Immunoadsorption for the treatment of a patient with severe thrombotic thrombocytopenic purpura resistant to plasma exchange: kinetics of an inhibitor of ADAMTS13.
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ADAM Proteins↗
Biomedical subjects
K Laczika
Publications and source records attributed to K Laczika.
Comparison of prone positioning and continuous rotation of patients with adult respiratory distress syndrome: results of a pilot study.
OBJECTIVE: To compare prone positioning and continuous rotational therapy with respect to oxygenation and hemodynamics in patients suffering from adult respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective pilot study. SETTING: Intensive care unit at a university hospital. PATIENTS: Twenty-six mechanically ventilated patients with ARDS from nontraumatic causes. INTERVENTIONS: Twelve patients were turned prone (group 1), 14 patients underwent continuous axial rotation from one lateral position to the other with a maximum angle of 124 degrees in specially designed beds (group 2). All patients had received inhaled nitric oxide (NO) therapy before positioning. MEASUREMENTS AND MAIN RESULTS: Gas exchange and hemodynamics were assessed using a pulmonary artery catheter. In both groups, an improvement in PaO2/RFIO2-ratio and intrapulmonary shunt fraction occurred after initiation of NO as well as during the first 72 hrs of positioning therapy. During the study period, seven patients died in group 1 and nine patients in group 2 (p = NS). Comparing the areas under the curve during the first 72 hrs, no significant differences with respect to PaO2/FIO2-ratio, PaCO2, positive end-expiratory and peak inspiratory pressure levels, intrapulmonary shunt fraction, the alveolar-arterial oxygen difference, and oxygen delivery and consumption, as well as cardiac index, pulmonary and arterial blood pressures, and pulmonary arterial occlusion pressure could be detected between the groups. Prone positioning was tolerated well, continuous rotational therapy had to be modified according to hemodynamic instability in three patients. CONCLUSIONS: In severe lung injury, continuous rotational therapy seems to exert effects comparable to prone positioning and could serve as alternative when prone positioning seems inadvisable.
Adult↗
Excellent disease eradication by myeloablative therapy and stem-cell transplantation in patients with acute myelogenous leukemia.
Between February 1982 and 1999, 118 consecutive patients (65 male, 53 female) with acute myelogenous leukemia (AML), with a median age of 35 years (range 17-56 years), received stem-cell grafts from a human leukocyte antigen-identical sibling (n = 71), one-antigen-mismatched family member (n=2), matched unrelated donor (n=15), one-antigen-mismatched unrelated donor (n = 4) or an autologous (n = 26) graft. At the time of transplant, 56 patients were in the first complete remission (CR), 27 in the second CR, 6 in untreated relapse, 17 in primary refractory, and 12 in refractory relapse. The French-American-British classification (FAB) subtypes were as follows: M1 (n=25), M2 (n=28), M3 (n=11), M4 (n =32), M5 (n=16), M6 (n = 6). For conditioning, most patients underwent total body irradiation-containing regimens. As of 28 February, 1999, probability of leukemia-free survival (LFS) is 58% for patients after related and 45% after unrelated stem-cell transplantation (SCT). The probability of LFS is 70% for patients given allogeneic transplants in the first CR compared with 33% for those beyond the first CR at SCT. In autologous stem-cell graft recipients, the probability of LFS is 37%. Transplant-related mortality was 28% after related, 20% after unrelated, and 4% after autologous SCT. Probability of relapse for patients given related-donor stem-cell grafts in the first CR and beyond the first CR is 30% and 67%, 55% after unrelated and 63% after autologous stem-cell grafting. Thus, myeloablative therapy followed by allogeneic stem-cell infusion has a high curative potential for patients with AML in remission and offers substantial benefits to patients in advanced disease.
Adolescent↗
Immunoadsorption in Goodpasture's syndrome.
Patients with Goodpasture's syndrome presenting with dialysis-dependent end-stage renal failure at diagnosis almost never regain independent renal function. We report a patient with a 100% crescentic lesion in whom reversal of dialysis dependence was achieved by immunoadsorption together with immunosuppression. In a second patient, early initiation of immunoadsorption was able to completely restore normal renal function as early as 1 month after the start of treatment. These data give evidence of the use of immunoadsorption as a hopeful alternative to conventional plasma exchange in patients with Goodpasture's syndrome showing advanced renal failure.
Adolescent↗
Safe and efficient emergency transvenous ventricular pacing via the right supraclavicular route.
