-
Autoimmunity Reviews Dec 2021Many therapies have been investigated for systemic sclerosis-associated interstitial lung disease (SSc-ILD), including immunosuppressive therapies, antifibrotic agents,... (Review)
Review
Many therapies have been investigated for systemic sclerosis-associated interstitial lung disease (SSc-ILD), including immunosuppressive therapies, antifibrotic agents, immunomodulators and monoclonal antibodies. There is a high unmet medical need to better understand the current evidence for treatment efficacy and safety. This systematic review aims to present the existing literature on different drug treatments investigated for SSc-ILD and to critically assess the level of evidence for these drugs. A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A structured literature search was performed for clinical trials and observational studies on the treatment of SSc-ILD with pharmaceutical interventions from 1 January 1990 to 15 December 2020. The quality of each reference was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. A total of 77 references were reviewed and 13 different treatments were identified. We found high-quality evidence for the use of cyclophosphamide, nintedanib, mycophenolate and tocilizumab. Therefore, we would posit that the clinical community has four valid options for treatment of SSc-ILD. Further research is mandatory to provide more evidence for the optimal treatment strategy in SSc-ILD, including the optimal time to initiate treatment, selection of patients for treatment and upfront combination therapy.
Topics: Antifibrotic Agents; Cyclophosphamide; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Scleroderma, Systemic
PubMed: 34718159
DOI: 10.1016/j.autrev.2021.102978 -
The Cochrane Database of Systematic... Jul 2022Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited... (Review)
Review
BACKGROUND
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by systemic inflammation, fibrosis, vascular injury, reduced quality of life, and limited treatment options. Autologous hematopoietic stem cell transplantation (HSCT) has emerged as a potential intervention for severe SSc refractory to conventional treatment.
OBJECTIVES
To assess the benefits and harms of autologous hematopoietic stem cell transplantation for the treatment of systemic sclerosis (specifically, non-selective myeloablative HSCT versus cyclophosphamide; selective myeloablative HSCT versus cyclophosphamide; non-selective non-myeloablative HSCT versus cyclophosphamide).
SEARCH METHODS
We searched for randomized controlled trials (RCTs) in CENTRAL, MEDLINE, Embase, and trial registries from database insertion to 4 February 2022.
SELECTION CRITERIA
We included RCTs that compared HSCT to immunomodulators in the treatment of SSc.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, extracted study data, and performed risk of bias and GRADE assessments to assess the certainty of evidence using standard Cochrane methods.
MAIN RESULTS
We included three RCTs evaluating: non-myeloablative non-selective HSCT (10 participants), non-myeloablative selective HSCT (79 participants), and myeloablative selective HSCT (36 participants). The comparator in all studies was cyclophosphamide (123 participants). The study examining non-myeloablative non-selective HSCT had a high risk of bias given the differences in baseline characteristics between the two arms. The other studies had a high risk of detection bias for participant-reported outcomes. The studies had follow-up periods of one to 4.5 years. Most participants had severe disease, mean age 40 years, and the duration of disease was less than three years. Efficacy No study demonstrated an overall mortality benefit of HSCT when compared to cyclophosphamide. However, non-myeloablative selective HSCT showed overall survival benefits using Kaplan-Meier curves at 10 years and myeloablative selective HSCT at six years. We graded our certainty of evidence as moderate for non-myeloablative selective HSCT and myeloablative selective HSCT. Certainty of evidence was low for non-myeloablative non-selective HSCT. Event-free survival was improved compared to cyclophosphamide with non-myeloablative selective HSCT at 48 months (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.16 to 0.74; moderate-certainty evidence). There was no improvement with myeloablative selective HSCT at 54 months (HR 0.54 95% CI 0.23 to 1.27; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not report event-free survival. There was improvement in functional ability measured by the Health Assessment Questionnaire Disability Index (HAQ-DI, scale from 0 to 3 with 3 being very severe functional impairment) with non-myeloablative selective HSCT after two years with a mean difference (MD) of -0.39 (95% CI -0.72 to -0.06; absolute treatment benefit (ATB) -13%, 95% CI -24% to -2%; relative percent change (RPC) -27%, 95% CI -50% to -4%; low-certainty evidence). Myeloablative selective HSCT demonstrated a risk ratio (RR) for improvement of 3.4 at 54 months (95% CI 1.5 to 7.6; ATB -37%, 95% CI -18% to -57%; RPC -243%, 95% CI -54% to -662%; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; low-certainty evidence). The non-myeloablative non-selective HSCT trial did not report HAQ-DI results. All transplant modalities showed improvement of modified Rodnan skin score (mRSS) (scale from 0 to 51 with the higher number being more severe skin thickness) favoring