[Juvenile-onset anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis with joint contractures before manifestation of myositis: a case report].

A 23-year-old man was admitted to our hospital with a one-year history of muscle weakness and atrophy. He had noticed contractures of the fingers of both hands from the age of 18. Examination revealed a skin rash including heliotrope rash and Gottron's sign, joint contractures in the extremities, dysphagia, extensive muscle weakness and marked muscle atrophy. The serum creatine kinase level was 272 |IU/l and muscle biopsy showed typical perifascicular atrophy but little lymphocyte invasion. There was no interstitial pneumonia or malignancy, but muscle tendons showed elevated CT values suggesting calcification or fibrosis. Anti-nuclear matrix protein 2 (NXP-2) antibody-positive dermatomyositis was diagnosed on the basis of the serum antibody level. Methylprednisolone pulse therapy ameliorated the skin rash and bulbar palsy, but muscle weakness, atrophy and joint contractures were resistant to the treatment. There have been no previous reports of young adults with anti-NXP-2 antibody-positive dermatomyositis in whom joint contracture became evident as early as 4 years beforehand, which is a important feature for differential diagnosis of dermatomyositis.

Pulsatile gonadotropin releasing hormone therapy for spermatogenesis in congenital hypogonadotropic hypogonadism patients who had poor response to combined gonadotropin therapy.

Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/ HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/ HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis.

Topical Betamethasone Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis with Ocular Involvement in the Acute Phase.

PURPOSE: To clarify the importance of administering topical steroids for the treatment of Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) with ocular involvement in the acute phase. DESIGN: Retrospective case series. METHODS: Using the medical records of acute SJS/TEN patients treated at the Kyoto Prefectural University of Medicine Hospital, Kyoto, Japan, between July 2006 and July 2017, the ocular findings, topical steroid dosage, systemic steroid dosage, and ocular sequelae were retrospectively examined. The level of cytokines in tear fluid and serum samples was also analyzed. RESULTS: This study involved 13 cases. In 10 cases in whom the clinical courses were recorded before the start of steroid therapy, the mean acute ocular severity score (AOSS: 3 = very severe; 2 = severe; 1 = mild; 0 = none) was 2.8 ± 0.4 points in the severest phase. The mean systemic steroid dose after steroid pulse therapy was 694 ± 386 mg and the mean topical steroid (0.1% betamethasone eye drop and ointment) dose was 13.4 ± 3.3 times daily in the severest phase. Analysis of cytokine levels of 4 cases showed that a cytokine storm occurred in the tear fluid after the steroid pulse therapy. At final follow-up, 16 eyes of 8 patients had a logMAR visual acuity of ≤0, and no serious ocular sequelae were observed. CONCLUSIONS: In patients with SJS/TEN, ocular surface inflammation remains strong even after systemic inflammation has improved post steroid pulse therapy, thus suggesting that both systemic and topical steroid therapy should be administered appropriately.

Efficacy of Pulse Methylprednisolone in Treatment of Acute Respiratory Distress Syndrome due to Malaria: A Randomized Controlled Clinical Trial.

