Malnutrition, Critical Illness Survivors, and Postdischarge Outcomes: A Cohort Study.

BACKGROUND: We hypothesized that preexisting malnutrition in patients who survived critical care would be associated with adverse outcomes following hospital discharge. METHODS: We performed an observational cohort study in 1 academic medical center in Boston. We studied 23,575 patients, aged ≥18 years, who received critical care between 2004 and 2011 and survived hospitalization. RESULTS: The exposure of interest was malnutrition determined at intensive care unit (ICU) admission by a registered dietitian using clinical judgment and on data related to unintentional weight loss, inadequate nutrient intake, and wasting of muscle mass and/or subcutaneous fat. The primary outcome was 90-day postdischarge mortality. Secondary outcome was unplanned 30-day hospital readmission. Adjusted odds ratios were estimated by logistic regression models adjusted for age, race, sex, Deyo-Charlson Index, surgical ICU, sepsis, and acute organ failure. In the cohort, the absolute risk of 90-day postdischarge mortality was 5.9%, 11.7%, 15.8%, and 21.9% in patients without malnutrition, those at risk of malnutrition, nonspecific malnutrition, and protein-energy malnutrition, respectively. The odds of 90-day postdischarge mortality in patients at risk of malnutrition, nonspecific malnutrition, and protein-energy malnutrition fully adjusted were 1.77 (95% confidence interval [CI], 1.23-2.54), 2.51 (95% CI, 1.36-4.62), and 3.72 (95% CI, 2.16-6.39), respectively, relative to patients without malnutrition. Furthermore, the presence of malnutrition is a significant predictor of the odds of unplanned 30-day hospital readmission. CONCLUSIONS: In patients treated with critical care who survive hospitalization, preexisting malnutrition is a robust predictor of subsequent mortality and unplanned hospital readmission.

Nucleated red blood cells, critical illness survivors and postdischarge outcomes: a cohort study.

BACKGROUND: Little is known about risk factors associated with out-of-hospital outcomes in survivors of critical illness. We hypothesized that the presence of nucleated red blood cells in patients who survived critical care would be associated with adverse outcomes following hospital discharge. METHODS: We performed a two-center observational cohort study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. All data were obtained from the Research Patient Data Registry at Partners HealthCare. We studied 2878 patients, age ≥ 18 years, who received critical care between 2011 and 2015 and survived hospitalization. The exposure of interest was nucleated red blood cells occurring from 2 days prior to 7 days after critical care initiation. The primary outcome was mortality in the 90 days following hospital discharge. Secondary outcome was unplanned 30-day hospital readmission. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both nucleated red blood cells and outcome. Adjustment included age, race (white versus nonwhite), gender, Deyo-Charlson Index, patient type (medical versus surgical), sepsis and acute organ failure. RESULTS: In patients who received critical care and survived hospitalization, the absolute risk of 90-day postdischarge mortality was 5.9%, 11.7%, 15.8% and 21.9% in patients with 0/µl, 1-100/µl, 101-200/µl and more than 200/µl nucleated red blood cells respectively. Nucleated red blood cells were a robust predictor of postdischarge mortality and remained so following multivariable adjustment. The fully adjusted odds of 90-day postdischarge mortality in patients with 1-100/µl, 101-200/µl and more than 200/µl nucleated red blood cells were 1.77 (95% CI, 1.23-2.54), 2.51 (95% CI, 1.36-4.62) and 3.72 (95% CI, 2.16-6.39) respectively, relative to patients without nucleated red blood cells. Further, the presence of nucleated red blood cells is a significant predictor of the odds of unplanned 30-day hospital readmission. CONCLUSION: In critically ill patients who survive hospitalization, the presence of nucleated red blood cells is a robust predictor of postdischarge mortality and unplanned hospital readmission.

Functional status, age, and long-term survival after trauma.

