Multiple Injection Group Research Articles

Human umbilical cord mesenchymal stem cells on treating osteoarthritis in a rabbit model: Injection strategies

Human umbilical cord mesenchymal stem cells (UCMSCs) are a novel stem-cell source to treat osteoarthritis (OA). Here we investigated the therapeutic effects of UCMSCs injection strategies on knee OA in a rabbit model. Thirty OA rabbits randomly received normal saline, a single dose of 1 × 106 UCMSCs, or three injections of 1 × 106 UCMSCs at 2, 4, 6 weeks. Articular cartilages were collected after 8 weeks. Macroscopic and histological assessments indicated that intra-articular injection of UCMSCs, both single and multiple injection, significantly reduced the formation of periarticular osteophytes and articular cartilage degeneration when compared with the control. Furthermore, both UCMSCs injections increased the expression of chondrogenic markers in the articular cartilage, and reduced the levels of TNF-α and IL-6 in synovium. Micro-CT showed significant reduction of sub-chondral bone degeneration and osteophytes in the multiple-injection group compared to the control and single-injection group. Taken together, intra-articular injection of UCMSCs for OA treatment is safe and effective. Single and multiple injection of UCMSCs had comparable reparative effect on cartilage lesions, while multiple injection of UCMSCs further exerted effect on enhancing subchondral bone volume.

Comparative effects of insulin pump and injection on gestational diabetes mellitus pregnancy outcomes and serum biomarkers

BACKGROUND Insulin injection is the basic daily drug treatment for diabetic patients. AIM To evaluate the comparative impacts of continuous subcutaneous insulin infusion (CSII). METHODS Based on the treatment modality received, the patients were allocated into two cohorts: The CSII group and the multiple daily injections (MDI) group, with each cohort comprising 210 patients. Comparative assessments were made regarding serum levels of serum-secreted frizzled-related protein 5, homocysteine, and C1q/TNF-related protein 9. Furthermore, outcomes such as fasting plasma glucose, 2-hour postprandial glucose levels, pain assessment scores, and the incidence of complications were evaluated post-treatment. RESULTS The CSII group displayed notably lower fasting plasma glucose and 2-h postprandial glucose levels in comparison to the MDI group (P < 0.05). Subsequent analysis post-treatment unveiled a significantly higher percentage of patients reporting no pain in the CSII group (60.00%) in contrast to the MDI group (36.19%) (P < 0.05). Additionally, the CSII group exhibited a markedly reduced occurrence of fetal distress and premature rupture of membranes compared to the MDI group (P < 0.05). However, there were no significant variances observed in other pregnancy outcomes between the two groups (P > 0.05). A statistical analysis revealed a significant difference in the incidence of complications between the groups (χ 2 = 11.631, P = 0.001). CONCLUSION The utilization of CSII via an insulin pump, as opposed to MDI, can significantly enhance the management of insulin administration in patients with GDM by diversifying the sites of insulin delivery. This approach not only promotes optimal glycemic control but also regulates metabolic factors linked to blood sugar, reducing the likelihood of adverse pregnancy outcomes and complications. The clinical relevance and importance of CSII in GDM management highlight its wide-ranging clinical usefulness.

Perioperative Insulin Pump Therapy Decreases Readmission Risk and Improves Outcomes in Patients with Diabetes.

