Efficacy of Local Oxygen-Ozone Therapy for the Treatment of Digital Ulcers Refractory to Medical Therapy in Systemic Sclerosis: A Randomized Controlled Study

2021 ◽  
Author(s):  
Serdar Kaymaz ◽  
Uğur Karasu ◽  
Hakan Alkan ◽  
Firdevs Ulutaş ◽  
Canan Albayrak Yaşar ◽  
...  

Abstract Background This study aimed to investigate the efficacy of local oxygen-ozone therapy in systemic sclerosis (SSc) patients with digital ulcers (DUs) who were resistant to medical therapy and had impairment in activities of daily living. Methods Participants’ demographic data, medical treatment, and clinical parameters (duration and number of Reynaud’s Phenomenon (RP) attacks, ulcer pain, grade, and diameter) were recorded. Twenty-five SSc patients with DUs were randomized to the ozone group (I) (n = 13) to receive medical treatment plus local oxygen-ozone therapy and the control group (II) (n = 12) to receive medical treatment only. Hand functions were assessed using the Health Assessment Questionnaire (HAQ) and Modified Hand Mobility in Scleroderma (HAMISm) test. Ulcer grade, clinical parameters, HAQ, mHAMIS scores were re-evaluated in all participants 4 weeks after the initiation of treatment. Results Demographic and clinical characteristics of the two groups showed no significant differences. At 4 weeks after the initial treatment, the efficacy rate was significantly higher in the ozone group than in the control group (92% versus 42%, p = 0.010). Clinical parameters, HAQ, and HAMISm scores were significantly improved in the treatment group compared to the control group (p < 0.05). Conclusion Local oxygen-ozone therapy was effective in the treatment of SSc patients with resistant DUs and improved clinical parameters and functional disability.

2021 ◽  
Author(s):  
Martin Iglesias ◽  
Iván Torre-Villalvazo ◽  
Patricia Butrón-Gandarillas ◽  
Tatiana S. Rodríguez-Reyna ◽  
Erik A. Torre-Anaya ◽  
...  

ABSTRACTBackgroundIn the hand, the Systemic Sclerosis (SS) is characteristically evidenced by Raynaud’s phenomenon (RP) and fibrosis of the skin, tendons, ligaments, and joints as well as digital ulcers with prolonged healing. Current medical treatment not always cure these complications. Local adipose-derived stromal vascular fraction (ADSVF) administration into the hands has been proposed as an emerging treatment for these complications, due to its proangiogenic, antifibrotic, and immunoregulatory activities. The objective of this controlled trial was to evaluate the safety and clinical effects of fat micrografts plus ADSVF administration into the hands of patients with SS.MethodsThis was an open-label, monocentric, randomized controlled study. Twenty patients diagnosed with SS were enrolled and assigned to the experimental or control group. Fat micrografts plus the ADSVF were injected into the right hand of experimental group patients. The control group continued to receive only medical treatment. Demographic, serologic data and disease severity were recorded. Digital oximetry, pain, Raynaud phenomenon (RP), digital ulcer healing (DUH), mobility, thumb opposition, vascular density of the nail bed, skin affection of the hand, Serologic antibodies, hand function, and quality of life scores were evaluated in both groups. The mean follow-up period was 168 days.The differences between before and after the intervention were analyzed with the Wilcoxon range test, and the differences between the control and experimental groups at 0 days and 168 days were analyzed with the Mann–Whitney U test.ResultsAdverse events were not observed in both groups. There were no changes in disease severity, serologic antibodies, nailfold capillaroscopy patterns, mobility, and hand function in both groups. There were significant improvements in pain, DUH and quality of life scores in the experimental group. RP improved significantly in both groups. However, on statistically comparing the results at 168 days between the groups, significant improvements were only observed in pain levels (p = 0.02) and DUH (p=0.003).ConclusionsThe injection of ADSVF plus fat micrografts is a reproducible, and safe technique. Pain and digital ulcers in the hands of patients with SS can be treated with this treatment.Trial RegistrationRetrospectively registered in ClinicalTrials.gov with identifier NCT04387825


2021 ◽  
Author(s):  
Martin Iglesias ◽  
Ivan Torre-Villalvazo ◽  
Patricia Butrón-Gandarillas ◽  
Tatiana S Rodríguez-Reyna ◽  
Erik A Torre-Anaya ◽  
...  