BACKGROUND: The association between functional status in trauma survivors and long-term outcomes is unknown. METHODS: We performed an observational cohort study on adult trauma patients (≥18 years), who required admission to the intensive care unit and who survived hospitalization between 1997 and 2011. The exposure of interest was a functional status defined as bed mobility, transfers, and gait level assessed at the time of hospital discharge. Adjusted odds ratios were estimated by multivariable logistic regression models. The primary outcome was all-cause, postdischarge mortality. RESULTS: We analyzed 3,565 patients with a mean (standard deviation) age of 55 (12.4) years; 60% were male, and 78% were white. The 720-day postdischarge mortality was 22.8%. In a logistic regression model, the lowest functional status category at hospital discharge was associated with 4-fold increased odds of 720-day postdischarge mortality (adjusted odds ratio 4.06 (95% confidence interval, 2.65-6.20, P < .001) compared with patients with independent functional status. We compared the odds of 720-day postdischarge mortality in patients with independent functional status and in patients in the lowest functional status category at hospital discharge. The odds of 720-day postdischarge mortality were stronger in older adults (≥65 years: adjusted odds ratio 3.34 [95% confidence interval, 1.72-6.50, P < .001]) than in younger adults (<65 years: adjusted odds ratio 2.53 [95% confidence interval, 1.39-4.60, P = .002]). Finally, improvement of functional status prior to discharge was associated with a 52% decrease in the odds of 720-day postdischarge mortality (adjusted odds ratio 0.48; 95% confidence interval, 0.30-0.75; P < .001) compared with patients without a change in functional status prior to discharge. CONCLUSION: In trauma intensive care unit survivors, functional status at hospital discharge is predictive of long-term mortality.

Functional Status in ICU Survivors and Out of Hospital Outcomes: A Cohort Study.

OBJECTIVES: Functional status at hospital discharge may be a risk factor for adverse events among survivors of critical illness. We sought to examine the association between functional status at hospital discharge in survivors of critical care and risk of 90-day all-cause mortality after hospital discharge. DESIGN: Single-center retrospective cohort study. SETTING: Academic Medical Center. PATIENTS: Ten thousand three hundred forty-three adults who received critical care from 1997 to 2011 and survived hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was functional status determined at hospital discharge by a licensed physical therapist and rated based on qualitative categories adapted from the Functional Independence Measure. The main outcome was 90-day post hospital discharge all-cause mortality. A categorical risk-prediction score was derived and validated based on a logistic regression model of the function grades for each assessment. In an adjusted logistic regression model, the lowest quartile of functional status at hospital discharge was associated with an increased odds of 90-day postdischarge mortality compared with patients with independent functional status (odds ratio, 7.63 [95% CI, 3.83-15.22; p < 0.001]). In patients who had at least 7 days of physical therapy treatment prior to hospital discharge (n = 2,293), the adjusted odds of 90-day postdischarge mortality in patients with marked improvement in functional status at discharge was 64% less than patients with no change in functional status (odds ratio, 0.36 [95% CI, 0.24-0.53]; p < 0.001). CONCLUSIONS: Lower functional status at hospital discharge in survivors of critical illness is associated with increased postdischarge mortality. Furthermore, patients whose functional status improves before discharge have decreased odds of postdischarge mortality.

The association of acute kidney injury in the critically ill and postdischarge outcomes: a cohort study*.

