Paul Kubilis

Clinical Significance of Nephrotoxicity in Patients Treated with Amphotericin B for Suspected or Proven Aspergillosis

The records of 239 immunosuppressed patients receiving amphotericin B for suspected or proven aspergillosis were reviewed to determine rates of nephrotoxicity, dialysis, and fatality. The mean and median durations of treatment were 20.4 and 15.0 days, respectively. The creatinine level doubled in 53% of patients and exceeded 2.5 mg/dL in 29%; 14.5% underwent dialysis; and 60% died. A multivariate Cox proportional hazards analysis showed that patients whose creatinine level exceeded 2.5 mg/dL (hazard ratio [HR], 42.02; P<.001), allogeneic bone marrow transplantation (BMT) patients (HR, 6.34; P<. 001), and autologous BMT patients (HR, 5.06; P=.024) were at greatest risk for requiring hemodialysis. Use of hemodialysis (HR, 3. 089; P<.001), duration of amphotericin B use (HR, 1.03 per day; P=. 015), and use of nephrotoxic agents (HR, 1.96; P=.017) were associated with greater risk of death, whereas patients undergoing solid organ transplantation were at lowest risk (HR, 0.46; P=.002). These data indicate that elevated creatinine levels during amphotericin B treatment are associated with a substantial risk for hemodialysis and a higher mortality rate, but the risks vary in different patient groups.

Risk factors for neonatal sepsis.

Objective To determine the associations between maternal characteristics, intrapartum events, and neonatal sepsis by multivariate analysis. Methods We enrolled 823 women from a high-risk population and analyzed maternal and neonatal demographic and outcome variables with univariate analysis and multivariate logistic modeling. Results Two-hundred sixteen women (26%) were colonized with group B streptococci, 82 (10%) developed chorioamnionitis, and 141 (17%) delivered prematurely. Cultureproven neonatal sepsis or meningitis was found in 15 of 833 (1.8%) neonates, and 101 of the remaining 818 (12.3%) infants were suspected to have sepsis or pneumonia. Multivariate analysis of risk factors for proven neonatal sepsis demonstrated a statistically significant association with decreasing gestational age, duration of internal monitoring for more than 12 hours (odds ratio [OR] 7.2, 95% confidence interval [CI] 1.6–32.2), maternal group B streptococcal infection (OR 4.2, 95% CI 1.4–13.1), chorioamnionitis (OR 4.4, 95% CI 1.2–16.1), and endometritis (OR 6.4, 95% CI 1.2–34.2). Conclusion Through the use of multivariate modeling, we determined that chorioamnionitis or endometritis, preterm delivery, group B streptococcal colonization, and a prolonged duration of internal monitoring are independent risk factors for neonatal sepsis. We postulate that the presence of a foreign body that traverses the birth canal may facilitate ascending peripartal infection.

Preradiotherapy computed tomography as a predictor of local control in supraglottic carcinoma

PURPOSE To determine the utility of pretreatment computed tomography (CT) for predicting primary site control in patients with supraglottic squamous cell carcinoma (SCC) treated with definitive radiotherapy (RT). MATERIALS AND METHODS Pretreatment CT studies in 63 patients were reviewed. Minimum length of follow-up was 2 years. Local recurrence and treatment complications resulting in permanent loss of laryngeal function were documented. Tumor volume was calculated using a computer digitizer, and pre-epiglottic space (PES) spread was estimated. The data were analyzed using a combination of Fishers exact test, logistic regression modeling, and multivariate analyses. Five-year local control rates were calculated using the product-limit method. RESULTS Local control rates were inversely and roughly linearly related to tumor volume, although there seemed to be a threshold volume at which primary site prognosis diminished. Local control was 89% in tumors less than 6 cm3 and 52% when volumes were > or =6 cm3 (P = .0012). The likelihood of maintaining laryngeal function also varied with tumor volume: 89% for tumors less than 6 cm3 and 40% for tumors > or =6 cm3 (P = .00004). Pre-epiglottic space involvement by tumor of > or =25% was associated with a reduced chance of saving the larynx (P = .0076). Multivariate analyses revealed that only tumor volume independently altered these end points. CONCLUSION Pretreatment CT measurements of tumor volume permits stratification of patients with supraglottic SCC treated with RT alone (which allows preservation of laryngeal function) into groups in which local control is more likely and less likely. Pre-epiglottic space spread is not a contraindication to using RT as the primary treatment for supraglottic SCC.

Influence of tidal volume on the distribution of gas between the lungs and stomach in the nonintubated patient receiving positive-pressure ventilation.