Abstract Background. In the hand, the Systemic Sclerosis (SS) is characteristically evidenced by Raynaud's phenomenon (RP) and fibrosis of the skin, tendons, ligaments, and joints as well as digital ulcers with prolonged healing. Current medical treatment not always cure these complications. Local adipose-derived stromal vascular fraction (ADSVF) administration into the hands has been proposed as an emerging treatment for these complications, due to its proangiogenic, antifibrotic, and immunoregulatory activities. The objective of this controlled trial was to evaluate the safety and clinical effects of fat micrografts plus ADSVF administration into the hands of patients with SS.Methods. This was an open-label, monocentric, randomized controlled study. Twenty patients diagnosed with SS were enrolled and assigned to the experimental or control group. Fat micrografts plus the ADSVF were injected into the right hand of experimental group patients. The control group continued to receive only medical treatment. Demographic, serologic data and disease severity were recorded. Digital oximetry, pain, Raynaud phenomenon (RP), digital ulcer healing (DUH), mobility, thumb opposition, vascular density of the nail bed, skin affection of the hand, Serologic antibodies, hand function, and quality of life scores were evaluated in both groups. The mean follow-up period was 168 days. The differences between before and after the intervention were analyzed with the Wilcoxon range test, and the differences between the control and experimental groups at 0 days and 168 days were analyzed with the Mann–Whitney U test.Results. Adverse events were not observed in both groups. There were no changes in disease severity, serologic antibodies, nailfold capillaroscopy patterns, mobility, and hand function in both groups. There were significant improvements in pain, DUH and quality of life scores in the experimental group. RP improved significantly in both groups. However, on statistically comparing the results at 168 days between the groups, significant improvements were only observed in pain levels (p = 0.02) and DUH (p=0.003).Conclusions. The injection of ADSVF plus fat micrografts is a reproducible, and safe technique. Pain and digital ulcers in the hands of patients with SS can be treated with this treatment. Trial Registration: Retrospectively registered in ClinicalTrials.gov with identifier NCT04387825


2019 ◽  
Vol 24 (2) ◽  
pp. 121-126 ◽  
Author(s):  
V. G. Atrushkevich ◽  
L. Yu. Orekhova ◽  
O. O. Yanushevich ◽  
E. Yu. Sokolova ◽  
E. S. Loboda

Relevance: to indentify if periodontal treatment which is presented by photoactivated disinfection (PAD) adjunctively to scaling and root planing (SRP) yield better outcomes than ozone therapy as an adjunct to SRP in periodontitis.Materials and methods: we examined 57 (mean age 49,3 ± 1,02) patients with chronic periodontitis, divided into groups, SRP + PAD, SRP + ozone therapy and SRP alone. Subgingival plaque samples were subjected to DNA extraction and real time PCR amplifcation for detection Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Tannerella forsythensis (Tf), Treponema denticola (Td), Aggregatibacter actinomycetemcomitans (Aa). The amount of periodontopathogens and clinical parameters including plaque index, clinical attachment loss, pocket depth, bleeding on probing were measured at baseline, after 40, 90 and 180 days.Results: the results in groups of PAD+SRP and ozone therapy+SRP showed an improvement in all clinical parameters PI, BOP, PD, CAL and the quantity of Pg, Td and Tf compared to the control group during an observation period.Conclusion: the results showed additional benefts from PAD and ozone therapy as an adjunctive treatment to SRP for patients of chronic periodontitis.