OBJECTIVE: Hospital readmissions contribute significantly to the cost of inpatient care and are targeted as a marker for quality of care. Little is known about risk factors associated with hospital readmission in survivors of critical illness. We hypothesized that acute kidney injury in patients who survived critical care would be associated with increased risk of 30-day postdischarge hospital readmission, postdischarge mortality, and progression to end-stage renal disease. DESIGN: Two center observational cohort study. SETTING: Medical and surgical ICUs at the Brigham and Women's Hospital and the Massachusetts General Hospital in Boston, Massachusetts. PATIENTS: We studied 62,096 patients, 18 years old and older, who received critical care between 1997 and 2012 and survived hospitalization. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: : All data was obtained from the Research Patient Data Registry at Partners HealthCare. The exposure of interest was acute kidney injury defined as meeting Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease Risk, Injury or Failure criteria occurring 3 days prior to 7 days after critical care initiation. The primary outcome was hospital readmission in the 30 days following hospital discharge. The secondary outcome was mortality in the 30 days following hospital discharge. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both acute kidney injury and readmission status. Adjustment included age, race (white vs nonwhite), gender, Deyo-Charlson Index, patient type (medical vs surgical) and sepsis. Additionally, long-term progression to End Stage Renal Disease in patients with acute kidney injury was analyzed with a risk-adjusted Cox proportional hazards regression model. The absolute risk of 30-day readmission was 12.3%, 19.0%, 21.2%, and 21.1% in patients with No Acute Kidney Injury, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Injury, and Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Failure, respectively. In patients who received critical care and survived hospitalization, acute kidney injury was a robust predictor of hospital readmission and post-discharge mortality and remained so following multivariable adjustment. The odds of 30-day post-discharge hospital readmission in patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, or Failure fully adjusted were 1.44 (95% CI, 1.25-1.66), 1.98 (95% CI, 1.66-2.36), and 1.55 (95% CI, 1.26-1.91) respectively, relative to patients without acute kidney injury. Further, the odds of 30-day post-discharge mortality in patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, or Failure fully adjusted per our primary analysis were 1.39 (95% CI, 1.28-1.51), 1.46 (95% CI, 1.30-1.64), and 1.42 (95% CI, 1.26-1.61) respectively, relative to patients without acute kidney injury. The addition of the propensity score to the multivariable model did not change the point estimates significantly. Finally, taking into account age, gender, race, Deyo-Charlson Index, and patient type, we observed a relationship between acute kidney injury and development of end-stage renal disease. Patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, Failure experienced a significantly higher risk of end-stage renal disease during follow-up than patients without acute kidney injury (hazard ratio, 2.03; 95% CI, 1.56-2.65; hazard ratio, 3.99; 95% CI, 3.04-5.23; hazard ratio, 10.40; 95% CI, 8.54-12.69, respectively). CONCLUSIONS: Patients who suffer acute kidney injury are among a high-risk group of ICU survivors for adverse outcomes. In patients treated with critical care who survive hospitalization, acute kidney injury is a robust predictor of subsequent unplanned hospital readmission. In critical illness survivors, acute kidney injury is also associated with the odds of 30-day postdischarge mortality and the risk of subsequent end-stage renal disease.

Rapid encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

Rho (D) immune globulin intravenous (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura. Common side effects of IV RhIG include mild hemolysis, febrile reaction and headache. Significant hemolysis with renal impairment is infrequently noted. A single case of irreversible encephalopathy following IV RhIG has been reported. We report a second case of encephalopathy following an infusion of IV RhIG for treatment of idiopathic thrombocytopenic purpura.

RF ablation with adjuvant therapy: comparison of external beam radiation and liposomal doxorubicin on ablation efficacy in an animal tumor model.

PURPOSE: To determine the critical thermal dosimetry and relative efficacy for RF ablation combined with external beam radiation (XRT) or liposomal doxorubicin (LD), in an animal tumor model. MATERIALS AND METHODS: This study was performed in two phases, in 13-18 mm diameter R3230 tumors subcutaneously implanted into Fischer rats. In phase 1, tumors (n = 30) were randomized into six groups. RF energy (titrated to 70 degrees C tip temperature) was applied for either 2.5 or 5 min (n = 15, each group). For each duration, one of three adjuvant therapies was applied (n = 5, each): no therapy (control), LD (1 mg intravenously, 30 min post-RF), or XRT (20 Gy at 1 Gy min(-1), within 2 h post-RF), with sacrifice at 48 h for pathologic analysis. In phase 2, thermal mapping was performed in 20 tumors throughout RF application (70 degrees C; 5 min), at 1.5-7 mm distances from the active electrode tip. Temperature profiles throughout the tumor were constructed and were used to interpolate temperatures over time at the critical ablation margin, to derive maximum threshold temperature, AUC (area under the curve) and CEM(43) (cumulative equivalent minutes at 43 degrees C). Ablation sizes and all calculated values were compared within and across experimental groups using MANOVA statistics with pair-wise T-test for individual comparisons. RESULTS: RF/XRT produced the largest coagulation (11.7 +/- 1.5 mm at 2.5 min, >or=15 +/- 0.7 mm at 5 min), followed by RF/LD, and then RF alone (p < 0.001 for all comparisons). RF/XRT demonstrated temperature threshold decreases from RF alone of 11.7 +/- 0.01 degrees C and 12.7 +/- 0.38 degrees C at 2.5 and 5 min respectively (with absolute thresholds of 42 degrees C for XRT compared to 52 degrees C for RF alone). RF/LD had decreases of 4.0 degrees C at 2.5 min and 4.4 degrees C at 5 min. Thermal dose requirements (AUC) decreased by 7.79% or 9.28% for RF/LD compared to >or=19.36% or 25.82% for RF/XRT at 2.5 and 5 min (p < 0.001). CEM(43) values followed similar patterns (p < 0.001), but with a reduction of 10(1) and 10(4) in magnitude for RF/LD and RF/XRT therapies at 5 min, respectively. CONCLUSIONS: For a standardized RF dose, the combination of high dose XRT and RF increased ablation size compared to RF and liposomal doxorubicin or RF alone. Increased ablation size is more closely associated with decreased temperature threshold necessary to induce coagulation, rather than the total thermal dose.

