Changes In Laboratory Data Research Articles

Acute alcoholic hepatitis – the role of modern hepatoprotectors

Alcoholic hepatitis is a progressive inflammatory-dystrophic lesion of the liver, the pathogenetic mechanism of which is based on alcoholic damage. Acute alcoholic hepatitis is defined primarily as an exacerbation of the chronic process of alcoholic liver disease. Two mechanisms are defined as the basis for the formation of alcohol-associated liver damage: primary (direct effect of ethanol on hepatocytes and oxidative stress provoked by it) and secondary (through changes in the gut-liver axis with dysbacteriosis and increased permeability of the intestinal wall). For the treatment of acute alcoholic hepatitis, mainly glucocorticosteroids are used, the action of which is directed at cytotoxic and inflammatory mechanisms of the pathogenesis of this disease. Also, phosphodiesterase inhibitors, broad-spectrum antibiotics (rifaximin), probiotics, prebiotics, synbiotics, enterosorbents and hepatoprotectors are actively used. Choosing a hepatoprotector that is effective and safe for patients is still a challenge. At the moment one of the most promising and optimal in terms of “price-quality” ratio drug from this group is a domestic drug from the group of combined hepatoprotectors – Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid). A clinical case of application of this drug in a patient diagnosed with acute alcoholic hepatitis combined with chronic alcoholic hepatopathy is presented. Not severe course (MELD: 16. Maddrey’s index: 14.04). Ademetionine was prescribed. On the background of the prescribed treatment slight improvements were noted, no significant changes in laboratory data were registered (MELD: 16, Maddrey index: 12.54). After replacement of the hepatoprotector by Remaxol, the following was observed: correction of the general condition, correction of the mental status, reduction of the severity of hepatosplenomegaly, normalization of laboratory parameters (MELD: 10. Maddrey’s index: 6.06). Based on the review of Russian and foreign literature, as well as personal experience in the use of Remaxol, we can conclude that this pharmacological agent contributes to a more favorable course of acute alcoholic hepatitis, a significant reduction in the risk of complications, as well as reducing the length of hospital stay and the cost of treatment.

#2793 Improvement of bone mineral density in kidney transplant recipients: it is just denosumab?

Abstract Background and Aims Post-transplant bone disease is a common complication after a kidney transplant. Several factors, including pre-existing CKD-MBD, steroid, and CNI immunosuppressive treatment, contribute to this condition and increase the risk of bone loss and fractures. Among various therapeutic strategies, Denosumab, a human monoclonal antibody against RANK-L, can decrease the risk of fracture in Kidney Transplant Recipients (KTRs). The most reported side effects are episodes of hypocalcemia, which are associated with an increase in parathyroid hormone (PTH) levels. The FDA recommends treating these episodes with calcium supplements and cholecalciferol; another alternative is the use of receptor activators (VDRa). To our knowledge, there are only a few case reports in the literature analyzing the effect of combined treatment with VDRa and Denosumab. In this observational study, we evaluated changes in laboratory data and bone density (BMD) assessed by DXA in KTRs that received Denosumab with or without VDRa supplementation. Method This retrospective study evaluated 18 kidney transplant recipients who started Denosumab therapy after transplantation. The patients were divided into two groups: those who started or increased vitamin D receptor agonist therapy within the first 6 months before the second dose of Denosumab, and those who did not. We analyzed at baseline (T0) and after 1 year from first Denosumab administration (T1) creatinine, calcium, phosphate, PTH, bone alkaline phosphatase (BALP), osteocalcin (OC), carboxy-terminal cross-linked telopeptides of type 1 collagen (CTX), and 25-OH vitamin D and BMD at vertebral lumbar spine, femoral neck and total Hip. Furthermore, we evaluated Trabecular Bone Score (TBS). We performed ANOVA and Kruskal-Wallis for continuous variables based on distribution and Fisher's test for categorical variables. To assess the correlation between variables, we used linear regression and the Pearson correlation coefficient. Additionally, we conducted logistic regression to analyze the outcomes. Results A total of 18 patients were included in the study cohort. Of these, 66.7% were females, and 33.3% were males, with an average age of 67 years (Table 1). 13 patients started or uptitrated VDRa within the first 6 months (VDRa group), while 5 did not (Control group). At baseline, the VDRa group had a lower eGFR and higher PTH compared to the Control group, although both were at the threshold of statistical significance (37.38 vs 52.20 mL/min/1.73 m², p = 0.060 and 106.77 vs 72.60 pg/mL, p = 0.069). However, they had significantly lower serum calcium levels (8.96 vs 9.90 mg/dL, p = 0.039). In terms of baseline bone structure, there were no significant differences between the two groups at any of the three sites examined. At 1 year the VDRa group had a significantly greater gain at the Total Hip (+0.08 vs −0.03 g/cm3, p = 0.048 and +10.81 vs −4.16%, p = 0.037). Additionally, the VDRa group had an increase in TBS, while the Control group had a reduction, and this absolute and percentage variation between the two was statistically significant (+0.07 vs −0.02, p = 0.034 and +6.14 vs −1.62, p = 0.043) (Table 2). In linear correlation analysis higher doses of VDRa were significantly and positively associated with Delta BMD at the Total Hip (r = 0.65, p = 0.003). However, a significant correlation was highlighted between VDRa dosage and PTH reduction (r = −0.51, p = 0.027). Finally, in univariate logistic regression analysis, the dosage of VDRA was significantly and positively associated with 5% BMD gain at the Total Hip (OR = 1.54, CI 1.08 to 1.89, p = 0.046) (Fig. 1). Conclusion After conducting our study, we found that the use of Denosumab had a positive impact on bone mineral density. In addition to that, we observed that the association with VDRa led to further improvement in BMD and better control of PTH. Despite having a small sample size, our study demonstrates that VDRa not only helps in correcting hypocalcemia but also enhances the effect of Denosumab.

Comparing iodized oil with polyvinyl alcohol for portal vein embolization in promoting liver remnant increase before partial hepatectomy

BackgroundTo compare the efficacy and safety of iodized oil versus polyvinyl alcohol (PVA) particles in portal vein embolization (PVE) before partial hepatectomy. MethodsFrom October 2016 to December 2021, 86 patients who planned to undergo hepatectomy after PVE were enrolled, including 61 patients post-PVE with PVA particles + coils and 25 patients post-PVE with iodized oil + coils. All patients underwent CT examination before and 2–3 weeks after PVE to evaluate the future liver remnant (FLR). The intercohort comparison included the degree of liver volume growth, changes in laboratory data, and adverse events. ResultsThere was no significant difference in the resection rate between the iodized oil group and the PVA particle group (68 % vs. 70 %, p = 0.822). In terms of the degree of hypertrophy (9.52 % ± 13.47 vs. 4.03 % ± 10.55, p = 0.047) and kinetic growth rate (4.07 % ± 5.4 vs. 1.55 % ± 4.63, p = 0.032), the iodized oil group was superior to the PVA group. The PVE operation time in the PVA particle group was shorter than that in the iodized oil group (121. 72 min ± 34.45 vs. 156. 2 min ± 71.58, p = 0.029). There was no significant difference in the degree of hypertrophy between the high bilirubin group and the control group (5.32 % ± 9.21 vs. 6.1 % ± 14.79, p = 0.764). Only 1 patient had a major complication. ConclusionsCompared with PVA particles, iodized oil PVE can significantly increase liver volume and the degree of hypertrophy without any significant difference in safety.

Relationship between elevated bilirubin levels and enhanced warfarin effects during biliary obstruction.

A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin. Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction. Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ = -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR. PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

Pneumatosis intestinalis with free air in the abdominal cavity caused by nintedanib.

This is the first case confirmed the association between PI development and nintedanib by the reproducibility of PI development. In patients taking a combination treatment with corticosteroid and nintedanib, clinicians should be careful regarding the development of PI although the patient improved only after discontinuation of nintedanib treatment.

Subchronic tolerance trials of graded oral supplementation with ornithine hydrochloride or citrulline in healthy adults

Ornithine and citrulline are amino acids used in dietary supplements and nutritional products consumed by healthy consumers, but the safe supplementation levels of these compounds are unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral ornithine (as hydrochloride) and citrulline. Healthy male adults (n = 60, age 41.4 ± 1.5 years) completed graded dosages of either ornithine hydrochloride (3.2, 6, 9.2, and 12 g/day) or citrulline (6, 12, 18, and 24 g/day) supplement for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, body weight, sleep quality, and mental self-assessment. In the ornithine hydrochloride supplementation group, minor increase in plasma aspartic acid and glutamic acid concentrations was observed at the highest intake dosages. In the citrulline supplementation group, minor changes in laboratory data for serum lactate dehydrogenase and plasma amino acid concentration of lysine, methionine, threonine, aspartic acid, glutamic acid, glutamine and ornithine, arginine, and citrulline itself were measured. No other changes in measured parameters were observed, and study subjects tolerated 4-week-long oral supplementation of ornithine hydrochloride or citrulline without treatment-related adverse events. A clinical, no-observed-adverse-effect-level (NOAEL) of ornithine hydrochloride and citrulline supplementation in healthy adult males was determined to be 12 g/day and 24 g/day (4 weeks), respectively.