Author(s):  
Saba Khan ◽  
Saima Akram Butt ◽  
Sobia Hassan ◽  
Rizma Khan

Objective: The present study aimed to evaluate the salivary miRNA31 expression in controls and cases and associate miRNA31 levels with clinical parameters of oral submucous fibrosis. Methods: This case control study was conducted in a hospital setup. A total of 50 individuals participated in the study with 25 subjects in group I (healthy individuals) and 25 subjects in group II 25 diagnosed cases of (oral submucous fibrosis). The sample size was calculated with open Epi version 3.01.  A detailed assessment of clinical parameters of oral submucous fibrosis was made. Unstimulated saliva samples were collected from all study subjects meeting the inclusion criteria and analysis of saliva samples was done by qRTPCR. Results: The results showed high expression levels of miRNA31 in oral submucous fibrosis as compared to the control group. The study demonstrated significantly higher median fold change of miRNA-31 expression level in OSMF patients as compared to the participants in the control group. Correlation between age of patients and miRNA31 fold change was discerned using the Spearman rank test that demonstrated a non-significant negative correlation. Conclusion: Increased expression levels of miRNA 31 among oral submucous fibrosis as compared to the control group make it a promising salivary biomarker that detects oral submucous fibrosis at an early stage of the disease.


Ozone Therapy ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Hilary Riva ◽  
Brenno Balestra ◽  
Olivier Giannini ◽  
Giuseppe Bonforte

Patients with systemic sclerosis often suffer from Raynaud’s phenomenon and in the most severe cases it causes digital ulceration and difficult healing. Treatment for these complications are not always resolutive and sometimes not well tolerated. The O2O3 therapy is a gas mixture that has several demonstrated effects including antiseptic, painkiller, microcirculation vasodilator, oxygen metabolism regulator and immunomodulation, and it can be personalised, administered to individual patient requirements. We decided to offer this treatment to our patients after the failure of traditional drugs and surgery without influencing the therapeutic program. The results obtained are interesting, and though more studies are needed to better understand the exact mechanism of action of O2O3 therapy, we believe that in the meantime, this therapy should be considered as treatment for the most severe cases.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 699.1-699
Author(s):  
S. H. Chang ◽  
J. B. Jun ◽  
Y. J. Lee ◽  
T. Y. Kang ◽  
Y. Park ◽  
...  

Background:Digital ulcer (DU) is a common clinical manifestation in patients with systemic sclerosis (SSc). About 70% of patients with SSc experience DUs during the first 10 years, which limit daily activities and may result in digital gangrene or amputation. Several vasoactive/vasodilating agents have been suggested for treatment, but few studies have compared the efficacy of those drugs.Objectives:The objective of our study was to compare the efficacy of medical treatment for SSc related-DUs, focusing on on endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitors (PDE5inh).Methods:In this prospective observational cohort study, we recruited patients who had one or more active SSc-related DUs and newly started or changed a medical treatment for SSc-related DUs from 13 medical centers in South Korea. The primary outcome was to compare the time to resolution of cardinal DU (CU) according to the treatments. The secondary outcomes included changes in the size or number of CU and changes in the number of DUs. CU was defined as the most clinically significant DU chosen by the investigators. Patients were followed up at every 4 weeks after enrollment until 12 weeks and finally at 24 weeks.Results:Seventy-one patients were enrolled. Seven patients were excluded due to follow-up loss or withdrawal of consent. A total of 64 patients were analyzed. Seventy-eight percent (n=50) were female. The mean age at enrollment was 49.6 ± 11.6 year-old, and the mean disease duration was 7.1 ± 5.9 years. Twenty-eights pateitns (43.8%) were limited SSc. Forty-nine patients (n=76.6%) started ERA treatment (bosentan=49). Eleven patients (17.2%) started PDE5inh treatment (n=9 for sildenafil, n=1 for udenafil, and n=1 for tadalafil). Four patients who started medication other than ERA or PDE5inh classified as other treatment groups. Seventeen patients (26.6%) were on background calcium channel blockers (CCBs). CU healed in 25 patients (39.1%) at 12 weeks and 43 patients (67.2%) at 24 weeks. The mean time to heal CUs were 54.4 ± 22.7 days at 12 weeks and 91.6 ± 49.2 days at 24 weeks. Time to heal CU was comparable among patients on ERA, PDE5inh, and others (p=0.53, figure 1). The CU area was comparable among the three groups at baseline, 12, and 24 weeks. The mean area of CU in patients on ERA at baseline at 12, and 24 weeks was 21.3±19.4 mm2, 8.2±14.6 mm2, and 4.6±7.7 mm2, respectively. The mean area of CU in patients with PDE5inh at baseline at 12, and 24 weeks was 26.2±28.1 mm2, 3.5±3.6 mm2, and 1.3±4.3 mm2. New DUs developed in 4 patients (8.3%) in ERA, whereas 4 patients (40.0%) in PDE5inh at 4 weeks. The use of ERA was significantly associated with less new DUs development than the use of PDE5inh at 4 weeks follow-up (RR for developing new DU patients on ERA, 0.21; 95% CI 0.06-0.70; p=0.02) At 24 weeks follow-up, none of the patients on CCB developed new DUs.Conclusion:The time to heal CU for ERA and PDEinh users was comparable in the current study. ERA treatment was associated with reduced new DU occurrence compared with PDE5inh treatment. None of the patients with CCB treatment developed new DU development at 24 weeks.Acknowledgments:This study was supported by Handok Pharmaceutical Inc., Seoul, Republic of Korea.Disclosure of Interests:Sung Hae Chang: None declared, Jae-Bum Jun Grant/research support from: Clinical trials; Corbus, JW Pharmaceutical, Speakers bureau: SK Chemical, Yun Jong Lee: None declared, Tae Young Kang: None declared, Yongbeom Park: None declared, Seung-Geun Lee: None declared, Shin-Seok Lee: None declared, Eun Bong Lee: None declaredFigure 1