Chemical tumor ablation with use of a novel multiple-tine infusion system in a canine sarcoma model.

PURPOSE: To determine whether larger confluent zones of ablation can be achieved in chemical ablation with use of a multiple-tine infusion device compared with standard needle infusion in a solid tumor model. MATERIALS AND METHODS: Multiple canine venereal sarcomas (N=42) were implanted in nine mildly immunosuppressed dogs (treated with 10 mg/kg cyclosporin A twice daily). Tumors incubated for 8-12 weeks grew to a diameter of 5.4 cm+/-1.0. With ultrasound guidance, 8-56 mL of 100% ethanol or 15% acetic acid (diluted in saturated saline solution) were injected in aliquots (2-8 mL) at multiple distances (radius of 0-2 cm) from the needle axis with use of a multiple-tine infusion device. Presence of fluid reflux at the needle puncture site and resultant coagulation diameters were measured within 1 hour and compared with the results of infusion with a standard 18-gauge needle. RESULTS: Multiple-tine infusion enabled greater fluid infusion (15 mL+/-3 to 53 mL+/-3 depending on protocol) than standard needle injection (8 mL+/-1) before reflux was observed at the puncture site (P<.01). Additionally, progressive gains in contiguous tumor coagulation were achieved because acetic acid was infused as far as 2 cm from the needle axis with the multiple-tine device (P<.01; R(2)=0.59; y=0.5x+2.9). Optimal coagulation was achieved with the infusion of 4-mL aliquots at 0.5 cm and 1.0 cm from the needle, followed by three 4-mL or 8-mL aliquots (40 degrees rotation between infusions) at 1.5 cm and 2.0 cm from the needle (32 mL+/-0 and 53 mL+/-3 total, respectively). This yielded confluent short-axis coagulation diameters of 4.9 cm+/-1.0 and 5.4 cm+/-1.0, respectively, which were significantly greater than the measurement of 3.1 cm+/-0.4 achieved with standard needle infusion (P<.01). Smaller and noncontiguous foci of coagulation foci (1.7 cm+- 0.5) were seen with the use of ethanol for standard needle and multiple-tine infusions. CONCLUSIONS: Chemical ablation with 15% acetic acid with use of a multiple-tine infusion device resulted in larger diameters of contiguous tumor coagulation and enabled greater volumes of infusion than standard needle infusion or ethanol ablation. This suggests that chemical ablation with acetic acid infused with use of a multiple-tine device may overcome some of the difficulties seen with the use of conventional needle chemical ablation injection alone, such as irregular ablation and fluid reflux up the needle tract.

Combination radiofrequency ablation with intratumoral liposomal doxorubicin: effect on drug accumulation and coagulation in multiple tissues and tumor types in animals.

