Relapsing Myopathy With Granulomatous Inflammation as Chronic Graft vs Host Disease Feature: A Case Report

BackgroundGraft-vs-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplant. Myopathy is a rare neuromuscular sign of chronic GVHD, with an incidence of less than 4% in all patients. The data are heterogeneous, and no standard criteria exists for diagnosis or treatment.Case ReportWe present the case of an 18-year-old man with acute lymphoblastic leukemia, who developed myopathy associated with GVHD 19 months after allogeneic hematopoietic stem cell transplant from an unrelated donor. The patient had a previous history of acute cutaneous and chronic hepatic GVHD. At the time of symptom onset, the immunosuppressive drugs were tapered. He developed with sudden symmetrical proximal muscle weakness that prevented him from walking. Diagnosis was confirmed using magnetic resonance imaging, electromyography, muscle enzymes, and muscle biopsy results. He initially responded to immunosuppressive therapy but relapsed after quick tapering of prednisone, requiring a prolonged course of steroids and an additional dose of immune globulin intravenous. At the moment of the publication, the patient has 9 months free from GVHD relapse.ConclusionsGVHD-associated myopathy is a rare complication of hematopoietic stem cell transplant and must be suspected in patients with sudden proximal muscle weakness and moderate pain. Diagnosis is challenging and must include magnetic resonance imaging, electromyography, muscle enzymes, and muscle biopsy results. Usually, all patients respond adequately to immunosuppression.     

发作性睡病的药物治疗进展

发作性睡病是致残性白天睡眠增多的最常见原因之一，其治疗旨在减少白天睡眠增多和猝倒，改善夜间睡眠紊乱、睡眠瘫痪及与睡眠有关的幻觉。2019年，组胺H3受体拮抗剂替洛利生（Pitolisant）和多巴胺及去甲肾上腺素再摄取抑制剂索利氨酯（Solriamfetol）分别在欧盟和美国上市，前者具有促醒和抗猝倒作用，后者也有促醒作用，且戒断症状和滥用的发生率更低。目前，控释型羟丁酸钠（FT218）、低钠型羟丁酸盐（JZP-258）、选择性去甲肾上腺素再摄取抑制剂（瑞波西汀，又称AXS-12）以及莫达非尼联合氟卡尼制剂（THN102）等药物仍在开发和测试中，均可作为治疗发作性睡病相关白天睡眠增多和猝倒的潜在药物。本文重点介绍这些最近研发的发作性睡病治疗药物。     

Mortality in patients with intracerebral hemorrhage associated with antiplatelet agents,oral anticoagulants or no antithrombotic therapy

The association between preceding treatment with antiplatelet agents (APs), vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) and mortality after intracerebral hemorrhage (ICH) remains unclear.The aim of this multicenter, prospective cohort study was to assess the risk for death after ICH in consecutive patients who were on treatment with APs, VKAs, DOACs, or no antithrombotic agent. The primary outcome was in-hospital death by day 30. ICH volume at admission and volume expansion were centrally assessed.Out of 598 study patients, in-hospital death occurred in 21% of patients who were on treatment with APs, 25% with VKAs, 30% with DOACs, and 13% with no antithrombotics. Crude death rate was higher in patients on antithrombotics as compared to patients receiving no antithrombotic agent. At multivariate analysis, age (HR 1.07; 95% CI 1.04–1.10), previous stroke (HR 1.83; 95% CI 1.14–2.93), GCS ≤8 at admission (HR 6.06; 95% CI 3.16–9.74) and GCS 9–12 (HR 3.38; 95% CI 1.81–6.33) were independent predictors of death. Treatment with APs (HR 1.29; 95% CI 0.61–2.76), VKAs (HR 1.42; 95% CI 0.70–2.88) or DOACs (HR 1.28; 95% CI 0.61–2.73) were not predictors of death in the overall study population, in non-trauma associated ICH as well as when GCS was not included in the model. ICH volume and volume expansion were independent predictors of death.In conclusion, preceding treatment with antithrombotic is associated with the severity of ICH. Age, previous stroke and clinical severity at presentation were independent predictors of in-hospital death in patients with ICH.     