2015 ◽  
Vol 24 (2) ◽  
pp. 114-117
Author(s):  
Alina Soare ◽  
◽  
Simona Pintilie ◽  
Ana Maria Gherghe ◽  
Alexandra Radu ◽  
...  

Background and objectives. Systemic sclerosis (SSc) is a multisystem connective tissue disease (CTD), being one of the most heterogeneous diseases of the spectrum of CTDs. It may associate other autoimmune diseases (AIDs), therefore in this study we aimed to evaluate the prevalence of other AIDs in a cohort of patients with SSc and to evaluate their prognosis in comparison to patients with SSc without this association. Patients and methods. We performed a retrospective study in patients with SSc satisfying the ACR 1980 or the ACR/EULAR 2013 criteria, who were evaluated between January 2005 and May 2014 in our SSc center. These patients were investigated according to the EUSTAR recommendations, including modified Rodnan Skin Score (mRSS), lung function tests (LFT), echocardiography etc. As a control group for evaluating the prevalence of the AIDs we used all patients with Rheumatoid Arthritis (RA) visiting our clinic between January-December 2005. Data of all RA patients were collected from the electronic database of the hospital. All AIDs mentioned in the discharge diagnoses were recorded. Between-group comparisons were made with the chi-square test for nominal variables and with the independent-sample t-test for numeric variables. Results. 144 patients with SSc were included: 88.8% females, 66.6% with the limited cutaneous subset of disease (lcSSc), mean age 53.9 ± 12.8 years, mean disease duration at study enrollment 5.1±10.5 years and a mean follow-up time of 3.7 ± 2.6 years. Prevalence of the AID in the SSc cohort was 19.4%, patients with lcSSc being more prone to associate other AID (p = 0.001). We noted a tendency towards less interstitial lung disease (p = 0.056) and less digital ulcers (p = 0.081) in patients with SSc and AIDs. Comparing skin involvement for each year of follow-up in patients with SSc with and without and AIDs we observed that the first tended to have lower and more stable values of the mRSS. Conclusion. Patients with SSc and AIDs tend to have a better outcome than the ones without this association. mRSS remains stable across the years in patients with SSc and AID, with lower values than the SSc patients.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 164-164
Author(s):  
N. Cristina ◽  
L. Groseanu ◽  
F. Berghea ◽  
A. Balanescu ◽  
V. Bojinca ◽  
...  

