Central Pontine Myelinolysis in a Child: Clinical Case

Background. Central pontine myelinolysis (CPM) is limited symmetric non-inflammatory demyelination in the middle part of pontine. This disease is based on electrolyte balance disorders. Although CPM was firstly described in adults, but it can also occur in children. Every new case of CPM in children has undeniable interest and high scientific and practical significance due to its low incidence. Clinical case description. The child, 7 years old, had acute development, lethargy, multiple vomiting, subfebrile fever, pains in epigastric region. It has happened after drinking an unknown herb growing in the yard and previously covered with the insecticide "Akarin", according to the mother. The child was hospitalized in the pediatric department at the place of residence. The patient developed strabismus, swallowing disorder, and muscle weakness on infusion therapy. Biochemical blood test has shown hypokalemia and hyponatremia. Head MRI has shown symmetrical focal lesion of heterogeneous structure in pontine. Conclusion. Distinctive feature of this case is the development of CPM in a child on the ongoing therapy of hypokalemia and hyponatremia. The timely provision of qualified medical care has favoured the child's recovery.

Association of Oxidative Stress Markers with Vascular Stiffness Parameters in Patients with Diabetic Neuropathy

Introduction: One of the most common chronic complications of diabetes mellitus is diabetic neuropathy. The aim of the study was to elucidate the association between selected markers of oxidative stress and markers of vascular stiffness and to contribute to the understanding of the pathophysiological links between oxidative stress and micro- and macrovascular complications of diabetes. Methods: We enrolled patients with type 2 DM (n = 49), with moderate to severe diabetic polyneuropathy of lower extremities, and a control group without microvascular complications (n = 29). The neuropathy group received alpha-lipoic acid infusion therapy. Sampling was performed before and after treatment to determine the level of oxidative markers (advanced glycation end-products—AGEs, glycation products of AOPP proteins, MDA malondialdehyde and oxidized LDL), parameters of metabolic control and parameters of vascular wall stiffness were measured by sphygmomanometry. Results: After the administration of alpha-lipoic acid, we demonstrated a significant reduction in the level of three selected oxidation markers (AOPP: p < 0.001, AGE: p < 0.001, oxLDL: p < 0.05). In contrast, the level of MDA did not change significantly (p = 0.83). Throughout the group, oxLDL was significantly correlated with central BP (SBP and DBP in the aorta, p < 0.05 and <0.01) and with the augmentation index (AiX/75 bpm, p < 0.01). AOPP significantly correlated with systolic BP in the aorta (p < 0.05). We did not find significant associations in the remaining oxidation markers. Conclusion: In our study, we demonstrated a reduction in the level of oxidative markers after alpha-lipoic acid administration and also an association between markers of oxidative damage to lipids and proteins (oxLDL and AOPP) and some parameters of vascular stiffness.

The usage and outcomes of dextran in the treatment of acute deep venous thrombosis