UNLABELLED: Infraclavicular and internal jugular central venous access are techniques commonly used for temporary transvenous pacing. However, the procedure still has a considerable complication rate, with a high risk/benefit ratio because of insertion difficulties and pacemaker malfunction. To enlarge the spectrum of alternative access sites, we prospectively evaluated the right supraclavicular route to the subclavian/innominate vein for emergency ventricular pacing with a transvenous flow-directed pacemaker as a bedside procedure. For 19 mo, 17 consecutive patients with symptomatic bradycardia, cardiac arrest, or torsade de pointes requiring immediate bedside transvenous pacing were enrolled in the study. The success rate, insertional complications, pacemaker performance, and patients' outcomes were recorded. Supraclavicular venipuncture was successful in all patients, in 16 of 17 at the first attempt. Adequate ventricular pacing was achieved within 1 to 5 min (median, 2 min) after venipuncture and within 10 s to 4 min (median, 30 s) after lead insertion (</=30 s in 15 of 17 patients). The median pacing threshold was 1 mA (range, 0.7 to 2.5 mA). No procedure-related complications were recorded. Throughout the pacing period of 1538 h (median: 62 h, range, 1-280 h) two reversible malfunctions caused by inadvertent lead dislodgement after 122 and 171 h were recorded; in one patient the pacemaker had to be removed because of local infection after 14 days of pacing. We conclude that the right supraclavicular route is an easy, safe, and effective first approach for transvenous ventricular pacing and might provide a useful alternative to traditional puncture sites, even in a preclinical setting. IMPLICATIONS: Temporary transvenous cardiac pacing can yield high complication rates especially under emergency conditions. We investigated emergency pacing via the right supraclavicular access in 17 consecutive hemodynamically compromised patients and found good safety, efficacy, and a low complication rate.
Aged↗
Comparison of conventional surgical versus Seldinger technique emergency cricothyrotomy performed by inexperienced clinicians.
BACKGROUND: Cricothyrotomy is the ultimate option for a patient with a life-threatening airway problem. METHODS: The authors compared the first-time performance of surgical (group 1) versus Seldinger technique (group 2) cricothyrotomy in cadavers. Intensive care unit physicians (n = 20) performed each procedure on two adult human cadavers. Methods were compared with regard to ease of use and anatomy of the neck of the cadaver. Times to location of the cricothyroid membrane, to tracheal puncture, and to the first ventilation were recorded. Each participant was allowed only one attempt per procedure. A pathologist dissected the neck of each patient and assessed correctness of position of the tube and any injury inflicted. Subjective assessment of technique and cadaver on a visual analog scale from 1 (easiest) to 5 (worst) was conducted by the performer. RESULTS: Age, height, and weight of the cadavers were not different. Subjective assessment of both methods (2.2 in group 1 vs. 2.4 in group 2) and anatomy of the cadavers (2.2 in group 1 vs. 2.4 in group 2) showed no statistically significant difference between both groups. Tracheal placement of the tube was achieved in 70% (n = 14) in group 1 versus 60% (n = 12) in group 2 (P value not significant). Five attempts in group 2 had to be aborted because of kinking of the guide wire. Time intervals (mean +/- SD) were from start to location of the cricothyroid membrane 7 +/- 9 s (group 1) versus 8 +/- 7s (group 2), to tracheal puncture 46 +/- 37s (group 1) versus 30 +/- 28s (group 2), and to first ventilation 102 +/- 42s (group 1) versus 100 +/- 46s (group 2) (P value not significant). CONCLUSIONS: The two methods showed equally poor performance.
Aged↗
Outcome and prognostic factors in critically ill cancer patients admitted to the intensive care unit.
OBJECTIVE: To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. DESIGN: Retrospective cohort study. SETTING: ICU at a university cancer referral center. PATIENTS: A total of 414 cancer patients admitted to the ICU during a period of 66 months. INTERVENTIONS: None. MEASUREMENTS: Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups: 1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU. MAIN RESULTS: ICU survival was 53%, and 1-yr survival was 23%. The 1-yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long-term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU. CONCLUSION: A combination of factors must be taken into account to estimate a critically ill cancer patient's prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.
APACHE↗
High concordance of karyotype analysis and RT-PCR for CBF beta/MYH11 in unselected patients with acute myeloid leukemia. A single center study.