Background:Two pivotal studies, RAPIDS-1 and RAPIDS-2 revealed that bosentan reduces the development of new digital ulcers (DUs) in patients with systemic sclerosis (SSc). However data regarding the long-term use of this dual endothelin antagonist receptor in the treatment of DUs is scarce.Objectives:The aim of the present study was to evaluate long term efficacy and safety profile of bosentan in patients with DUs related to SSc.Methods:A prospective observational case-control study, conducted between 2014 and 2020 enrolled 65 SSc patients with ≥1 active DUs at baseline, who received bosentan therapy. Demographic and clinical features, including DUs incidence and patients subjective perception of DU pain and/or Raynaud’s Phenomenon, were collected. Nailfold videocapillaroscopy was performed in all patients.Results:The study included 51 females and 14 males, with a mean age of 52.6 years, 30 with diffuse subset, most of them with late scleroderma pattern (46/65). Number of DUs at baseline was 4.55 (±2.8), median duration of treatment was 25.95 (±19.4) months. Microangiopathy evolution score (MES) was 5.1 (2.19), visual analog scale (VAS) for DU was 77.9, VAS for Raynaud was 73.4.Patients receiving bosentan had clinically significant reduction in the mean number of DU (p<0.001). The effect was most powerful for the first 6 months of treatment, but the improvement was sustained until 24 months’ follow-up, when the mean DU number reached a plateau that was kept until end of study. 6 month and 24 month evaluations also revealed significant decrease in the VAS for DU (p<0.05) and in the VAS for Raynaud (p<0.01). Statistically significant difference was noted between bosentan-treated and the control group with respect to the decrease in the mean number of digital ulcers. (p=0.005).There was a clear trend towards an improvement in MES score, between baseline and the next follow-up assessments (p=0.003). The difference was statistically significant when compared to control group, but only for the first 18 months of treatment (p<0.001).14 patients (28.75%) discontinued bosentan therapy for administrative reasons. The median time among patients who interrupted the treatment was 6.9 months. An accelerated development of new DU was described 6 months after (p=0.02). Following recommencement of bosentan, the mean number of DU has rapidly decreased (p=0.008). There was no significant difference between patients who temporarily discontinued bosentan for 6 or 12 months.Bosentan was stopped due to lack of efficacy in 2 cases and due to side effects in 7 cases: 4 elevated liver enzymes, 1 severe trombocytopenia, 1 dyspneea agravation and low blood pressure.Conclusion:The present data suggest that treatment with endothelin receptor antagonist bosentan was associated with a significant reduction in the mean number of DU in patients with SSc. The beneficial effect of bosentan persisted throughout the study but was most evident in the first 6 months of treatment. Statistical analysis showed a significant improvement of the microangiopathy evolution score from baseline to end of therapy. 14 patients had a high relapse rate due to potential rebound effect, 6 months after bosentan withdrawal.The drug was reintroduced succesfully for 10 (70%) patients with a significant decrease in the number of DU.References:[1]UK Scleroderma Study Group: digital vasculopathy in systemic sclerosis, Rheumatology, Volume 54, Issue 11, November 2015, Pages 2015[2]Groseanu L, Berghea F, Bojinca V, et al AB0779 Long term follow-up of a systemic sclerosis group treated with bosentan, Annals of the Rheumatic Diseases 2018;77:1523-1524.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1104.1-1105
Author(s):  
I. Gaisin ◽  
Z. Bagautdinova ◽  
M. Glavatskikh ◽  
N. Maximov ◽  
R. Valeeva ◽  
...  