To evaluate the impact of temporary insulin pump use during hospitalization on glycemia, postoperative complications, and cost/utilization in perioperative patients with diabetes. Patients (n=159) with type 2 diabetes and hospitalized for elective surgery were recruited from three hospitals. Subjects were categorized into the insulin pump group and the multiple daily subcutaneous insulin injection group according to their treatment therapy. Data were collected at admission, discharge, and 3 months post-discharge. Subjects in the CSII group who were still on insulin therapy transitioned from CSII to MDII; however, their daily insulin dosages were lower than those in the MDII group (15.31±10.98 U/d vs. 23.48±17.02 U/d, P=0.015) after discharge. In terms of medical costs, the CSII group had significantly higher hospitalization costs than the MDII group (112.36±103.43 thousand RMB vs. 82.65±77.98 thousand RMB, P=0.043). After 3 months, the CSII group had significantly lower outpatient costs than the MDII group (3.17±0.94 thousand RMB vs. 3.98±1.76 thousand RMB, P ˂ 0.001). In the MDII group, 10 patients reported severe postoperative complications requiring re-hospitalization; there were no similar reports in the CSII group. Temporary use of insulin pump therapy for perioperative patients with diabetes results in a reduction in blood glucose and blood glucose fluctuation during hospitalization, HbA1c, and the risk of postoperative complication and readmission, thus significantly decreasing costs in this complex patient cohort. Further work is needed to better understand indications for utilizing pump therapy based on diabetes phenotype and the complexity of planned surgical intervention.

The effectiveness of leucocyte-poor platelet-rich plasma injections on symptomatic early osteoarthritis of the knee: the PEAK randomized controlled trial.

Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections. A total of 102 patients were recruited. The follow-up period was 12 months, at intervals of six weeks, 12 weeks, six months, and 12 months. KOOS-Total significantly improved in all groups at these time intervals compared to pre-injection. There was an improvement in EQ-5D-5L index scores in saline and single injection groups, but not in the multiple injection group. Comparison of treatment groups showed no additional beneficial effect of single or multiple PRP injections above that displayed in the saline injection group. Subjective patient satisfaction and recommendation of treatment received demonstrated a similar pattern in all the groups. There was no indication of superiority of either single or multiple PRP injections compared to saline injections. There is no evidence that single or multiple PRP had any additional beneficial effect compared to saline injection up to 12 months, follow-up after treatment of early stage symptomatic OA of the knee. Cite this article: Bone Joint J2022;104-B(6):663-671.

Factors associated with glycemic variability in children with type 1 diabetes mellitus based on flash glucose monitoring system.

Patients with classical type 1 diabetes mellitus (T1DM) require lifelong dependence on exogenous insulin therapy due to pancreatic beta-cell destruction and absolute insulin deficiency. T1DM accounts for about 90% of children with diabetes in China, with a rapid increase in incidence and a younger-age trend. Epidemiological studies have shown that the overall glycated haemoglobin (HbA1c) and compliance rate are low in Chinese children with T1DM. Optimal glucose control is the key for diabetes treatment, and maintaining blood glucose within the target range can prevent or delay chronic vascular complications in patients with T1DM. Therefore, this study aims to investigate the glycemic control of children with T1DM from Hunan and Henan Province with flash glucose monitoring system (FGMS), and to explore factors associated with glycemic variability. A total of 215 children with T1DM under 14 years old were enrolled continuously in 16 hospitals from August 2017 to August 2020. All subjects wore a FGMS device to collect glucose data. Correlation of HbA1c, duration of diabetes, or glucose scan rates with glycemic variability was analyzed. Glucose variability was compared according to the duration of diabetes, HbA1c, glucose scan rates and insulin schema. HbA1c and duration of diabetes were positively correlated with mean blood glucose, standard deviation of glucose, mean amplitude of glucose excursions (MAGE), and coefficient of variation (CV) of glucose (all P<0.01). The glucose scan rates during FGMS wearing was significantly positively correlated with time in range (TIR) (P=0.001) and negatively correlated with MAGE and mean duration of hypoglycemia (all P<0.01). Children with duration ≤1 year had lower time below range (TBR) and MAGE when compared with those with duration >1 year (all P<0.05). TIR and TBR in patients with HbA1c ≤7.5% were higher (TIR: 65% vs 45%, TBR: 5% vs 4%, P<0.05), MAGE was lower (7.0 mmol/L vs 9.4 mmol/L, P<0.001) than those in HbA1c >7.5% group. Compared to the multiple daily insulin injections group, TIR was higher (60% vs 52%, P=0.006), MAGE was lower (P=0.006) in the continuous subcutaneous insulin infusion group. HbA1c was lower in the high scan rates (≥14 times/d) group (7.4% vs 8.0%, P=0.046), TIR was significantly higher (58% vs 47%, P<0.001), and MAGE was lower (P<0.001) than those in the low scan rate (<14 times/d) group. The overall glycemic control of T1DM patients under 14 years old in Hunan and Henan Province is under a high risk of hypoglycemia and great glycemic variability. Shorter duration of diabetes, targeted HbA1c, higher glucose scan rates, and CSII are associated with less glycemic variability.

