Therapeutic plasma exchange in pediatric intensive care: Indications,results and complications

Therapeutic plasma exchange (TPE) is an effective treatment method in selective indications. Secondary to access and technical features, it is more difficult to apply in pediatric population than adults. The aim of this study is investigate safety, clinical indications, and results of this method in critically ill pediatric patients who need TPE treatment. All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 4 years (2015–2019) were evaluated retrospectively. TPE procedures (635) were performed for 135 patients. Median age was 34 months (10‐108). Ninety‐seven patients had mechanical ventilation support. Sepsis with multiple organ failure was the most frequent indication and accounted for 44.4% (n = 60) of the indications followed by hematological and neurological diseases (19.2% and 9.6% respectively). TPE was performed alone in 469 cases (73.9%), in combination with continuous renal replacement therapy in 154 cases (24.2%), and additional to extracorporeal membrane oxygenation in 12 cases (1.9%). Hematological disease and sepsis subgroups had the highest intubation rate, mechanical ventilation period, PRISM score, organ failure count, and mortality. Fresh frozen plasma (FFP) was the most frequently used replacement fluid in 90.4% of the procedures. The most frequent anticoagulant used in TPE was acid citrate dextrose solution (79.3%). Procedural complications were detected in 104 cases (16.3%) and occurred during TPE sessions. Overall survival rate was 78.5%. We found that the non‐survivor group had significantly higher rates of organ failures (P = 0.0001), higher PRISM scores on admission (P = 0.0001), and higher rates of invasive ventilation support needed (P = 0.012). TPE is a treatment method which can be safely provided in healthcare facilities with necessary medical and technical requirements. Although it is riskier to provide such treatment to critically ill children, complications can be minimized in experienced healthcare facilities. Overall results are good and can vary depending on indication.     

Langmuir Probe Perturbations during In Situ Monitoring of Pulsed Laser Deposition Plasmas

The recent advancements in pulsed laser deposition (PLD) control via plasma diagnostics techniques have been positive and raised questions on the limitation of some techniques, such as the Langmuir probe (LP). The particularities of laser-produced plasma can lead to incorrect interpretation of collected electrical signal. In this paper, we explored the limitations of LP as a technique for in situ PLD control by performing investigations on several metallic plasmas, expanding in various Ar atmosphere conditions. Sub-microsecond modulation was seen in the reconstructed IV characteristics attributed to non-equilibrium dynamics of the ejected charges. A perturbative regime was recorded for Ar pressures higher than 2 Pa, where ionic bursts were observed in the electron saturation region. This perturbation was identified as a plasma fireball. A non-linear multifractal model was developed here to explore these new regimes of the LP. The strange attractors characterizing each fireball were reconstructed, and their evolution with the Ar pressure is discussed. Both short- and long-time non-linear behavior were correlated via probe bias, and the pressure effect on the strange attractor’s defining the fireball-like behavior was investigated. A good correlation was noticed between the simulated data and experimental findings.     

New Q waves after bypass grafting: Correlations between graft patency, ventriculogram and surgical venting technique

New Q waves were observed in 35 (11%) of 321 patients undergoing saphenous vein bypass grafting with an overall mortality rate of 1.1%. Twenty-eight (80%) had postoperative arteriograms and ventriculograms and are reported. Ventricular venting was used intra-operatively in 17 patients and atrial venting in 11. The incidence of new Q wave was 22% in patients with ventricular venting and 5.5% in those with atrial venting (p less than 0.05). Complete or incomplete revascularization did not affect the incidence of new Q waves. New Q waves appeared in a zone of myocardium supplied by a grafted artery in all except two patients with ventricular venting in whom Q waves occurred within the zone of myocardium supplied by diseased ungrafted vessels. In the ventricular venting group, seven (41%) demonstrated an improved or unchanged postoperative ventriculogram and ten (59%) had deteriorated ventriculograms. In 11 patients with atrial venting, nine (82%) showed improved or unchanged postoperative ventriculograms and two (18%) had deteriorated ventriculograms. Ventricular venting patients with improved or unchanged postoperative ventriculograms had 7% graft closure as compared to 5% of those with atrial venting (pNS). Graft closure rate was 44% in ventricular venting and 20% (pNS) of patients with atrial venting who had deteriorated left ventriculograms. These findings indicate poor correlation between new Q waves and graft closure. Improved postoperative ventriculograms corrleated well with graft patency despite new Q waves. The etiology of new post bypass graft Q waves are varied. They include ventricular trauma and conduction delays resulting from surgery or venting, as well as infarction. This may be due to compromised arterial inflow either in nonoperated vessels or in the vessels distal to the anastomosis with patent grafts, or due to occluded grafts.     