Cerebral Metabolic Stress Improves after Voxelotor Treatment in Pediatric Sickle Cell Disease

Introduction In sickle cell disease (SCD), hemoglobin S rapidly forms intracellular polymers in the deoxygenated state, resulting in red blood cell sickling, hemolysis, and vaso-occlusion. These changes alter cerebral perfusion and dramatically increase risk for neurocognitive deficits and stroke (Bush et al., 2014; Wang et al., 2021). Voxelotor (Oxbryta®) is an inhibitor of HbS polymerization that has been shown to significantly improve anemia and reduce hemolysis in sickle cell disease. However, it is unknown whether these changes are accompanied by improvements in perfusion and reductions in cerebral metabolic stress. Here we employ two novel optical techniques known as frequency-domain near-infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to non-invasively monitor regional changes in oxygen extraction fraction (OEF), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) as markers of cerebral metabolic stress in a pilot cohort of children with SCD beginning voxelotor. Our primary objective was to test the hypothesis that voxelotor decreases CBF, OEF, and CMRO2 from pre-treatment levels. We also explored the relationship between CBF, OEF, and CMRO2 and hemoglobin. Methods Children ages 4 to 17 years old with SCD (HbSS or HbS-thalassemia) were enrolled at Children's Healthcare of Atlanta. Participants who met study criteria started open label voxelotor at recommended dose. Participants were monitored prior to treatment initiation, as well as at weeks 4, 8, and 12 weeks. At each study visit, laboratory measurements of anemia (CBC, Retic) and FDNIRS/DCS measurements of regional cerebral blood flow, oxygen extraction fraction, and oxygen metabolism were made (Lee et al., 2022). Transcranial Doppler ultrasound (TCD, middle cerebral artery, internal carotid artery, and carotid bifurcations) along with markers of hemolysis (LDH, T.Bili) were performed at weeks 0 and 12. Paired Wilcoxon signed-rank tests were used to test whether all measures were significantly different from pre-treatment levels. Linear mixed-effects regression models with random-intercept at the patient level were used to examine the association of the relative change in each outcome measure (OEF, CBF, and CMRO2) from pre-treatment levels and delta changes in laboratory data. These models were two-level and accounted for repeated measures nested within each patient. Results Ten of the 12 recruited patients met study criteria. All patients were HbSS on stable dose of hydroxyurea (Table 1). Following initiation of voxelotor, the median (interquartile range, IQR) blood hemoglobin levels increased by 1.2 (0.4, 1.5) g/dL at week 4 (p=0.023); these increases persisted at weeks 8 and 12. Bilirubin was significantly decreased at week 12 (p=0.008), and LDH increased, although the trend was not statistically significant (p=0.24). While TCD velocities were unchanged at week 12, significant decreases in OEF, CBF, and CMRO2 were observed by week 4 (all p < 0.05) that persisted at weeks 8 and 12 (Table 2). Across all time points, relative changes in OEF, CBF, and CMRO2 from pre-treatment levels were inversely associated with changes in hemoglobin (p = 0.0015, 0.071, and 0.020, respectively). Discussion Non-invasive FDNIRS/DCS was used to successfully measure changes in regional cerebral blood flow and oxygen utilization in response to treatment with voxelotor. Results suggest that voxelotor treatment in children with SCD reduces cerebral metabolic stress by improving oxygen delivery to the tissue. Work is ongoing to validate these measurements with MRI. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Dose Escalation and Expansion of Abbv-383 in Combination with Anti-Cancer Regimens in Relapsed or Refractory Multiple Myeloma