Comparison of Single-Injection and Multiple-Injection Thoracic Paravertebral Block in Preventing Pain after Video-Assisted Thoracoscopic Surgery

Aim: In our study, we aimed to compare the effect of single and multiple thoracic paravertebral block (TPVB) patients who underwent video asisted thoracoscopic surgery (VATS) on hemodynamic parameters, postoperative visual analog scale (VAS) and sedation scores, and total analgesic consumption. Materials and Method: The ASA II-III, age between 18 to 65 years, and body mass index lower than thirty, 60 patients who underwent elective VATS were included to this study. Patients were divided into two groups as single (Group S), (n:30) and multiple (Group M), (n:30) TPVB. Block was performed at T6 level in Group S and at T4, T6, T8 levels in Group M by using 21 mL 0.5 % bupivacaine. Intravenous patient controlled analgesia (PCA) was performed for both groups after surgery. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), peripheral oxygen saturation (SpO2), Ramsay sedation score (RSS), tramadol consumption during 24 hours, resting and coughing VAS scores were recorded before PCA and at 30th, first, second, 6th, 12th, 20th, and 24th hours of postoperative periods. 50 mg iv dexketoprophene was administered when coughing VAS score above the 4. Despite the iv dexketoprophene, in case of consistent pain 1 gr iv paracetamol was given to the patients, and all additional analgesic requirement was recorded. Results: Hemodynamic parameters were similar in both groups during postoperative period (p&gt;0.05). VAS scores were higher in Group M but there were not statistically significant (p&gt;0.05). Additional analgesic requirement was significantly higher in Group M, (p&gt;0.04). Cumulative tramadol consumption was comparable between the groups, (p&gt;0.05). Conclusion: In TPVB, it was observed that single and multiple injections provided similar postoperative pain scores and postoperative cumulative tramadol consumption, but we observed a high additional analgesic requirement in multiple injection group. Based on this result, we concluded that there would be no need to disturb patient comfort and prolong the procedure by applying multiple injections.

Assessing the Efficacy of Superior Hypogastric Nerve Block as a Possible Treatment Option for Bladder Pain Syndrome

Introduction: Chronic pelvic pain (CPP), and its subtype of interstitial cystitis/bladder pain syndrome (IC/BPS) can be debilitating and difficult conditions to treat. A new treatment modality being explored is the superior hypogastric (plexus) nerve block (SHPB). While previously indicated to relieve conditions related to chronic abdominal and pelvic pain, there is a paucity of evidence for use in IC/BPS patients. We aim to explore the efficacy of SHPB therapy in this population. Methods: This is a retrospective, single institution study including patients with IC/BPS or CPP who underwent SHPB during a 7-year span. Parameters analyzed include number of treatments, percentage of pain improvement after treatment, and multiple demographic and disease variables. Results: A total of 30 patients (26 CPP; 4 IC/BPS) were included in the study and 80% completed pain scores after their first injection (n=24). Fourteen patients had &gt;50% pain improvement (58.3%), 10 had &gt;70% improvement (41.7%) and 5 patients had 100% improvement (20.8%) after their first injection. Greater pain improvement was seen in the multiple vs. single injection group (52.3% vs. 20.8%, p=0.013). There was no significant difference in pain improvement between CPP and IC/BPS groups (42.2% vs. 50.0%, p= 0.630). Conclusion: SHPB may be useful as an alternative therapy for IC/BPS patients who have failed previous treatment options. Additional high-powered studies are needed to validate the safety and efficacy of SHPB in this population.