Identification of the inversion 16 in patients with acute myeloid leukemia (AML) is of great practical value since these patients have a relatively favorable prognosis, especially when treated with high-dose cytarabine. We compared the results of cytogenetic analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) for core binding factor (CBF) beta/myosin heavy chain (MYH11) in 241 unselected cases of AML. In contrast with other studies, we found a high concordance between these 2 methods. Eighteen of 241 patients showed a cytogenetic anomaly of the chromosome 16. We detected the fusion transcript by RT-PCR in all 18 cases and in 2 additional patients with AML without any cytogenetic anomaly of chromosome 16. One patient had a normal diploid karyotype, and the second patient showed a trisomy 22 in karyotype analysis, which often is associated with inv(16). Only 8 of 20 CBF beta/MYH11-positive patients had M4Eo morphologic features. The much higher discrepancy between cytogenetic analysis and RT-PCR in other studies, especially in AMLs other than M4Eo, possibly indicates the necessity for PCR screening regardless of the French-American-British classification.
Acute Disease↗
Prolonged third remission in a patient with acute promyelocytic leukemia after consolidation chemotherapy with intermittent intermediate dose ara-C and maintenance with intermittent all-trans retinoic acid (ATRA).
The benefit of all-trans-retinoic acid (ATRA) in the front line therapy of acute promyelocytic leukemia (APL) is well established, but its role in postremission therapy and in the treatment of relapse is currently under investigation. Moreover, the impact of cytosine arabinoside (Ara-C) in the therapy of APL has been questioned in recent studies. We report a prolonged third molecular remission (MR) in a patient with hyperleukocytotic APL after induction with ATRA, consolidation chemotherapy (CT) with intermittent intermediate dose Ara-C and maintenance therapy with intermittent ATRA. While the first two remissions were relatively short (8 months and 11 months, resp.), the duration of the third continuous CR (49+ months) is more than twice as long as the length of the two previous remissions combined. In this case Ara-C followed by intermittent ATRA maintenance was a safe and effective therapy for relapsed disease. A third molecular remission of such duration and quality is unusual.
Antineoplastic Combined Chemotherapy Protocols↗
Influence of prothrombin complex concentrates on plasma coagulation in critically ill patients.
OBJECTIVE: To evaluate thrombogenicity of prothrombin complex concentrates (PCCs) in critically ill patients. DESIGN: Prospective clinical study. SETTING: Medical intensive care unit at a university hospital. PATIENTS: 16 consecutive patients suffering from acquired deficiencies of coagulation factors and with either overt bleeding from any site or a planned invasive procedure. INTERVENTIONS: 2000 factor IX units of PCCs intravenously. MEASUREMENTS AND RESULTS: Prothrombin time (PT), activated partial prothrombin time, fibrinogen, platelet count, plasma levels of coagulation factors II, V, VII, VIII, IX, X, antithrombin, protein C, thrombin-antithrombin complex (TAT), prothrombin fragment F(1+2), and the fibrin degradation product D-dimer were measured prior to and 1, 3, and 24 h after administration of PCCs. PT as well as coagulation factors II, VII, IX, and X, TAT, and F(1+2) showed a significant increase after administration of PCCs. All other parameters remained unchanged. CONCLUSIONS: Administration of PCCs induces thrombin generation. No evidence for induction of disseminated intravascular coagulation in biochemical terms could be found. When rapid correction of acquired coagulation factor disturbances is warranted, the use of PCCs seems reasonable, but the elevated risk of intravascular thrombus formation should be kept in mind.
Adult↗
[Ernst Klee: Auschwitz, national socialist medicine and its victims].
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Concentration Camps↗
Prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis.
The aim of the present study was to evaluate the potential prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis. Twenty-eight patients with gram-positive sepsis were compared to 11 patients with gram-negative sepsis and 15 healthy volunteers. Sepsis was defined by the criteria of Bone et al. (Crit. Care Med. 21, 5447-5463, 1993) and by isolation of at least two positive blood cultures with gram-positive/gram-negative bacteria. Plasma samples for determination of the immunological parameters were collected daily. Analysis of cytokines and adhesion molecules was performed on days 0 (day of sepsis criteria fulfillment), 4, and 7 (or 1 day before death). In the gram-positive group 10 of 28 patients died; in the gram-negative group 4 of 11 died. Only sELAM-1 plasma concentrations were found to be a useful early parameter in predicting patients' outcome in gram-positive sepsis. sELAM-1 concentrations at the onset of the study (day 0) were significantly higher in the nonsurviving patients than those in the survivors. MIP-1 alpha levels were significantly higher only on days 4 and 7. With regard to the measured plasma concentrations we believe that MIP-1 alpha is not a useful parameter for predicting patients' prognosis. The increase of sVCAM-1 might play a role in the pathogenesis of gram-positive sepsis; however, it could not be relied upon as an early prognostic parameter. The potential role of TGF-beta 2 in the development of gram-positive sepsis could not evaluated in the present study, whereas routine measurements of TGF-beta 2 offered no additional prognostic information.
