Harmonization of Osteoporosis Guidelines: Paving the Way for Disrupting the Status Quo in Osteoporosis Management in the Asia Pacific

In the Asia Pacific (AP) region, osteoporosis and its consequence of fragility fractures are not widely recognized as a major public health problem. Several challenges including underdiagnosis and undertreatment exist. The Asia Pacific Consortium on Osteoporosis (APCO) is a nonpartisan and apolitical organization comprising musculoskeletal experts and stakeholders from both private and public sectors who have united to develop tangible solutions for these substantive challenges. APCO's vision is to reduce the burden of osteoporosis and fragility fractures in the AP region. Heterogeneity in both scope and recommendations among the available clinical practice guidelines (CPGs) contribute to the large osteoporosis treatment gap in the Asia Pacific. APCO has therefore developed a pan Asia-Oceania harmonized set of standards of care (The Framework), for the screening, diagnosis, and management of osteoporosis. First, a structured analysis of the 18 extant AP CPGs was completed. Subsequently, a prioritization of themes and agreement on fundamental principles in osteoporosis management were made through a Delphi process of consensus building. This approach, ensuring the opinions of all participating members were equally considered, was especially useful for a geographically diverse group such as APCO. It is hoped that the Framework will serve as a platform upon which new AP national CPGs can be developed and existing ones be revised. APCO is currently embarking on country-specific engagement plans to embed the Framework in clinical practice in the AP region. This is through partnering with regulatory bodies and national guidelines development authorities, through peer-to-peer health care professional education and by conducting path finder audits to benchmark current osteoporosis services against the Framework standards. The principles underpinning the harmonization of guidelines in the AP region can also be utilized in other parts of the world that have similar socioeconomic diversity and heterogeneity of healthcare resources. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

慢病管理模式结合中药分期辨证治疗糖尿病肾病的获益与思考

糖尿病肾病已成为导致慢性肾衰竭和新进入透析的重要原因,也是糖尿病致死的重要原因。而且目前尚缺少疗效满意的治疗药物。本文提出为减少糖尿病肾病的危害,对本病的防治策略应重心前移,防控长期化。通过回顾文献,结合笔者的临床研究,对本病的流行病学特点进行分析,提出了防治糖尿病肾病进展的几个途径,应提倡实施个体化的长期的慢病管理模式,早诊断,早治疗,运用中医药辨证论治,多管齐下控制蛋白尿进展。以期达到延缓糖尿病肾病进展,提高患者生存质量的目的。     

18F‐fluoride PET as a noninvasive imaging biomarker for determining treatment efficacy of bone active agents at the hip: A prospective,randomized, controlled clinical study

The functional imaging technique of ¹⁸F‐fluoride positron emission tomography (¹⁸F‐PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if ¹⁸F‐PET can be used as an early biomarker of treatment efficacy at the hip. Twenty‐seven treatment‐naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n = 13) or calcium and vitamin D only (control group, n = 14). Subjects in the TPT group were treated with 20 µg/day teriparatide for 12 weeks. ¹⁸F‐PET scans of the proximal femur, pelvis, and lumbar spine were performed at baseline and 12 weeks. The plasma clearance of ¹⁸F‐fluoride to bone, K_i, a validated measurement of bone formation, was measured at four regions of the hip, lumbar spine, and pelvis. A significant increase in K_i was observed at all regions of interest (ROIs), including the total hip (+27%, p = 0.002), femoral neck (+25%, p = 0.040), hip trabecular ROI (+21%, p = 0.017), and hip cortical ROI (+51%, p = 0.001) in the TPT group. Significant increases in K_i in response to TPT were also observed at the lumbar spine (+18%, p = 0.001) and pelvis (+42%, p = 0.001). No significant changes in K_i were observed for the control group. Changes in BMD and bone turnover markers were consistent with previous trials of teriparatide. In conclusion, this is the first study to our knowledge to demonstrate that ¹⁸F‐PET can be used as an imaging biomarker for determining treatment efficacy at the hip as early as 12 weeks after initiation of therapy.     

Implementing and Evaluating Evidence-Based Treatments in Schools: Successes and Lessons Learned

This pilot study presents a community's attempt to enhance their school mental health partnership by collaborating with a university to implement the Youth Experiencing Success in School (Y.E.S.S.) Program, a school mental health program composed of evidence-based treatments (EBTs) for children with disruptive behavior problems (Owens et al, in press). The study sought to replicate the effectiveness of the Y.E.S.S. Program and evaluate treatment effectiveness under high university involvement conditions (HUI: services provided by university graduate students) and low university involvement conditions (LUI: services provided by community professionals). HLM analyses indicated that the rates of improvement for the HUI and LUI conditions did not differ significantly for any treatment outcome variable. When these two treatment groups were combined, teachers reported that treated children demonstrated significant improvements in symptoms, social functioning, and classroom functioning, whereas control children on a waiting list did not. Results replicated some of the positive effects of the Y.E.S.S. Program and offer grounds for optimism that, with sufficient technical support, EBTs can retain their effectiveness when delivered by community professionals in schools in under-served communities. Successes and lessons learned from the process of transporting EBTs to the community via a school-mental health partnership are presented.     