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

Association of HLA-DP/DQ and STAT4 polymorphisms with ankylosing spondylitis in Southwest China

Ankylosing spondylitis (AS) is a highly heritable complex inflammatory arthritis disease. Genetic factors are thought to be crucial in the pathogenesis of AS. However, few data are available on the relationship between HLA-DP/DQ and STAT4 polymorphisms and AS susceptibility in the Chinese population. Therefore, we examined HLA-DP/DQ and STAT4 polymorphisms (rs3077, rs9277535, rs7453920 and rs7574865) in a total of 779 subjects, including 400 AS and 379 age- and sex-matched healthy controls in Chinese. No significant difference was observed between AS patients and healthy controls in the allele frequency of rs3077, rs9277535 and rs7574865. However, there was a significant association between the HLA-DQ rs7453920 G/A variant and AS patients, with minor allele A correlated with a reduced risk of AS (allelic frequency, adjusted OR = 0.66, 95% CI = 0.55–0.78, p = 4.0E − 06; dominant model, adjusted OR = 0.75, 95% CI = 0.66–0.85, p = 1.1E − 05). Moreover, the haplotypes block AAA and GGA in the HLA gene significantly correlated with reduced risk of AS. This is the first study demonstrating the significant associations of SNP rs7453920 and the haplotypes in the HLA gene with the risk of AS in Southwest Chinese population. This research sheds new light on the significant relationship between HLA polymorphisms and AS.     

Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: A new strategy for cancer therapy

A combination of various therapeutic approaches has emerged as a promising strategy for cancer treatment. A safe and competent nano-delivery system is thus in urgent demand to facilitate the simultaneous transport of various therapeutic agents to cancer cells and a tumor region to achieve synergistic effect. Gold nanoparticles (GNPs) and mesoporous silica nanoparticle (MSNs) were fabricated herein as potential candidates for drug delivery. Serving as gatekeepers, GNPs (5 nm in diameter) were attached onto the amino-functionalized MSNs (denoted as NMSNs) via a relatively weak gold–nitrogen bonding. The resulting nanohybrids (denoted as GCMSNs) were uptaken by cells, and the detachment of GNPs and subsequent intracellular drug release from NMSNs were achieved by competitive binding of intracellular glutathione to GNPs. In addition to the function of gatekeeping, GNPs also play another role as the oxidative stress elicitor. Our in vitro studies revealed that GCMSNs induced higher oxidative stress in lung cancer cells (A549) than in normal cells (3T3-L1). This growth inhibitory effect found in the cancer cells was likely induced by mitochondria dysfunction originated from the GCMSN-induced, oxidative stress-triggered mitochondria-mediated autophagy. The redox-responsive nanohybrids were further loaded with camptothecin and the intensified synergistic therapeutic effects were observed associated with combined chemotherapy and oxidative stress strategy. The results clearly demonstrate that such unique nanohybrids hold great promise for selective and effective cancer treatments.     

The effect of Origanum majorana tea on motor and non-motor symptoms in patients with idiopathic Parkinson's disease: A randomized controlled pilot study

AimsThe effect of Origanum majorana tea consumption on motor and non-motor symptoms was investigated in patients with idiopathic Parkinson's disease, measured by validated tools.MethodsSixty patients with idiopathic Parkinson's disease and under conventional medication were enrolled voluntarily in the study. All participants were randomized on double-blind to placebo or Origanum majorana. Clinical assessment with validated tools (UPDRSIII, NMSS, and BDI) was done before Origanum majorana or placebo consumption (Day 0) and at the end of the experiment (Day 30).ResultsThe treatment groups were similar at baseline on demographic and clinical variables. During the course of study, nine participants withdrew for reasons of noncompliance and inability to follow-up. Fifty-one participants completed the study. Upon completion of 30 days of treatment, Origanum majorana tea consumption did not decrease the UPDRSIII score ([UPDRSIII^] D0 = 18.76 ± 8.58, D30 = 16.52 ± 7.96, p = 0.069) at the p value was 0.07. However, a statistically significant improvement was noted in NMSS and BDI scores (p < 0.0001 and p < 0.0001, respectively). Assessment of the UPDRSIII, NMSS and BDI scores of the patients did not reflect any improvement with placebo. No side effect was detected during the study^.ConclusionThese findings show improvement of depressive and non-motor signs in patients with Parkinson's disease in the group that consumed Origanum majorana tea in combination with conventional therapy. Improvement of motor signs may need an extended treatment period. However, more research with a large number of participants and lasting longer than 1 month is needed to argue these findings.