Adult↗
Detection of the WT1 transcript by RT-PCR in complete remission has no prognostic relevance in de novo acute myeloid leukemia.
The WT1 gene is expressed in 73-100% of patients with acute myelogenous leukemia (AML) and is thought to play a role in maintaining the viability of leukemic cells. WT1 has been proposed as a marker for minimal residual disease in leukemia. We obtained serial blood or bone marrow samples from patients with de novo AML at diagnosis, during therapy, and up to 95 months after diagnosis and analyzed for WT1 gene expression by RT-PCR to determine whether gene expression was predictive of relapse. Forty-four patients had WT1-positive AML and achieved a complete remission (CR) following chemotherapy and 24 patients underwent unrelated donor (n = 4), sibling donor (n = 13) or autologous (n = 7) marrow transplantation. After achieving CR 62% of the patients became WT1-negative, while 38% remained WT1-positive. There was no difference in the disease-free survival (DFS) and survival from remission between WT1-positive and -negative patients (P > 0.1). Following BMT, 32% of the patients analyzed in CR within the first 100 days after transplantation were WT1 PCR positive. Detection of WT1 transcripts within 100 days following BMT did not affect DFS and overall survival (OS) after transplantation (P > 0.1). Ten of 11 patients who are in continuous CR following chemotherapy or BMT for more than 3 years were transiently WT1-positive during the observation period. Four of these patients displayed the WT1 transcript at the last examination. Thirteen of 39 patients were WT1 PCR negative within 4 months before clinical onset of relapse and eight patients were WT1 PCR negative at time of relapse. These data indicate that: (1) achievement of WT1 negativity is not associated with longer DFS, survival from remission, or OS after transplantation; (2) not all patients who relapse become WT1 positive again; (3) long-term remitters frequently display the WT1 transcript. Thus, we conclude that the monitoring of WT1 gene expression by qualitative RT-PCR during treatment and CR is of very limited value.
Acute Disease↗
Comparison of oxygen cost of breathing with pressure-support ventilation and biphasic intermittent positive airway pressure ventilation.
OBJECTIVE: To assess the oxygen cost of breathing with either pressure-support ventilation (PSV) or biphasic intermittent positive airway pressure ventilation (BIPAP). DESIGN: Prospective, randomized, crossover study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Twenty clinically stable and spontaneously breathing patients after long-term mechanical ventilation. INTERVENTIONS: Patients were randomized to start on either PSV or BIPAP, and measurements were performed after an adaptation period of 30 mins. Immediately after, the ventilatory mode was changed and after another 30-min adaptation period, the same measurements were performed. MEASUREMENTS AND MAIN RESULTS: Indirect calorimetry was performed during each ventilatory mode for a period of 30 mins. Oxygen consumption, energy expenditure, CO2 production, and respiratory quotient did not differ significantly between the two ventilatory modes, regardless of the patients' randomization. There were no statistically significant differences with regard to respiratory rate, minute volume, and blood gas analysis. All patients tolerated both ventilatory modes without any signs of discomfort. CONCLUSIONS: Pressure support ventilation and BIPAP are both used for weaning patients gradually from the ventilator. BIPAP may be advantageous in patients not breathing sufficiently with PSV, since no patient effort is necessary with use of this ventilatory mode.
Adult↗
Diagnostic validity of pulmonary artery catheterization for residents at an intensive care unit.
OBJECTIVE: To assess the amount of additional information provided by measurements derived from pulmonary artery catheter (PAC) use beyond that derived from clinical evaluation by intensive care residents. METHODS: One hundred forty-nine consecutive patients undergoing right-heart catheterization were prospectively included in the study. Before inserting a PAC, physicians had to predict pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), systemic vascular resistance index (SVRI), cardiac index (CI), mixed venous oxygen saturation (SvO2), oxygen delivery (DO2), oxygen consumption (VO2), and pulmonary shunt fraction (Qs/Qt) by selecting a given option on a questionnaire. Ranges of options were chosen to create clear clinical differences among them. RESULTS: The correct value was predicted in a median of 50% of cases (range, 45-63%). PAP was predicted correctly in 55%, PCWP in 46%, SVRI in 63%, CI in 62%, SvO2 in 45%, DO2 in 45%, VO2 in 51%, and Qs/Qt in 51%. A significant difference was found between estimated and measured values for all parameters (p < 0.01). No significant differences were detected between more and less experienced physicians. There was no significant difference between estimated and measured values with respect to the different courses of intensive care unit admissions or the different indications for PAC insertion. CONCLUSION: In a selected group of critically ill patients, the PAC adds valuable and clinically relevant information to clinical assessment in about 50% of cases. Its use should not be withheld in patients with unclear hemodynamic and metabolic profiles.
