ResearchPad - cyclophosphamide https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Naringenin mitigates autoimmune features in lupus-prone mice by modulation of T-cell subsets and cytokines profile]]> https://www.researchpad.co/article/elastic_article_15753 Naringenin is flavonoid mainly found in citrus fruits which has shown several biological properties. In this work, we evaluated the therapeutic potential of the flavonoid Naringenin. Five-month-old B6.MRL-Faslpr/J lupus-prone mice were administered daily orally with Naringenin for seven months. We showed that Naringenin treatment at 50 or 100 mg/kg inhibited the splenomegaly and decreased the levels of anti-nuclear and anti-dsDNA autoantibodies. Furthermore, a reduction in serum concentration of TNF-α, IFN-γ and IL-6 was observed in the mice provided with Naringenin. Interestingly, serum levels of IL-10 increased. Naringenin decreased the frequency and absolute numbers of splenic effector memory T cells. Additionally, in order to be able to evaluate whether Naringenin prevented kidney damage, twelve-week-old MRL/MpJ-Faslpr/J mice, an accelerated lupus model, were orally administered with Naringenin at 100 mg/kg for six weeks. Surprisingly, Naringenin treatment prevented kidney damage and reduced the development of fibrosis similar to cyclophosphamide group. Moreover, Naringenin treatment increased the percentage of regulatory T cells in this aggressive model of lupus. Together, these results suggest a potential ability of Naringenin to reduce the autoimmunity in lupus-prone mice by modulation of T-cell subsets and cytokines profile that mitigate the development of important lupus clinical manifestations.

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<![CDATA[Adrenocortical carcinoma masquerading as pheochromocytoma: a histopathologic dilemma]]> https://www.researchpad.co/article/N2abbb711-6929-4ebd-a627-293991490a7a

Summary

Adrenocortical carcinoma (ACC) is an aggressive cancer that originates in the cortex of the adrenal gland and generally has a poor prognosis. ACC is rare but can be more commonly seen in those with cancer predisposition syndromes (e.g. Li-Fraumeni and Lynch Syndrome). The diagnosis of ACC is sometimes uncertain and it requires the use of precise molecular pathology; the differential diagnosis includes pheochromocytoma, adrenal adenoma, renal carcinoma, or hepatocellular carcinoma. We describe a case of a 57-year-old woman with Lynch Syndrome and metastatic ACC who was initially diagnosed as having pheochromocytoma. The tumor was first identified at 51 years of age by ultrasound followed by a CT scan. She underwent a left adrenalectomy, and the histopathology identified pheochromocytoma. Two years later, she had tumor recurrence with imaging studies showing multiple lung nodules. Following a wedge resection by video-assisted thoracoscopic surgery (VATS), histopathology was read as metastatic pheochromocytoma at one institution and metastatic ACC at another institution. She later presented to the National Institutes of Health (NIH) where the diagnosis of ACC was confirmed. Following her ACC diagnosis, she was treated with mitotane and pembrolizumab which were stopped due to side effects and progression of disease. She is currently receiving etoposide, doxorubicin, and cisplatin (EDP). This case highlights the importance of using a multi-disciplinary approach in patient care. Thorough evaluation of the tumor’s pathology and analysis of the patient’s genetic profile are necessary to obtain the correct diagnosis for the patient and can significantly influence the course of treatment.

Learning points:

  • Making the diagnosis of ACC can be difficult as the differential diagnosis includes pheochromocytoma, adrenal adenoma, renal carcinoma, or hepatocellular carcinoma.

  • Patients with Lynch Syndrome should undergo surveillance for ACC as there is evidence of an association between Lynch Syndrome and ACC.

  • Conducting a complete tumor immunoprofile and obtaining a second opinion is very important in cases of suspected ACC in order to confirm the proper diagnosis.

  • A multi-disciplinary approach including genetic testing and a thorough evaluation of the tumor’s pathology is imperative to ensuring that the patient receives an accurate diagnosis and the appropriate treatment.