Comparison of Single-Injection and Multiple-Injection Thoracic Paravertebral Block in Preventing Pain after Video-Assisted Thoracoscopic Surgery

Aim: In our study, we aimed to compare the effect of single and multiple thoracic paravertebral block (TPVB) patients who underwent video assisted thoracoscopic surgery (VATS) on hemodynamic parameters, postoperative visual analog scale (VAS) and sedation scores, and total analgesic consumption. Materials and Method: The ASA II-III, age between 18 to 65 years, and body mass index lower than thirty, 60 patients who underwent elective VATS were included to this study. Patients were divided into two groups as single (Group S), (n:30) and multiple (Group M), (n:30) TPVB. Block was performed at T6 level in Group S and at T4, T6, T8 levels in Group M by using 21 mL 0.5 % bupivacaine. Intravenous patient-controlled analgesia (PCA) was performed for both groups after surgery. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), peripheral oxygen saturation (SpO2), Ramsay sedation score (RSS), tramadol consumption during 24 hours, resting and coughing VAS scores were recorded before PCA and at 30th, first, second, 6th, 12th, 20th, and 24th hours of postoperative periods. 50 mg iv dexketoprophene was administered when coughing VAS score above the 4. Despite the iv dexketoprophene, in case of consistent pain 1 gr iv paracetamol was given to the patients, and all additional analgesic requirement was recorded. Results: Hemodynamic parameters were similar in both groups during postoperative period (p&gt;0.05). VAS scores were higher in Group M but there were not statistically significant (p&gt;0.05). Additional analgesic requirement was significantly higher in Group M, (p&gt;0.04). Cumulative tramadol consumption was comparable between the groups, (p&gt;0.05). Conclusion: In TPVB, it was observed that single and multiple injections provided similar postoperative pain scores and postoperative cumulative tramadol consumption, but we observed a high additional analgesic requirement in multiple injection group. Based on this result, we concluded that there would be no need to disturb patient comfort and prolong the procedure by applying multiple injections.

Proliferation and Directional Differentiation of iNKT Cells Derived from DBA/1 Mice Thymus.

The rates of invariant natural killer T (iNKT) cells in vivo are very low, and the amounts of cells obtained directly from the body are hard enough to fulfill their potential in clinical application. To overcome this problem, we subcutaneously injected alpha-galactosylceramide (α-GalCer) into DBA/1 mice and thymic single cells were isolated and cultured in vitro. Fluorescence-activated cell sorting was used to detect the iNKT cells and their subsets in the thymus after the injection of α-GalCer by different methods. In addition, in vitro changes of single-cell suspensions and their cytokines in culture supernatants were assessed. Compared with the α-GalCer multiple subcutaneous injection group, the rates of iNKT cells in the α-GalCer single subcutaneous injection group were markedly higher at each time point, while the highest levels of iNKT1 and iNKT2 cells were observed on day 4 and 8, respectively. In α-GalCer single subcutaneous injection for 8 days and thymic mononuclear cell cultured for 14 days group, the expansion rate of iNKT cells was significantly faster than the other groups, while it reached a peak for iNKT1 cells. Interferon-gamma was consistent with the development of iNKT1 cells, however no difference was found between the cultured iNKT cells in vitro and the natural iNKT cells in vivo in terms of cytokine production. Herein, we introduced a method in which antigenic stimulation in vivo and directed induction in vitro yielded high levels of iNKT cells with specific functions.

Comparisons of efficacy and safety in insulin glargine and lixisenatide plus glulisine combination therapy with multiple daily injection therapy in Japanese patients with type 2 diabetes.

