The close association between osteoarthritis (OA) and obesity is well established. Mechanisms linking obesity and OA involve multifactorial phenomena such as systemic factors (i.e. adipokines and ...pro-inflammatory cytokines), hormonal disturbances (hyperinsulinemia) and muscule changes (i.e. sarcopenia and lower muscular tone). The concomitant increasing prevalence of the two diseases have major health, social and economic consequences. However, to date no specific recommendation for the medical management of obese patients with OA have been published. Current recommendations only specify that obese patients must lose weight and practice regular physical activity in addition to the usual care. Weight loss improves not only OA symptoms but also metabolic abnormalities and cardiovascular risk factors commonly altered in subjects with obesity. OA symptoms' improvement has been shown to become clinically relevant from a weight loss > 5% of the body weight. In case of morbid obesity, bariatric surgery may be the only alternative for pain relief. After bariatric surgery, an appropriate calcium and vitamin D intake is recommended, since it has been shown that bariatric surgery was associated with a reduction in the bone mineral density and increased risk of fractures. An exercise program is essential for preserving healthy muscles during weight loss. Non-steroidal anti-inflammatory drugs and corticosteroids must be avoided, especially in obese patients with metabolic syndrome. In such patients symptomatic slow acting drugs for OA (i.e. glucosamine, chondroitin) and some anti-oxidant drugs (i.e. curcumin, ginger extracts, copper) may be helpful thanks to their excellent benefit/risk ratio and their mode of action which may have a positive impact on both OA and obesity-related metabolic disorders. Recent research focuses on the development of molecules aimed for promoting the production of heme oxygenase (HO-1). HO-1 decreases the production of oxygen free radicals and protects tissues from oxidative stress in the insulin resistance syndrome. Intra-articular (IA) injections of hyaluronic acid and corticosteroid have few adverse events. However, physicians must inform patients that IA treatments have a lower success rate in obese patients than in those with normal body mass index. Spa therapy contributes to relief pain, favour weight-loss and reduces metabolic abnormalities with a favourable risk/benefit balance.
No disease-modifying treatments are currently available for osteoarthritis (OA). While many therapeutic approaches are now being investigated it is ethical to resort to alternative solutions as that ...we already possess. There are many reasons for thinking that, at sufficiently high doses, glucosamine (GlcN) sulphate possesses a clinically relevant effect on OA pain. Wide inter-individual variations in the symptomatic effects of GlcN are explained by the extreme variability of its bioavailability. In studies evaluating its structure-modifying effect, GlcN was more effective than placebo in reducing the rate of joint space narrowing in patients with knee OA. More recent data suggest that GlcN may be effective in the primary prevention of OA in sportsmen. There is no controversy concerning the safety of GlcN which does not differ to that of placebo. Several studies have recently revealed an unexpected effect of GlcN on cardiovascular mortality. After adjusting for confounding factors, the regular consumption of GlcN correlated with a 27% reduction in mortality and a 58% reduction in deaths from cardiovascular causes. These data confirm animal studies demonstrating a protective effect of GlcN against cancer and cardiovascular diseases due to modulation of the O-GlcNAcylation pathway. Disorders in O-GlcNAcylation are involved in diabetes, obesity and cancers, which all feature chronic low-grade inflammation (CLGI). By regulating CLGI, GlcN may be beneficial to the symptoms of OA, its outcome and to that of the concomitant chronic pathologies, making GlcN as a valuable candidate for the treatment of OA in patients with metabolic syndrome, diabetes or cardiovascular diseases.
Viscosupplementation with intra-articular injections of hyaluronic acid is recommended as a second line treatment for knee OA, after failure of non-pharmacological modalities and usual pain killers. ...Nevertheless there are still controversies regarding clinical relevance of its effects. Research is looking for the best way to improve the performance of viscosupplementation in order to obtain a faster, longer-lasting and more pronounced effect. Antioxidants have been assessed in combination with hyaluronic acid because the injected hyaluronate is rapidly degraded by the reactive oxygen species, present in large amounts in the OA synovial fluid, limiting its residence time into the joint. Sorbitol and mannitol which have intrinsic free radical scavenger properties have been the most studied antioxidants. Sodium hyaluronate and polyols develop together a complex based on a dense network of hydrogen bonds which do not modify the visco-elsatic properties of hyaluronic acid. The oxygen free radicals neutralization by mannitol has been proven to delay the degradation of both linear and cross-linked HA in several in vitro models of oxidative stress. The antioxidant effect of these polyols may also play a role in accelerating onset of analgesia, as demonstrated in a double blind controlled trial comparing a mannitol-modified viscosupplement to regular hyaluronic acid. The addition of mannitol and sorbitol to hyaluronic acid does not alter the safety and local tolerability. In summary, adding a polyol to hyaluronic acid may improve the effects of viscosupplementation by reducing the rate of degradation of HA leading to a faster effect on pain relief without increasing the risk of adverse effect.