PURPOSE: To determine whether use of radiofrequency (RF) ablation combined with intravenously (IV) administered liposomal doxorubicin, as compared with use of RF ablation or doxorubicin alone, facilitates increased tissue coagulation and interstitial drug accumulation in animal models. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. In experiment 1, multiple canine sarcomas were implanted in seven mildly immunosuppressed dogs and grown to a mean diameter of 4.8 cm. Tumors were assigned to three treatment groups: internally cooled RF ablation (12 minutes, 2000-mA pulsed technique) followed by IV liposomal doxorubicin (10 mg per animal) (n = 6), RF ablation alone (n = 6), and liposomal doxorubicin alone (n = 4). In experiment 2, the livers and kidneys of 10 rabbits and the thigh muscles of 10 rats were randomly assigned to one of two treatment groups: conventional RF ablation (90 degrees C +/- 2, 5 minutes) followed by IV liposomal doxorubicin (5 mg per rabbit, 1 mg per rat) or RF ablation alone (n = 5, each). Coagulation diameter and interstitial doxorubicin concentration (tissues were homogenized in acid alcohol, with doxorubicin extracted for 24 hours at 5 degrees C and quantified with fluorimetry) were measured 48 hours after treatment and compared. Multivariate analysis of variance and subsequent pairwise t tests (alpha = .05, two-tailed test) were performed. RESULTS: Data are means +/- standard errors of the mean. A larger diameter of tumor destruction was observed in canine sarcomas treated with RF ablation-liposomal doxorubicin (3.7 cm +/- 0.6) compared with that in tumors treated with RF ablation (2.3 cm +/- 0.1) or liposomal doxorubicin (0.0 cm +/- 0.0) alone (P < .01). A new finding was a completely necrotic red zone (1.6 cm +/- 0.7) surrounding the central RF ablation-induced white coagulation zone. Greater but nonuniform drug uptake was observed particularly in this red zone (77.0 ng/g +/- 18.2) compared with uptake in the central zone (15.1 ng/g +/- 3.2), peripheral area of untreated tumor (38.9 ng/g +/- 8.0), and tumors treated with liposomal doxorubicin alone (43.9 ng/g +/- 6.7 for all regions) (P < .01 for all individual comparisons). In experiment 2, use of combined therapy led to increased coagulation in all tissues (liver: 17.6 mm +/- 3.1, P = .03; kidney: 11.0 mm +/- 3.1, P = .03; muscle: 13.1 mm +/- 1.3, P < .01) compared with use of RF ablation alone (liver, 13.4 mm +/- 1.5; kidney, 7.9 mm +/- 0.7; muscle, 8.6 mm +/- 0.5). Combined therapy, as compared with liposomal doxorubicin therapy alone, was also associated with increased doxorubicin accumulation in liver, kidney, and muscle (1.56 microg/g +/- 0.34, 4.36 microg/g +/- 1.78, and 3.63 microg/g +/- 1.43, respectively, vs 1.00 microg/g +/- 0.18, 1.23 microg/g +/- 0.32, and 0.87 microg/g +/- 0.53, respectively) (P < or = .01 for all individual comparisons). CONCLUSION: Use of RF ablation combined with liposomal doxorubicin facilitates increased tissue coagulation and interstitial doxorubicin accumulation in multiple tissues and tumor types and may be useful for treatment of large tumors and achieving an ablative margin within the untreated tissue surrounding RF ablation-treated tumors.

Radiofrequency tumor ablation: insight into improved efficacy using computer modeling.

OBJECTIVE: To use computer modeling of the Bio-Heat equation to demonstrate factors influencing RF ablation tissue heating. CONCLUSION: Computer modeling demonstrates the importance of energy deposition, tumor and background tissue electrical and thermal conductivity, and perfusion on RF ablation outcomes.

Reduced tumor growth with combined radiofrequency ablation and radiation therapy in a rat breast tumor model.