Objective: To study the efficacy of pulse methylprednisolone (MPS) therapy in patients with malaria-associated acute respiratory distress syndrome (ARDS). Materials and methods: The study was a randomized, single-blind, placebo-controlled trial with a total sample size of 44 patients. The total random number table was used on a computer for randomization. The sample size was divided into either the study group that received pulse MPS therapy along with the standard therapy to manage acute lung injury (ALI)/ARDS or the control group that received a placebo in the form of 100 mL of normal saline with the standard therapy to manage ALI/ARDS. The primary outcome was defined as either death of the patient or discharge from the hospital. The sequential organ failure assessment (SOFA) score, the lung injury score (LIS), duration of stay in the medical intensive care unit (MICU), number of days for which mechanical ventilation was required, and the rate of secondary infections between the study and the control groups were also calculated. Statistically significant differences among continuous variables were analyzed by t-test, and differences between categorical variables were assessed by Chi-squared test. Results: A total of 30 patients passed initial screening, out of which 60% were males and 40% were females. About 73.3% of the patients fell between the age groups of 36-45 years. A total of 20 patients (66.7%) were discharged from the hospital, while the remaining 10 patients succumbed to death in the intensive care unit (ICU) (33.3%). The outcome of death or discharge was found to be independent of the use of pulse MPS therapy (p = 0.44). No statistically significant difference was found between the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, SOFA score, and LIS between the two groups. Furthermore, the differences between the mean duration of stay in the MICU, the mean duration for the provision of mechanical ventilation (p = 0.41), and the rate of secondary infections (p = 0.46) remained unaffected with the use of pulse MPS therapy. Conclusion: Pulse MPS therapy has not shown any clear-cut benefit in the management of malaria-associated ARDS, and in fact, the continuous use of this treatment in hospitals may lead to worsened outcomes. A novel, effective therapy for this grave complication needs to be developed to reduce the morbidity and mortality in such patients, which is frequently encountered. The development of a robust surveillance system is required for adequate monitoring and early diagnosis of this complication, along with larger multicentric randomized clinical trials. Disclosures: Approval was granted by the Institutional Ethics Committee (IEC). All participants were only selected after taking their written informed consent. The authors have no conflicts of interest or acknowledgments to report. How to cite this article: Tiwari S, Kursange S, Goyal A, et al. Efficacy of Pulse Methylprednisolone in Treatment of Acute Respiratory Distress Syndrome due to Malaria: A Randomized Controlled Clinical Trial. J Assoc Physicians India 2023;71(11):36-39.

Treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy.

BACKGROUND: IgA nephropathy is a typical chronic glomerulonephritis that tends to occur in childhood. METHOD: We reviewed the report on pathogenesis, treatment strategy with multidrug therapy and tonsillectomy pulse therapy for childhood-onset severe IgA nephropathy to clarify the pathophysiology and treatment of IgA nephropathy in childhood. RESULTS: In recent years, it has been found that the pathogenesis at onset is associated with aberrant glycosylation at the IgA1 hinge. Given this genetic background, the aberrantly glycosylated IgA1immune complex produced by antigen-stimulated T cells and B cells is deposited in the glomeruli. Inflammation is induced via activation of the complement, macrophages and mesangial cells, and glomerular damage progresses thereafter. Treatment is selected according to the severity of IgA nephropathy. In order to prevent the development of renal damage, it is important to control the associated immune responses. For severe IgA nephropathy, in particular, multidrug therapy with prednisolone, immunosuppressants, and angiotensin enzyme synthesis inhibitors and tonsillectomy methylprednisolone pulse therapy are now performed- and, as a result, the number of renal deaths has decreased and the long-term prognosis has improved. CONCLUSION: The prognosis of IgA nephropathy is improving. In the future, it will be important to develop a treatment method that takes into consideration the fact that children are in their growth and development stage and, therefore, seeks to minimizes side effects.

Short-term Side Effects of Pulse Steroid Treatment in Children.

This study is aimed to evaluate pediatric patients, who were hospitalised in the Department of Pediatrics, University of Health Sciences, Adana City Training and Research Hospital, Turkey, between January, 2019 and January, 2020, and treated with pulse steroid therapy and the early side effects of their treatment. The fasting blood glucose levels of the patients during treatment were statistically significantly higher than those prior to the treatment. The most common side effects observed in the patients were dermatological (48.5%), psychiatric (31.4%), and gastrointestinal (31.4%). Hypertension was detected in seven patients (20%) after treatment; and continued in three, who subsequently underwent antihypertensive treatment. Pulse steroid treatment was administered for a median of five days (3-11 days). It was found that 24 patients responded to treatment, 11 patients did not respond, and one patient died. There is a shortage of studies in literature on pulse steroid therapy and its side effects, especially focusing on children. Multicentre and randomised controlled studies are needed comprising different patient groups to evaluate the efficacy and complications associated with its use. Key Words: Children, Side effect, Pulse steroid treatment.

Progressive, refractory macrophage activation syndrome as the initial presentation of anti-MDA5 antibody positive juvenile dermatomyositis: a case report and literature review.