Abstract Viscosupplementation (VS) with hyaluronic acid is currently used by physicians to treat osteoarthritis. However, many aspects of this treatment remain questionable and subject of ...controversy. A group of 8 experts in this field, from European countries, met to debate on 24 statements previously listed by the group members. Based on an extensive research of the literature and expert opinion, a consensus position has been proposed for each statement. Agreement was achieved on some recommendations. In particular, the expert achieved unanimous agreement in favor of the following statements: VS is an effective treatment for mild to moderate knee OA; VS is not an alternative to surgery in advanced hip OA; VS is a well-tolerated treatment of knee and other joints OA; VS should not be used only in patients who have failed to respond adequately to analgesics and NSAIDs; VS is a “positive” indication but not a “lack of anything better” indication; the dosing regimen must be supported by evidence-based medicine; cross-linking is a proven means for prolonging IA residence time of HA; the best approach to inject accurately knee joint is the lateral mid-patellar one; when VS is performed under fluoroscopy, the amount of radiopaque contrast agent must be as low as possible to avoid viscosupplement dilution. These clear recommendations have been established to help practitioners in the use of viscosupplementation.
Obesity and radiological severity have been identified to be independent predictors of a low rate of response to viscosupplementation (VS), in patients with knee osteoarthritis (OA). Is that enough ...to formally refute VS in such patients in whom surgery is sometimes contraindicated?
To compare pain and function scores before and 6 months after knee VS, according to the weight status (obese versus non obese), the radiological severity (mild/moderate versus severe) and both combined.
Post-hoc analysis of a prospective, double blind, randomized, multicentre trial, comparing 2 viscosupplements, in patients with symptomatic knee OA. Patients were classified according to body mass index (BMI < or ≥ 30 kg.
), OARSI radiological grade (1-2 versus 3) and OMERACT-OARSI response criteria (Yes/No). WOMAC between-group comparisons (obese versus non-obese, OARSI 1-2 versus 3, and both combined) in all patients and in OMERACT-OARSI Responders, were achieved using Mannn-Whitney U test.
One-hundred and sixty-six patients were analyzed: 28.3% were obese, 44% were OARSI grade 3, 42,2% were neither obese nor OARSI 3, whereas 14.5% were obese and OARSI 3. At baseline WOMAC pain score did not differ according to the patients sub-groups (p > 0.05). Six months after VS, WOMAC pain decreased significantly in all patient sub-groups (all p < 0.01). At month 6, WOMAC pain sub-score was significantly lower in non-obese than in obese patients (4.9 ± 4.1 versus 7.1 ± 4.9; p = 0.008) and in patients OARSI 1-2 versus 3 (4.8 ± 4.3 versus 6.4 ± 4.5; p = 0.009). However, in responder patients there was no difference in pain score and pain decrease related to the weight status and the radiological score.
These results do not confirm our previous conclusions that recommended not performing VS in obese patients with severe knee OA. Although the chances of being a responder were much reduced in these patients, the benefit of patients who respond to treatment was similar to that of subjects with normal weight and mild/moderate OA. Different pain phenotypes, more than overweight and advanced disease, might be the main reason for the success or failure of VS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.•By neutralizing a key inflammatory factor in the cytokine release syndrome in COVID-19, ...tocilizumab (TCZ) can block the cytokine storm and reduce the severity of the disease.•Our case-control study found that patients treated with TCZ had a lower index of mortality and/or invasive mechanical ventilation (IMV) requirement than patients without TCZ.•This result strongly suggests that TCZ may reduce the number of IMV requirements and/or mortality in patients with severe SARS-CoV-2 pneumonia.•This idea needs to be confirmed and spread in the medical community.
No therapy has proven to be effective yet to reduce mortality and/or invasive mechanical ventilation (IMV) requirement in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment.
We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: mortality and/or IMV requirement.
Thirty patients were treated with TCZ and 176 patients were treated without TCZ. TCZ was used in patients in critical condition (oxygen therapy flow at TCZ onset was 10.5 L/min and 14/30 patients had ≥ 50% lung involvement on CT scan) as a rescue treatment (8/30 patients who died were not admitted in USC in regard to their comorbidities). However, mortality and/or IMV requirement were lower in patients with TCZ than in patients without TCZ (27% vs 52%, p = 0.009).
Despite the small sample size in the TCZ group, this result suggests that TCZ reduces mortality and/or IMV requirement in patients with severe SARS-CoV-2 pneumonia. This notion needs to be confirmed and spread in the medical community.
Chronic pain and functional impairment interfere with the quality of life of subjects suffering from temporomandibular joint (TMJ) disorders. Intra-articular (IA) hyaluronic acid (HA) injections have ...been shown to alleviate pain and improve mandibular mobility in patients with TMJ osteoarthritis (OA).
The primary aim of the study was to identify the prognostic factors of patient satisfaction for a single IA injection of a mannitol-modified crosslinked HA (HANOX-M-XL) in patients with TMJ-OA. The second goal was to obtain clinical data on effectiveness, safety and mandibular mobility throughout a six-month follow-up period.
