Nanoparticles functionalized with stem cell secretome and CXCR4-overexpressing endothelial membrane for targeted osteoporosis therapy

Background Osteoporosis is a chronic condition affecting patients’ morbidity and mortality and represents a big socioeconomic burden. Because stem cells can proliferate and differentiate into bone-forming cells, stem cell therapy for osteoporosis has been widely studied. However, cells as a live drug face multiple challenges because of their instability during preservation and transportation. In addition, cell therapy has potential adverse effects such as embolism, tumorigenicity, and immunogenicity. Results Herein, we sought to use cell-mimicking and targeted therapeutic nanoparticles to replace stem cells. We fabricated nanoparticles (NPs) using polylactic-co-glycolic acid (PLGA) loaded with the secretome (Sec) from mesenchymal stem cells (MSCs) to form MSC-Sec NPs. Furthermore, we cloaked the nanoparticles with the membranes from C–X–C chemokine receptor type 4 (CXCR4)-expressing human microvascular endothelial cells (HMECs) to generate MSC-Sec/CXCR4 NP. CXCR4 can target the nanoparticles to the bone microenvironment under osteoporosis based on the CXCR4/SDF-1 axis. Conclusions In a rat model of osteoporosis, MSC-Sec/CXCR4 NP were found to accumulate in bone, and such treatment inhibited osteoclast differentiation while promoting osteogenic proliferation. In addition, our results showed that MSC-Sec/CXCR4 NPs reduce OVX-induced bone mass attenuation in OVX rats. Graphical Abstract

Trajectories of chemosensory and cognitive functions up to 1.5 years after acute COVID-19

There is an increasing recognition of neurological manifestations from SARS-CoV-2 infection. Quantifications of such manifestations and their long-term dynamics in the general infected population are of essence in understanding the health and socioeconomic burden of neurological complications of COVID-19. Through rigorous empirical testing of over 800 volunteers, we present here repeated cross-sectional and longitudinal data that depict the trajectories of chemosensory functions, cognitive performances and depressive symptoms up to 1.5 years after acute COVID-19 in discharged patients with respect to non-infected controls. Overall, deficits in smell, taste and chemesthesis slowly resolved within about a year of discharge. Concerningly, cognitive impairments –– independent of elevated depressive symptoms and evident even in those with nonsevere disease –– showed no sign of improvement over time. In people over 50 years, COVID-19 was associated with a substantially increased risk for mild cognitive impairment. Our findings urge for cognitive and emotional interventions targeting COVID-19 convalescents.

Investigation on Quality of Life and Economic Burden of Children with Cerebral Palsy in Changzhou

Based on the data of children with cerebral palsy (CP) in Changzhou obtained by the Disabled Persons’ Federation, this study sampled some children with CP and investigated their survival status, treatment cost, and family burden so as to provide scientific decision-making basis and policy suggestions for coping with disease hazards and improving children’s quality of life. In this study, a simple random sampling method was used to conduct household surveys of the selected children with CP. The economic burden of CP is measured by direct and indirect methods, and the quality of life of patients of children with CP and their families is analyzed qualitatively and quantitatively by the EuroQol Five Dimensions (EQ-5D) Questionnaire. The average family economic burden of each case of CP in Changzhou was about 4,188,500 yuan, of which the direct medical burden was 205,800 yuan and the indirect economic burden was 3,982,700 yuan. The socioeconomic burden of CP in Changzhou is as high as about 2.244 billion yuan. From the EQ-5D measurement results of 55 children with CP, the average index score was 0.423, which was lower than the national general population level. The proportions of patients with CP who have problems in the five aspects of action, self-care, daily activities, pain/discomfort, and anxiety/depression are 72.73%, 81.82%, 81.82%, 83.64%, and 92.73%, respectively, which are significantly higher than those of the national general population. The average score of the Visual Analogue Scale (VAS) is 58.09, which is significantly lower than the national general population level. The only major factor affecting the quality of life of patients with CP and their families is the health status represented by the EQ-5D score. To liberate and develop the labor ability of patients and their direct caregivers through clinical treatment, rehabilitation, and special education is the most effective way to reduce the socioeconomic burden of CP. Relevant government departments should perform their duties, integrate social assistance resources, implement early intervention, and launch targeted support and assistance policy.

Complications of Stroke

Stroke is one of the leading causes of disability and mortality and can cause a serious socioeconomic burden. Some of the comorbidities and secondary complications of stroke can threaten the patient's life or cause serious pain or negatively affect the patient's involvement in rehabilitation or worsen daily life activities or make it difficult to bring the patient into the community and workplace. This chapter focuses on the symptoms and signs, diagnosis, and management of these comorbidities and complications. It highlights diagnosis and treatment of cardiac problems, sleep disorders, deep vein thrombosis, pulmonary embolism, dysphagia, malnutrition, and pneumonia. Depression, central post-stroke pain, upper limb problems after stroke, spasticity, bladder dysfunction are also discussed in this chapter.