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<![CDATA[Serum Axl predicts histology-based response to induction therapy and long-term renal outcome in lupus nephritis]]> https://www.researchpad.co/article/5c6b261bd5eed0c484289315

Axl is a receptor tyrosine kinase with important functions in immune regulation. We investigated serum levels of soluble (s)Axl in lupus nephritis (LN) in association with renal disease activity, tissue damage and treatment response. We surveyed 52 patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III/IV LN and 20 healthy controls. Renal biopsies were performed at the time of active LN and post-treatment. Patients were classified as clinical responders (CRs) or clinical non-responders based on the American College of Rheumatology (ACR) criteria. Improvement by ≥50% in renal activity index scores defined histological responders (HRs). sAxl levels were elevated in patients compared to controls (median: 18.9 ng/mL), both at baseline (median: 45.7; P<0.001) and post-treatment (median: 41.2 ng/mL; P<0.001). Baseline sAxl levels were higher in patients with class IV (median: 47.7 ng/mL) versus class III (median: 37.5 ng/mL) nephritis (P = 0.008), and showed moderate correlations with albuminuria (r = 0.30, P = 0.030) and creatinine (r = 0.35, P = 0.010). Baseline sAxl levels decreased in CRs (P = 0.002) and HRs (P<0.001), but not in non-responders; levels ≥36.6 ng/mL yielded a >5 times higher probability of histology-based response (odds ratio, OR: 5.5; 95% confidence interval, CI: 1.2–25.1). High post-treatment sAxl levels were associated with worsening in chronicity index scores (P = 0.025); low levels predicted favourable renal outcome (creatinine ≤88.4 μmol/L) 10 years after the baseline renal biopsy (area under the curve: 0.71; 95% CI: 0.54–0.89). In conclusion, sAxl may prove useful as a marker of renal activity, histological response to immunosuppression, and renal damage progression in LN. Persistently high sAxl levels after completion of treatment may be indicative of a need for treatment intensification.

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<![CDATA[BEST: Next-Generation Biomedical Entity Search Tool for Knowledge Discovery from Biomedical Literature]]> https://www.researchpad.co/article/5989da7dab0ee8fa60b993f4

As the volume of publications rapidly increases, searching for relevant information from the literature becomes more challenging. To complement standard search engines such as PubMed, it is desirable to have an advanced search tool that directly returns relevant biomedical entities such as targets, drugs, and mutations rather than a long list of articles. Some existing tools submit a query to PubMed and process retrieved abstracts to extract information at query time, resulting in a slow response time and limited coverage of only a fraction of the PubMed corpus. Other tools preprocess the PubMed corpus to speed up the response time; however, they are not constantly updated, and thus produce outdated results. Further, most existing tools cannot process sophisticated queries such as searches for mutations that co-occur with query terms in the literature. To address these problems, we introduce BEST, a biomedical entity search tool. BEST returns, as a result, a list of 10 different types of biomedical entities including genes, diseases, drugs, targets, transcription factors, miRNAs, and mutations that are relevant to a user’s query. To the best of our knowledge, BEST is the only system that processes free text queries and returns up-to-date results in real time including mutation information in the results. BEST is freely accessible at http://best.korea.ac.kr.

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<![CDATA[Study on the Cytotoxic, Genotoxic and Clastogenic Potential of Attalea phalerata Mart. ex Spreng. Oil Pulp In Vitro and In Vivo Experimental Models]]> https://www.researchpad.co/article/5989da58ab0ee8fa60b8f520

Attalea phalerata Mart. ex Spreng. (Arecaceae), popularly known as “bacuri”, is used in Brazilian folk medicine. Its oil is used orally to relieve pulmonary congestion and joint pain. In topical applications, it is applied as an effective hair tonic and anti-dandruff. The in natura pulp and its nuts are used as food because of its nutritional value. Despite its use in folk medicine, there is a lack of data regarding its in vivo/in vitro cytotoxic/genotoxic and clastogenic effects. Therefore, in this study, we evaluated the cytotoxic, genotoxic and clastogenic effects of Attalea phalerata Mart. ex Spreng. oil (APMO) in vitro and in vivo. For the analysis of cytotoxic potential, the Artemia salina and MTT (3-(4,5-dimethizzol-zyl)-2,5-diphenyltetrazolium bromide) assays were performed. Possible cytotoxic, genotoxic and clastogenic effects of APMO intake were determined by performing the comet and micronucleus assays. Male and female Wistar rats were orally treated with doses of 125, 250, 500 or 1000 mg.kg-1 of the APMO daily for 28 consecutive days (four weeks). The results showed that the APMO did not induce cell death in the experiments of Artemia salina and MTT, indicating that it has no cytotoxicity. The APMO did not cause significant damage to the DNA of the rats in the four doses used when compared to the negative control group (saline + Tween® 80). The APMO did not present any significant increase in micronucleated polychromatic erythrocytes (MNPCEs) for the four tested doses. When compared to the positive control group, all groups (comet and micronucleus tests) were statistically different. These data suggest that the administration of Attalea phalerata Mart oil. ex Spreng does not cause cytotoxicity, genotoxicity and clastogenicity in experimental models in vitro and in vivo following oral administration in this study.