BACKGROUND: Macrophage activation syndrome (MAS) is a severe and under-recognized complication of rheumatologic diseases. We describe a patient who presented with rapidly progressive, refractory MAS found to have anti-MDA5 antibody Juvenile Dermatomyositis (JDM) as her underlying rheumatologic diagnosis. CASE PRESENTATION: We describe a 14-year-old female who at the time of admission had a history of daily fevers for 6 weeks and an unintentional sixteen-pound weight loss. Review of systems was significant for cough, shortness of breath, chest pain, headaches, sore throat, muscle aches, rash, nausea, and loss of appetite. An extensive initial workup revealed findings consistent with an autoimmune process. While awaiting results of her workup she had clinical decompensation with multi-organ system involvement including pancytopenias, interstitial lung disease, hepatitis, cardiac involvement, gastrointestinal distension and pain, feeding intolerance, extensive mucocutaneous candidiasis, and neuropsychiatric decline. Due to her decompensation, significant interstitial lung disease, and likely underlying rheumatologic condition she was started on high dose pulse steroids and mycophenolate. An MRI was performed due to her transaminitis and shoulder pain revealing significant myositis. Intravenous immunoglobulin was then initiated. The myositis antibody panel sent early in her workup was significant for anti-MDA5 and anti-SSA-52 antibodies. Despite high dose pulse steroids, mycophenolate, and IVIG, her disease progressed requiring escalating therapies. Ultimately, she responded with resolution of her MAS as well as significant and steady improvement in her feeding intolerance, interstitial lung disease, cardiac dysfunction, myositis, arthritis, and cutaneous findings. CONCLUSIONS: JDM in the pediatric patient is rare, as is MAS. In patients with complex rheumatologic conditions and lack of response to treatment, it is important to continually assess the patient's clinical status with MAS in mind, as this may change the treatment approach. Without proper recognition of this complication, patients can have a significant delay in diagnosis leading to life-threatening consequences.

Cytokine Release Syndrome in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Case Series of 25 Patients and Review of the Literature.

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of immunotherapy. Unlike other immune-related adverse events, CRS triggered by immune checkpoint inhibitors (ICIs) is not well described. The clinical characteristics and course of 25 patients with ICI-induced CRS from 2 tertiary hospitals were abstracted retrospectively from the medical records and analyzed. CRS events were confirmed by 2 independent reviewers and graded using the Lee et al. scale. The median duration of CRS was 15.0 days (Q1; Q3 6.3; 29.8) and 10 (40.0%) had multiple episodes of CRS flares. Comparing the clinical factors and biomarkers in Grades 1-2 and 3-5 CRS, we found that patients with Grades 3-5 CRS had following: (i) had longer time to fever onset [25.0 days (Q1; Q3 13.0; 136.5) vs. 3.0 days (Q1; Q3 0.0; 18.0), p=0.027]; (ii) more cardiovascular (p=0.002), neurologic (p=0.001), pulmonary (p=0.044) and rheumatic (p=0.037) involvement; (iii) lower platelet count (p=0.041) and higher urea (p=0.041) at presentation compared to patients with Grades 1-2 CRS. 7 patients (28.0%) with Grades 1-2 CRS were rechallenged using ICIs without event. 9 patients (36.0%) were treated with pulse methylprednisolone and 6 patients (24.0%) were treated with tocilizumab. Despite this, 3 patients (50%) who received tocilizumab had fatal (Grade 5) outcomes from ICI-induced CRS. Longer time to fever onset, lower platelet count and higher urea at presentation were associated with Grade 3-5 CRS. These parameters may be used to predict which patients are likely to develop severe CRS.

Effect of pulsed intravenous methylprednisolone with alternative low-dose prednisone on high-risk IgA nephropathy: a 18-month prospective clinical trial.

Full-dose prednisone (FP) regimen in the treatment of high-risk immunoglobulin A nephropathy (IgAN) patients, is still controversial. The pulsed intravenous methylprednisolone combined with alternative low-dose prednisone (MCALP) might have a more favorable safety profile, which has not been fully investigated. Eighty-seven biopsy-proven IgAN adult patients and proteinuria between 1 and 3.5 g/24 h after ACEI/ARB for at least 90 days were randomly assigned to 6-month therapy: (1) MCALP group: 0.5 g of methylprednisolone intravenously for three consecutive days at the beginning of the course and 3rd month respectively, oral prednisone at a dose of 15 mg every other day for 6 months. (2) FP group: 0.8-1.0 mg/kg/days of prednisone (maximum 70 mg/day) for 2 months, then tapered by 5 mg every 10 days for the next 4 months. All patients were followed up for another 12 months. The primary outcome was complete remission (CR) of proteinuria at 12 months. The percentage of CR at 12th and 18th month were similar in the MCALP and FP groups (51% vs 58%, P = 0.490, at 12th month; 60% vs 56%, P = 0.714, at 18th month). The cumulative dosages of glucocorticoid were less in the MCALP group than FP group (4.31 ± 0.26 g vs 7.34 ± 1.21 g, P < 0.001). The analysis of the correlation between kidney biopsy Oxford MEST-C scores with clinical outcomes indicated the percentages of total remission was similar between two groups with or without M1, E1, S1, T1/T2, and C1/C2. More patients in the FP group presented infections (8% in MCALP vs 21% in FP), weight gain (4% in MCALP vs 19% in FP) and Cushing syndrome (3% in MCALP vs 18% in FP). These data indicated that MCALP maybe one of the choices for IgAN patients with a high risk for progression into ESKD.Trial registration: The study approved by the Chinese Clinical Trial Registry (registration date 13/01/2018, approval number ChiCTR1800014442, https://www.chictr.org.cn/ ).

Características sociodemográficas e clínicas na internação de adolescentes submetidos a pulsoterapia com glicocorticoides / Sociodemographic and clinical characteristics in the hospitalization of dolescents submitted to pulsotherapy with glycocorticoids / Características sociodemográficas y clínicas en la hospitalización de dolescentes sometidos a pulsoterapia con glicocorticoides

Introdução: Adolescentes com Lúpus Eritematoso Sistêmico desenvolvem doença autoimune inflamatória sistêmica, demandando assistência de enfermagem especializada. Objetivo: Levantar as características sociodemográficas e clínicas de adolescentes com Lúpus Eritematoso Sistêmico submetidos a pulsoterapia com glicocorticoides em um serviço especializado em saúde do adolescente. Material e Método: Estudo descritivo, retrospectivo quantitativo, realizado em uma enfermaria de um hospital universitário no Estado do Rio de Janeiro, Brasil, cuja amostra incluiu 12 prontuários de adolescentes internados no período de janeiro a julho de 2021, submetidos ao protocolo de pulsoterapia com glicocorticoide, totalizando 23 internações. Os dados foram coletados no período de maio a julho. Resultados: Das 23 internações para realização de pulsoterapia, 95,7% (n=22) foram em decorrência das complicações oriundas do Lúpus. As queixas predominantes durante a internação foram as dores articulares, edema e febre. Sobre o conhecimento dos adolescentes em relação a doença, foi possível identificar que 50% (n=6) possuíam conhecimento. A maioria dos adolescentes era do sexo feminino (75%), raça branca (50%) e faixa etária de 14 a 16 anos (75%), com ensino fundamental incompleto (58,3%) e renda familiar de 1 a 2 salários-mínimos (83,3%). Conclusão: É importante levantar as características sociodemográficas e clínicas dos adolescentes com Lúpus, pois favorece a realização de um plano assistencial de enfermagem individualizado e integral, dadas as necessidades dessa população.(AU)