Abstract Objectives: When ventilating a nonintubated patient in cardiac arrest, the European Resuscitation Council has recently recommended a decrease in the tidal volume from 0.8 to 1.2 L to 0.5 L, partly in an effort to decrease peak flow rate, and therefore, to minimize stomach inflation. The purpose of the present study was to examine the validity of the European Resuscitation Councils recommendation in terms of gas distribution between lungs and stomach in a bench model that simulates ventilation of a nonintubated patient with a self‐inflatable bag representing tidal volumes of 0.5 and 0.75 L. Design: A bench model of a patient with a nonintubated airway was used consisting of face mask, manikin head, training lung (lung compliance, 50 mL/cm H2 O; airway resistance, 5 cm H2 O/L/sec), adjustable lower esophageal sphincter pressure (LESP) and simulated stomach. Setting: University hospital laboratory. Subjects: Thirty healthcare professionals. Interventions: Healthcare professionals performed 1‐min bag‐mask ventilation at each LESP level of 5, 10, and 15 cm H2 O at a rate of 12 breaths/min, using an adult and pediatric self‐inflating bag, respectively. Volunteers were blinded to the LESP, which was randomly varied. Measurements and Main Results: Both types of self‐inflating bags induced stomach inflation, with higher stomach and lower lung tidal volumes when the LESP was decreased. Lung tidal volume with the pediatric bag was significantly (p < .05) lower at all LESP levels when compared with the adult bag, and ranged between 240 mL at an LESP of 15 cm H2 O and 120 mL at an LESP of 5 cm H2 O. Stomach tidal volume with the adult bag ranged between 250 mL at an LESP of 15 cm H2 O and increased to 550 mL at an LESP of 5 cm H2 O. Stomach tidal volume with the pediatric bag was significantly lower (p < .05) at all LESP levels when compared with the adult bag and ranged between 70 mL at an LESP of 15 cm H2 O and 300 mL at an LESP of 5 cm H2 O. Conclusions: Our data support the recommendation of the European Resuscitation Council to decrease tidal volumes to 0.5 L when ventilating a cardiac arrest victim with an unprotected airway. A small tidal volume may be a better trade‐off in the basic life support phase, as this may provide reasonable ventilation while avoiding massive stomach inflation. (Crit Care Med 1998; 26:364‐368) When ventilating a nonintubated cardiac arrest patient, the European Resuscitation Council has recently recommended a decrease in the tidal volume from 0.8 to 1.2 L [1] to 0.5 L [2], partly in an effort to decrease peak flow rate, and therefore, to minimize stomach inflation. Ventilation volume has an effect on pH, CO2 elimination, and oxygenation when pulmonary blood flow is extremely low, such as during cardiopulmonary resuscitation (CPR) or shock [3]. The Airway and Ventilation Management Working Group of the European Resuscitation Council [2] stated that ventilating a nonintubated cardiac arrest patient with a smaller tidal volume may be a better trade‐off in order to provide reasonable ventilation, while avoiding massive stomach inflation that may result in life‐threatening pulmonary complications. The gas distribution between lungs and stomach during positive‐pressure ventilation in a nonintubated airway depends on patient characteristics (lower esophageal sphincter pressure [LESP], airway resistance, and respiratory system compliance) and performance variables of the rescuer applying positive‐pressure ventilation (tidal volume, peak flow rate, and upper airway pressure). Thus, assessing the above‐mentioned recommendation in a clinical study is difficult to perform due to many confounding variables that are difficult to control and to evaluate when emergently managing therapy during CPR. As an example of the usefulness of laboratory models of ventilation, the American Heart Association [1] recommended increasing inspiratory time when ventilating a nonintubated cardiac arrest patient [1,4]. For example, such a model has the advantage that each variable of respiratory mechanics can be controlled and adjusted to investigate a certain hypothesis. We [4,5] previously studied the effect of tidal volume and peak flow rate on gas distribution between lungs and stomach during mechanical positive‐pressure ventilation, using a modification of the earlier described bench model of an unprotected airway. Although a mechanical ventilator is a valuable tool to study gas distribution in an unprotected airway, a self‐inflatable bag is the device usually used by the emergency medical service and in the hospital during the initial care of a cardiac arrest victim. Thus, the purpose of the present study was to examine the validity of the European Resuscitation Council recommendation [2] in terms of gas distribution between lungs and stomach in a bench model that simulates positive‐pressure ventilation of a nonintubated patient with self‐inflatable bags representing tidal volumes of 0.5 L and 0.75 L. Since observations in an animal model [6] showed that the LESP decreases rapidly after an untreated cardiac arrest, we further evaluated the effect of a decreased LESP on gas distribution between lungs and stomach in this model.

Can pretreatment computed tomography predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy

PURPOSE To determine if pretreatment computed tomography (CT) can predict local control in T3 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy (RT). METHODS AND MATERIALS Forty-two patients with previously untreated T3 squamous cell carcinoma of the glottic larynx were treated for cure with RT alone; all had a minimum 2-year follow-up. Tumor volumes and extent were determined by consensus of two head and neck radiologists on pretreatment CT studies. A tumor score was calculated and assigned to each primary lesion depending on the extent of laryngeal spread. Sclerosis of any laryngeal cartilage was recorded. The specific CT parameters assessed were correlated with local control. RESULTS Tumor volume was a significant predictor of local control. For tumors measuring < 3.5 cm3, local control was achieved in 22 of 26 patients (85%), whereas for tumors > or = 3.5 cm3, local control was achieved in 4 of 16 patients (25%) (p = 0.0002). Sensitivity and specificity using this cutpoint were 85% and 75%, respectively. Tumor score as a measure of anatomic extent was also found to be a significant predictor of local control. The local control rate for tumors assigned a low tumor score (< or = 5) was 78% (21 of 27) compared to 33% (5 of 15) for tumors assigned a high tumor score (6, 7, or 8) (p = 0.008). A significant decrease in the local control rate was observed for cancers involving the paraglottic space at the false vocal cord level (14 of 16 [88%] vs. 12/26 [46%]) (p = 0.010), cancers involving the face of the arytenoid (15 of 18 [83%] vs. 11 of 24 [46%]) (p = 0.024), and tumors involving the interarytenoid region (25 of 36 [69%] vs. 1 of 6 [17%]; p = 0.020). There were 12 patients with sclerosis of both the ipsilateral arytenoid and the adjacent cricoid cartilage. These patients showed a significant decrease in local control (4 of 12 [33%]). CONCLUSION Pretreatment CT can stratify patients with T3 glottic carcinoma into groups more or less likely to be locally controlled with definitive RT. The local control rate for these tumors can be improved using a CT-based tumor profile; the ideal CT profile for a radiocurable T3 glottic larynx carcinoma is volume < 3.5 cm3 and no or single laryngeal cartilage sclerosis.

Increased nadh oxidase activity in the retina of the BBZ/WOR diabetic rat

This morphological study demonstrates a role for endothelial cells in generating reactive oxygen species in early stages of retinopathy in the BBZ/Wor rat, an obese, noninsulin dependent model of diabetes. Hyperglycemia induced pseudohypoxia results in an imbalance in cytosolic NADH/NAD+. In the oxygen-rich environment of the retina, NADH oxidase generates superoxide radical which is dismutated to hydrogen peroxide. Localization of hydrogen peroxide by the cerium NADH oxidase enzyme activity cytochemical localization technique shows a statistically significant increase of peroxide localization in the central retina of diabetic rats as compared to age-matched, nondiabetic controls. Endothelial cell dysfunction, indicated by leakage of endogenous serum albumin, coincided with areas of NADH oxidase activity localization. In diabetic rats there are increased levels of fibronectin in areas of hydrogen peroxide localization. This in vivo, morphological study is the first demonstration of oxidative injury and endothelial cell dysfunction in the retina of a spontaneous, noninsulin dependent model of diabetes.

A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team.

Our aim was to identify financial and outcome benefits of therapeutic intervention by a multidisciplinary antimicrobial treatment team composed of pharmacists, a clinical microbiologist, and an infectious disease specialist. Of 252 consecutive inpatients receiving suboptimal intravenous antibiotics identified by the clinical pharmacist, 127 were prospectively randomized to intervention and 125 to a control group. The groups were similar with regard to severity of illness, infection type, and time from admission to randomization. Physicians received timely, detailed reviews of relevant microbiologic and clinical data with recommendations of possible optimal antibiotic choices, dosages, and rationales. Median length of stay after randomization for control and intervention groups was 9.0 days and 5.7 days, respectively (3.3‐day difference, p=0.0001). Fifteen (12.0%) and eight patients (6.3%), respectively, died, although the time‐specific mortality risk was not significantly different when length of postrandomization follow‐up and time to death were taken into account. Physician acceptance of suggestions was 89%. Median patient charges for radiology, laboratory, pharmacy, and room were reduced by

Exercise training in the debilitated aged: Strength and functional outcomes

4404/intervention, and median hospital costs were reduced by

Respiratory system compliance decreases after cardiopulmonary resuscitation and stomach inflation: impact of large and small tidal volumes on calculated peak airway pressure

2642/intervention. A multidisciplinary antimicrobial therapy team can be a useful information source for physicians, improve outcomes in hospitalized patients receiving intravenous antimicrobials, and result in substantial cost savings.

Evaluation of pretreatment computed tomography as a predictor of local control in T1/T2 pyriform sinus carcinoma treated with definitive radiotherapy

OBJECTIVE Resistance and endurance training result in gains in fitness in the aged. It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength, endurance, and function in this population. DESIGN Randomized, controlled trial. SETTINGS AND PATIENTS Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home. They were older than 60 yrs with impairment in at least one physical activity of daily living. Seventy-eight subjects volunteered and 58 (mean age, 75 yrs; 9 women, 49 men) completed the intervention and initial posttest. Only one subject withdrew because of injury or disinterest. INTERVENTION Thrice-weekly resistance training (using an isokinetic dynamometer) and twice-weekly endurance training for 4 to 8 weeks. MAIN OUTCOMES Isometric strength in dominant arm and leg, heart rate response to timed endurance test, and activities of daily living score. RESULTS The mean change in isometric strength across the muscle movements tested was 32.8% in the training group and 10.2% in the control group (difference, 22.6%; 95% confidence interval, 6.2% to 39.0%). No change in heart rate during exercise was seen in the training group. Trained subjects tended to have a greater improvement in functional activity than control subjects, which was statistically significant (p = .04) for those subjects who at enrollment were most dysfunctional (i.e., activities of daily living score less than 13 [maximum score 26]). CONCLUSION This group of debilitated elderly patients effectively performed resistance training and increased their strength, with the most impaired gaining the most function. Few in the group could effectively perform endurance training.