HEMOPERFUSION USING THE LPS-SELECTIVE MESOPOROUS POLYMERIC ADSORBENT IN SEPTIC SHOCK: A MULTICENTER RANDOMIZED CLINICAL TRIAL.

ABSTRACT: Extracorporeal hemoperfusion (EHP) may improve the course and outcomes of patients with septic shock by targeting cytokines or bacterial endotoxins (lipopolysaccharide [LPS]). Here, we present the results of a multicenter randomized controlled trial ( clinicaltrials.gov/ct2/show/NCT04827407 ) to assess the efficiency and safety of Efferon LPS hemoperfusion cartridges engineered for multimodal targeting LPS, host-derived cytokine, and damage-associated molecule pattern molecules. Patients with intra-abdominal sepsis (IAS) and septic shock (Sepsis-3) were subjected to EHP procedures (n = 38). Control patients with IAS and septic shock (n = 20) were treated using conventional protocols without EHP. The primary end point was resolution of septic shock. Secondary end points included MAP, vasopressor drug dose, partial pressure of arterial oxygen/fraction of inspired oxygen ratio, Sequential Organ Failure Assessment score, length of stay in the intensive care unit, and satisfaction with device use by a 5-point Likert scale. Clinical laboratory tests for a blood cells count, lactate and creatinine concentration, nephelometry test for C-reactive protein, immunochemiluminescent test for procalcitonin, and immunoenzyme analysis for IL-6 concentration were used to monitor the EHP effect versus the control group. Data were analyzed followed the intention-to-treat approach. Wilcoxon STATA 16.0 (StataCorp, College Station, TX) and Excel 2019 with XLStat 2019 add-in (Addinsoft, Paris, France) were used for statistical analysis of the results. The Fine and Gray method of competing risks was used to analyze the primary end point and other data representing the time to event. EHP resulted in a significant and rapid increase in MAP and partial pressure arterial oxygen/fraction of inspired oxygen ratio, progressive decline in norepinephrine doses, and multiorgan deficiency, as evaluated by Sequential Organ Failure Assessment scores. Importantly, EHP led to significantly rapid cumulative mechanical ventilation weaning compared with the control group (subdistribution hazard ratio, 2.5; P = 0.037). Early 3-day mortality was significantly reduced in the Efferon LPS versus control group; however, no significant improvements in survival in 14 and 28 days were revealed. Laboratory tests showed rapidly decreased levels of LPS, procalcitonin, C-reactive protein, IL-6, creatinine, leukocytes, and neutrophils only in the Efferon LPS group. Results demonstrate that EHP with Efferon LPS is a safe procedure to abrogate septic shock and normalize clinical and pathogenically relevant biomarkers in patients with IAS.

Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia.

Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30−300 mg/day and albumin/creatinine ratio 3−30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.

[Grisel's syndrome causing torticollis in children].

This is a case report of an eight-year-old boy with CT-confirmed changes bringing attention to Grisel's syndrome as a differential diagnosis to torticollis. The syndrome - also known as atlantoaxial subluxation - is a complication to operations or infections in the ear, nose and throat region. It usually presents as a slightly flexed and rotated neck, and characteristic radiographic findings. Complications include neurological symptoms and rarely spinal cord compression. The treatment is debated, but it takes the underlying cause and immobilisation in consideration. In severe cases, repositioning in general anaesthesia or even surgical fusion may be necessary.

Sudden vs Pressure Wean From Nasal Continuous Positive Airway Pressure in Infants Born Before 32 Weeks of Gestation: A Randomized Clinical Trial.

Importance: Nasal continuous positive airway pressure (nCPAP) is a well-established treatment of respiratory distress syndrome in preterm infants. Suboptimal weaning from nCPAP may be associated with lung injury, pulmonary morbidity, and infant weight gain. To our knowledge, the best weaning strategy from nCPAP is unknown. Objective: To compare the effect of sudden wean and pressure wean from nCPAP in very preterm infants. Design, Setting, and Participants: A randomized, clinical, open-label, multicenter trial was conducted at 6 neonatal intensive care units in Denmark from September 2012 to December 2016 and included infants born before 32 weeks of gestation. Interventions: Sudden wean with discontinuation of nCPAP without a prior reduction in pressure. Pressure wean with gradual pressure reduction prior to the discontinuation of nCPAP. Main Outcome and Measures: The primary outcome was weight gain velocity from randomization to postmenstrual age 40 weeks. Secondary outcomes included other measures of growth, nCPAP and the duration of oxygen supplementation, postmenstrual age at successful wean and at discharge, successful wean at the first attempt, the number of attempts to wean, and the length of the hospital stay. Prespecified subgroup analyses by gestational age were performed. Results: Of the 372 randomized infants, 185 (49.7%) were randomized to sudden wean and 187 infants (50.3%) to pressure wean. A total of 177 infants in both groups completed the trial (median gestational age for sudden and pressure wean, 30 weeks [interquartile range, 29-31]; male: sudden wean, 89 [50%]; pressure wean, 96 [54%]). There was no difference in mean [SD] weight gain velocity from randomization to 40 weeks postmenstrual age between the 2 groups (22 [6] g/kg/day). No difference was found in any of the secondary outcomes. More infants born before 28 weeks of gestation were successfully weaned from nCPAP during the first attempt in the pressure wean group compared with the sudden wean group (risk difference, 31%; 95% CI, 13%-50%), but there was no difference in the duration of nCPAP and oxygen supplementation. Conclusions and Relevance: Overall, we found no difference in weight gain velocity or any of the secondary outcomes between very preterm infants who were randomized to sudden wean or pressure wean from nCPAP. However, among infants born before 28 weeks' gestation, infants from the pressure wean group were more often successfully weaned during the first attempt without a longer total duration of nCPAP treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01721629.

[Rhabdomyosarcoma in the urogenital region of a child]. / Rabdomyosarkom i urogenitalregionen hos et barn.

We describe a relatively rare case of botryoid rhabdomyosarcoma (RMS) in a 15-month-old female presenting with fever, abdominal pain, urinary retention, haematuria and a tumour protruding through the urethra. The diagnosis was verified by cystoscopy with biopsy and MRI. She was treated with combined chemotherapy and surgery. Early diagnosis and treatment are crucial to the prognosis. RMS should be considered as a differential diagnosis in cases whose symptoms include urinary retention, haematuria, urinary incontinence and atypical abdominal pain, and a primary ultrasound scan should be done. Cystoscopy and MRI should be considered, especially in cases involving atypical urological symptoms.