Introduction: Adolescents with Systemic Lupus Erythematosus develop systemic inflammatory autoimmune disease, requiring specialized nursing care. Objective: To survey the sociodemographic and clinical characteristics of adolescents with Systemic Lupus Erythematosus undergoing pulse therapy with glucocorticoids in a specialized service in adolescent health. Material and Method: Descriptive, quantitative retrospective study, carried out in a ward of a university hospital in the State of Rio de Janeiro, Brazil, whose sample included 12 medical records of adolescents hospitalized from January to July 2021, submitted to the pulse therapy protocol with glucocorticoid, totaling 23 hospitalizations. Data were collected from May to July. Results: Of the 23 hospitalizations for pulse therapy, 95.7% (n=22) were due to complications from Lupus. The predominant complaints during hospitalization were joint pain, swelling and fever. About the knowledge of adolescents and the disease, it was possible to identify that 50% (n=6) had knowledge. Most adolescents were female (75%), white (50%) and aged between 14 and 16 years (75%), with incomplete primary education (58.3%) and family income of 1 to 2 salaries-minimum (83.3%). Conclusion: It is important to survey the sociodemographic and clinical characteristics of adolescents with Lupus, as it favors the implementation of an individualized and comprehensive nursing care plan, given the needs of this population.(AU)

Introducción: Los adolescentes con Lupus Eritematoso Sistémico desarrollan enfermedad autoinmune inflamatoria sistémica, requiriendo atención de enfermería especializada. Objetivo: Relevar las características sociodemográficas y clínicas de adolescentes con Lupus Eritematoso Sistémico en tratamiento de pulso con glucocorticoides en un servicio especializado en salud del adolescente. Material y Método: Estudio descriptivo, cuantitativo, retrospectivo, realizado en una sala de un hospital universitario del Estado de Río de Janeiro, Brasil, cuya muestra incluyó 12 prontuarios de adolescentes hospitalizados de enero a julio de 2021, sometidos al protocolo de pulsoterapia. con glucocorticoide, totalizando 23 hospitalizaciones. Los datos fueron recolectados de mayo a julio. Resultados: De las 23 hospitalizaciones por pulsoterapia, el 95,7% (n=22) fueron por complicaciones del Lupus. Las quejas predominantes durante la hospitalización fueron dolor articular, hinchazón y fiebre. Sobre el conocimiento de los adolescentes y la enfermedad, fue posible identificar que el 50% (n=6) tenía conocimiento. La mayoría de los adolescentes eran del sexo femenino (75%), blancos (50%) y con edades entre 14 y 16 años (75%), con instrucción primaria incompleta (58,3%) y renta familiar de 1 a 2 salarios mínimos (83,3%). Conclusión: Es importante relevar las características sociodemográficas y clínicas de los adolescentes con Lupus, ya que favorece la implementación de un plan de atención de enfermería individualizado e integral, dadas las necesidades de esta población.(AU)

Comparison of pulse-dose and high-dose corticosteroids with no corticosteroid treatment for COVID-19 pneumonia in the intensive care unit.

Corticosteroid dosing in the range of 0.5-2 mg/kg/day of methylprednisolone equivalents has become a standard part of the management of intensive care unit (ICU) patients with COVID-19 pneumonia based on positive results of randomized trials and a meta-analysis. Alongside such conventional dosing, administration of 1 gm of methylprednisolone daily (pulse dosing) has also been reported in the literature with claims of favorable outcomes. Comparisons between such disparate approaches to corticosteroids for Coronavirus disease 2019 (COVID-19) pneumonia are lacking. In this retrospective study of patients admitted to the ICU with COVID-19 pneumonia, we compared patients treated with 0.5-2 mg/kg/day in methylprednisolone equivalents (high-dose corticosteroids) and patients treated with 1 gm of methylprednisolone (pulse-dose corticosteroids) to those who did not receive any corticosteroids. The endpoints of interest were hospital mortality, ICU-free days at Day 28, and complications potentially attributable to corticosteroids. Pulse-dose corticosteroid therapy was associated with a significant increase in ICU-free days at Day 28 compared to no receipt: adjusted relative risk (aRR): 1.45 (95% confidence interval [CI]: 1.05-2.02; p = 0.03) and compared with high-dose corticosteroid administration (p = 0.003). Nonetheless, receipt of high-dose corticosteroids-but not of pulse-dose corticosteroids-significantly reduced the odds of hospital mortality compared to no receipt: adjusted Odds ratio (aOR) 0.31 (95% CI: 0.12-0.77; p = 0.01). High-dose corticosteroids reduced mortality compared to pulse-dose corticosteroids (p = 0.04). Pulse-dose corticosteroids-but not high-dose corticosteroids-significantly increased the odds of acute kidney injury requiring renal replacement therapy compared to no receipt: aOR 3.53 (95% CI: 1.27-9.82; p = 0.02). The odds of this complication were also significantly higher in the pulse-dose group when compared to the high-dose group (p = 0.05 for the comparison). In this single-center study, pulse-dose corticosteroid therapy for COVID-19 pneumonia in the ICU was associated with an increase in ICU-free days but failed to impact hospital mortality, perhaps because of its association with development of severe renal failure. In line with existing trial data, the effect of high-dose corticosteroids on mortality was favorable.

