A rare case of monozygotic triplets with Duchenne muscular dystrophy

Twins with Duchenne muscular dystrophy (DMD) have been widely studied. We report the first rare case of monozygotic triplets with DMD who shared consistent phenotypes, including delayed motor and language milestones, muscle wasting and weakness, joint contracture, and lumbar lordosis. Muscle magnetic resonance imaging and biopsy revealed the similar muscle injury characteristics and dystrophin absence. Short tandem repeat analysis confirmed monozygosity. A de novo mutation (exon 49–52 deletion) was found in the triplets but not in their mother. Treatment included prednisone, idebenone, and rehabilitation management. At the 2-year follow-up, motor function had deteriorated, and muscle fatty infiltration was more extensive and severe. Our case offers a unique opportunity for genetic and therapeutic research. Furthermore, it highlights the critical role of genetic factors in DMD phenotypes and provides a potential choice for treatment observations.     

Dual-Energy Computed Tomography Pulmonary Angiography: Comparison of Vessel Enhancement between Linear Blended and Virtual Monoenergetic Reconstruction Techniques

Introduction

Optimal opacification of the pulmonary vasculature is a fundamental factor of a diagnostic quality computed tomography pulmonary angiogram (CTPA). This retrospective study examined the feasibility of utilising a noise-optimised monoenergetic reconstruction of the dual-energy computed tomography pulmonary angiogram (DE-CTPA) as an additional protocol to increase vessel opacification.

Longitudinal blood pressure patterns and cardiovascular disease risk

Abstract

Observational and interventional studies have unequivocally demonstrated that “present”, i.e. single-occasion, blood pressure is one of the key determinants of cardiovascular disease risk. Over the past two decades, however, numerous publications have suggested that longitudinal blood pressure data and assessment of long-term blood pressure exposure provide incremental prognostic value over present blood pressure. These studies have used several different indices to quantify the overall exposure to blood pressure, such as time-averaged blood pressure, cumulative blood pressure, blood pressure trajectory patterns, and age of hypertension onset. This review summarises existing research on the association between these indices and hard cardiovascular outcomes, outlines the strengths and weaknesses of these indices, and provides an overview of how longitudinal blood pressure changes can be measured and used to improve cardiovascular disease risk prediction.

• KEY MESSAGES

• Numerous recent publications have examined the relation between cardiovascular disease and long-term blood pressure (BP) exposure, quantified using indices such as time-averaged BP, cumulative BP, BP trajectory patterns, and age of hypertension onset.

• This review summarises existing research on the association between these indices and hard cardiovascular outcomes, outlines the strengths and weaknesses of these indices, and provides an overview of how longitudinal BP changes can be measured and used to improve cardiovascular disease risk prediction.

• Although longitudinal BP indices seem to predict cardiovascular outcomes better than present BP, there are considerable differences in the clinical feasibility of these indices along with a limited number of prospective data.

     

Lenalidomide plus dexamethasone for proliferative glomerulonephritis with monoclonal immunoglobulin deposits

Objective To evaluate the efficacy and safety of lenalidomide plus dexamethasone (LD) in patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Methods The clinicopathological data of PGNMID patients who were treated with LD protocol from January 2010 to October 2019 were retrospectively analyzed. Results All of 6 patients received LD treatment for≥3 months after renal biopsy in Jinling Hospital. During the follow-up period of 6 to 19 months, 3 patients achieved renal remission, and the renal remission rate was 50%(3/6). Light microscopy showed membranoproliferative glomerulonephritis and immunofluorescence showed single kappa type IgG3 was deposited in the mesangial region and the vascular loop. Before taking LD scheme, the median urinary protein were 7.76(1.27, 14.57) g/24 h, the median serum creatinine was 118.5(70.7, 289.1) μmol/L, and the median albumin was 34.5(22.4, 37.5) g/L. The concentration of serum free kappa and lambda light chain was increased in 5 patients, but the serum free light chain ratio was normal. Hypocomplementemia was detected in two cases. Six patients underwent bone marrow flow cytometry, and 2 patients had elevated monoclonal plasma cells, accounting for 0.7% and 0.5%, respectively. Immunofixation electrophoresis suggested that 1 patient had positive serum M protein for kappa type IgG3. At the last follow-up, median urine protein was 3.33(0.33, 11.23) g/24 h, median serum creatinine was 108.7(80.4, 160.9) μmol/L, and median albumin was 35.9(24.5, 45.6) g/L. The concentration of serum free light chain in 4 patients from 5 patients with elevated serum free light chain was lower than that before taking the drug. Decreased level of serum complement in two cases returned to normal after treatment. The M spike did not turn negative during the follow-up in one patient. Adverse events included anemia, neutropenia, limb numbness and upper respiratory tract infection. Conclusion This study reports for the first time that LD protocol may be effective in treating PGNMID, but more attention should be paid to the hematological adverse events of lenalidomide.     

Demonstration of In Vitro Host-Guest Complex Formation and Safety of para-Sulfonatocalix[8]arene as a Delivery Vehicle for Two Antibiotic Drugs

The macrocycle para-sulfonatocalix[8]arene, sCX[8], was examined with 2 antibiotic drugs, ciprofloxacin (CIP) and isoniazid. The drugs were shown to form complexes with sCX[8] using proton nuclear magnetic resonance, thermogravimetric analysis, fluorescence spectroscopy, and molecular modeling. Both drugs form 1:1 hydrated (H₂O: 13%-14% w/w) host-guest complexes, with sCX[8] binding around the pyridine ring of isoniazid, and around the piperazine and cyclopropane rings of CIP. From proton nuclear magnetic resonance, the binding constant of isoniazid to sCX[8] was 6.8 (±0.3) × 10³ M^?1. Addition of 2 equivalents of sCX[8] to CIP resulted in a 58% decrease in fluorescence, and time-resolved fluorescence anisotropy of CIP doubles with sCX[8]. Each drug binds into the cavity of the macrocycle, with binding stabilized via combinations of hydrogen bonding, electrostatic interactions, π-π stacking, and hydrophobic effects. The safety of sCX[8] was examined in vitro with human embryonic kidney 293 cells. The IC₅₀ of sCX[8] was 559 μM, which is a minimum of 5-fold higher than the concentration that would be used in the clinic. The in vitro effect of sCX[8] on the action of CIP was examined on a panel of bacterial lines. The results showed that sCX[8] has no inherent antibiotic activity and had no negative effect on the action of CIP.     

Helping Smokers Quit: The Smoking Cessation Leadership Center Engages Behavioral Health by Challenging Old Myths and Traditions

Smoking is much more common among persons with behavioral health conditions (mental illnesses and/or substance use disorders). Persons with these disorders are more likely to die from smoking-related causes than any other reason. Studies have shown that stopping smoking can improve mental health function, as well as improve outcomes for substance use disorders. Yet, for a variety of reasons, smoking cessation has not been integrated into the treatment of behavioral health conditions, and in many instances tobacco use was not only condoned but encouraged. Beginning in 2007, the Smoking Cessation Leadership Center (SCLC) began engaging relevant agencies in an attempt to stimulate more vigorous smoking cessation activities. Partners included the federal Substance Abuse and Mental Health Services Administration, advocacy organizations such as the National Alliance on Mental Illness and Community Anti-Drug Coalitions of America, and clinical groups such as the American Psychiatric Nurses Association, the American Psychiatric Association, American Psychological Association, National Council on Behavioral Health, and National Association of State Mental Health Program Directors. A signature program featured 16 individual state summits involving agencies and groups from multiple sectors, all aiming to lower smoking rates in behavioral health populations. These activities mark an evolving culture change within behavioral health.     

RhPDCD5 combined with dexamethasone increases antitumor activity in multiple myeloma partially via inhibiting the Wnt signalling pathway

Multiple myeloma (MM) is one of the most common hematological malignancies and characterized by the clonal accumulation of malignant plasma cells. Significant progress has been made in MM treatment recently, while MM still remains incurable. Our previous studies showed that the recombined human programmed cell death 5 (rhPDCD5) can promote MM apoptosis induced by dexamethasone (Dex). Here, we expanded the findings by showing that the rhPDCD5 alone could not induce an obvious growth inhibition of U266 cells (a MM cell line). Of note, with the combination of dexamethasone (Dex), the growth of MM cells was significantly inhibited and accompanied with the cell cycle arrest in G0/G1. For mechanism study, we found that the combination treatment of rhPDCD5 plus Dex downregulated the mRNA and protein expressions of Wnt effectors including β‐catenin, β‐catenin (Ser675), TCF4, survivin and c‐Myc when compared to Dex only. Moreover, the activation of WNT pathway induced by LiCl can also be inhibited by this combination treatment. Taken together, our study demonstrated that the combination of rhPDCD5 and Dex can suppress the proliferation of multiple myeloma cells partially via inhibiting the WNT signalling pathway.     

基于抗菌药物分级管理的我院抗菌药物医嘱评价

摘 要 目的：明确我院三级抗菌药物（非限制使用级、限制使用级、特殊使用级）不合理使用情况的特点及差异,为临床规范使用抗菌药物提供理论依据。 方法：对我院736份出院病历的1 228条抗菌药物医嘱逐条进行合理性点评,并对三级抗菌药物医嘱不合理使用率、分布特点、类型进行比较。 结果：我院三级抗菌药物不合理使用率差异不全相同,以限制使用级为最高（25.0%）,特殊使用级最低（9.8%）,两者比较差异有统计学意义（P<0.01）。以头孢菌素为主的β内酰胺类抗菌药物的不合理医嘱最多。三级抗菌药物不合理用药类型差异有统计学意义（P<0.05）。“抗菌药物用法用量不适宜”、“围手术期预防性使用抗菌药物不合理”为非限制使用级及限制使用级抗菌药物的主要不合理医嘱构成。而“遴选抗菌药物不适宜”则为特殊使用级抗菌药物的主要不合理医嘱构成。结论：我院抗菌药物不合理使用情况较普遍。医院需针对各级抗菌药物使用中存在的主要问题加强抗菌药物的管理。