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<![CDATA[Comparison of renal response to four different induction therapies in Japanese patients with lupus nephritis class III or IV: A single-centre retrospective study]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc215

The recent recommendations for the management of lupus nephritis suggest that racial background should be considered while choosing induction therapy. However, the responses to different induction regimens have been poorly studied in Japanese population. Here, we assessed the renal response to different induction therapies in Japanese patients with lupus nephritis class III or IV. The records of 64 patients with biopsy-proven lupus nephritis class III or IV were retrospectively evaluated according to therapy received: monthly intravenous cyclophosphamide (IVCY), the Euro-lupus nephritis trial (ELNT) protocol-IVCY, tacrolimus (TAC), or mycophenolate mofetil (MMF). We investigated cumulative complete renal response (CR) rates and relapse rates for each group for 3 years. Organ damage was assessed with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). There were 22 patients on monthly IVCY, 18 on ELNT-IVCY, 13 on TAC, and 11 on MMF. Lower systemic lupus erythematosus disease activity index (SLEDAI) and higher CH50 were found in the TAC group at baseline (p<0.01 and p<0.01, respectively). There were no significant differences of cumulative CR rates and relapse free survival for 3 years among the four different therapeutic regimens (p = 0.2 and p = 0.2, respectively). There was a tendency to have early response and early relapse in TAC group and late response in MMF group. The SDI increase over 3 years was found more frequently in the TAC group than in the monthly-IVCY group (p = 0.04). Multivariate analysis indicated that CR at 3 months was independent prognosticator for low damage accrual. Regarding lower damage accrual, early CR achievement might be essential in induction therapy regardless of immunosuppressant choice.

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<![CDATA[Minimal Residual Disease at First Achievement of Complete Remission Predicts Outcome in Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia]]> https://www.researchpad.co/article/5989daf0ab0ee8fa60bc1192

We evaluated the prognostic effect of minimal residual disease at first achievement of complete remission (MRD at CR1) in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). A total of 97 patients received treatment in our center between 2007 and 2012 were retrospectively reviewed in this study. Patients were divided into two arms according to the post-remission therapy (chemotherapy alone or allogeneic hematopoietic stem cell transplantation (allo-HSCT)) they received. MRD was detected by four-color flow cytometry. We chose 0.02% and 0.2% as the cut-off points of MRD at CR1 for risk stratification using receiver operating characteristic analysis. The 3-year overall survival (OS) and leukemia free survival (LFS) rates for the whole cohort were 46.2% and 40.5%. MRD at CR1 had a significantly negative correlation with survival in both arms. Three-year OS rates in the chemotherapy arm were 70.0%, 25.2%, 0% (P = 0.003) for low, intermediate, and high levels of MRD at CR1, respectively. Three-year OS rates in the transplant arm were 81.8%, 64.3%, 27.3% (P = 0.005) for low, intermediate, and high levels of MRD at CR1, respectively. Multivariate analysis confirmed that higher level of MRD at CR1 was a significant adverse factor for OS and LFS. Compared with chemotherapy alone, allo-HSCT significantly improved LFS rates in patients with intermediate (P = 0.005) and high (P = 0.022) levels of MRD at CR1, but not patients with low level of MRD at CR1 (P = 0.851). These results suggested that MRD at CR1 could strongly predict the outcome of adult ALL. Patients with intermediate and high levels of MRD at CR1 would benefit from allo-HSCT.