The effects of systemic and intratumoral interleukin-12 treatment in C6 rat glioma model

Abstract

Objective: Cytokine based immunotherapy has long been an exciting field for many investigators aiming to provide an effective alternative treatment modality for glioma management. Among these cytokines, interleukin-12 (IL-12) plays a crucial role in mediating inflammatory and antitumoral activity on the host defence. We have investigated the therapeutic role of systemic and local delivery of IL-12 in C6 rat glioma model and compared these two modalities.

Methods: The donor C6 glioma cells were injected stereotactically to 32 Wistar rats and right frontal tumor formation was established in all subjects. The rats were evenly divided into four groups as intratumoral (i.t.) control group (Group IA), intraperitoneal (i.p.) control group (Group IB), i.t. treatment group (Group II) and i.p. treatment group (Group III). Magnetic resonance imaging were performed to 12 rats (three from each group) on the seventh post-inoculation day. Recombinant mouse IL-12 (rmIL-12) was administered via i.t. (0.1 μg 5 μl/day/rat) and i.p. (0.1 μg 20 μl/day/rat) routes to treatment groups between days 9 and 11 following tumor inoculation, for 3 consecutive days. The rats which were unresponsive to the external stimuli, unable to feed themselves or having severe neurological impairment were decapitated and the specimens were histopathologically examined.

Results: The subjects of Group III (i.p.) showed a statistically significant prolongation in survival time (mean=39 days) when compared to the control group (mean=31.7 days) (p=0.035) and Group II (i.t.) (mean=24.5 days) (p=0.005). Histopathologic examination of Group III revealed markedly increased intratumoral and peritumoral lymphocyte infiltration compared with the other groups.

Conclusion: This study demonstrated that systemic administration of IL-12 in C6 glioma model in rats prolongs the survival, probably by stimulating the cellular immunity leading to lymphocytic infiltration.     

Management and outcome of patients with acute traumatic subdural hematomas and pre-injury oral anticoagulation therapy

Abstract

Background: Acute subdural hematomas (aSDHs) are found in up to one-third of patients with severe traumatic brain injury and are associated with an unfavorable outcome in the majority of cases. Mortality ranges between 40 and 60%, but was reported to be even higher in patients undergoing oral anticoagulation therapy (OAT) at the time of injury. The objective of this study is to specifically report on the peri-operative management and outcome of patients with aSDH and pre-injury OAT.

Material and Methods: From June 2002 to June 2006, all patients with OAT who underwent surgical treatment of aSDH were retrospectively analysed. Results of pre-operative blood tests, the peri-operative and surgical management and the clinical courses were assessed. Patient outcome is reported according to the Glasgow Outcome Scale (GOS) at 6 months.

Results: Eleven (10.3%) out of 107 patients with aSDH were on OAT. Patients with OAT were significantly older than patients without OAT (72.4 ± 9.3 versus 59.9 ± 17.5 years; p<0.05, Mann–Whitney U-test). Intensity of head trauma was moderate in four and severe in seven patients with a median pre-operative Glasgow Coma Scale (GCS) of 8. Median pre-treatment prothrombin time and international normalized ratio were 23% (range: 10–65%) and 3.3 (range: 1.5–10.6), respectively. Replacement therapy consisted of administration of prothrombin complex concentrates, vitamin K and FFP (fresh frozen plasma). In four patients, antithrombin was additionally given to prevent disseminated intravascular coagulation. Surgical treatment consisted of craniotomy (n=10) or craniectomy (n=1) and hematoma evacuation with intracranial pressure probe placement. Low molecular weight heparin was administered as pharmacological prophylaxis of thrombembolic events in an increasing dose post-operatively. At 6 months, six out of 11 patients survived with a median GOS of 4. All-cause mortality was 45.5%. A pre-operative GCS of ≤ 8 was not associated with an increased risk of mortality (p>0.5, Fisher's exact test). No relevant rebleedings or thrombembolic complications were observed. The mortality rate of patients who did not undergo OAT was 50%.

Conclusion: A large number of patients with aSDH are on pre-injury OAT. Specific replacement therapy facilitates successful clot evacuation without bleeding complications. The overall outcome of these patients does not seem to differ from historical cohorts with aSDH without OAT, but a large prospective multicenter study is warranted to answer that question.     

IL-10 Synergizes with IL-4 and IL-13 in Inhibiting Lysosomal Enzyme Secretion by Human Monocytes and Lamina Propria Mononuclear Cells from Patients with Inflammatory Bowel Disease

Tissue injury and inflammation in inflammatorybowel disease (IBD) are associated with enhancedmonocytic lysosomal enzyme release. In this study,peripheral monocytes and lamina propria mononuclearcells (LPMNC) were isolated from IBD patients andnormal controls. Cells were stimulated withlipopolysaccharide after treatment with IL-13, IL-4, andIL-10, and enzyme secretion was assessed by using thecorresponding p-nitrophenyl glycosides as substrates.Molecular forms of cathepsin D were examined to describethe mode of enzyme release. IL-10 and IL-4 stronglydown-regulate enzyme secretion in IBD monocytes. IBD monocytes showed a diminished responsiveness tothe inhibitory effect of IL-13. Impaired monocyteresponse was not found with combinations of IL-13 andIL-10 or IL-4 and IL-10. LPMNC from involved IBD mucosa showed significantly higher enzyme secretioncompared with LPMNC from noninvolved IBD mucosa butresponded inefficiently to either IL-4, IL-13, or IL-10alone. However, combined treatment with IL-10 and IL-4 or IL-10 and IL-13 strongly suppressedenzyme release by these cells. Both the precursor andmature forms of cathepsin D were elevated in IBDpatients. While IL-13 reduced mainly the precursor form, the effect of IL-4 and IL-10 concerns both theprecursor and mature form of cathepsin D. Our resultsfavor the potent clinical utility of combined treatment,thus improving chances of developing effective treatments for human IBD.     

Regenerated Silk Fibroin Nanofibrous Matrices Treated with 75% Ethanol Vapor for Tissue-Engineering Applications

As an excellent biocompatible and biodegradable protein polymer, silk fibroin (SF) has found wide applications, particularly serving as therapeutic agent for tissue-engineering applications, on which both post-spin treatment and sterilization processing are crucial to drug-loaded matrices. To find a safe, effective and appropriate post-spin treatment and sterilization approach for drug-loaded biomaterial matrices is one of the major problems in the field of tissue engineering at present. In this work, a simple, safe and effective approach skillfully integrating post-spin treatment with sterilization processing was developed to drug-loaded SF nanofibrous matrices. Electrospun SF nanofibrous matrices from its aqueous solution were post-treated with 75% ethanol vapor. ¹³C-NMR and WAXD analysis demonstrated that such post-spin treatment rendered the structure of SF nanofibrous matrices transform from the silk I form to the silk II form. Furthermore, biological assays suggested that as-treated SF nanofibrous matrices significantly promoted the development of murine connective tissue fibroblasts. Skillfully integrated with novel sterilization processing, 75% ethanol vapor treatment could be a potential approach to designing and fabricating diverse drug-loaded SF nanofibrous matrices serving as therapeutic agents for tissue-engineering applications in that it can effectively protect the drug from losing compared with traditional post-spin treatment and sterilization processing.     

Correlation Between Cryogenic Parameters and Physico-Chemical Properties of Porous Gelatin Cryogels

In the present work, we have performed an in-depth physico-chemical and bio-physical evaluation of a series of previously described porous gelatin scaffolds (S. VanVlierberghe, V. Cnudde, P. Dubruel, B. Masschaele, A. Cosijns, I. DePaepe, P.J.S. Jacobs, L. VanHoorebeke, J.P. Remon and E. Schacht, Biomacromolecules 8, 331 (2007)). All scaffolds were prepared by a cryogenic treatment and subsequent freeze-drying. Three types of scaffolds were prepared by using different gelatin concentrations and cooling protocols. Type-I hydrogels were composed of cone-like pores with decreasing diameter from top (330 μm) to bottom (20–30 μm). Type-II and type-III scaffolds contained spherical pores with an average diameter of 135 (type II) and 65 μm (type III), respectively. The physico-chemical and bio-physical properties studied include the water uptake capacity and kinetics, the mechanical properties and the enzyme-mediated degradation. We can conclude that the pore geometry affects the water uptake capacity, the mechanical properties and the degradation profile of the hydrogels. Type-I hydrogels possess the highest water uptake, the lowest compression modulus and the fastest enzyme mediated degradation, indicating a clear effect of the pore morphology (elongated channels for type I versus spherical pores for types II and III) on the physico-chemical and bio-physical properties of the materials. In contrast to the effect of the pore geometry (channel-like versus spherical), the pore size does not significantly affect the water uptake, the mechanical properties and the enzyme mediated degradation in the investigated pore size range (65–135 μm). To the best of our knowledge, this is the first report in which the effects of a cryogenic treatment on the hydrogel network properties are investigated in such detail.