Objectives In this study, we retrospectively compared the outcomes of patients with acute deep vein thrombosis treated with dextran 40 infusion and unfractionated heparin with those of patients treated with unfractionated heparin alone. Methods We evaluated 104 patients with the diagnosis of acute deep vein thrombosis. The pain complaints of the patients at the time of admission and the pain complaints in the calf with dorsiflexion of the foot were evaluated with the visual analogue pain scale, and the calf diameter of affected limbs was measured. Fifty five patients had dextran 40 infusion and unfractionated heparin treatment concomitantly (Group HD), while 49 patients had unfractionated heparin treatment (Group H). Heparin dose was adjusted to obtain 1.5- to 2.5-fold of normal activated partial thromboplastin time in both groups. Oral anticoagulant, warfarin sodium, was administered in the first day and resumed. Unfractionated heparin infusion therapy was resumed until international normalized ratio values of 2–2.5 were obtained. Dextran 40 infusion therapy was administered for 3 days. Calf diameters, current pain, and calf pain at foot dorsiflexion were recorded at 48 h and 72 h. 65 patients were distal, and 39 patients were proximal and popliteal acute DVT. None of the patients had phlegmasia. All were acute DVT. Results At 48 and 72 h of therapy, it was determined that the decrease of the calf diameter and the pain were more significant both at 48th and 72nd hours in the Group HD. The calf circumference change, especially at 72 h, was 2.58 ± 0.39 cm in the group receiving heparin + dextran, while it was 1.76 ± 0.56 cm in the group receiving only heparin. ( p = 0.000). While there were only 1.24 ± 1.02 people in the group that received dextran at 72 h, leg pain persisted in 3.35 ± 1.11 people in the other group. ( p = 0.000). Evaluation was made only with calf vein diameter measurement. When patients with Homan’s sign were evaluated for their calf pain at foot dorsiflexion; both groups had decreased pain at 48th and 72nd hours. Conclusion In this study, we observed that the use of dextran 40 infusion therapy concomitantly with unfractionated heparin accelerates recovery substantially and decreases patient complaints significantly in early stages. In particular, reduction in leg pain and calf circumference reduction were more adequate in the dextran group. The early decrease in the calf circumference will have clinical consequences such as less heparin intake, earlier return to normal life, and a decrease in the total cost of treatment. Since the antithrombotic and anticoagulant effects of dextran are well known, we think that its use in this treatment as well as venous thromboembolism prophylaxis should be discussed.

Efficacy of Outpatient Infusion Therapy in Pediatric Patients With Post-Concussive Headaches

ObjectiveThe objective of this study is to determine the relative efficacy of an intravenous therapy for post-concussive headaches in a pediatric population, as compared to oral therapy.BackgroundPost traumatic headache is extremely common in the acute and chronic phases after concussion. To date, there is still not significant evidence-based treatment protocols defined for treatment.Design/MethodsPediatric patients who were treated for post-concussive headaches at an outpatient infusion clinic from 2016 to 2018 were selected for inclusion in the study. Clinic visits before and after infusions were reviewed to determine changes in headache score (HA), symptom severity score (SSS), and self-reported symptom relief. The control group received only oral therapy for their headaches. The infusion consisted of parenteral ketorolac, compazine, diphenhydramine, and a normal saline bolus (20 mg/kg). Of the 95 patients who were treated in clinic, 53 patients were selected for a retrospective chart review.ResultsFollowing infusion therapy, overall mean HA and SSS scores were both reduced (1.6346, SD 1.8997, p < 0.0001 and 23.0385, SD 29.4971, p < 0.0001 respectively). Oral therapy demonstrated a similar mean overall reduction in HA and SS scores (1.4151, SD 1.4992, p < 0.0001 and 25.4906, SD 30.2042, p < 0.0001). While both groups achieved a reduction in HA and SS scores, there was not a statistically significant difference in reduction of symptoms scores between the oral and infusion groups.ConclusionsInfusion therapy is as effective at reducing HA and SSS as established oral therapies. It is hypothesized that infusion therapy may have a shorter time to headache abortion than oral therapy based on pharmacokinetics. Further, some physicians are unwilling to allow an athlete to return to play while taking suppressive medication. Future studies may show that an infusion could allow a more rapid return to play and resolution of symptoms.

Disturbance of Vancomycin Infusion Flow during Multidrug Infusion: Influence on Endothelial Cell Toxicity

Background: Phlebitis is a common side effect of vancomycin peripheral intravenous (PIV) infusion. As only one PIV catheter is frequently used to deliver several drugs to hospitalized patients through the same Y-site, perturbation of the infusion flow by hydration or other IV medication may influence vancomycin exposure to endothelial cells and modulate toxicity. Methods: We assessed the toxicity of variations in vancomycin concentration induced by drug mass flow variations in human umbilical vein endothelial cells (HUVECs), simulating a 24 h multi-infusion therapy on the same line. Results were expressed as the percentage of viable cells compared with a 100% control, and the Kruskal–Wallis test was used to assess the toxicity of vancomycin. Results: Our results showed that variations in vancomycin concentration did not significantly influence local toxicity compared to a fixed concentration of vancomycin. Nevertheless, the loss of cell viability induced by mechanical trauma mimicking multidrug infusion could increase the risk of phlebitis. Conclusion: To ensure that vancomycin-induced phlebitis must have other causes than variation in drug mass flow, further in vitro experiments should be performed to limit mechanical stress to frequent culture medium change.