Urolithiasis in Germany: Trends from the National DRG Database

<b><i>Introduction:</i></b> Urolithiasis is a common disease leading to a high socioeconomic burden due to treatment costs and sickness leave. The aim of this study was to evaluate recent trends in the incidence of urolithiasis in Germany and in the use of therapeutic interventions. <b><i>Methods:</i></b> Treatment data for all in-patient hospital episodes for urolithiasis between 2005 and 2016 were extracted from the national DRG statistics at DESTATIS and analysed with regard to the corresponding procedures according to the OPS code. <b><i>Results:</i></b> Incidence for urolithiasis was stable at around 120,000 cases per year during the observation period with a male:female ratio of 2:1. Rising numbers were noted for patients &#x3e;80 years. Nevertheless, the number of coded procedures rose significantly with a marked disproportionate transition from extracorporeal shock wave lithotripsy towards ureterorenoscopy. Percutaneous nephrolithotomy was performed more frequently on a smaller scale. <b><i>Discussion/Conclusion:</i></b> While the global incidence of urolithiasis is still rising, Germany, as other Western countries, has reached a plateau. There is a remarkable trend towards invasive treatment of even asymptomatic kidney stones. Besides the effects on individual patients with increased risk for complications, this results in a higher monetary burden to the health care system and society.

Chinese Medicine for Coronavirus Disease 2019 (COVID-19): A GRADE-Assessed Systematic Review and Meta-Analysis

Coronavirus disease 2019 (COVID-19) has caused enormous public health and socioeconomic burden globally. This study aims to evaluate the efficacy and safety of Chinese medicine (CM) against COVID-19. Eleven databases were searched on April 30, 2021, and 52 studies were included. The RoB 2.0, ROBINS-I, and GRADE tools were employed to assess the risks and evidence grades. The findings with moderate certainty in GRADE showed that compared with routine treatment (RT), Lianhua Qingwen granules (LHQW) adjunctive to RT showed significantly improved efficacy rate (relative risk (RR) = 1.19, 95% confidence interval (CI): [1.09, 1.31]), febrile score (standard mean difference (SMD) = −1.21, 95% CI: [−1.43, −0.99]), and computerized tomography (CT) lung images (RR = 1.23, 95% CI: [1.10, 1.38]); Qingfei Paidu decoction (QFPD) plus RT significantly shortened the length of hospital stay (SMD = −1.83, 95% CI: [−2.18, −1.48]); Feiyan Yihao formula (FYYH) plus RT significantly improved the clinical efficacy rate (RR = 1.07, 95% CI: [1, 1.15]), febrile time (SMD = −0.02, 95% CI: [−0.23, 0.19]), and time to negative PCR test for COVID-19 (SMD = −0.72, 95% CI: [−0.94, −0.51]). Adjunctive effects of CM with lower certainty of evidence were found, including the improvements of symptoms, laboratory findings, and mortality. No or mild adverse events were observed in most of the studies. In conclusion, the current evidence indicates that CM formulae, particularly LHQW, QFPD, and FYYH, have adjunctive effects on the standard treatment of COVID-19.

The LUCID study: living with ulcerative colitis; identifying the socioeconomic burden in Europe

Background Ulcerative colitis (UC) is an inflammatory bowel disease with increasing prevalence worldwide. Current treatment strategies place considerable economic and humanistic burdens on patients. The aim of this study was to determine the socioeconomic burden of UC in adult patients in European countries in a real-world setting. Methods In this retrospective, cross-sectional and observational pan-European study, patients with moderate or severe UC were assigned to ARM 1 and patients who had moderate or severe UC but achieved mild or remission status 12 months before index date (or clinical consultation date), were assigned to ARM 2. Clinical and medical resource use data were collected via electronic case report forms, and data on non-medical and indirect costs, and health-related quality of life (HRQoL) were collected via patient and public involvement and engagement (PPIE) questionnaires. Per-patient annual total costs per ARM and per country were calculated using the collated resource use in the last 12 months (between the start of the documentation period and patient consultation or index date) and country specific unit costs. Quality of life was described by arm and by country. Results In the physician-reported eCRF population (n = 2966), the mean annual direct medical cost was €4065 in ARM 1 (n = 1835) and €2935 in ARM 2 (n = 1131). In the PPIE population (ARM 1, n = 1001; ARM 2, n = 647), mean annual direct cost was €4526 in ARM 1 and €3057 in ARM 2, mean annual direct non-medical cost was €1162 in ARM 1 and €1002 in ARM 2, mean annual indirect cost was €3098 in ARM 1 and €2309 ARM 2, and mean annual total cost was in €8787 in ARM 1 and €6368 in ARM 2. HRQoL scores showed moderate to high burden of UC in both groups. Conclusions The cost and HRQoL burden were high in patients in both ARM 1 and ARM 2 indicating unmet needs in the UC active population.

miRNAs as Therapeutic Tools in Alzheimer’s Disease

Alzheimer’s disease (AD), an age-dependent, progressive neurodegenerative disorder, is the most common type of dementia, accounting for 50–70% of all dementia cases. Due to the increasing incidence and corresponding socioeconomic burden of dementia, it has rapidly emerged as a challenge to public health worldwide. The characteristics of AD include the development of extracellular amyloid-beta plaques and intracellular neurofibrillary tangles, vascular changes, neuronal inflammation, and progressive brain atrophy. However, the complexity of the biology of AD has hindered progress in elucidating the underlying pathophysiological mechanisms of AD, and the development of effective treatments. MicroRNAs (miRNAs, which are endogenous, noncoding RNAs of approximately 22 nucleotides that function as posttranscriptional regulators of various genes) are attracting attention as powerful tools for studying the mechanisms of diseases, as they are involved in several biological processes and diseases, including AD. AD is a multifactorial disease, and several reports have suggested that miRNAs play an important role in the pathological processes of AD. In this review, the basic biology of miRNAs is described, and the function and physiology of miRNAs in the pathological processes of AD are highlighted. In addition, the limitations of current pharmaceutical therapies for the treatment of AD and the development of miRNA-based next-generation therapies are discussed.