Background:Raynaud’s phenomenon (RP) secondary to rheumatic diseases (RD) can progress to irreversible tissue damage with digital ulceration, scarring and, rarely, gangrene requiring amputation1. Current medical treatments for RP are far from ideal: they are often either ineffective and/or poorly tolerated, thus a significant proportion of patients discontinue drug therapy2.Objectives:To determine RP expression levels and to evaluate the long-term efficacy of iloprost and alprostadil in RP patients with RD.Methods:Indicated therapy with intravenous iloprost (n=10), alprostadil (n=17) or their combinations (n=13) was carried out for three years in patients with secondary RP in RD. Frequency of Raynaud’s attacks, digital ulcers (DU) formation and pain intensity on visual analogue scale (VAS) were evaluated. A control group included 30 patients with RP in RD who did not receive prostanoid therapy. By factor analysis method a generalized index of RP expression was identified, on the basis of which levels of RP expression were determined.Results:“RP expression” scale, revealed as an indicator of RP generalized manifestation, was an average value of two subscales: (1) consisted of 4 indices “DU”, “digital pitting scars”, “phalange amputation” and “frequency of Raynaud’s attack”, (2) included 3 indicators: “intensity of pain”, “duration of illness”, “whitening of fingers”. Correlation of subscales showed their reliability (r=0.294, p=0.053). RP final expression (severity) was 1.51±0.86. A low level of RP expression had values below 0.65, a high level – over 2.37. At baseline, the high level of RP severity was defined in 16 (22.9%) patients, medium – in 43 (61.4%), low – in 11 (15.7%).RP treatment with iloprost was effective in the healing of DU in 100% of patients and led to decrease of RP expression generalized index from 2.25 [1; 3] to 1.75 [1; 2] (p=0.012). Alprostadil therapy reduced pain intensity on VAS (p<0.05) and numbness during Raynaud’s attacks (p<0.01) and decreased RP expression from 1 [1; 2] to 1 [0.5; 1.5] (p=0.038). Patients on prostanoids combination had new DU and amputations; pain intensity reduced by 47% (p<0.05), RP expression generalized indicator did not change.Conclusion:Based on RP clinical manifestations in RD patients, a generalized index of RP expression was identified and levels of RP severity were determined. Treatment with iloprost or alprostadil has significant effects on reducing the clinical manifestations of RP with a corresponding decrease in its severity. Iloprost is indicated in patients with medium and high levels of RP expression index, alprostadil – with medium and low index and non-effectiveness of calcium channel blockers.References:[1]Hughes M, Herrick AL. Digital ulcers in systemic sclerosis.Rheumatology (Oxford) 2017;56 (1):14–25.[2]Kowal-Bielecka O, Fransen J, Avouac J et al. Update of EULAR recommendation for the treatment of systemic sclerosis.Ann Rheum Dis2017;76(8):1327–39.Acknowledgments:Professor LP. Anan’evaDisclosure of Interests:Ilshat Gaisin Speakers bureau: Boehringer Ingelheim, KRKA, Berlin-Chemie Menarini, Sanofi, Zukhra Bagautdinova: None declared, Marianna Glavatskikh: None declared, Nikolay Maximov Speakers bureau: Pfizer, KRKA, Rosa Valeeva: None declared, Oxana Desinova: None declared, Rushana Shayakhmetova: None declared


2017 ◽  
Vol 18 (4) ◽  
pp. 265-269 ◽  
Author(s):  
Carlos Estrela ◽  
Rafaella M Chaves ◽  
Paula C Cardoso ◽  
Terezinha de JE Barata ◽  
João B de Souza ◽  
...  

ABSTRACT Aim This study aims to assess the effect of ozone gas on dentin exposed to Streptococcus mutans biofilm by evaluation of mineral content [log calcium-to-phosphorus (Ca/P)] using energy-dispersive X-ray (EDX) spectroscopy. Materials and methods Five human third molars were sectioned into four slices of dentin and distributed in four groups: I – control (no treatment); II – ozone therapy; III – biofilm development; IV – ozone therapy followed by biofilm development. Mineral content (log Ca/P) was evaluated by EDX. Data were analyzed by analysis of variance and Tukey's test (p < 0.05). Results Results showed that the mineral content of control group (I) was similar to ozone group (II), and was statistically higher than biofilm (III) and ozone + biofilm (IV). The lowest log Ca/P was determined in biofilm group (III). Conclusion It can be concluded that ozone gas did not grant preventive effects of demineralization by S. mutans biofilm on dentin surface. Clinical significance Ozone gas therapy may be an alternative noninvasive treatment aiming to reduce the levels of caries-associated microorganisms. This therapy may, thereby, be an alternative and/or complementary treatment strategy in preventive dentistry. How to cite this article Chaves RM, Estrela C, Cardoso PC, de JE Barata T, de Souza JB, de Torres EM, Estrela CRA, Magalhães APR, Lopes LG. Ozone Gas Effect on Mineral Content of Dentin exposed to Streptococcus mutans Biofilm: An Energy-dispersive X-ray Evaluation. J Contemp Dent Pract 2017;18(4):265-269.


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