Perioperative infusion therapy

Perioperative infusion support of surgical patients is the main and non-alternative element of treatment. At the same time, the tactics of infusion therapy continues to be the subject of study. Ideas about the optimal quantitative and qualitative composition of the fluid transfused to patients are being revised as ideas about the pathogenesis of critical conditions evolve. The basis of pathogenetic analysis of compensatory hemodynamic capabilities, as a point of application of infusion treatment, previously consisted mainly of invasive monitoring techniques, replaced in recent years by the control of routine parameters with proven high correlation with invasive ones. In current studies devoted to the problems of infusion correction of hemodynamic abnormalities, the most discussed issues are the applicability of isotonic and balanced polyionic crystalloids, less often colloidal solutions in various clinical situations, and the results of such studies do not always allow to unambiguously determine the choice of infusion media, and sometimes simply incomparable. Some researchers advocate the use of isotonic crystalloids, some works prove the best effectiveness of balanced salt solutions. With the volumes of treatment corresponding to the perioperative period, in most studies there are no differences in the effectiveness of the main composite groups of crystalloids at all. We see the reason for this in the peculiarities of randomization methods, when statistical limitations do not allow us to avoid discrete data analysis: their comparative grouping occurs according to the principle of selecting a target parameter, and all the others are classified as auxiliary or secondary. It seems to us that the involvement of arrays of data obtained in real clinical practice as a result of a combination of local theoretical and empirical ideas about corrective treatment regimens correlated with their effectiveness could smooth out the inconsistency of the results of such studies, especially since clinicians have a sample with a volemic load at their disposal, allowing them to predict the hemodynamic reaction of the patient's body to infusion and a set of routine parameters for more fine-tuning of therapy.

Trident cold atmospheric plasma blocks three cancer survival pathways to overcome therapy resistance

Therapy resistance is responsible for most cancer-related death and is mediated by the unique ability of cancer cells to leverage metabolic conditions, signaling molecules, redox status, and other pathways for their survival. Interestingly, many cancer survival pathways are susceptible to disturbances in cellular reactive oxygen species (ROS) and may therefore be disrupted by exogenous ROS. Here, we explore whether trident cold atmospheric plasma (Tri-CAP), a gas discharge with exceptionally low-level ROS, could inhibit multiple cancer survival pathways together in a murine cell line model of therapy-resistant chronic myeloid leukemia (CML). We show that Tri-CAP simultaneously disrupts three cancer survival pathways of redox deregulation, glycolysis, and proliferative AKT/mTOR/HIF-1α signaling in this cancer model. Significantly, Tri-CAP blockade induces a very high rate of apoptotic death in CML cell lines and in primary CD34+ hematopoietic stem and progenitor cells from CML patients, both harboring the therapy-resistant T315I mutation. In contrast, nonmalignant controls are minimally affected by Tri-CAP, suggesting it selectively targets resistant cancer cells. We further demonstrate that Tri-CAP elicits similar lethality in human melanoma, breast cancer, and CML cells with disparate, resistant mechanisms and that it both reduces tumor formation in two mouse models and improves survival of tumor-bearing mice. For use in patients, administration of Tri-CAP may be extracorporeal for hematopoietic stem cell transplantation therapy, transdermal, or through its activated solution for infusion therapy. Collectively, our results suggest that Tri-CAP represents a potent strategy for disrupting cancer survival pathways and overcoming therapy resistance in a variety of malignancies.

Antibacterial Activity and Optimal Treatment of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae

Objectives: This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant Klebsiella pneumoniae (BSIs-CRKP).Methods: A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations.Results: The MIC90 of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried blaKPC-2 and blaNDM-1. A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%.Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP.