High-dose Methylprednisolone Treatment Research Articles

Outcome of the Modified St. Jude Total XV Protocol in Turkish Children with Newly Diagnosed Acute Lymphoblastic Leukemia: A Single-Center Retrospective Analysis

The prognostic factors and outcomes of Turkish children with newly diagnosed acute lymphoblastic leukemia (ALL), treated with the Modified St. Jude Total XV Protocol, which was adjusted by adding high-dose methylprednisolone (HDMP) before induction in the original protocol, were assessed in this study. The Modified St. Jude Total XV Protocol was administered to 183 newly diagnosed ALL patients, aged 1-18 years, between 1 January 2008 and 30 January 2016. HDMP was applied at doses of either 10 mg/kg/day (Group A) or 20 mg/kg/day (Group B) for 7 days before induction and then tapered over the next 7 days to 5 or 10 mg/kg/day, and continued at 2 mg/kg/day for 2 weeks during the induction phase. Absolute blast count (ABC) in peripheral blood and minimal residual disease (MRD) in bone marrow were assessed at the end of the initial 7-day HDMP treatment. MRD in the bone marrow was evaluated on day 15 and at the end of the induction period. The follow-up for these patients ended on 15 July 2019. The 5-year event-free (EFS) and overall survival (OS) rates for all patients were 85.6±2.6% and 89.2±2.3%, respectively. The rate of good response to steroids (defined as ABC in peripheral blood of less than 1000/mm3 on day 7) was 88% and 97% of children achieved complete remission after induction. The survival rate and infection frequency did not show statistically significant differences between Group A and B. EFS and OS correlated with initial leukocyte count, age of 10-18 years at diagnosis, CD20 positivity at diagnosis, and gram-negative bacterial infection during remission induction. The remarkable response rates on days 7 and 15, along with the promising EFS and OS results in childhood ALL patients treated with the Modified St. Jude Total XV Protocol, highlight the early and substantial response effect of HDMP. At the onset of induction, short-term HDMP can be initiated, preferably at 10 mg/kg/day for the first 7 days, to minimize potential side effects.

The role of methylprednisolone in severe COVID-19 patients: a meta-analysis.

The purpose of this study is to assess the effectiveness of methylprednisolone in severe COVID-19. PubMed, the Cochrane Library and Web of Science were searched for literatures comparing methylprednisolone and control treatment in severe COVID-19 patients. Statistical pooling was reported as risk ratio (RR) with corresponding 95% confidence interval (CI). The outcomes of interest in the literature survey were mortality and adverse events. A total of 13 studies were included, including 3,138 patients with severe COVID-19, of which 1,634 patients were treated with methylprednisolone and 1,504 patients were treated with control treatment. Five of the 13 studies reported severe adverse events. Our meta-analysis indicates that methylprednisolone treatment in COVID-19 patients is associated with a significant reduction in mortality (RR 0.62, 95% CI 0.46-0.85, p = 0.003) compared to control treatment, without an increased risk of adverse events (RR 1.20, 95% CI 0.92-1.56, p = 0.17). Moreover, high-dose methylprednisolone treatment (RR 0.57; 95% CI 0.40-0.82, p = 0.003) and short-course methylprednisolone treatment (RR 0.54; 95% CI 0.38-0.89, p = 0.01) found to significantly reduce mortality. Additionally, it was found that younger severe COVID-19 patients (RR 0.40; 95% CI 0.20-0.80, p = 0.01) had better outcomes to methylprednisolone than older patients. Methylprednisolone was correlated with lower mortality compared with control treatment in severe COVID-19 patients without increasing serious adverse reactions. Furthermore, high-doses and short-term of methylprednisolone treatment were linked with better younger COVID-19 reported higher benefit from methylprednisolone than older COVID-19 patients.

Abstract 101: Prehospital High-Dose Methylprednisolone Treatment Reduces Norepinephrine Need Following Resuscitated Out-of-Hospital Cardiac Arrest

Background: Resuscitated out-of-hospital cardiac arrest (OHCA) patients are hemodynamically unstable and have high mortality. Norepinephrine (NE) is recommended to maintain mean arterial pressure (MAP) above 65 mmHg, but excessive NE use, and a continuously low MAP are both associated with poor outcomes in OHCA. The glucocorticoid methylprednisolone (MP) has anti-inflammatory properties and may increase arterial sensitivity to NE, thereby improving MAP and reducing NE need. Aims: To determine if prehospital anti-inflammatory MP treatment could lower the need for NE without affecting MAP values following OHCA. Methods: The STEROHCA trial was a randomized, blinded, placebo-controlled, multicenter study, including adult comatose patients resuscitated from OHCA due to presumed cardiac etiology, and with a minimum of five minutes of return of spontaneous circulation. The intervention was intravenous MP 250 mg or placebo, administered prehospitally. In this sub-study, we repeatedly measured NE dose and MAP from admission until 48h and compared differences between the two groups at each time point. Results: In the STEROHCA trial, 137 patients were randomized to MP (n=68) or placebo (n=69). Patients were mainly male (85%) with a median age of 66 years (IQR 56, 75). The MP group demonstrated significantly lower NE use (mcg/kg/min) at 24h (0.22 (0.15; 0.31) vs. 0.38 (0.28; 0.49), p=0.02), 42h (0.13 (0.07; 0.20) vs. 0.25 (0.17; 0.35), p=0.03), and 48h (0.08 (0.03; 0.15) vs. 0.23 (0.15; 0.33), p=0.004), Figure 1 . We observed a higher MAP in the MP group with significantly higher MAP values (mmHg) at 6h (75 (72; 78) vs. 70 (67; 73), p=0.03), 12h (75 (71; 78) vs. 69 (66; 72), p=0.01), 18h (76 (73; 79) vs. 69 (66; 72), p=0.003), 24h (77 (74; 80) vs. 71 (68; 74), p=0.01), and 48h (86 (82; 89) vs. 79 (76; 82), p=0.004), Figure 1 . Conclusions: Prehospital treatment with high-dose MP reduced the need for NE while improving MAP values in resuscitated OHCA patients for the initial 48h of admission.

Novel Approach to Investigate the Effect of High-Dose Methylprednisolone on Erythrocyte Morphology: White Light Diffraction Microscopy

Abstract The present study focuses on quantitative phase imaging of erythrocytes with the aim to evaluate the effects of high-dose methylprednisolone (HDMP) on erythrocytes in vivo under physiological conditions in human blood samples. Samples from ten patients, prescribed to be treated with 1000 mg/day intravenous methylprednisolone for 5 days, were analyzed by white light diffraction phase microscopy (WDPM) for quantitative imaging. WDPM, an optical measurement technique, enables single shot measurement and low speckle noise using white light. Quantitative phase imaging performed with this experimental setup allowed the determination of erythrocyte morphology with 9 different parameters. In vivo quantitative analysis of erythrocytes by WDPM, which is a simple and reliable method, shows that HDMP treatment has no significant effect on erythrocyte morphology. With the developing technology, interdisciplinary studies on individuals under treatment should play an important role in elucidating the interaction between steroids and erythrocytes.

Diagnosis and treatment of allograft rejection in islet transplantation

Islet transplantation stabilizes glycemic control in patients with complicated diabetes mellitus. Rapid functional decline could be due to islet allograft rejection. However, there is no reliable method to assess rejection, and treatment protocols are absent. We aimed to characterize diagnostic features of islet allograft rejection and assess effectiveness of high-dose methylprednisolone treatment. Over a median follow-up of 61.8 months, 22% (9 of 41) of islet transplant recipients experienced 10 suspected rejection episodes (SREs). All first SREs occurred within 18 months after transplantation. Important features were unexplained hyperglycemia (all cases), unexplained C-peptide decrease (ΔC-peptide, 77.1% [−59.1% to −91.6%]; ΔC-peptide:glucose, −76.3% [−49.2% to −90.4%]), predisposing event (5 of 10 cases), and increased immunologic risk (5 of 10 cases). At 6 months post-SRE, patients who received protocolized methylprednisolone (n = 4) had significantly better islet function than untreated patients (n = 4), according to C-peptide (1.39 ± 0.59 vs 0.14 ± 0.19 nmol/L; P = .007), Igls score (good [4 of 4 cases] vs failure [3 of 4 cases] or marginal [1 of 4 cases]; P = .018) and β score (6.0 [6.0-6.0] vs 1.0 [0.0-3.5]; P = .013). SREs are prevalent among islet transplant recipients and are associated with loss of islet graft function. Timely treatment with high-dose methylprednisolone mitigates this loss. Unexplained hyperglycemia, unexpected C-peptide decrease, a predisposing event, and elevated immunologic risk are diagnostic indicators for SRE.

Şiddetli COVID-19 Pnömonisi Olan Hastalarda Yüksek Doz Metilprednizolon ve 6 mg Deksametazonun Tedavi Etkinliğinin Karşılaştırılması

Introduction: The course of SARS-CoV-2 disease has a clinical spectrum ranging from mild upper respiratory tract infection to fulminant pneumonia. The use of corticosteroids is recommended in the treatment of severe COVID-19 pneumonia. The present study aimed to compare the efficacy of high-dose methylprednisolone and dexamethasone treatment in patients hospitalized with severe COVID-19 pneumonia. Materials and Methods: The participants were divided into Group M, receiving ≥250 mg intravenous methylprednisolone therapy, and Group D receiving 6 mg intravenous dexamethasone therapy. The efficacy of treatments, length of hospital stays, ventilator requirements, anti-cytokine treatment requirements, and mortality rates were evaluated in both groups. Results: Two hundred eighty-eight (69.1%) patients received dexamethasone and 129 (30.9%) received methylprednisolone. While overall mortality in the study was 11%, this rate was 10.4% in Group D and 12.4% in Group M (p> 0.05). The rate of patients requiring intensive care was 15.8% in total, with a rate of 14.6% in Group D and 18.6% in Group M (p> 0.05). However, the total length of hospital stay was nine (7-39) days in Group M and 13 (7-29) days in Group D (p= 0.009). Anticytokines were required in 14.4% of the patients during treatment [40 in Group D, 20 in Group M (p> 0.05)]. Conclusion: In this study, it was determined that early methylprednisolone treatment shortened the hospital stay. In addition, there was no statistically significant difference between Group M and Group D in terms of mechanical ventilation requirement, which showed an additional positive effect. However, mortality rates in patients receiving dexamethasone were found to be lower than in those receiving methylprednisolone, yet this difference did not reach statistical significance.

Effectiveness Of Anakinra Therapy On Covid-19 Patients In Icu

Background: There is no consensus on effective treatments for COVID-19 disease yet. Our aim; To observe the clinical and laboratory results of anakinra treatment on intensive care patients and to contribute to the literature on its usefulness. Material and Methods: The characteristics of the patients receiving Anakinra treatment in the COVID ICU of xx were retrospectively reviewed. The patients' ages, gender, mechanical ventilation (MV) duration, length of stay in the intensive care unit, CRP, procalcitonin, LDH, IL-6, lymphocyte, Dv dimer, ferritin values and the corticosteroid doses they received in addition to Anakinra treatment were also evaluated. In addition, the data of the patient group who did not receive Anakinra but received high-dose (≥250 mg) methylprednisolone (MPZ) treatment were compared with the present patient data and evaluated in terms of treatment effectiveness. Results: When the patients that receiving Anakinra+high-dose MPZ are compared with the patient group receiving only high-dose MPZ,it was seen that the mortality rate is significantly higher (P=0.038), MV and hospitalization days in the intensive care unit were significantly longer in patients receiving Anakinra (p=0.001, p=0.004). However, there was no significant difference in secondary reproduction rates between the two groups (P=0.484). As the mean hospitalization days of the group receiving Anakinra + high-dose MPZ and the group receiving Anakinra + low-dose (<250mg) MPZ were found to be significantly longer in the group receiving Anakinra + high-dose steroids (p=0.018), there was no significant difference in terms of MV time and mortality rates (p=0.193, p=1.0). Conclusion: In our study, the patients who received Anakinra treatment had a longer hospitalization day and MV period, and the higher mortality rate was attributed to this patient group who had a more severe course. It was observed that the use of anakinra treatment after low-dose and high-dose MPZ treatment did not cause a significant difference in mortality rates. However, due to the small number of patients and the heterogeneity of the patient group, more comprehensive and randomized studies are needed.

Xanthomatous sypophysitis secondary to a ruptured Rathke's cleft cyst

Abstract Introduction Hypophysitis (HP) is a rare disease which develops secondary to chronic or acute inflammation of the pituitary gland and may cause symptoms related to pituitary dysfunction and mass compression. HP can be classified based on the anatomical location of pituitary involvement (adenohypophysitis, infundibulo-neurohypophysitis, or panhypophysitis), the etiology (primary or secondary), and the histopathology (lymphocytic, granulomatous, xanthomatous, IgG4, necrotizing, or mixed forms). Lymphocytic HP is the most common subtype of primary HP, while xanthomatous HP (XHP) is considered the rarest form, with 35 reported cases, to date. In our report, we describe a case with panhypopituitarism due to XHP secondary to the rupture of an Rathke's cleft cyst (RCC). Clinical Case A 35-year-old woman was initially admitted to a Gynecology clinic with a 2-year history of amenorrhea and headache. She was started on cabergoline 0.5 mg twice a week for macroprolactinoma. Due to persistent amenorrhea with low gonadotropins, she was referred to our Endocrinology clinic. Her pituitary function profile revealed panhypopituitarism (Table 1) and a 13×11×12 mm sized sellar mass with diffuse enhancement which sustained toward the infundibulum and dura was observed on the gadolinium-enhanced pituitary MRI. The patient underwent an endoscopic endonasal transsphenoidal approach for tumor resection and thick yellowish fluid draining from the lesion was observed (Figure 1). The histopathological diagnosis was reported as a rupture of an Rathke's cleft cyst and a xanthomatous hypophysitis. The surgery did not improve the symptoms/pituitary functions, however, headache recovered immediately after the first dose of high dose methylprednisolone treatment. Conclusion The exact mechanism by which XHP occurs still remains unclear. The development of the characteristic histopathological lesion which consists of lipid-laden “foamy” histiocytes and CD68 positive macrophages has been previously attributed to the extension of an autoimmune/lymphocytic spectrum. On the other hand, various recent case presentations have reported to consider the inflammatory process of XHP related to the rupture of a RCC. XHP is an uncommon inflammatory process of the pituitary gland which should be included in the differential diagnoses, if a patient presents with headache, panhypopituitarism and if yellowish fluid is drained from a cystic lesion intraoperatively. In agreement with the recent reports, our case presentation may also indicate a recommendation to classify XHP as secondary hypophysitis which could be caused by a ruptured cystic lesion. Here, we present a patient with XHP which developed as an inflammatory response to a ruptured RCC and the transsphenoidal surgery did not improve the symptoms/pituitary functions, while headache recovered immediately after the first dose of high dose methylprednisolone treatment.

A CASE REPORT OF BEHÇET'S DISEASE WITH CORONARY ARTERY INVOLVEMENT

ABSTRACT
 We present a case of coronary artery thrombosis due to Behçet's disease. A 49-year-old female patient, diagnosed with Behçet's disease and followed up by us, applied to the emergency department with sudden onset of pressure-type chest pain, and was evaluated as acute myocardial infarction due to elevated cardiac enzymes and ST segment elevation in the anterior leads on electrocardiography (ECG). Coronary angiography revealed near-total thrombosis in the lumen of the left anterior descending artery (LAD) and in the circumflex (CX) artery,it was intervened with anticoagulant therapy. The patient's cardiac risk was found to be low and differential diagnosis was made in terms of myocardial infarction. Thereupon, the causes of hypercoagulability were investigated in the patient who was consulted to us, and acute phase reactants were found to be high. This was related to the coronary artery involvement of Behçet's disease and in addition to the treatment containing antiaggregant, statin, angiotensin receptor blocker, intravenous (IV) high-dose methylprednisolone and cyclophosphamide-mesna treatment was given for immunosuppressive purposes. It should not be forgotten that there may be vascular involvement due to Behçet's disease and coronary arteries may also be affected.

Alemtuzumab induced hemodynamic change in relapsing multiple sclerosis occurs independent of corticosteroid premedication – a retrospective multicentre study

Background Alemtuzumab (ATZ), a highly effective disease modifying treatment for relapsing multiple sclerosis (MS), is associated with the rare risk of intracerebral hemorrhage. Increase of blood pressure (BP) was hypothesized to be causative, but prior administration of high-dose methylprednisolone (HDMP) is a potential confounder.Objective To analyze BP change in MS patients treated with ATZ and prior HDMP treatment compared to patients receiving HDMP only for acute relapse.Methods In this retrospective study, 30 patients treated with ATZ/HDMP and 60 age-, sex- and disability-matched controls treated with HDMP were included. Primary endpoint was the change of systolic BP (SBP) between before ATZ cycle and the maximum value measured during the treatment cycle; secondary endpoints were change in diastolic BP (DBP) and heart rate (HR).Results Change of SBP observed in ATZ/HDMP treated patients was significantly higher than in HDMP controls (mean maximal change of 12.8 vs. 8.1 mmHg, p = 0.033). An increase of SBP exceeding 20% from baseline was observed in 5 (16.7%) patients on ATZ/HDMP compared to 3 (5.0%) on HDMP (p = 0.078). The day after the 1st ATZ infusion, mean HR was higher in the ATZ/HDMP group compared to HDMP controls (82.5 vs. 73.2 bpm, p = 0.005), although there was no significant group difference over time.Conclusions ATZ treatment induced a slight, but significant increase in SBP independent of HDMP. Although hemodynamic alterations alone seem unlikely as putative mechanism for cerebral bleedings, strict cardiovascular monitoring is recommended to reduce rare, but severe cardiovascular side effects.

Efficacy of Plasma Exchange Treatment for Demyelinating Optic Neuritis Associated with Various Serum Antibodies: A Prospective Cohort Study.

Introduction To evaluate the value of plasma exchange (PE) for patients with three subtypes of demyelinating optic neuritis (ON): aquaporin-4 (AQP4) antibody-positive ON (AQP4-ON), myelin oligodendrocyte glycoprotein (MOG) antibody-positive ON (MOG-ON), and AQP4 and MOG double-antibody-seronegative ON (D-ON).MethodsA single-center prospective study compared the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at most severe onset, 1 day before intravenous high-dose methylprednisolone (IVMP) treatment, 1 day before PE treatment, after five-cycles of PE therapy, and at 1-, 3-, and 6-month follow-up visits. The proportions of eyes in each visual outcome category were also compared. Logistic regression and a receiver operating characteristic curve were used to analyze predicted factors for VA improvement.ResultsA total of 124 ON attacks of 122 patients were included. No significant differences were found in BCVA (P = 0.659) before and after PE therapy for 22 D-ON attacks, but VA improved in two of six MOG-ON patients. In 95 AQP4-ON patients suffering 96 attacks, the mean logMAR BCVA markedly improved and was steadily maintained after five-cycles of PE treatments (adjusted P < 0.001), with VA exhibiting a significantly increasing trend (adjusted P = 0.001) after PE treatment. The combination of the number of previous ON episodes and the time window to PE treatment showed accuracy of 74.7% for predicting an improvement in BCVA score ≥ 2 levels. In addition, a combination of logMAR VA before PE and the time window to PE treatment resulted in 83.4% accuracy in predicting whether VA would regain 1.0 logMAR.ConclusionPE therapy effectively improves visual outcomes for AQP4-ON patients, but offers limited value for D-ON patients. Early initiation greatly increases likelihood of achieving VA improvement.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-022-00344-w.

Clinical Relevance of Polymorphonuclear Myeloid-Derived Suppressor Cells in Autoimmune-Blistering Disorders Pemphigus Vulgaris and Bullous Pemphigoid

Clinical Relevance of Polymorphonuclear Myeloid-Derived Suppressor Cells in Autoimmune-Blistering Disorders Pemphigus Vulgaris and Bullous Pemphigoid

Correlation between serum levels of endothelin-1 and disease severity in patients with neuromyelitis optica spectrum disorders

Neuromyelitis optica spectrum disorders (NMOSD) are aquaporin-4 antibody-mediated diseases of the central nervous system. Endothelin-1 (ET-1) is an inflammatory cytokine released by vascular endothelial cells and activated astrocytes. Previous studies have reported the aberrant expressions of cytokines/chemokines in patients diagnosed with NMOSD. However, the serum levels of ET-1 in NMOSD patients remain unknown. The purpose of this study was to measure the serum levels of ET-1 and other immune-related cytokines/chemokines in patients with NMOSD, and to investigate the correlation between serum ET-1 levels and clinical characteristics of NMOSD. Thirty-eight patients with NMOSD and twenty-eight healthy controls (HCs) were recruited in this study. The serum concentrations of ET-1 and other cytokines/chemokines were measured, and their correlations to the clinical features of patients with NMOSD were analyzed. The serum levels of ET-1 in patients with NMOSD were significantly higher than those in HCs (P = 0.0001). The serum concentrations of ET-1 were positively correlated with the Expanded Disability Status Scale score (r = 0.428, P = 0.0183). High-dose intravenous methylprednisolone treatment significantly reduced the levels of ET-1 and interleukin (IL)-6 in blood, but significantly increased the serum concentrations of IL-10 in NMOSD patients. No correlations were found between serum ET-1 levels and the concentrations of other cytokines/chemokines in these patients. ET-1 and IL-6 might exert pro-inflammatory effects in the pathogenesis of NMOSD, whereas IL-10 played an anti-inflammatory role in this process. ET-1 might be a potential biomarker for predicting the severity of NMOSD. However, the serum levels of ET-1 were not correlated with the changes of other cytokines/chemokines in patients with NMOSD. The involvement of ET-1 in the development of NMOSD needs to be further studied.

Vision improvement in severe acute isolated optic neuritis after plasma exchange treatment in Chinese population: a prospective case series study.

Background:Plasma exchange (PE) is often considered as an effective treatment for neuromyelitis optica spectrum disorder (NMOSD) and several inflammatory demyelinating disorders of the central nervous system. This study aimed to evaluate the visual outcomes of Chinese patients with severe acute isolated optic neuritis (ON) who received PE therapy after high-dose intravenous methylprednisolone (IVMP) treatment.Methods:Thirty-seven acute isolated ON patients experiencing their first attack of severe visual impairment without neurological disability were recruited. All subjects received five cycles of double-filtration plasmapheresis. Visual acuity (VA) was documented at onset, 1 day before PE treatment, at each cycle of PE therapy and at the 1-month follow-up visit.Results:This study included 26 female (70.3%) and 11 male (29.7%) subjects, and 18 subjects (48.6%) had bilateral involvement. The time window between onset and PE treatment was 27.3 ± 12.7 days (range: 6–53 days). Mean VA (logMAR) of the studied eyes at onset, 1-day before PE treatment/after IVMP and after the fifth PE treatment were 3.41 ± 1.50, 2.61 ± 1.64 and 1.66 ± 1.52, respectively (p < 0.001). Nineteen eyes (51.4%) showed no light perception at the onset, and 17 eyes (45.9%) improved to Snellen VA >20/800 after IVMP and PE treatments, among which five eyes (13.5%) recovered to Snellen VA 20/20 (p < 0.001). Predictors of good visual outcome included body mass index [odds ratio (OR) = 0.734, p = 0.044], serum AQP4 antibody-positive status (OR = 0.004, p = 0.001), bilaterality (OR = 0.042, p = 0.008) and time window from onset to PE therapy per 1 day (OR = 0.79, p = 0.002).Conclusion:This study revealed that PE treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. Better visual outcomes can be achieved with early PE treatment.

Tigecycline-induced sustained severe hypoglycemia: a case report

BackgroundTigecycline, the first glycylcycline-class drug, is a broad-spectrum antibiotic with activity against multi-drug resistant (MDR) organisms. We describe a case of sustained and severe hypoglycemia in a patient treated with tigecycline for pneumonia due to MDR Klebsiella pneumoniae.Case presentationA 74-year-old man was admitted for treatment of pneumonia. At admission he had prediabetes. In the hospital he developed renal failure. On day 3, the patient experienced severe shortness of breath. He was intubated and transferred to the intensive care unit (ICU) for ventilator support. In the ICU the antibiotic regimen was cefoperazone and sulbactam (1 g every 12 h). Continuous Renal Replacement Therapy was started on that day. Test for anti-neutrophil cytoplasmic antibodies (ANCA) was positive, and so the nephrologist and rheumatologist agreed on a diagnosis of ANCA-associated vasculitis, with renal and pulmonary involvement and acute renal failure. Plasmapheresis, and high-dose methylprednisolone treatment were started on day 6, and there was obvious improvement in the patient’s condition. The steroid regimen was gradually tapered to oral prednisone (35 mg every day) on day 19. Afterwards, the patient’s pneumonia worsened. Sputum culture showed Klebsiella pneumoniae sensitive to only tigecycline. Tigecycline treatment (100 mg every 12 h) was administered on day 20. Hypoglycemia started about 37 h after the first dose of tigecycline. Infusion of 50% glucose through the femoral vein was required for over 20 h to maintain normal blood glucose concentrations. Tigecycline was stopped, but the hypoglycemia resolved only after a further 34 h. The insulin and C-peptide levels were found to be markedly elevated during the hypoglycemia. The Naranjo scale score of 7 indicated that the likelihood of tigecycline causing severe hypoglycemia was “probable.”ConclusionThis is the first report of sustained severe hypoglycemia due to tigecycline. Oversecretion of insulin appears to have been the cause of the hypoglycemia in our patient. The mechanism needs to be investigated.

Acute kidney injury in childhood-onset nephrotic syndrome: Incidence and risk factors in hospitalized patients.

BackgroundNephrotic syndrome (NS) is the most common glomerulopathy in children. Acute kidney injury (AKI) is a common complication of NS, caused by severe intravascular volume depletion, acute tubular necrosis, interstitial nephritis, or progression of NS. However, the incidence and risk factors of childhood-onset NS in Korea are unclear. Therefore, we studied the incidence, causes, and risk factors of AKI in hospitalized Korean patients with childhood-onset NS.MethodsWe conducted a retrospective review of patients with childhood-onset NS who were admitted to our center from January 2015 to July 2017. Patients with decreased renal function or hereditary/secondary NS, as well as those admitted for management of other conditions unrelated to NS, were excluded.ResultsDuring the study period, 65 patients with idiopathic, childhood-onset NS were hospitalized 90 times for management of NS or its complications. Of these 90 cases, 29 met the Kidney Disease Improving Global Outcomes criteria for AKI (32.2%). They developed AKI in association with infection (n = 12), NS aggravation (n = 11), dehydration (n = 3), and intravenous methylprednisolone administration (n = 3). Age ≥ 9 years at admission and combined use of cyclosporine and renin-angiotensin system inhibitors were risk factors for AKI.ConclusionAKI occurred in one-third of the total hospitalizations related to childhood-onset NS, owing to infection, aggravation of NS, dehydration, and possibly high-dose methylprednisolone treatment. Age at admission and use of nephrotoxic agents were associated with AKI. As the AKI incidence is high, AKI should be considered during management of high-risk patients.

Spinal Cord Injury without Radiological Abnormality in Adults: Clinical and Radiological Discordance.

Patients with spinal cord injury without radiological abnormality (SCIWORA) show varying clinical prognostic courses independent of radiological findings. The fact that patients cannot be evaluated using a specific terminologic standard has led to the emergence of the real SCIWORA definition. In this study, clinical progressions of 11 patients diagnosed with SCIWORA were analyzed, and terminologic differences were discussed. The clinical findings of 11 adults with a diagnosis of SCIWORA at the time of diagnosis and in the long term were analyzed according to the ASIA classification scheme. The presence of a correlation between radiological findings from the early and late periods and the clinical findings was investigated. High-dose methylprednisolone treatment was administered to all newly diagnosed patients in the early period, and the clinical response was observed. Clinical, prognostic, and radiological comparisons with SCIWORA cases reported in the literature were conducted. Seven patients received a diagnosis of cervical SCIWORA, and 4 patients had thoracal SCIWORA. Neurologic findings at the time of diagnosis and in the early and late periods vary independent of radiological findings. In the cases where significant neurologic recovery was not observed within the first 3 days, significant recovery also was not seen in the later period. In the cases where neurologic recovery was seen, improvements in sphincter function and sensory and motor deficits were observed. In patients diagnosed with SCIWORA, early neurologic response is the determining factor for prognosis. Clinical findings and prognosis demonstrate no correlation with radiological findings.

Short-Course High-Dose Methylprednisolone Induces Differentiation and Apoptosis of Myeloid Leukemic Cells

Differentiation therapy with all-trans retinoic acid significantly improved the outcome of patients with acute promyelocytic leukemia (APL).Therefore, researchers are still exploring the possibility of differentiation therapy for patients with acute myeloblastic leukemia (AML) other than APL. On the other hand, based on in vitro experiments on induction of differentiation of mouse myeloid leukemic cells with certain steroid hormones, we have demonstrated that short-course (3 to 7 days) high-dose methylprednisolone (HDMP) treatment can induce terminal differentiation of leukemic cells in children with APL and in other subtypes of AML (AML-M1, AML-M2, AML-M4 and AML-M7). HDMP treatment has also been shown to induce apoptosis of myeloid leukemic cells in vivo and in vitro.

Patient-reported adverse effects of high-dose intravenous methylprednisolone treatment: a prospective web-based multi-center study in multiple sclerosis patients with a relapse.

In a prospective multi-center observational study, we evaluated the frequency, severity, and impact on activities of daily living (ADL) of adverse effects (AEs) of high-dose intravenous methylprednisolone (IVMP) in relapsing remitting multiple sclerosis (MS) patients with a relapse. Online self-report questionnaires stating IVMP’s most common AEs were completed at baseline, the 2nd day of treatment, and 1 day and 1 week after treatment. Eighty-five patients were included, 66 completed the baseline questionnaire, and 59 completed at least one post-baseline questionnaire. Patients reported on average 4 (median) AEs; two (3.4 %) reported no AE. Most frequent was change in taste (61 %), facial flushing (61 %), sick/stomach pain (53 %), sleep disturbance (44 %), appetite change (37 %), agitation (36 %), and behavioral changes (36 %). Of all AEs, 34.3 % were severe and 37.9 % impacted on ADL. A 3-day course resulted in 4 (median) AEs and a 5-day course in 7. All patients with high disease impact had two or more AEs, compared with 79 % of those with low impact (p < 0.01). Of patients with high disability, 45 % had severe AEs, compared with 16 % of those with low disability. Severe central nervous system (CNS)-related AEs occurred two times more frequently in patients with high disease impact, and two-and-a-half times more frequently in patients with high disability. Therefore, in virtually all patients, high-dose IVMP leads to AEs, with about one of three AEs being severe with impact on ADL. Patients with high disease impact or high disability may experience more (severe) AEs, due to a higher occurrence of severe CNS-related AEs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-016-8183-3) contains supplementary material.

Effect of short-term, high-dose methylprednisolone on oxidative stress in children with acute immune thrombocytopenia.

BackgroundImmune thrombocytopenia (ITP) is the most common cause of acquired childhood thrombocytopenia and is characterized by increased immune-mediated destruction of circulating thrombocytes. Oxidative damage may be involved in ITP pathogenesis; paraoxonase (PON) and arylesterase (ARE) enzymes are closely associated with the cellular antioxidant system. We investigated the effect of short-term high-dose methylprednisolone (HDMP) treatment on the total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and PON and ARE enzymatic activity in children with acute ITP.MethodsThirty children with acute ITP constituted the study group and 30 healthy children constituted the control group. Children with acute ITP were treated with HDMP: 30 mg/kg for 3 days, then 20 mg/kg for 4 days. The TOS, TAC, OSI, PON, and ARE levels were determined before and after 7 days of HDMP treatment.ResultsThe TAC level (P<0.001), and PON (P<0.001) and ARE (P=0.001) activities were lower and the TOS (P=0.003) and OSI (P<0.001) levels were higher in children with acute ITP than those in healthy children in the control group. We also observed statistically significant increases in the TAC (P<0.01), PON (P<0.001) and ARE levels (P=0.001) and decreases in the TOS (P<0.05) and OSI levels (P<0.05) with 7 days of HDMP treatment compared to their values before treatment.ConclusionOur study demonstrated increased oxidative stress (OSI and TOC) and decreased antioxidant capacity (TAC), PON, and ARE in ITP patients and that steroid treatment could be effective in reducing the oxidative stress.