This was an observational single-arm prospective trial with a six-month follow-up.
patients with TMJ-OA which is not relieved by analgesics and/or non-steroidal-anti-inflammatory drugs and/or orthotics, with radiological evidence of TMJ-OA. All patients received a single IA injection of 1 ml HANOX-M-XL in the target TMJ. The primary endpoint was patient satisfaction on day 180. The main secondary outcome measures were pain variation on a 11-point numeric scale (0-11) between the date of injection and month six, the variation over time of the Maximum Inter-Incisal Opening Distance (MIIOD) and the patient's assessment of effectiveness. Predictive factors of success or failure were also studied. All adverse events were recorded.
36 subjects (mean age 55.3 years, mean disease duration 98 months), covering a total of 52 injected TMJs, were included. Between baseline and endpoint, the average pain while chewing decreased dramatically from 6.9 ± 1.2 to 2.9 ± 1.3 (p < 0.0001) and the MIIOD increased from 29 ± 7 to 35 ± 5 mm (p < 0.01). On day 180, all patients were satisfied with the treatment, with 34 patients (94%) rating it as highly effective or effective. Tolerability was good in all but one patient. In the multivariate analysis, patient satisfaction on day 180 was highly correlated with the pain while chewing score, pain on palpation score and the decrease of pain over time (all p < 0.0001) but not with MIIOD, gender, age, bruxism, articular noise and symptom duration. Previous viscosupplementation was also related to higher satisfaction (p = 0.01).
Despite a long history of pain, most of the patients with symptomatic TMJ-OA benefited from a single injection of HANOX-M-XL, as shown by the sustained (up to 6 months) decrease in pain and improvement in mandibular mobility, with no safety concerns.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An advanced radiological stage and obesity are predictive of poorer and shorter responses to viscosupplementation in patients with knee osteoarthritis (OA). Very little is known regarding the impact ...of other factors such as sport practice, comorbidities, or anatomical features of OA.
This study aimed to investigate patients' and OA characteristics associated with the duration of the effectiveness (DE) of viscosupplementation in patients with knee OA. It was a cross-sectional, single-centre clinical trial in patients with knee OA treated with intra-articular (IA) hyaluronic acid (HA) injection(s) within the previous 3 years. The investigators collected data regarding demographic and radiographic features (Kellgren-Lawrence grade and involved knee compartments), dosing regimen (single or repeat injections), the presence and volume of joint effusion, previous or concomitant IA corticosteroid injection, the number of previous viscosupplementations, and comorbidities. Patients completed a questionnaire including the self-assessment of DE (the number of weeks during which viscosupplementation was effective on symptoms), the activity level (sedentary, active, or athletic), and the level of sport activity (light, moderate, or intensive). Predictors of the DE were studied in bivariate and multivariate analyses.
In total, 105 patients (149 knees) were analysed (62% women, mean age 66.1 ± 13.2 years, mean BMI 27.5 ± 7.5 kg/m
). The mean DE was 48.2 ± 24.8 weeks. In bivariate analysis, the predictors of a shorter DE were BMI > 27.5 kg/m
, more than three previous viscosupplementations, Kellgren-Lawrence grade 4, sedentary patients, and multicompartmental involvement. In the multivariate analysis, four independent factors remained associated with a shorter DE: BMI > 27.5 kg/m
, multicompartmental knee involvement, number of viscosupplementations >3, and sedentary lifestyle. A statistically significant association between a longer DE and arterial hypertension was found, suggesting a beneficial effect of certain antihypertensive medications.
This study confirms that being overweight significantly reduces the duration of the effectiveness of viscosupplementation. It also shows that viscosupplementation is more lastingly effective in unicompartmental OA and among active or athletic patients. The duration of effectiveness decreases when the treatment is repeated more than three times.
Viscosupplementation (VS) is a symptomatic treatment for knee and other joint osteoarthritis (OA). Despite a long history of use, conflicting opinions remain on the best clinical indications and the ...most appropriate patients to be treated with intra-articular hyaluronic acid (IA-HA), the optimal dosing regimen and the modalities of retreatment. A multidisciplinary committee of European experts on OA (EUROVISCO) was constituted to formulate recommendations, aimed at helping physicians in the decision-making and the optimal achievement of VS. Before each session members were tasked to collate an exhaustive literature review. Level of evidence and strength of recommendation were based on the level of agreement for each item according to the Delphi method. In 2015, a consensus position was proposed for 24 statements. Among those that obtained a consensual agreement, the working group stressed that VS is effective in mild/moderate knee OA but is not an alternative to surgery in advanced OA, and that dosing regimen must be supported by controlled trials. In 2018, two decision algorithms for the retreatment with IA-HA in knee OA were published. Among the key recommendations, the experts recommended to re-treat every year patients with high risk of OA progression, even if not symptomatic. In 2020, EUROVISCO published two sets of recommendations for the design of clinical trials on the disease-modifying effect of VS and for optimizing the results of VS. The working group underlined that an accurate analysis of radiological features and symptoms and a careful clinical examination may improve the chances of success of VS, as well as good technique of injection and the use of imaging guidance. Based on the exhaustive analysis of the literature and their own clinical experience, the EUROVISCO experts offer a wide range of recommendations intended to help practitioners, particularly in certain cases where the specific characteristics of the patients make the therapeutic decision difficult.
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