PURPOSE: To determine whether use of combined radiofrequency (RF) ablation and external-beam radiation therapy increases end-point survival beyond that with either RF ablation or radiation therapy alone in an animal tumor model. MATERIALS AND METHODS: With a protocol approved by the institutional animal care and use committee, R3230 mammary adenocarcinoma (12.5 mm +/- 0.6 [standard deviation]) was implanted subcutaneously into 107 female Fischer 344 rats. Initially, 42 tumors were randomized into four treatment groups: (a) RF ablation (70 degrees C for 5 minutes) alone, (b) RF ablation followed by radiation therapy with a total dose of 20 Gy, (c) 20-Gy radiation alone, and (d) no treatment. Another 19 tumors were randomized to receive (e) RF ablation (70 degrees C for 5 minutes) followed by 5-Gy radiation, (f) 5-Gy radiation alone, or (g) no treatment. Animals were followed up until survival end point (either until tumor growth to 30 mm in diameter, or for 120 days if no tumor was seen in mammary fat pad or chest wall). Results were analyzed with the Kaplan-Meier method. Histopathologic analysis was performed in 15 additional tumors at survival end point and 18 other representative tumors at other specified end points. RESULTS: Combined RF ablation and 20-Gy radiation resulted in complete local control in nine (82%) of 11 tumors, compared with one (9%) of 11 tumors treated with RF ablation alone and one (17%) of six treated with RF ablation and 5-Gy radiation (P < .001). No local control was achieved in rats with radiation therapy alone or in controls. Median end-point survival was 12 days for controls, 20 days with RF ablation or 5-Gy radiation alone, 30 days with RF ablation plus 5-Gy radiation, 40 days with 20-Gy radiation alone, and 120 days with RF ablation plus 20-Gy radiation. Mean end-point survival was 13 days +/- 5 (standard deviation) for the control group, 34 days +/- 31 with RF ablation alone, and 43 days +/- 16 with 20-Gy radiation alone. Mean survival was significantly greater with 20-Gy radiation and RF ablation combined: 94 days +/- 34 (P < .001 compared with all other groups). Mean survival for rats that received 5-Gy radiation with RF ablation versus without was 46 days +/- 37 versus 24 days +/- 11, respectively. CONCLUSION: Combined RF ablation and external-beam radiation therapy increased animal survival compared with that with either of the treatments alone or with no treatment.

Rapid irreversible encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

Intravenous Rho (D) immune globulin (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura (ITP). Common side effects of IV RhIG include mild hemolysis, febrile reaction, and headache. Significant hemolysis with renal impairment following IV RhIG has been reported. We report a case of irreversible encephalopathy 48 hr following an infusion of IV RhIG for treatment of ITP.

Hybrid radiofrequency and cryoablation device: preliminary results in an animal model.

PURPOSE: To determine whether the simultaneous application of combined bipolar radiofrequency (RF) ablation and cryoablation in a hybrid system produces larger ablation zones than RF or cryoablation alone. MATERIALS AND METHODS: Multiple 15-minute ablations were performed in ex vivo bovine liver (n = 167) with a hybrid applicator system with RF ablation alone (0.3-0.7 A), cryoablation alone (3,500 psi, two freeze/thaw cycles), and combined RF/cryoablation (0.4-0.7 A, 1,000-3,500 psi) with use of a novel applicator consisting of two 2.5-cm active bipolar RF poles located on the same 18-gauge needle separated by two embedded cryoablation nozzles. Resultant coagulation diameters were compared with use of analysis of variance for more than three groups or Student t tests for two groups. Confirmation of the optimal parameters of combination RF/cryoablation was performed by reassessing a range of argon pressure (1,000-3,500 psi) and RF current (0.4-0.7 A) in in vivo porcine liver (n = 36). Arrays of two to four RF/cryoablation applicators were also assessed in ex vivo (n = 54) and in vivo (n = 12) liver. RESULTS: In ex vivo liver, simultaneous RF/cryoablation (0.6 A, 3,000 psi) produced 3.6 cm +/- 0.4 of short-axis coagulation. This was significantly larger than that achieved with optimal RF alone or cryoablation alone (1.5 cm +/- 0.3 and 1.6 cm +/- 0.3, respectively; F = 95; P < .01). The coagulation diameter with simultaneous combination RF/cryoablation was related in parabolic fashion to argon pressure and current with a multivariate r(2) of 0.68. For in vivo liver, optimal combination RF/cryoablation achieved 3.3 cm +/- 0.2 of coagulation, which was significantly larger than that achieved with RF alone (1.1 cm +/- 0.1; P < .01) or cryoablation alone (1.1 cm +/- 0.1 and 1.3 cm +/- 0.1; F = 203; P < .01). The greatest contiguous coagulation was achieved with multiple-applicator arrays. For ex vivo liver, short-axis coagulation measured 5.3 cm +/- 0.1, 6.4 cm +/- 0.1, and 7.6 cm +/- 0.1 for two-, three-, and four-applicator arrays, respectively. For in vivo liver, two-, three-, and four-applicator arrays produced 5.1 cm +/- 0.2, 5.8 cm +/- 0.5, and 7.0 cm +/- 0.5 of confluent coagulation, respectively. CONCLUSION: Simultaneous combination RF and cryoablation with use of a novel applicator design yielded significantly larger zones of coagulation than either modality alone. The large ablation diameters achieved warrant further investigation of the device.