ABSTRACTAims/IntroductionMultiple daily injection therapy for early glycemic control in patients with type 2 diabetes mellitus is associated with hypoglycemia and weight gain. This study aimed to compare the efficacy (time in range of glucose level 70–180 mg/dL), safety (time below range level 1 of glucose <70 mg/dL), glycemic variability changes, therapeutic indices, body mass index and titration periods between multiple daily injection and insulin glargine U100 and lixisenatide (iGlarLixi) combination (iGlarLixi + insulin glulisine; injected once daily [evenings]) therapies using intermittent continuous glucose monitoring.Materials and MethodsA total of 40 hospitalized patients with type 2 diabetes were randomly assigned to the iGlarLixi + insulin glulisine group or the multiple daily injection group. An intermittent continuous glucose monitoring system was attached, and each injection was adjusted to achieve the target glucose level according to the respective titration algorithm. Times in and below the range were analyzed using data collected on days 11–13 of the intermittent continuous glucose monitoring.ResultsThe time in range did not significantly differ between the groups. However, the time below range level 1 was lower in the iGlarLixi + insulin glulisine group (P = 0.047). The changes in glycemic variability, therapeutic indices and body mass index were not significantly different between the groups, although the titration period was significantly shorter in the iGlarLixi + insulin glulisine group (P = 0.033).ConclusionsiGlarLixi + insulin glulisine combination therapy is safe and equally efficacious as multiple daily injection therapy for glycemic control, while avoiding hypoglycemia risk and reducing the number of injections are required.

Effects of single and multiple transplantations of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice

BackgroundCurrently, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in various diseases, including POF; however, their underlying mechanism and dosage for POF treatment remain unclear. This study aimed to compare the effect of single and multiple injections of hUC-MSCs on ovarian function repair in chemotherapy-induced POF.MethodsFemale mice were intraperitoneally injected with 30 mg/kg busulfan and 120 mg/kg cyclophosphamide (CTX) to induce POF. In the single hUC-MSC injection group, hUC-MSCs were transplanted into mice D7 after CTX and busulfan administration, while in the multiple injection group, hUC-MSCs were transplanted on D7, D14, and D21 after CTX and busulfan administration. We evaluated the ovarian morphology, fertility, follicle-stimulating hormone and estradiol concentrations, follicle count, POF model, and cell transplantation results. In addition, real-time polymerase chain reaction, immunohistochemistry, and miRNA and mRNA chips were used to evaluate the effect of the cell therapy.ResultsOvary size, number of follicle at all developmental stages, and fertility were significantly reduced in the POF group compared with the control. Under hUC-MSC treatment, the ovarian morphology and follicle count were significantly restored, and fertility was significantly increased. By comparing the single and multiple hUC-MSC injection groups, we found that the anti-Müllerian hormone and Ki-67 levels were significantly increased in the multiple hUC-MSC group on D60 after chemotherapy. The expression of stimulating hormone receptors, inhibin α, and inhibin β was significantly restored, and the therapeutic effect was superior to that of the single hUC-MSC injection group.ConclusionThese results indicate that hUC-MSCs can restore the structure of injured ovarian tissue and its function in chemotherapy-induced POF mice and ameliorate fertility. Multiple hUC-MSC transplantations have a better effect on the recovery of ovarian function than single hUC-MSC transplantation in POF.

Intrahepatic cholestasis induced by α-naphthylisothiocyanate can cause gut-liver axis disorders

Clinical studies have shown that Intrahepatic cholestasis is closely related to intestinal injury. The gut-liver axis theory suggests that the intestine and liver are closely related, and that bile acids are important mediators linking the intestine and liver. We compared two cholestasis models: a single injection model that received a single subcutaneous ANIT injection (75 mg/kg), and a multiple subcutaneous injection model that received an injection of ANIT (50 mg/kg) every other day for 2 weeks. We used Transmetil (ademetionine 1,4-butanedisulfonate) to relieve intrahepatic cholestasis in the multiple injection group. In the multiple injection group, we found increased hepatic bile duct hyperplasia, increased fibrosis of the liver, increased small intestine inflammation and oxidative damage, increased harmful bile acids, decreased bile acids transporter levels. After treatment with Transmetil, the liver and gut injuries were relieved. These results suggest that intrahepatic cholestasis can cause disorders of the gut-liver axis.

