CHANGES IN LEVELS OF CARTILAGE OLIGOMERIC PROTEINASE AND URINARY C-TERMINAL TELOPEPTIDE OF TYPE II COLLAGEN IN SUBJECTS WITH KNEE OSTEOARTHRITIS AFTER DEXTROSE PROLOTHERAPY: A RANDOMIZED CONTROLLED TRIAL

ObjectiveTo assess the effects of dextrose prolotherapy in patients with knee osteoarthritis on the levels of serum cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen, and on the Western Ontario McMaster Universities Index and numerical rating scale score for pain.MethodsA randomized controlled trial, in which participants were randomly allocated into 2 groups, receiving injections of either hyaluronic acid or dextrose prolotherapy. The hyaluronic acid group received 5 injections, 1 each on weeks 1, 2, 3, 4 and 5, and the dextrose prolotherapy group received 3 injections, 1 each on weeks 1, 5 and 9. Serum cartilage oligomeric proteinase, urinary C-terminal telopeptide of type II collagen, Western Ontario McMaster Universities Index score, and numerical rating scale score for pain were measured at baseline and 3 weeks after the last injection. Comparative analysis was conducted using Wilcoxon test within groups and analysis of covariance (ANCOVA) test between groups.ResultsA total of 47 participants (21 allocated to hyaluronic acid, 26 allocated to dextrose prolotherapy) completed the protocol. Both interventions resulted in significant improvements in numerical rating scale scores for pain, total Western Ontario McMaster Universities Index scores, and its subscales score. However, the dextrose prolotherapy outperformed hyaluronic acid in numerical rating scale score for pain and level of urinary C-terminal telopeptide of type II collagen, with score changes differences of 0.93 (p = 0.042) and 0.34 (p = 0.048), respectively. No significant changes in level of serum cartilage oligomeric proteinase were found in either group.ConclusionDextrose prolotherapy is an alternative injection therapy for knee osteoarthritis, which was found to be associated with a significant reduction in urinary C-terminal telopeptide of type II collagen compared with hyaluronic acid injection. Neither injection method resulted in reduced serum cartilage oligomeric proteinase.LAY ABSTRACTKnee osteoarthritis is a common musculoskeletal disorder, which is one of the most frequent causes of disability in elderly people. To improve patients’ quality of life, prolotherapy has been developed as a non-operative treatment option for osteoarthritis. This study compared the effectiveness of dextrose prolotherapy with that of standard therapy using hyaluronic acid injections. Both interventions were effective in terms of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score improvement and numerical rating scale score changes. Cartilage repair was assessed by measuring levels of specific biomarkers of cartilage breakdown: urinary C-terminal telopeptide of type II collagen (uCTX-II) and serum cartilage oligomeric matrix protein (sCOMP). Dextrose prolotherapy was more effective than hyaluronic acid in reducing these biomarkers and decreasing patients’ pain. Dextrose prolotherapy is therefore recommended for use in patients with knee osteoarthritis, since it gives better results, is cost beneficial, and is suitable for use in low-resource settings. Dextrose prolotherapy may help to repair cartilage in knee OA, as it reduces the uCTX-II level.Key words: knee osteoarthritis, prolotherapy, hyaluronic acid, COMP, uCTX-II, functional outcome

Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder, which is one of the most common causes of disability in elderly people (1–3). Several studies have demonstrated the effectiveness of hyaluronic acid (HA) injections, and recent guidelines have recommended their use in knee OA (4, 5). Xin has shown that intra-articular injection of HA (Adant®, Meiji Seika Pharma Co., Ltd., Tokyo, Japan. Manufactured by microbial fermentation and Artz®, Dispo: Seikagaku Corporation, Tokyo, Japan. Manufactured by the extraction of cockscomb), can significantly reduce both the visual analogue scale (VAS) score for pain and the Lequesne index (6). In contrast to these findings, however, a meta-analysis concluded that treatment of knee OA with HA injection did not result in a significantly different outcome from intra-articular placebo, despite the higher costs compared with other common non-operative intra-articular modalities (7).Regenerative therapy is an alternative approach that has been considered for OA, due to its potential to aid tissue regeneration, improve clinical manifestations, and repair damaged tissue structure, which is the underlying pathological condition in OA (8). An example of a currently developing regenerative approach is prolotherapy, an injection-based modality for treating chronic musculoskeletal pain through the use of substances such as dextrose, phenol-glycerine-glucose (P2G), or sodium morrhuate (9). Previous reports have demonstrated the effectivity of prolotherapy in significantly reducing the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score relative to saline injections and at-home exercise over 18 weeks after injection (10–12). In line with these findings, other reports have shown the promising effects of prolotherapy for tissue regeneration through radiological and arthroscopy-based assessments of cartilage repair (13).Cartilage oligomeric matrix protein (COMP) and urinary C-terminal telopeptide of type II collagen (uCTX-II) are specific biomarkers used to evaluate cartilage break-down in OA. Increased levels of these biomarkers can indicate the severity and prognosis of OA(14). Meanwhile, decrease in levels of both biomarkers has been assumed which indicates the improvement in cartilage (15). COMP and uCTX-II are recommended as promising specific bio-markers in OAcases based on Burden of disease, Investigative, prognostic, efficacy of intervention, and diagnostic (BIPED) criteria, as stated in a systematic review (16).Although previous reports have demonstrated promising potential of HA-based therapy and dextrose prolotherapy (DPT) in improving functional outcome in knee OA, none have compared the efficacy of those modalities in cartilage repair by assessing specific biomarkers, such as serum COMP (sCOMP) and uCTX-II. Hence, the aim of this study was to compare the effects of intra-articular HAand DPT on cartilage repair in knee OA, by measuring the changes in sCOMP and uCTX-II biomarkers.     

Accuracy of four dental age estimation methods in determining the legal age threshold of 18 years among South Indian adolescents and young

The aim of this study was to compare the accuracy, specificity and sensitivity of four commonly used methods of dental age estimation in a sample of south Indian adolescents and young adults aged between 14 and 30 years, with an age threshold of 18 years, using receiver operating characteristic curves (ROC) and the area under the curve (AUC). A total of 1070 orthopantomograms (535 males and 535 females) of adolescents and young adults of south Indian origin were collected retrospectively and interpreted. The effectiveness of each method was evaluated by using sensitivity (Se), specificity (Sp), likelihood ratios (LR+ and LR-) and AUC. Among all methods, I3M< 0.08 resulted in better values of AUC, Se and Sp which were 0.950, 91.5%, 97.8% and 0.950, 88.5% and 98.6% in males and females, respectively. For “stage H” of Demirjian’s system, the AUC, Se and Sp were 0.940, 84.9%, 97.7% and 0.930, 79.9% and 98.5% in males and females, respectively. The use of the Olze et al “stage 1 (or higher)” root pulp visibility and “stage D” of third molar eruption were not recommended in the studied population due to the greater percentage of third molars with incomplete mineralization in younger age groups and impaction. Taking into account the values of Se, Sp, both positive and negative LRs, we recommend the use of the cut-off value of I3M< 0.08 to discriminate adults and minors in south Indian adolescents and young adults.     

Normative data of olfactory abilities using cultural adaption Sniffin’ sticks smell test in different age groups

Objectives:To assess olfactory abilities using a culturally adapted Sniffin’ Sticks smell test in different age groups.Methods:This was a cross-sectional study, conducted at Otorhinolaryngology outpatient clinic of Universiti Kebangsaan Malaysia Medical Centre, Secondary Science School, and Children Learning Centre in Kuala Lumpur, Malaysia, from August 2019 until December 2021.Results:In 450 healthy participants, the cut-off points of the threshold discrimination identification (TDI) scores at the 10th percentile for olfactory abilities were 19 in children, 30.1 in adolescents, 32.1 in young adults, 31.1 in middle-aged adults, and 28.6 in older adults. The children had significantly lower olfactory abilities, with the Bonferroni post-hoc tests of p<0.001. The young adults had higher olfactory abilities than older adults (p<0.05). The results showed that the identification score was highest in middle-aged adults (p<0.001). The discrimination score was the highest in young adults (p<0.001). The best odor threshold performance was observed in adolescents (p<0.001). The TDI score showed a significant difference in olfactory abilities between men and women (p=0.001).Conclusion:Using a culturally adapted smell test, our population was able to identify, discriminate, and perceive odorants better than the European population. This data will help clinicians and researchers with a tool to reliably establish the correct results of olfactory function in our population. Women had better olfactory abilities than men.     

Thoracic surgery in United Arab Emirates

The United Arab Emirates (UAE) has undergone a significant change in its population and economy in the last decades and in parallel its healthcare system has evolved rapidly to provide advanced, innovative and world-leading care. At the forefront of this revolution in healthcare is the development of a multidisciplinary multimodality thoracic service provision, offered at quaternary referral hospitals amalgamating academics, training, research and innovation. Previously, thoracic service care was limited to single providers at various public and private hospitals, usually performing lower complexity cases. Most complex thoracic cases were repatriated outside the UAE. This practice was replaced with the opening of Cleveland Clinic Abu Dhabi (CCAD), in 2015, which created a multidisciplinary thoracic program. This included the start of a mini-invasive surgical and lung transplantation program. Since that time other public and private hospitals have emerged providing care in a similar model. The impact of these programs has been a decreased transfer of patients abroad for treatment. Under the umbrella of the Emirates Thoracic Society (ETS) a platform for greater collaboration aimed at improving patient care, potential research and physician education has been created. Direct links have been established with world-leading Thoracic surgery and Respiratory Medicine Centers facilitating this development and offering support and guidance. This article charts these changes in thoracic care in the recent past, present, and delineates plans for the future in the UAE.     

Characteristics of Conventional and Microwave Sintered Iron Ore Preform

In this study, compacted hematite (Fe₂O₃) preforms were made and sintered at various temperatures, such as 1250 °C and 1300 °C, using both conventional and microwave sintering methods. The density, porosity, microhardness, cold crushing strength, microphotographs, and X-ray diffraction (XRD) analysis of the sintered preforms were used to evaluate the performance of the two sintering methods. It was found that microwave sintered preforms possessed lesser porosity and higher density than conventionally sintered preforms owing to uniform heating of the powdered ore in microwave sintering method. Furthermore, it was also observed that microwave sintered preforms exhibited relatively higher cold crushing strength and hardness than conventionally sintered preforms. Thus, the overall results revealed that microwave sintering yielded better properties considered in the present study.     

Subcutaneous Rituximab for the Treatment of B-Cell Hematologic Malignancies: A Review of the Scientific Rationale and Clinical Development

Abstract

Rituximab (MabThera^®/Rituxan^®), a chimeric murine/human monoclonal antibody that binds specifically to the transmembrane antigen CD20, was the first therapeutic antibody to enter clinical practice for the treatment of cancer. As monotherapy and in combination with chemotherapy, rituximab has been shown to prolong progression-free survival and, in some indications overall survival, in patients with various B-cell malignancies, while having a well-established and manageable safety profile and a wide therapeutic window. As a result, rituximab is considered to have revolutionized treatment practices for patients with B-cell malignancies. A subcutaneous (SC) formulation of rituximab has been developed, comprising the same monoclonal antibody as the originally marketed formulation [rituximab concentrate for solution for intravenous (IV) infusion], and has undergone a detailed, sequential clinical development program. This program demonstrated that, at fixed doses, rituximab SC achieves non-inferior serum trough concentrations in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia, with comparable efficacy and safety relative to the IV formulation. The added benefit of rituximab SC was demonstrated in dedicated studies showing that rituximab SC allows for simplified and shortened drug preparation and administration times resulting in a reduced treatment burden for patients as well as improved resource utilization (efficiency) at the treatment facility. The improved efficiency of delivering rituximab’s benefit to patients may broaden patient access to rituximab therapy in areas with low levels of healthcare resources, including IV-chair capacity constraints. This article is a companion paper to G. Salles, et al., which is also published in this issue.

Funding

F. Hoffmann-La Roche Ltd.

     

Oral contrast medium in PET/CT: should you or shouldn’t you?

Purpose It has been suggested that the use of computed tomography (CT) positive contrast agents has led to attenuation-induced artefacts on ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/CT) systems. Consequently, centres may withhold the use of such agents. Whilst there is theoretical evidence to support the aforementioned claim, the clinical relevance of the induced artefacts has not been widely established. Moreover, the potential benefits of bowel enhancement on PET/CT have yet to be formally evaluated. We therefore prospectively examined PET/CT studies to assess whether the use of oral contrast medium induces clinically relevant artefacts and whether the use of these agents is diagnostically helpful.Methods Over a 2-month period, ¹⁸F-FDG PET/CT images were prospectively reviewed from 200 patients following Gastrografin administration 2 h prior to examination. Both a radiologist and a nuclear medicine physician reviewed the images for contrast medium-mediated clinically relevant artefacts. Artefacts were sought on the CT attenuation-corrected images and were compared with the appearance on non-attenuated-corrected images. The number of examinations in which the oral contrast aided image interpretation was also noted.Results There were no oral contrast medium-induced clinically significant artefacts. In 38 of the 200 patients, oral contrast aided image interpretation (owing to differentiation of mass/node from bowel, discrimination of intestinal wall from lumen or definition of the anatomy of a relevant site). In 33 of these 38 patients, the anatomical site of interest was the abdomen/pelvis.Conclusion The use of oral contrast medium in ¹⁸F-FDG PET studies should not be withheld as it improves image interpretation and does not produce clinically significant artefacts.     

The safety,efficacy, and cost-effectiveness of intraoperative cell salvage in metastatic spine tumor surgery

Background Context

Metastatic spine tumor surgery (MSTS) is associated with substantial blood loss, therefore leading to high morbidity and mortality. Although intraoperative cell salvage with leukocyte depletion filter (IOCS-LDF) has been studied as an effective means of reducing blood loss in other surgical settings, including the spine, no study has yet analyzed the efficacy of reinfusion of salvaged blood in reducing the need for allogenic blood transfusion in patients who have had surgery for MSTS.