Radiofrequency ablation: Effect of pharmacologic modulation of hepatic and renal blood flow on coagulation diameter in a VX2 tumor model.

PURPOSE: To determine whether pharmacologic agents can be used to modulate blood flow in hepatic and renal tumors sufficiently to alter the extent of radiofrequency (RF)-induced coagulation. MATERIALS AND METHODS: VX2 tumors (8-15 mm) were implanted in the liver (n = 25) or kidney (n = 8) of 33 New Zealand White rabbits. RF was applied to tumors for 6 minutes with use of conventional electrodes (125 mA +/- 35; 90 degrees C +/- 2 degrees C tip temperature). In the hepatic model, blood flow was modulated with use of halothane, epinephrine, or arsenic trioxide (2-6 mg/kg). Laser Doppler flowmetry was used to quantify changes in hepatic blood flow. Correlation of blood flow with induced coagulation diameter was performed. RF ablation was then performed in a renal model with and without arsenic trioxide. RESULTS: For liver tumors, halothane and arsenic trioxide reduced blood flow to 40.3% +/- 17.8% and 29% +/- 15% of normal, respectively, whereas epinephrine increased blood flow to 207.8% +/- 97.9%. Correlation of blood flow to coagulation diameter was demonstrated (R(2) = 0.40). Coagulation measured 7 mm +/- 1 with epinephrine, 10 mm +/- 1 with normal blood flow, 12 mm +/- 3 with halothane, and 13 mm +/- 3 with arsenic trioxide (P <.04 compared with controls). In the renal model, arsenic trioxide decreased blood flow (44% +/- 16%) and increased coagulation diameter (10.9 mm +/- 1) compared with controls (84% +/- 11% and 7.6 mm +/- 1; P <.01, both comparisons). CONCLUSIONS: RF-induced coagulation necrosis in rabbit hepatic and renal tumors is affected by tumor blood flow. Pharmacologic modulation of tumor blood flow may provide a noninvasive way to decrease blood flow during thermally mediated ablation therapy, potentially enabling the creation of larger zones of coagulation necrosis.

Image-guided percutaneous chemical and radiofrequency tumor ablation in an animal model.

PURPOSE: To determine whether combining acetic acid instillation before radiofrequency (RF) ablation can improve local tissue electrical conductivity, RF energy deposition, intratumoral heating, and tumor necrosis in a large animal model. MATERIALS AND METHODS: Multiple hypovascular canine venereal sarcomas were implanted in 11 mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to 4.2 cm +/- 0.6 in diameter. Treatment strategies included 10% and 15% acetic acid diluted in distilled water, 10% and 15% acetic acid diluted in saturated NaCl solution, 50% acetic acid, and 100% ethanol, with 6 mL of each injected alone or in combination with RF ablation (internally cooled, 1-cm tip; 12 minutes). Two additional control groups were studied in which tumors received either RF alone or distilled water injected alone. Comparisons were also made with groups treated with 36% NaCl with and without RF ablation. Resultant coagulation for these ablative strategies, along with local temperatures and RF parameters such as impedance, current, and power, were compared. RESULTS: Increasing coagulation was observed with increasing acetic acid concentrations (1.7 cm +/- 0.4, 2.8 cm +/- 0.6, and 3.5 cm +/- 0.3 for 10%, 15%, and 50% acetic acid alone, respectively; P <.01). The combination of RF ablation with acetic acid resulted in greater coagulation than with either therapy alone (P <.05). However, maximum heating and coagulation were observed with 10% acetic acid diluted in NaCl, with which the entire tumor (diameter, 4.5 cm +/- 0.4) was completely ablated in every case. This was equivalent to results for tumors treated with 36% NaCl combined with RF. RF with a 50% acetic acid concentration resulted in coagulation measuring only 3.7 cm +/- 0.3 (P <.01). Significantly greater RF heating (89.7 degrees C +/- 12.3 at 10 mm) was observed when the tumors were pretreated with 10% or 15% acetic acid in saturated NaCl, compared with 67.9 degrees C +/- 13.7 observed when acetic acid was diluted in water (P <.02). RF combined with ethanol produced less coagulation (2.8 cm +/- 0.3) than combinations with acetic acid because rapid and irreversible impedance increases were observed. CONCLUSION: Addition of acetic acid injections to RF ablation substantially increases tumor destruction compared with RF or injection therapy alone. However, lower acetic acid concentrations in saturated NaCl produced greater tumor coagulation, suggesting that, in this hypovascular tumor model, alterations in electrical conductivity play a more important role in increasing tumor ablation efficiency than do the additional ablative effects of acetic acid.