The intraocular pressure changes following intravitreal bevacizumab injections in an Indian population

Aim: To assess the changes in Intraocular pressure (IOP) after intravitreal bevacizumab therapy. Design: Prospective, Observational, Tertiary care hospital based study. Participants: 95 patients receiving intravitreal bevacizumab, for varying indications, were included. Materials and Methods: A study of the change in intraocular pressure of 95 patient eyes receiving intravitreal injection of bevacizumab for varying indications was performed at 4hours, 2 weeks and 6 weeks post injection. Results: There was a statistically significant increase in IOP 4 hours post injection [p value= .000; 95% confidence limits of -2.07 to -1.11; mean difference of -1.59]. There was no statistical significance in IOP rise at 2 weeks (p= 0.32; 95 % confidence limits of -1.13 and 0.18; mean difference of -0.47) or at 6 weeks (p= 1.00; 95% confidence limits of -0.86 to 0.44; mean difference of -0.21). The endpoint IOP in the single injection and multiple injection groups was statistically insignificant (t=-0.32, df = 92, significance value=0.749, 95% confidence interval -1.48 to 1.07). Conclusion: Although a statistically significant short-term rise in IOP was observed, this increase was clinically insignificant. The IOP reverted towards baseline values on subsequent visits at 2 weeks and 6 weeks post-injection. The number of injections did not have any effect on the IOP change. Clinical significance: Our study evaluated the effect of intravitreal injection of bevacizumab on intraocular pressure in an Indian population and found no clinically significant rise in the same. Keywords: Bevacizumab, Intraocular pressure, VEGF-A.

Pre-Gestational Diabetes and Pregnancy Outcomes.

IntroductionPre-gestational, type 1 and type 2 diabetes are associated with adverse neonatal outcomes and increased rates of emergency caesarean sections.MethodsWe studied pregnancy outcomes associated with pre-gestational diabetes in 174 women who attended the National Maternity Hospital in Dublin, Ireland, between 2015 and 2017.ResultsFifty women (28.6%) had type 2 diabetes mellitus, and 124 women (71.4%) had type 1 diabetes mellitus. Women with type 2 diabetes mellitus were older (36 vs. 34 years, p 0.02) and had a higher BMI (32.6 vs. 26.2 kg/m2, p 0.00). Duration of diabetes mellitus in type 1 and type 2 was 15.7 and 5.7 years, respectively, and mean HbA1c in type 2 diabetes mellitus at booking was 44.5 mmol/mol (6.2%) and in type 1 diabetes mellitus was 56.3 mmol/mol (7.3%). Forty women (32%) with type 1 diabetes mellitus used continuous subcutaneous insulin infusion. In our cohort, 45.4% had a caesarean delivery. Offspring of patients with multiple dose injections were lighter (3.58 kg) than infants of continuous subcutaneous insulin infusion-treated patients (3.75 kg). More emergency caesarean sections were observed in the continuous subcutaneous insulin infusion group than in the group treated with multiple dose injections (37.5% vs. 28.5%), while the elective caesarean section rate was higher in the multiple dose injection group (17.8% vs. 12.5%). Women treated with continuous subcutaneous insulin infusion had a higher rate of miscarriage (25% vs. 19%) with more congenital malformations (10% vs. 2.3%).ConclusionsWomen in our study with pre-gestational diabetes were overweight, were older and had long-standing diabetes mellitus. Our patients with type 2 diabetes had a higher BMI, were older, had a shorter duration of diabetes mellitus and had better diabetes control compared to women with type 1 diabetes. Women treated with continuous subcutaneous insulin infusion had a higher rate of miscarriage with more congenital malformations. The initial inadequate diabetes control was significantly improved during pregnancy.