Background: Multiple myeloma (MM) is a plasma cell cancer that remains incurable despite recent advances in currently available therapies. Bispecific antibodies (BSAbs) are a new class of interventional agents that combine target specificity, safety profile of monoclonal antibodies and the potency of T-cell mediated cellular cytotoxicity. B-cell maturation antigen (BCMA) is a surface marker that is highly expressed on malignant plasma cells and amenable to targeting by BSAbs. ABBV-383 is a fully human BSAb that targets BCMA and CD3 on the surface of MM cells and T cells respectively, resulting in T-cell activation and selective destruction of BCMA-positive MM cells. ABBV-383 displays low affinity CD3 binding and bivalent BCMA binding, which potentially will lead to a favorable safety profile with more convenient dosing intervals and robust efficacy. In the dose-escalation cohorts of ≥40 mg Q3W (n=24), the objective response rate (ORR) was 79%, with a very good partial response or better (≥VGPR) rate of 63%, and a complete response (CR) rate of 29% at the data cutoff date; with median time on study of 6.1 months (Blood (2021) 138 (Supplement 1): 900). These responses are expected to deepen with additional follow-up. The most common adverse events (AEs) occurring in ≥ 20% of patients was cytokine release syndrome which was predictable and manageable. Preclinical data support the hypothesis that combining ABBV-383 with current anti-MM regimen may increase the efficacy of ABBV-383. This study will evaluate the combination of ABBV-383 with pomalidomide-dexamethasone (Pd), lenalidomide-dexamethasone (Rd), daratumumab-dexamethasone (Dd) or nirogacestat (Niro) in patients with RRMM. Study design and methods: This open-label, multi-center, phase 1b, dose-escalation and expansion study (NCT05259839) will evaluate the safety profile, tolerability, preliminary efficacy, pharmacokinetics and recommend phase 2 dose of ABBV-383 in combination with Pd, Rd, Dd or Niro for the treatment of patients (n=270) with RRMM. Adult patients (≥ 18 or ≥20 years in Japan) with documented progression of RRMM after last treatment regimen based on IMWG criteria, and an ECOG performance test ≤ 2 will be enrolled across ~45 centers. Patients must be naïve to treatment with ABBV-383 or any BCMA-targeted therapy. Dose escalation of ABBV-383 will follow BOIN design with three planned dose levels. Treatment will be administered intravenously on Day 1 of each cycle. Dose-limiting toxicities (DLT) are defined per protocol and will be evaluated for dose escalation decisions in cycle 1. Patients will receive study treatment until documented disease progression according to IMWG response criteria per investigator assessment or patient meets other protocol criteria for discontinuation of treatment. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome will be graded according to American Society for Transplantation and Cellular Therapy 2019 guidelines. Other AEs will be graded according to the National Cancer Institute Common Terminology Criteria for AEs, version 5.0. After the last dose of treatment, each patient will have an end of treatment visit, a safety follow-up approximately 90 days after the last dose, and a survival follow up every 12 weeks for up to 12 months. The primary endpoint of this study is to determine the DLTs of ABBV-383 when given in combination with anti-myeloma regimens (Pd, Rd, or Dd) or Niro in patients with RRMM. Efficacy endpoints include overall response rate (defined as partial response + VGPR + CR + stringent CR), VGPR, progression-free survival, duration of response, time to progression and minimal residual disease negativity. Safety and tolerability of ABBV-383 (in combination with anti-cancer regimens) will be assessed by evaluating AEs, physical examinations, and changes in laboratory data and vital signs, as well as drug discontinuation or dosing modification due to AEs. The number and percentage of subjects experiencing a DLT will be summarized. ABBV-383 pharmacokinetics will be summarized for each combination cohort and compared against the historical monotherapy data. Response rates will be summarized, and statistical analysis of time-to-event efficacy endpoints will be conducted using Kaplan-Meier methodology.

Development of cutaneous sarcoidosis to permanent eyebrow makeup procedure

The article summarizes the data on historical aspects, epidemiology, etiopathogenesis, clinical picture, diagnosis and treatment of skin sarcoidosis. Sarcoidosis is a chronic multisystem disease from the group of granulomatoses of unknown etiology, the morphological feature of which is the development of epithelioid cell granulomas without caseous necrosis with the processes of dystrophy, destruction and fibrosis in the tissues of various organs. Diagnosis and differential diagnosis of sarcoidosis are based on clinical examination, changes in laboratory data, X-ray methods and skin biopsy. The differential diagnosis includes many dermatoses, including tuberculoid type of leprosy, tuberculous lupus, lichen planus, annular granuloma, etc. In the treatment of sarcoidosis of the skin, corticosteroid drugs are used, including prolonged action. In case of resistance or contraindications, synthetic antimalarial and immunosuppressive agents are prescribed.&#x0D; According to the literature, cases of granulomatous reactions after permanent makeup procedures have become more frequent. The tattoo procedure is widespread and considered to be safe, but adverse reactions, particularly sarcoidosis of the skin, may develop.&#x0D; The etiology of sarcoidosis has been studied for more than 150 years and remains poorly understood until now. There are increasingly frequent reports in the literature about the development of immune granulomatous inflammation reactions after a numerous of cosmetic procedures, such as tattooing, botulinum toxin A injection, hyaluronic acid injections, permanent makeup, biorevitalization, facial modeling fillers, blepharoplasty. The increasing number of cases of skin sarcoidosis due to cosmetological manipulations is the subject of great scientific interest, and the growth of publications on this topic is an evidence of modern etiopathogenetic mechanisms of the disease development.&#x0D; Here is our clinical observation of skin sarcoidosis without systemic manifestations in a 54-year-old patient after permanent eyebrows make-up procedure outside the medical organization, without prior examination and lack of follow-up (the skin process is subacute; polymorphism of the rash is noted; rashes on the skin in the eyebrow area are represented by merging papules, foci correspond to the area of pigment injection). According to the results of physical, laboratory and instrumental studies, many epithelioid cell granulomas without caseous necrosis were found. The patient received a course of intraocular pricking with a prolonged glucocorticoid drug (Betamethasone suspension, No. 5), which led to a complete regression of rashes. Recommendations for the removal of pigment are given.&#x0D; In order to prevent infection and minimize the risks of complications, a high level of qualification of a dermatocosmetologist working in a specialized medical institution is a prerequisite for permanent makeup.

MO101: Atypical Haemolytic Uremic Syndrome Associated with COVID-19: Case Report

BACKGROUND AND AIMSRenal manifestations are common in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report here the case of a patient with confirmed SARS-CoV-2 infection with the clinical picture of atypical haemolytic uremic syndrome (aHUS).METHODCase reportRESULTSOur case is a 31-year-old man with a nasopharyngeal swab with real-time reverse-transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 positive, who was hospitalized in the Clinic of Infectious Diseases. His medical history had a respiratory illness of 7-day evolution characterized by cough, fever, dyspnoea, muscle pain, nausea, vomiting and non-bloody diarrhoea, and decreased urine output with dark colour urine. The chest computed tomography (CT) scan showed few rounded ground-glass opacities.Laboratory tests at admission revealed the following: (i) acute kidney injury stage 3 with a serum creatinine of 3.85 mg/dL (basal value 0.9 mg/dL); serum urea 221 mg/dL. His urinary volume in the first 24 h of hospitalization was 800 mL. (ii) Severe haemolytic anaemia with haemoglobin (Hgb) level of 3.7 g/dL, and peripheral smear showing large number of schistocytes, haptoglobin <10 mg/dL and indirect bilirubin 9.7 mg/dL, direct coombs testing was negative; reticulocyte count 8.9%. (iii) Severe thrombocytopaenia with platelet count of 25 000/µL, prothrombin time 45%, international normalized ratio 1.7, D-dimer 1082 ng/dL and fibrinogen 880 mg/dL.Increased blood levels of enzymes and inflammatory markers were present: lactate dehydrogenase 1867 U/L and protein C reactive 9.1 mg/dL. Electrolyte disturbances characterized by hyperkalaemia, hyperphosphatemia, hypocalcaemia and severe metabolic acidosis. Dynamic changes of laboratory data are presented in Table 1.Table 1.Dynamic changes of laboratory dataLaboratory dataDay 0Day 3Day 7Day 11Day 15Day 19Total serum bilirubin (mg/dL)16.454.8625.8914.69.74.2PT (%)455867889999LDH (U/L)55218671704768667455Serum urea (mg/dL)22121579635645Serum creatinine (mg/dL)3.851.570.70.60.50.6RBC ×106/µL1.221.611.723.233.763.98Hgb (g/dL)3.75.26.58.99.19.3PLTs (K/µL)2533395698178WBC (K/µL)11.224.522.316.214.511.3D-dimer (ng/dL)108246456893423035001800PCR (mg/dL)8.579.117.625.234.451.62Serum fibrinogjen (mg/dL)880647556550450450PT, prothrombin time; LDH, lactate dehydrogenase; RBC, red blood cell; Hgb, haemoglobin; PLT, platelet cell count; WBC, white blood cell; PCR, protein C reactive.The usual liver panel tests, alkaline phosphatase, γ-glutamyl transferase and albuminemia were normal. Toxic hepatitis was excluded. Hepatobiliary and spleen imaging (ultrasonography) was normal.ELISA serologic tests for HIV, hepatitis B, hepatitis C virus and cytomegalovirus were negative. Serological and virological tests for hepatitis A, B, C, HIV and CMV were negative. Stool was negative for Shiga toxin-producing Escherichia coli (STEC).The results of antinuclear antibodies and anti-smooth-muscle antibodies were negative, C3 serum level was mildly depressed (82 mg/dL; normal range 88–201 mg/dL) and C4 serum level was normal (20 mg/dL; normal range 10–44 mg/dL). ADAMTS13 activity was 90% on day 10.He was treated with broad spectrum antibiotics, intravenous dexamethasone and supportive therapy. One week from admission, renal function recovered, and 1 week after intravascular haemolysis and thrombocytopaenia recovered. The patient was hospitalized for 21 days.CONCLUSIONClose monitoring and early intervention can help for a better outcome of SARS-CoV-2 patients complicated with aHUS.

Urinary Protein-to-creatinine Ratios Predict Recurrence in Pediatric and Young Adult Cases of Minimal Change Nephrotic Syndrome.

High-dose steroids are required for the treatment of minimal change nephrotic syndrome (MCNS), especially for episodes of recurrence. Predicting and avoiding recurrence can help reduce the steroid dose, but prediction is currently difficult. We herein examined whether changes in laboratory data, especially the urinary protein- to-creatinine ratio (UTP/UCr), can predict clinical recurrence. We also assessed differences in clinical features between children and young adults. We included 36 patients with MCNS; for each case, we retrospectively studied laboratory data during stable remission and pre-recurrence, with the "stable" period defined as all but the 6 weeks before recurrence, and pre-recurrence defined as the 4±2 weeks before recurrence. UTP/UCr, serum albumin, etc. were measured every 5 years during stable periods. We divided patients into cohorts by age at recurrence, < 15 years and ≥ 15 years, and compared stable and pre-recurrence values for the two groups. UTP/UCr values during stable periods tended to be higher in younger patients. UTP/UCr and serum albumin showed statistically significant changes during pre-recurrence periods, but only in those aged ≥ 15 years. Thus, clinical features of recurrence differed depending on age. Signs of recurrence can be confirmed via UTP/UCr or serum albumin several weeks before recurrence in patients ≥ 15 years.

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Efficacy and Safety of Dapagliflozin in Children With Inherited Proteinuric Kidney Disease: A Pilot Study

Randomized trial of different initial intravenous immunoglobulin regimens in Kawasaki disease.

BackgroundWe aimed to assess the efficacy of different initial intravenous immunoglobulin (IVIG) regimens in Kawasaki disease (KD) patients to find more cost‐effective therapy options.MethodsA multicenter, open‐label, blind‐endpoint randomized controlled trial was conducted from January 2014 to December 2015. Patients with KD, within 10 days of illness, were randomly assigned to receive different IVIG regimens (Group A, 2 g/kg once; Group B, 1 g/kg for 2 consecutive days; Group C, 1 g/kg once) and aspirin 30mg/kg/d. Primary outcomes included hours to defervescence and development of coronary artery lesions during the study period. Major secondary outcomes included total fever days, total dose of IVIG, changes of laboratory data, length of stay, and hospitalization expenses. (ClinicalTrials.gov: NCT02439996).ResultsA total of 404 patients underwent randomization. No difference was found in the outcomes of defervescence among three groups at 6, 12, 24, and 36 hours after completion of initial IVIG infusion. There were no differences in the incidence of coronary artery lesions during the study period (at week 2, month 1, month 3, and month 6 of illness), changes of laboratory data, total fever days, and length of stay. Group C patients had the lowest total dose of IVIG (mean: 1.2 vs 2.2 vs 2.1 g/kg; P < 0.001) and hospitalization expenses (mean: 8443.8 vs 10798.4 vs 11011.4 Chinese Yuan; P < 0.001) than other two groups.ConclusionsA single dose of 1g/kg IVIG is a low‐cost treatment with the same efficacy as 2 g/kg IVIG and can be an option for the initial therapy of KD patients.

MO563HIGH DIALYSATE MAGNESIUM AND CORONARY ARTERY CALCIFICATION IN MAINTENANCE HEMODIALYSIS PATIENTS*

Abstract Background and Aims Cardiovascular calcification is highly prevalent among patients with end-stage renal disease (ESRD). Low normal serum magnesium has been linked to a more severe degree of vascular calcification and a decrease in patient survival. An inhibitory effect of extracellular magnesium on osteogenic transformation of vascular smooth muscle cells and the upregulation of anti-calcification protein have been confirmed in vitro. Increased dialysate magnesium concentration has also been shown to lower calcification propensity of the serum of maintenance hemodialysis (HD) patients. Method This study is an investigator initiated, single-blinded, parallel-group, matched case-control clinical trial that investigated the effect of high dialysate magnesium concentration for 24 weeks on the progression of coronary artery calcification (CAC) in maintenance HD patients. The changes in laboratory data and bone mineral density (BMD) were also examined. Seventy-six ESRD patients underwent CAC screening by multi-slice computed tomography and BMD measurement by dual-x-ray absorptiometry. Only patients with Agatston score&amp;gt;300 were included. They were matched according to the initial CAC score that fell within 20% of one another. Twenty patients were assigned to high dialysate magnesium concentration of 1.75 mEq/L and the matched controls were kept on standard dialysate magnesium concentration of 0.7 mEq/L. CAC and BMD measurements were repeated after 24 weeks. Laboratory data were obtained prior to dialysis at study entry, 8-week intervals during the study and 2 weeks after the study ended. Results There were no significant differences in age, sex, BMI, underlying diseases, dialysis vintage, medications, baseline CAC scores and BMD. The median baseline CAC Agatston score (Volume score) were 1923 (720) and 1672 (785) in the standard and high dialysate groups, respectively. At the end of the study, a significant increase in the CAC score was observed in both groups. Because majority of the included patients had severe calcification burden at baseline, patients were categorized into 2 subgroups using the median baseline CAC Agatston (1600) and Volume scores (700) as cut-offs. Among patients with CAC Agatston score &amp;lt;=1600, CAC score increased significantly in the standard dialysate magnesium group (P&amp;lt;0.01) but was stable in the high dialysate magnesium group (P=0.33). Among patients with CAC Agatston score &amp;gt;1600, the severity of CAC worsened in both groups. The progression of CAC was analyzed by the difference between the follow-up and the baseline square root transformed Agatston and Volume scores. In subgroup of patients with less severe calcification, more patients in the standard dialysate magnesium group progressed compared to the high dialysate magnesium group (P=0.03). In subgroup of patients with more severe calcification, the number of progressors were comparable among the 2 groups. Serum and ionized magnesium levels increased substantially during the study and returned to baseline after the return to standard dialysate magnesium concentration. The highest predialysis serum magnesium was 3.8 mg/dL. Most patients who received high dialysate magnesium reported the disappearance of symptoms of muscle cramps (P=0.01) and requested the high dialysate magnesium be continued after the end of the study. There were no significant changes in serum calcium, phosphate or PTH levels. The decline in BMD was observed in both groups but the difference did not reach statistical significance. Conclusion High dialysate magnesium was well tolerated and could ameliorate the progression of CAC in maintenance HD patients with mild to moderate vascular calcification.

Initial Serum C-reactive Protein Level as a Predictor of Increasing Serum Vancomycin Concentration During Treatment.

Vancomycin has a narrow therapeutic window, and an increase in its serum concentration-to-dose ratio during treatment can cause renal toxicity. Therefore, this study was aimed at finding a marker to identify patients at risk of increasing serum vancomycin during treatment. This was a retrospective cohort study of patients treated with vancomycin at Kanazawa University Hospital, Japan, from April 2012 to May 2015. Spearman correlation coefficients were calculated to determine the correlations between changes in vancomycin concentration-to-dose ratio and initial values or changes in laboratory data and other parameters. In addition, a multiple regression analysis was conducted. One hundred ninety-nine patients for whom 2 or more points of data on therapeutic drug monitoring (TDM) of intravenous vancomycin treatment were available and did not undergo dialysis were included in the study. Changes in vancomycin concentration-to-dose ratio were associated with C-reactive protein (CRP) and sodium (Na) levels on the initial day of TDM and with changes in white blood cell count, Na, and estimated glomerular filtration rates (eGFRs). Multiple regression analysis helped identify CRP and Na levels on the initial day of TDM and change in eGFR as independent influencing variables. A high serum CRP level on the initial day of TDM is an independent predictor of increasing vancomycin concentration-to-dose ratio in patients receiving intravenous vancomycin treatment, even if eGFR remains unchanged.

Efficacy and tolerability of perampanel as adjunctive treatment of focal and generalized tonic-clonic epileptic seizures in children over 4 years of age

The article is a short review of an observational study that proves the good efficacy and tolerability of perampanel suspension in the adjunctive treatment of epilepsy in children over 4 years of age. The study demonstrated a high level of 50% responders: 47% with focal seizures, 65% with transition of focal seizures to bilateral tonic-clonic seizures, 65% with primary generalized tonic-clonic seizures. Cessation of seizures was achieved in 12%, 19% and 55% of patients, respectively. The most common side-effects were fatigue (26%), nasopharyngitis (19%), lightheadedness, irritability, fever (13% each), and vomiting (11%). There were no significant clinical negative changes in cognitive functions according to the assessment on the Aldenkamp-Baker scale, both on the total score and subscales. Also, there were no significant changes in laboratory data, vital functions and ECG parameters.

Long-term treatment of pulmonary arterial hypertension with macitentan in Japanese patients

Objective: Macitentan, a novel dual endothelin receptor antagonist, was approved for the treatment of pulmonary arterial hypertension (PAH) in Japan. However, long-term effects in Japanese patients of macitentan are currently unavailable. This study sought to assess the long-term efficacy and safety of macitentan in Japanese patients with PAH.Methods: In this multicenter, open-label, clinical extension study (JapicCTI-121986), efficacy was evaluated based on the change from baseline at 24, 48, 72, 96 and 120-week in the 6-minute walk distance (6MWD), World Health Organization (WHO) functional class, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels. In addition, the time to a hospitalization related to PAH and a morbidity/mortality event was determined. As for safety, the incidence of adverse events and changes in laboratory data and vital signs were assessed.Results: Macitentan was administered at a once-daily dose of 10 mg in 30 PAH patients with a median treatment period of 2.4 years (range, 229–1037 days). The improvements in 6MWD, WHO functional class and NT-pro-BNP at week 24 were maintained throughout the long-term follow-up. Hospitalization related to PAH occurred in 2 patients. Levels of liver enzyme and hemoglobin remained unchanged throughout the study period.Conclusions: This study suggests that the long-term use of macitentan is well tolerated and effective in Japanese patients with PAH. We concluded that macitentan can be a possible approach to reduce morbidity/mortality in Japanese PAH patients.