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<![CDATA[Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice]]> https://www.researchpad.co/article/5989daffab0ee8fa60bc60d5

Clinical application of cyclophosphamide (CP) as an anticancer drug is often limited due to its toxicity. CP is metabolized mainly in the liver by cytochrome P450 system into acrolein which is the proximate toxic metabolite. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Therefore, the present study aimed at investigating the role of essential oils extracted from fennel, cumin and clove as natural antioxidants in the alleviation of hepatotoxicity induced by CP through assessment of hepatotoxicity biomarkers (AST, ALT, ALP), histopathology of liver tissues as well as other biochemical parameters involved in the metabolism of CP. The data of the present study showed that treatment of male mice with cyclophosphamide (2.5 mg/Kg BW) as repeated dose for 28 consecutive days was found to induce hepatotoxicity through the elevation in the activities of AST, ALT, and ALP. Combined administration of any of these oils with CP to mice partially normalized the altered hepatic biochemical markers caused by CP, whereas administration of fennel, clove or cumin essential oils alone couldn’t change liver function indices. Moreover, CP caused histological changes in livers of mice including swelling and dilation in sinusoidal space, inflammation in portal tract and hepatocytes, as well as, hyperplasia in Kuppfer cells. However, co-administration of any of the essential oils with CP alleviated to some extent the changes caused by CP but not as the normal liver. CP was also found to induce free radical levels (measured as thiobarbituric acid reactive substances) and inhibited the activities of superoxide dismutase, glutathione reductase, and catalase as well as activities and protein expressions of both glutathione S-transferase (GSTπ) and glutathione peroxidase. Essential oils restored changes in activities of antioxidant enzymes (SOD, CAT, GR, GST, and GPx) caused by CP to their normal levels compared to control group. In addition, treatment of mice with CP was found to induce the protein expression of CYP 3A4, 2B1/2, 2C6, 2C23. Moreover, the present study showed that essential oils reduced the expression of CYPs 2E1, 3A4 but could not restore the expression of CYP 2C6 and 2C23 compared to CP-treated mice. Interestingly, pretreatment of mice with essential oil of clove was found to restore activities of DMN-dI, AHH, and ECOD which were induced by CP to their normal control levels. It is concluded that EOs showed a marked hepatoprotective effect against hepatotoxicity induced by CP. In addition, co-administration of CP with any of these oils might be used as a new strategy for cancer treatment to alleviate the hepatotoxicity induced by CP.

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<![CDATA[Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells]]> https://www.researchpad.co/article/5989dac8ab0ee8fa60bb307d

Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5’-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

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<![CDATA[Capecitabine in Combination with Standard (Neo)Adjuvant Regimens in Early Breast Cancer: Survival Outcome from a Meta-Analysis of Randomized Controlled Trials]]> https://www.researchpad.co/article/5989db39ab0ee8fa60bd43a3

Capecitabine has been investigated in early breast cancer in several studies, but it was undefined that whether it could improve survival. To investigate whether the addition of capecitabine affected survival in patients with early breast cancer, a meta-analysis was conducted and overall survival (OS), disease-free survival (DFS), and toxicity were assessed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for studies between January 2006 and April 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived. Seven trials with 9097 patients, consisted of 4 adjuvant and 3 neoadjuvant studies, were included in this meta-analysis. Adding capecitabine showed no improvement in DFS (HR = 0.93; 95% CI, 0.85–1.02; P = 0.12), whereas a significant improvement in OS was observed (HR = 0.85; 95% CI, 0.75–0.96; P = 0.008). A sub-analysis of DFS showed that benefit of capecitabine derived from patients with triple negative subtype and with extensive axillary involvement. Safety profiles were consistent with the known side-effects of capecitabine, but more patients discontinued scheduled treatment in the capecitabine group. Combining capecitabine with standard (neo)adjuvant regimens in early breast cancer demonstrated a significantly superior OS, and indicated DFS improvement in some subtypes with high risk of recurrence. Selection of subtypes was a key to identify patients who might gain survival benefit from capecitabine.

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<![CDATA[BRCAness as a Biomarker for Predicting Prognosis and Response to Anthracycline-Based Adjuvant Chemotherapy for Patients with Triple-Negative Breast Cancer]]> https://www.researchpad.co/article/5989db01ab0ee8fa60bc6cfb

Background

Triple-negative breast cancer (TNBC) is a heterogeneous tumor that encompasses many different subclasses of the disease. In this study, we assessed BRCAness, defined as the shared characteristics between sporadic and BRCA1-mutated tumors, in a large cohort of TNBC cases.

Methods

The BRCAness of 262 patients with primary TNBCs resected between January 2004 and December 2014 was determined through the isolation of DNA from tumor tissue. Classification of BRCAness was performed using multiple ligation-dependent probe amplification (MLPA). The tumor subtypes were determined immunohistochemically using resected specimens.

Results

Of the 262 TNBCs, the results of the MLPA assays showed that 174 (66.4%) tumors had BRCAness. Patients with BRCAness tumors were younger than patients with non-BRCAness tumors (P = 0.003). There was no significant difference between the two groups regarding their pathological stages. The BRCAness group had a significantly shorter recurrence-free survival (RFS) compared with the non-BRCAness group (P = 0.04) and had a shorter overall survival (OS) although this did not reach statistical significance. Adjuvant treatments with anthracycline-based regimens provided significantly greater benefits to the BRCAness group (P = 0.003 for RFS, and P = 0.03 for OS). Multivariate Cox proportional hazard model analysis showed that BRCAness was an independent negative prognostic factor, and the anthracycline-based adjuvant chemotherapy was an independent positive prognostic factor for both RFS and OS in TNBC.

Conclusions

The 66.4% patients of TNBCs showed BRCAness. BRCAness is essential as a biomarker in the subclassification of TNBCs and might be of use for predicting their prognosis. Furthermore, this biomarker might be a predictive factor for the effectiveness of anthracycline-based adjuvant chemotherapy for patients with TNBCs.

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<![CDATA[Generalized Additive Mixed-Models for Pharmacology Using Integrated Discrete Multiple Organ Co-Culture]]> https://www.researchpad.co/article/5989d9d6ab0ee8fa60b65fdf

Integrated Discrete Multiple Organ Co-culture (IDMOC) is emerging as an in-vitro alternative to in-vivo animal models for pharmacology studies. IDMOC allows dose-response relationships to be investigated at the tissue and organoid levels, yet, these relationships often exhibit responses that are far more complex than the binary responses often measured in whole animals. To accommodate departure from binary endpoints, IDMOC requires an expansion of analytic techniques beyond simple linear probit and logistic models familiar in toxicology. IDMOC dose-responses may be measured at continuous scales, exhibit significant non-linearity such as local maxima or minima, and may include non-independent measures. Generalized additive mixed-modeling (GAMM) provides an alternative description of dose-response that relaxes assumptions of independence and linearity. We compared GAMMs to traditional linear models for describing dose-response in IDMOC pharmacology studies.

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<![CDATA[Investigating the Mutagenicity of a Cold Argon-Plasma Jet in an HET-MN Model]]> https://www.researchpad.co/article/5989da0eab0ee8fa60b78cd5

Objective

So-called cold physical plasmas for biomedical applications generate reactive oxygen and nitrogen species and the latter can trigger DNA damage at high concentrations. Therefore, the mutagenic risks of a certified atmospheric pressure argon plasma jet (kINPen MED) and its predecessor model (kINPen 09) were assessed.

Methods

Inner egg membranes of fertilized chicken eggs received a single treatment with either the kINPen 09 (1.5, 2.0, or 2.5 min) or the kINPen MED (3, 4, 5, or 10 min). After three days of incubation, blood smears (panoptic May-Grünwald-Giemsa stain) were performed, and 1000 erythrocytes per egg were evaluated for the presence of polychromatic and normochromic nuclear staining as well as nuclear aberrations and binucleated cells (hen’s egg test for micronuclei induction, HET-MN). At the same time, the embryo mortality was documented. For each experiment, positive controls (cyclophosphamide and methotrexate) and negative controls (NaCl-solution, argon gas) were included. Additionally, the antioxidant potential of the blood plasma was assessed by ascorbic acid oxidation assay after treatment.

Results

For both plasma sources, there was no evidence of genotoxicity, although at the longest plasma exposure time of 10 min the mortality of the embryos exceeded 40%. The antioxidant potential in the egg’s blood plasma was not significantly reduced immediately (p = 0.32) or 1 h (p = 0.19) post exposure to cold plasma.

Conclusion

The longest plasma treatment time with the kINPen MED was 5–10 fold above the recommended limit for treatment of chronic wounds in clinics. We did not find mutagenic effects for any plasma treatment time using the either kINPen 09 or kINPen MED. The data provided with the current study seem to confirm the lack of a genotoxic potential suggesting that a veterinary or clinical application of these argon plasma jets does not pose mutagenic risks.

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<![CDATA[Double-Blind Controlled Randomized Trial of Cyclophosphamide versus Methylprednisolone in Secondary Progressive Multiple Sclerosis]]> https://www.researchpad.co/article/5989daaaab0ee8fa60ba9013

Background

Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far.

Objective

To compare CPM to methylprednisolone (MP) in SPMS.

Methods

Randomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m2 body surface area—MP: 1g) every four weeks for one year, and every eight weeks for the second year. The primary endpoint was the time to EDSS deterioration, when confirmed sixteen weeks later, analyzed using a Cox model.

Results

Due to recruitment difficulties, the study was terminated prematurely after 138 patients were included (CPM, n = 72; MP, n = 66). In the CPM group, 33 patients stopped treatment prematurely, mainly due to tolerability, compared with 22 in the MP group. Primary endpoint: the hazard ratio for EDSS deterioration in the CPM in comparison with the MP group was 0.61 [95% CI: 0·31–1·22](p = 0·16). According to the secondary multistate model analysis, patients in the CPM group were 2.2 times more likely ([1·14–4.29]; p = 0.02) to discontinue treatment than those in the MP group and 2.7 times less likely (HR = 0.37, 95% CI: 0.17–0.84; p = 0.02) to experience disability progression when they did not stop treatment prematurely. Safety profile was as expected.

Conclusion

Although the primary end-point was negative, secondary analysis suggested that CPM decreases the risk of progression in SPMS, but its use may be limited by low tolerability.

Trial Registration

Clinicaltrials.gov NCT00241254

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<![CDATA[Prognosis for Hospitalized Patients with Systemic Lupus Erythematosus in China: 5-Year Update of the Jiangsu Cohort]]> https://www.researchpad.co/article/5989dac1ab0ee8fa60bb0df9

Objective

To identify early signs associated with poor prognosis in Chinese patients with systemic lupus erythematosus (SLE) through a large population-based follow-up study.

Methods

Medical records of > 2,500 SLE patients that first hospitalized between 1999–2009 were collected from 26 centers across Jiangsu province, China, and entered into a database. These patients were followed-up for 5 to 15 years, and those remained contact and had known survival status in 2015 were assessed for the association of factors presented at the initial hospitalization with mortality at two time points (≤1year and > 1year). The independency of mortality factors was evaluated using multivariate Cox regression analysis.

Results

Among 1,372 patients we assessed, 92.3% were women and 17.2% were deceased in 2015. The main causes of death were infection (30.1%), neuropsychiatric impairment (14.8%), renal failure (14.4%) and cardiopulmonary involvement (8.5%). Hazard ratios (HR) of independent predictors for mortality (≤1year and > 1year, respectively) included hospital presentation of neuropsychiatric involvement (2.03 and 1.91), cardiopulmonary involvement (1.94 and 1.61) and increased serum creatinine (2.52 and 2.58). Patients older than 45 years and with disease durations more than 2 years at admission had unfavorable short-term outcome (HR 1.76 and 1.79), while the presence of anti-dsDNA and anti-Sm antibodies indicated diverse prognosis after 1 year (HR 1.60 and 0.45). Treatment with cyclophosphamide was beneficial for patient’s first-year outcome (HR 0.50), and anti-malarial drugs significantly reduced the risk of mortality over different time points (HR 0.48 and 0.54). SLEDAI score, proteinuria or hypocomplementemia was not independently associated with the outcome in this cohort.

Conclusion

SLE patients presented with vital organ damages rather than active disease at initial hospitalization are likely to have a poor outcome, especially for those with neuropsychiatric, cardiopulmonary involvements and renal insufficiency. Early and effective intervention with the use of anti-malarial drugs may decrease mortality.

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