THE EFFECT OF SINGLE VERSUS MULTIPLE INTRA-ARTICULAR INJECTION OF SYNOVIAL FLUID MESENCHYMAL STEM CELLS ON RAT TEMPOROMANDIBULAR JOINT WITH INDUCED ARTHRITIS. BIOCHEMICAL AND HISTOLOGIC ANALYSIS

Introduction: Osteoarthritis (OA) is the most common chronic musculoskeletal disorder. Nowadays, the role of synovial fluid mesenchymal stem cells (SF MSCs) is increasingly attributed to the treatment of Temporomandibular joint osteoarthritis. This study aimed to compare single versus multiple intra-articular injection of SFMSCs in terms of macroscopic, biochemical, and histological analysis. Material & methods: 18 young adult male 200–300 grams albino rats were used in the current study divided randomly into 3 equal groups. Group (A) comprised control in which OA was induced with no treatment, group (B) comprised MSCs single intra-articular injection group, and group (C) comprised MSCs multiple intra-articular injection group. Biochemical and histologic analysis were performed. Results: histological findings showed that both groups B, C showed regeneration of meniscus and retrodiscal tissues, but group C was superior in regeneration compared to group B. Biochemical analysis showed that TNF-α and IL-1B had the highest value in the control group, followed by the single injection group, while the lowest value was found in multiple injections group respectively. Conclusion: Multiple Intra-articular SF MSCs is a potential disease-modifying therapy for patients suffering from TMJ-OA.

Unexpected Bone Resorption in Mentum Induced by the Soft-Tissue Filler Hyaluronic Acid: A Preliminary Retrospective Cohort Study of Asian Patients.

As one of the most commonly used soft-tissue fillers, hyaluronic acid is generally considered safe and efficacious. However, evident bone resorption in mentum was observed. In this study, the authors analyzed the impact of hyaluronic acid on bone resorption in mentum and the influencing factors. The authors retrospectively compared the computed tomographic scans of patients with or without mentum augmentation using hyaluronic acid. The body mass index- and sex-matched control group was selected randomly. Semimandibular bone resorption index was calculated as the ratio of bone thickness in the incisive fossa to that in the mandibular symphysis. Injection volume, injection interval, the number of injections, product, complication were also recorded. From January of 2014 to June of 2019, 80 patients (160 cases) and 80 controls were recruited. The bone resorption index in the hyaluronic acid injection cohort was significantly lower than in the controls (75.25 ± 10.02 versus 82.86 ± 6.38; p = 0.000). Patients injected with greater than or equal to 1 ml per time were more susceptible to bone erosion compared with patients injected with less (68.89 ± 10.84 versus 76.49 ± 9.42; p = 0.000). There was no significant difference between one- versus multiple-injection groups and short-injection-interval versus long-injection-interval (≥6 months) groups. Furthermore, no reduced aesthetics were realized. Hyaluronic acid injection could induce bone resorption in the mentum; nevertheless, the aesthetics were not impaired. The severity of the bone loss was positively correlated with the injection volume per time; therefore, large-volume injection of hyaluronic acid should be performed with caution. The patients should be fully informed about this complication preoperatively. Therapeutic, III.

Change of VOR gain and pure-tone threshold after single low-dose intratympanic gentamicin injection in Meniere’s disease

Background: Intratympanic gentamicin injection (ITG) is a well-accepted means to treat intractable Meniere’s disease (MD).Aims/Objectives: To investigate change of vestibule-ocular reflex (VOR) gain and pure-tone threshold after low-dose ITG for MD.Methods: Sixteen patients with definite MD who were treated by low-dose ITG were retrospectively reviewed. We defined VOR gain difference as an amount of decreased gain in video head impulse test one month after ITG. Patients were classified into two groups: single injection vs. multiple injections. Multiple injections group was composed of patients with poor vertigo control after initial ITG who required second or third ITG later in follow up period.Results: VOR gain differences of both horizontal and posterior canal plane were higher than those of anterior canal plane. Between two groups, mean VOR gain difference of horizontal canal plane in multiple injections group was lower than that in single injection group. Only two patients showed increased pure-tone threshold more than 10 dB.Conclusion and significance: Our results suggest that ITG appears to cause a differential loss of function across three semicircular canals. Furthermore, if VOR gain difference of horizontal canal is relatively low after initial ITG, patient might have poor vertigo control and be required another ITG.

Multiple intra-articular injections of allogeneic bone marrow-derived stem cells potentially improve knee lesions resulting from surgically induced osteoarthritis: an animal study.

Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 106 MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II. Within the PBS injection (control group), typical progressive degenerative changes were revealed in the various knee structures. In the single MSC injection (single group), osteoarthritic changes were attenuated, but still appeared, especially in the medial compartments involving fibrillation of the articular cartilage, osteophyte formation in the medial plateau, and longitudinal tear of the meniscus. In the multiple-injections group, the smoothness and texture of the articular cartilage and meniscus were improved. Histologically, absence or reduction in matrix staining and cellularity were noticeable in the control and single-injection groups, respectively, in contrast to the multiple-injections group, which showed good intensity of matrix staining and chondrocyte distribution in the various cartilage zones. Osteoarthritis Research Society International (OARSI) scoring showed significantly better results in the multiple-injections group than in the other groups. Immunohistochemically, collagen I existed superficially in the medial femoral condyle in the single group, while collagen II was more evident in the multiple-injections group than the single-injection group. A single injection of MSCs was not enough to restore the condition of osteoarthritic joints. This is in contrast to multiple injections of MSCs, which had the ability to replace lost cells, as well as reducing inflammation. Cite this article: Bone Joint J 2019;101-B:824-831.

Effect of platelet-rich plasma on temporomandibular joint cartilage wound healing: Experimental study in rabbits

PurposeThe aim of the study is to evaluate the effect of platelet-rich plasma (PRP) injection on temporomandibular joint (TMJ) cartilage and subchondral bone healing. Materials and methodsSixteen New Zealand rabbits were divided into two groups, including single PRP and multiple PRP injection groups. Sodium mono-iodoacetate (MIA) was injected bilaterally into the TMJ of all rabbits to create osteoarthritis (OA). PRP was injected once into the right TMJ in the single PRP group and was injected three times (once a week) into the right TMJ in the multiple injection group 4 weeks after injection of MIA. At the time of each PRP injection, isotonic NaCl solution was injected into the left TMJ in the control groups. All animals were sacrificed 30 days after the first PRP injection. ResultsAs a result of the histological evaluation, there was no statistically significant difference in cartilage and subchondral bone regeneration between the groups (p > 0.05). ConclusionsAlthough there was no statistically significant difference between PRP and control groups, it was seen that improvement were better in PRP groups. According to the Results of our study, it seems that different methods should be tried to investigate the efficacy of PRP on the TMJ healing.

Single vs. repeated matrix metalloproteinase-13 knockdown with intra-articular short interfering RNA administration in a murine osteoarthritis model

ABSTRACTPurpose: Our aims were 1) to estimate the duration of short interfering RNA (siRNA) effect on matrix metalloproteinase-13 (Mmp-13) levels by a single intra-articular injection using a mouse knee osteoarthritis (OA) model and 2) to test whether repeated injections results in any additional suppressive effect on cartilage degradation compared to a single injection. Materials and Methods: OA was induced in 9 weeks old male C57BL/6 mice by destabilization of medial meniscus (DMM). Chemically modified siRNA targeted for Mmp-13 was injected into the knee joint at 1 week post-DMM surgery. Control group of knees received that for non-targeted genes. Synovial tissue was collected to measure Mmp-13 expression levels by quantitative polymerase chain reaction (qPCR) at 2, 3, and 6 weeks after surgery in each group. To test the effect of multiple injections, we created four experiment groups according to the number of injections. Histological assessment of articular cartilage was performed at 8 weeks post-DMM surgery. Results: In the Mmp-13 siRNA-treated group, expression levels of Mmp-13 mRNA were decreased by 40% compared to the control group at 2 weeks after surgery (p = 0.04), before returning to baseline at 3 weeks after surgery. A significant improvement in the histological score was observed in all Mmp-13 siRNA-treated groups compared to the control group (p < 0.05). However, no significant differences were seen between the single and multiple injection group. Conclusions: Our results suggested that the duration of siRNA effect in the knee joint lasts for at least 1 week, and that no further benefit is achieved by multiple injections.