Predictors of hemorrhagic transformation after intravenous recombinant tissue plasminogen activator: prognostic value of the initial apparent diffusion coefficient and diffusion-weighted lesion volume.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a potentially dangerous complication of thrombolytic therapy. Recent studies suggest that diffusion-weighted MRI (DWI) can help to predict the risk of intracerebral hemorrhage (ICH) after thrombolysis. We sought to examine which pretreatment DWI parameters and clinical data are predictive of ICH after intravenous thrombolysis. METHODS: We retrospectively reviewed our prospective stroke database for patients with ischemic stroke treated with intravenous recombinant tissue plasminogen activator (rtPA) within 3 hours from symptom onset who had DWI before treatment and MRI with T2* sequence or CT 24 to 48 hours later to assess for ICH over the past 4 years. We measured the volumes and voxel-by-voxel apparent diffusion coefficient (ADC) values of the initial DWI lesions and retrieved demographic data, risk factors, National Institutes of Health Stroke Scale (NIHSS) scores on admission, and blood tests results. We examined several variables using univariate and multivariate regression analyses to determine predictors of ICH. RESULTS: Twenty-nine patients fulfilled our inclusion criteria; 17 patients (58%) had ICH, and of these 4 (13%) had symptomatic ICH and fatal outcome. On univariate analysis, higher systolic blood pressure, NIHSS score, serum glucose level, volume of initial DWI lesion, and absolute number of voxels with ADC value < or =550x10(-6) mm2/s were statistically associated with ICH, and all were subjected to multivariate analysis. However, only the absolute number of voxels, ie, volume of ischemic tissue on DWI, with ADC < or =550x10(-6) mm2/s emerged as an independent predictor of ICH. CONCLUSIONS: Our findings suggest that volumetric ADC analysis can be used to assess ICH risk after thrombolysis. This may be particularly helpful if rtPA is to be given outside the 3-hour window.

The stroke patient who woke up: clinical and radiological features, including diffusion and perfusion MRI.

BACKGROUND AND PURPOSE: Time of stroke onset is uncertain for patients who wake from sleep with stroke. Functional imaging techniques may allow estimation of benefit and risk of acute stroke therapy. We compared the clinical and multimodal MRI findings of patients with uncertain stroke onset with those with known onset time. METHODS: Patients imaged within 24 hours of ischemic stroke onset between January 1997 and June 2000 were identified from a prospective stroke registry. Clinical and imaging data from patients with known stroke onset (group I) were compared with those who woke with stroke (group II). RESULTS: A total of 364 patients were identified, of whom 100 (27%) woke from sleep with stroke. Group I and group II did not differ in age, gender, National Institutes of Health Stroke Scale, or TOAST (Trial of Org 10172 in Acute Stroke Treatment) diagnoses. Time from stroke onset was shorter in group I (mean 6.0 versus 13.3 hours, P<0.001); time from detection did not differ between groups (6.0 versus 5.9 hours). Within 3 hours, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) lesion volumes were similar in both groups; DWI-PWI mismatch was present in 82% of group I and 73% of group II patients. Mean apparent diffusion coefficient of water (ADC) of group I patients was negatively associated with DWI volume (beta=-0.324, P=0.004) and time from stroke onset (beta=-0.238, P=0.031) in multivariate analysis. The mean ADC of group II patients was lower than that of group I patients within 3 hours of stroke detection (mean 556 versus 665 microm2/s, P<0.01), but individual group II patients had ADC values as high as 742 microm2/s, in addition to a DWI-PWI mismatch pattern. CONCLUSIONS: Onset time is uncertain in over one quarter of acute ischemic stroke patients. Clinical features of these patients do not differ significantly from those with known onset time. Some patients who wake with stroke seem to have favorable imaging characteristics for acute stroke therapy. Further study is needed to determine whether criteria for therapy based on imaging parameters can safely be applied to these patients.