Contraindications to Magnesium Sulfate and Alternative Seizure Prophylaxis for Severe Preeclampsia [09L

INTRODUCTION: Intravenous magnesium sulfate is considered first-line seizure prophylaxis for preeclampsia, reducing the risk of eclampsia by half. Absolute or relative contraindications to this medication include myasthenia gravis, severe renal failure, cardiac ischemia, heart block and pulmonary edema. Levetiracetam, an alternative antiepileptic drug considered safe in pregnancy, has been suggested in such cases though its efficacy remains uncertain. Our objective was to determine how frequently alternative anticonvulsant medications are administered for seizure prophylaxis in severe preeclampsia and to identify the documented indications in such cases. METHODS: IRB approved, retrospective cohort study of women with a diagnosis of preeclampsia at 34 weeks of gestation or greater who received seizure prophylaxis at a tertiary university hospital from 2014-2017. Demographics, clinical characteristics and contraindications to magnesium sulfate, if present, were evaluated. Patients were excluded if they had a pre-existing seizure disorders or incomplete medical records. RESULTS: A total of 1,370 patients were included; 3.2% (n=44) received levetiracetam for seizure prophylaxis. Most of the levetiracetam group (79.5%) initially received magnesium. The most commonly documented contraindication was pulmonary edema (n=14) which was confirmed by imaging (either ultrasound or chest x-ray) in less than half of cases; other reasons included changes in laboratory data (n=11; increasing serum creatinine, serum magnesium &gt;7 mg/dL), development of additional signs/symptoms (n=11; hypotension, headache, vision changes, decreased urine output) and patient refusal (n=3). Five cases did not document any contraindication. CONCLUSION: The use of alternative anticonvulsant medications in preeclampsia, which may be less efficacious, must be reserved for true contraindications to magnesium sulfate.

Safety and immunogenicity of trivalent inactivated influenza vaccine in adults 60 years of age and older: a phase II, a randomized, comparative trial in Kazakhstan

ABSTRACT Background The study was aimed at comparative evaluation of seasonal influenza vaccine RIBSP versus commercial vaccine VAXIGRIP® for immunogenicity and safety in the course of clinical trial phase II on healthy subjects up to 60 years. Methods The trial involved 150 subjects in randomized 2:1 groups that received either RIBSP vaccine or comparator vaccine VAXIGRIP®. One dose (0.5 ml) of either vaccine contained 15 µg of hemagglutinin of each influenza virus strain recommended by WHO for the Northern hemisphere in 2016–2017 flu season. The observation period lasted 21 days. The trial was registered at ClinicalTrials.gov identifier NCT 03016143. Results Assessment of immunogenic activity of the vaccine under study showed that in 21 days the portion of participants with 4-fold seroconversions was 80.0% to А/H1N1; 65.0% to А/H3N2 and 64.0% to B virus. Antibody titer increase factor in the group of subjects that received RIBSP vaccine was 13.4 for А/H1N1; 5.2 for А/H3N2 and 5.2 for B virus. The subjects that received RIBSP vaccine demonstrated 88% seroprotection rate against А/H1N1; 75% against А/H3N2 and 61% against B virus. In the course of evaluating the vaccine safety, no serious adverse events were recorded. All changes of laboratory data were slight and single in most cases. All recorded local reactions have been light in character and these have been predicted reactions observed at vaccination against influenza. Conclusion Comparison vaccines RIBSP and VAXIGRIP®, showed similar immunogenic activity. The RIBSP vaccine is safe and immunogenic for the elderly and conforms to international criteria in CPMP/BWP/214/96.

Left versus right-sided percutaneous transhepatic biliary drainage in relief of malignant obstruction

Background: Biliary tree obstruction and consequent jaundice occur in 70%–90% of these patients and have important consequences mainly for the patient's quality of life, morbidity, and overall mortality. Percutaneous transhepatic biliary drainage (PTBD) is an excellent palliative procedure to drain the bile ducts in malignant obstruction. We compared left- and right-sided approach in relief of malignant obstruction. The most common causes of malignant biliary obstruction (MBO) include pancreatic adenocarcinoma, hilar cholangiocarcinoma, ampullary/duodenal adenocarcinoma, gallbladder adenocarcinoma, lymphoma, and compressive metastatic peri-portal lymph node Materials and Methods: This study was a prospective, hospital-based study performed for 2 years from 2016 to 2018. PTBD was performed either through right in 16 patients or left approach in 15 patients. Two approaches were compared in terms of clinical and technological success, changes in laboratory data, internalization and survival. Results: (1) Rate of technological success was 100%. (2) There was a significant reduction in bilirubin, alanine transaminase (ALT), and alkaline phosphatase (ALP) levels after the procedure in both the approaches, but the decrease was more in the right-sided approach. Only the decrease in bilirubin levels was statistically significant. The decrease in albumin was attributed to the progression of the disease. (3) Clinical success was seen in 93.33% and 93.75% in left- and right-sided approach. (4) Internalization was done in 86.67% patients in the left-lobe approach, while as in right-lobe approach, it was done in 93.75% patients. Conclusion: PTBD causes a significant reduction in the bilirubin level, irrespective of the amount of liver drained or the type of drainage (external/internal). In our study, the reduction in bilirubin, ALT and ALP was more in the right-lobe approach. However, only reductions in levels of bilirubin were statistically significant.