Clinical efficacy and safety of combination therapy of tocilizumab and steroid pulse therapy for critical COVID-19 in HD patients.

BACKGROUND: Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. METHODS: From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. RESULTS: Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0-1 L/min within 3 weeks post-administration. CONCLUSION: TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.

Endoscopic trans-ethmosphenoid optic canal decompression is an optimal choice to save vision for indirect traumatic optic neuropathy.

PURPOSE: To evaluate and compare the effectiveness of endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) and steroid pulse therapy (SPT) for indirect traumatic optic neuropathy (ITON). DESIGN: Prospective interventional case series. METHODS: Total 140 monocular ITON patients from January 2017 to June 2019 were recruited, including 100 patients received ETOCD (56 patients received ETOCD only and 44 patients received ETOCD combined with SPT before surgery), and 40 patients received SPT only. Their visual acuity (VA) and visual evoked potential (VEP) were analysed before and after treatments. Initial VA, lag time, causes of injuries and age were analysed for evaluating prognosis of treatment. RESULTS: In contrast with patients received SPT only (15/40 = 38%), the effective rate of patients received ETOCD only and patients received ETOCD combined with SPT were both significantly better (46/56 = 82%, p < 0.001 and 30/44 = 68%, p = 0.005). Whether with SPT before ETOCD or not, after ETOCD, patients with VA improvement showed no significant difference. And 59/76 (77.6%) patients showed improvement within 24 hours. Patients who had residual visions achieved higher effective rate than those with no light perception (56/58 = 97% and 20/42 = 48%; p < 0.001) after ETOCD. For patients with long lag time of 21-90 days, 23/32 (72%) patients presented with vision improvement. Moreover, VEP was significantly improved after ETOCD. No severe complications were observed. CONCLUSIONS: Endoscopic trans-ethmosphenoid optic canal decompression (ETOCD) is an effective and safe therapy for ITON, which is more effective than SPT. Even for patients with failure in responding to SPT, the successfully physical decompression is the most effective way to rescue optical nerve from permanent damage.

An expanded-access clinical study of thiotepa (DSP-1958) high-dose chemotherapy before autologous hematopoietic stem cell transplantation in patients with malignant lymphoma.

Thiotepa, an antineoplastic ethylenimine alkylating agent that can penetrate the central nervous system, was recently approved in Japan as high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (HSCT) for patients with malignant lymphoma. To further evaluate the safety and efficacy of thiotepa, a multicenter, open-label, non-comparative, expanded access program was undertaken in Japan, including a larger population of Asian patients with malignant lymphoma. Intravenous thiotepa (200 mg/m2/day) was administered over 2 h on days -4 and -3 before scheduled HSCT, plus intravenous busulfan (0.8 mg/kg) over 2 h every 6 h on days -8, -7, -6 and -5. In the safety analysis population (N = 51), 25 patients (49.0%) had primary central nervous system lymphomas. The most common treatment-emergent adverse event was febrile neutropenia (49/51 [96.1%]). No unexpected safety events were observed, and no event resulted in death or treatment modification. Forty-seven patients (92.2%) had engraftment (neutrophil count ≥ 500/mm3 for three consecutive days after bone-marrow suppression and HSCT). The survival rate at day 100 post-transplantation was 100%. These data confirm the safety of thiotepa prior to autologous HSCT for patients with malignant lymphoma.Trial registration: JapicCTI-173654.