Catheterization, Swan-Ganz↗
Competitive CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction for quantitative assessment of minimal residual disease during postremission therapy in acute myeloid leukemia with inversion(16): a pilot study.
PURPOSE: (1) Quantification of minimal residual disease (MRD) by competitive CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction (RT-PCR) in patients with acute myeloid leukemia (AML) and inversion(16) [inv(16)] during postremission therapy, (2) comparison of this method with conventional two-step RT-PCR, and (3) evaluation of a potential prognostic value. PATIENTS AND METHODS: MRD of six consecutive adult patients with AML and inv(16)(p13;q22) or t(16;16)(p13;q22) who entered complete remission (CR) was monitored by competitive CBFbeta/MYH11 RT-PCR in their bone marrow (BM) during postremission therapy with high-dose cytarabine (HiDAC) or after BM transplantation with a matched unrelated-donor marrow (MUD-BMT) during an observation period of 4.5 to 27 months after initiation of treatment. RESULTS: Competitive PCR showed a gradual decline by at least 4 orders of magnitude after 7 to 9 months in patients in continuous CR (CCR), while one patient who relapsed after 13.5 months only achieved a reduction by 2 orders of magnitude at the end of consolidation therapy. A rapid decrease below the detection limit was observed within 1 month in two patients after MUD-BMT. A temporary reappearance of molecular MRD was observed in these patients during immunosuppression for graft-versus-host disease (GvHD). After reduction of immunosuppression, the level of MRD dropped again below the PCR detection limit. Molecular monitoring by conventional two-step RT-PCR yielded comparable results only when multiple assays per time point were performed, while single-assay RT-PCR gave misleading results. CONCLUSION: Competitive RT-PCR is a valuable tool for molecular monitoring during postremission chemotherapy, as well as after BMT.
Adolescent↗
[Experiences with inhalative nitric oxide in internal medicine intensive care patients with adult respiratory distress syndrome].
Inhalative nitric oxide (NO) has recently been included in the therapeutic armament for the treatment of ARDS. We evaluated the effect of inhalative NO on hemodynamic and oxygen transport parameters in 30 internal intensive care patients suffering from ARDS. All patients received a pulmonary artery catheter. Hemodynamics were assessed prior to NO therapy and after 1, 6, 12, and 24 h. 80% (n = 24) of the patients were classified as therapy responders. The median NO dose was 15 ppm (range 5 to 40 ppm). The PaO2/FiO2--ratio increased significantly after initiation of NO (p = 0.0002) while the pulmonary shunt fraction (Qs/Qt) decreased significantly (p = 0.0019). All other measured or calculated parameters including arterial and pulmonary arterial blood pressure remained unchanged. No negative effects of the therapy could be observed. Inhalative NO improves oxygenation in most intensive care patients with ARDS and thus offers the possibility to reduce invasiveness of mechanical ventilation.
Administration, Inhalation↗
Renal tolerability of four different once-daily dose regimen of netilmicin in critical care patients.
A prospective, randomized trial was conducted in a medical intensive care unit to assess safety and tolerability of four different dose regimens of intravenous netilmicin given once daily in the treatment of febrile episodes in critically ill patients. Eighty patients with febrile episodes during their stay in the intensive care unit were included in the study. The patients were randomized into four groups: Group 1 received a single daily dose of netilmicin based upon weight, age and renal function according to a dosage nomogram [13] (mean dose 298 +/- 29 mg, median 300 mg, range 250-350 mg), group 2 received 150% of this standard dose (mean 418 +/- 45 mg, median 400 mg, range 350-500 mg), group 3 200% (mean 525 +/- 41 mg, median 500 mg, range 400-550 mg) and group 4 250% (mean 710 +/- 39 mg, median 650 mg, range 600-750 mg). Duration of treatment was six days. Positive cultures were obtained in 29 patients. Serum creatinine and creatinine clearance, as well as netilmicin trough levels and levels of alpha 1-microglobulin showed no significant difference between the groups before, during, and after therapy. Our results indicate that with once daily dosing even high doses of netilmicin are well tolerated in patients with a creatinine clearance of > 70 ml/min before therapy. Necessary precautions include monitoring of drug trough levels (< 1 mg/L) and maintenance of adequate volume status.
Acute Kidney Injury↗