A phase II trial of 2,5,-diaziridinyl 3,6-bis (carboethoxy amino) 1,4-benzoquinone (AZQ,NSC 182986) in recurrent primary brain tumors

Summary Forty-one patients with recurrent primary malignant brain tumors were treated with 2,5-diaziridinyl 3,6-bis (carboethoxyamino), 1,4-benzoquinone (AZQ) at an initial dose of 6–8 mg/m²/ day × 5 days. Courses were repeated monthly upon recovery of myelosuppression. Six of 25 evaluable patients (24%) showed definite tumor regression, and 7 (28%) showed disease stability as determined by monthly CT scans and neurologic examination. For all patients receiving one course of AZQ, the response rate was 16% (6 of 37 patients) and the stable disease rate 19%. The estimated median time to tumor progression with AZQ was 54 weeks for the responding patients and 36 weeks for the stable patients. Toxicity consisted of myelosuppression, primarily thrombocytopenia, which was delayed and cumulative. Other toxicities were uncommon. Further clinical trials in patients with malignant primary brain tumors, including combination studies with other drugs, are indicated.Supported by NCI Contract NO1-CM-97277     

Airway Pressure Release Ventilation: An Alternative Ventilation Mode for Pediatric Acute Hypoxemic Respiratory Failure

Airway pressure release ventilation (APRV) is a relatively new mode of mechanical ventilation. The use of this model of ventilation in pediatrics has been limited. The authors describe their experience with this mode of ventilation in a series of pediatric hypoxemic respiratory failure patients. Three patients with acute hypoxemic respiratory failure (AHRF) were treated with APRV, when oxygenation did not improve with pressure control ventilation (PCV). The mean age of the patients was 5.8 ± 1.3 months. Fractional oxygen concentration decreased from 0.97 ± 0.02 for PCV to 0.68 ± 0.12 for APRV, peak airway pressure fell from 36.6 ± 11.5 cm H₂O for PCV to 33.3 ± 5.7 cm H₂O for APRV, mean airway pressure increased from 17.9 ± 5.9 cmH₂O for PCV to 27 ± 2.6 cmH₂O for APRV and release tidal volume increased from 8.3 ± 1.5 mL/kg for PCV to 13.2 ± 1.1 mL/kg for APRV after 1 h. APRV may improve oxygenation in pediatric AHRF when conventional mechanical ventilation fails. The APRV modality may provide better oxygenation with lower peak airway pressure.     

In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase-mediated cancer diagnosis and therapy

As part of the development of enzyme-mediated cancer imaging and therapy, a novel technology to entrap water-insoluble radioactive molecules within solid tumors, we show that a water-soluble, radioactive quinazolinone prodrug, ammonium 2-(2'-phosphoryloxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ(2-P)), is hydrolyzed by alkaline phosphatase to a water-insoluble, radiolabeled drug, 2-(2'-hydroxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ(2-OH)). Biodistribution data suggest the existence of two isoforms of the prodrug (IQ(2-P(I)) and IQ(2-P)), and this has been confirmed by their synthesis and characterization. Structural differences of the two isoforms have been examined using in silico molecular modeling techniques and docking methods to describe the interaction/binding between the isoforms and human placental alkaline phosphatase (PLAP), a tumor cell, membrane-associated, hydrolytic enzyme whose structure is known by X-ray crystallographic determination. Docking data show that IQ(2-P), but not IQ(2-P(I)), fits the active binding site of PLAP favorably and interacts with the catalytic amino acid Ser(92), which plays an important role in the hydrolytic process. The binding free energies (DeltaG(binding)) of the isoforms to PLAP predict that IQ(2-P) will be the better substrate for PLAP. The in vitro incubation of the isoforms with PLAP leads to the rapid hydrolysis of IQ(2-P) only and confirms the in silico expectations. Fluorescence microscopy shows that in vitro incubation of IQ(2-P) with mouse and human tumor cells causes the extracellular, alkaline phosphatase-mediated hydrolysis of the molecule and precipitation of fluorescent crystals of IQ(2-OH). No hydrolysis is seen in the presence of normal mouse and human cells. Furthermore, the intratumoral injection of 125IQ(2-P) into alkaline phosphatase-expressing solid human tumors grown s.c. in nude rats results in efficient hydrolysis of the compound and retention of approximately 70% of the injected radioactivity, whereas similar injection into normal tissues (e.g., muscle) does not produce any measurable hydrolysis (approximately 1%) or retention of radioactivity at the injected site. These studies support the enzyme-mediated cancer imaging and therapy technology and show the potential of such quinazolinone derivatives in the in vivo radiodetection (123I/124I) and therapy (131I) of solid tumors.     

Risk of intracranial hemorrhage with anticoagulation therapy in melanoma patients with brain metastases

Venous thromboembolism (VTE) is a frequent complication in melanoma patients with brain metastases (BM). The management of these patients is challenging because of the high risk of intracranial hemorrhage (ICH) and the limited data available on the safety of anticoagulation in this scenario. We reviewed the treatments and outcomes among melanoma patients with BM and VTE at our institution to determine the safety of anticoagulation in these patients. A retrospective chart review was performed to identify melanoma patients with BM who were diagnosed with VTE. The clinical characteristics of the BM and the VTE, the treatments given for VTE, subsequent ICH, and overall survival (OS) were determined. The characteristics and outcomes were compared between patients who received systemic anticoagulation and those who did not. A total of 74 evaluable melanoma patients with BM and VTE were identified. Fifty-seven (77%) patients received systemic anticoagulation. There was no significant difference in the number (P=0.40) or the maximum diameter (P=0.55) of brain metastasis between the patients who received anticoagulation and those who did not. Two (4%) patients who received anticoagulation developed ICH, which was not statistically different from the patients who did not receive anticoagulation (0%, P=1.00). There was a trend toward longer OS from VTE among patients who received systemic anticoagulation (median OS: 4.2 vs. 1.2 months, P=0.06). Anticoagulation for VTE did not significantly increase the risk of ICH or decrease OS in patients with melanoma BM. These data support the safety of systemic anticoagulation for VTE in these patients.