/- 0.5; p < 0.05), and a higher CSI (1.27 +/- 0.10 vs. 0.91 +/- 0.07; p < 0.05) compared to animals receiving the 0.4% cholesterol iron supplemented diet. The 7 alpha-hydroxylase levels were lower in the animals on the iron-deficient diet compared to those receiving the control diet (0.42 +/- 0.08 vs 1.17 +/- 0.40 pmol/mg per minute; p = 0.07)., Conclusions: These data suggest that an iron-deficient diet (1) alters hepatic enzyme metabolism, which, in turn, (2) increases gallbladder bile cholesterol and promotes cholesterol crystal formation. We conclude that iron deficiency plays a previously unrecognized role in the pathogenesis of cholesterol gallstone formation in women.

During the course of four recent dose-intense chemotherapy trials, the routine practice of transfusing patients with platelet counts < 20,000/microliters was changed to a more conservative style of management limiting prophylactic transfusions to patients with platelet counts < 5000/microliters. One hundred seventy-nine episodes of thrombocytopenia in 46 patients enrolled in four dose-intense chemotherapy trials were evaluated. Thirty-two patients had advanced carcinoma of the ovary, 10 had pelvic sarcomas, and 4 had cervical cancer. Of the 179 episodes of thrombocytopenia evaluated, 100 exhibited severe thrombocytopenia (platelet count < 20,000/microliters). Of these 100 episodes, 30 received prophylactic platelet transfusions while 70 did not. Thirty-eight episodes of thrombocytopenia were 5000-10,000/microliters, 24 of which received prophylactic platelet transfusions while 14 did not. Eighteen episodes (10%) of thrombocytopenia resulted in minor bleeding and all occurred during severe thrombocytopenia. Minor bleeding occurred in 27% of episodes of severe thrombocytopenia receiving prophylactic platelet transfusions versus 14% not transfused (P = 0.2). Of the 38 episodes of thrombocytopenia 5000-10,000/microliters, minor bleeding occurred in 17% receiving prophylactic platelet transfusions versus 24% not transfused (P = 0.95). None of the 179 episodes of thrombocytopenia resulted in major bleeding, including 70 episodes of thrombocytopenia < 20,000/microliters not receiving prophylactic platelet transfusions which included 14 episodes of thrombocytopenia between 5000-10,000/microliters. In conclusion, in women with gynecologic cancer and chemotherapy-induced thrombocytopenia, we safely limited prophylactic platelet transfusions for episodes of thrombocytopenia < 5000/microliters. We hope our study will prompt prospective, randomized trials evaluating the need of prophylactic platelet transfusions for chemotherapy-induced thrombocytopenia in patients with solid tumors.