HSCT over cyclophosphamide. At two years, non-myeloablative selective HSCT showed an MD in mRSS of -11.1 (95% CI -14.9 to -7.3; ATB -22%, 95% CI -29% to -14%; RPC -43%, 95% CI -58% to -28%; moderate-certainty evidence). At 54 months, myeloablative selective HSCT at showed a greater improvement in skin scores than the cyclophosphamide group (RR 1.51, 95% CI 1.06 to 2.13; ATB -27%, 95% CI -6% to -47%; RPC -51%, 95% CI -6% to -113%; moderate-certainty evidence). The NNTB was 4 (95% CI 3 to 18). At one year, for non-myeloablative non-selective HSCT the MD was -16.00 (95% CI -26.5 to -5.5; ATB -31%, 95% CI -52% to -11%; RPC -84%, 95% CI -139% to -29%; low-certainty evidence). No studies reported data on pulmonary arterial hypertension. Adverse events In the non-myeloablative selective HSCT study, there were 51/79 serious adverse events with HSCT and 30/77 with cyclophosphamide (RR 1.7, 95% CI 1.2 to 2.3), with an absolute risk increase of 26% (95% CI 10% to 41%), and a relative percent increase of 66% (95% CI 20% to 129%). The number needed to treat for an additional harmful outcome was 4 (95% CI 3 to 11) (moderate-certainty evidence). In the myeloablative selective HSCT study, there were similar rates of serious adverse events between groups (25/34 with HSCT and 19/37 with cyclophosphamide; RR 1.43, 95% CI 0.99 to 2.08; moderate-certainty evidence). The non-myeloablative non-selective HSCT trial did not clearly report serious adverse events.
AUTHORS' CONCLUSIONS
Non-myeloablative selective and myeloablative selective HSCT had moderate-certainty evidence for improvement in event-free survival, and skin thicknesscompared to cyclophosphamide. There is also low-certainty evidence that these modalities of HSCT improve physical function. However, non-myeloablative selective HSCT and myeloablative selective HSCT resulted in more serious adverse events than cyclophosphamide; highlighting the need for careful risk-benefit considerations for people considering these HSCTs. Evidence for the efficacy and adverse effects of non-myeloablative non-selective HSCT is limited at this time. Due to evidence provided from one study with high risk of bias, we have low-certainty evidence that non-myeloablative non-selective HSCT improves outcomes in skin scores, forced vital capacity, and safety. Two modalities of HSCT appeared to be a promising treatment option for SSc though there is a high risk of early treatment-related mortality and other adverse events. Additional research is needed to determine the effectiveness and adverse effects of non-myeloablative non-selective HSCT in the treatment of SSc. Also, more studies will be needed to determine how HSCT compares to other treatment options such as mycophenolate mofetil, as cyclophosphamide is no longer the first-line treatment for SSc. Finally, there is a need for a greater understanding of the role of HSCT for people with SSc with significant comorbidities or complications from SSc that were excluded from the trial criteria.
Topics: Adult; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Randomized Controlled Trials as Topic; Scleroderma, Systemic
PubMed: 35904231
DOI: 10.1002/14651858.CD011819.pub2 -
Molecules (Basel, Switzerland) Sep 2021We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models.... (Review)
Review
We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.
Topics: Animals; Antineoplastic Agents; Brain Diseases; Deoxyadenosines; Humans; Inflammation; Metabolic Diseases; Neoplasms; Signal Transduction
PubMed: 34641429
DOI: 10.3390/molecules26195886 -
Renal Failure 2023This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).
METHODS
A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.
RESULTS
The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.
CONCLUSIONS
Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did' not include results on other adverse events.
Topics: Humans; Lupus Nephritis; Cyclophosphamide; Induction Chemotherapy; Network Meta-Analysis; Treatment Outcome; Immunosuppressive Agents; Tacrolimus; Mycophenolic Acid; Remission Induction; Randomized Controlled Trials as Topic
PubMed: 38087473
DOI: 10.1080/0886022X.2023.2290365 -
Life (Basel, Switzerland) Oct 2022Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present... (Review)
Review
Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities and pharmaceutical and food applications. In addition, the study identified essential oils rich in alpha-phellandrene and summarized their main biological activities as a preliminary screening to encourage subsequent studies on their single components. With this review, we selected and critically analyzed 99 papers, using the following bibliographic databases: PubMed, SciELO, Wiley and WOS, on 8 July 2022. Data were independently extracted by four authors of this work, selecting those studies which reported the keyword "alpha-phellandrene" in the title and/or the abstract, and avoiding those in which there was not a clear correlation between the molecule and its biological activities and/or a specific concentration from its source. Duplication data were removed in the final article. Many essential oils have significant amounts of alpha-phellandrene, and the species and are frequently cited. Some studies on the above-mentioned species show high alpha-phellandrene amounts up to 82.1%. There were 12 studies on alpha-phellandrene as a pure molecule showed promising biological functions, including antitumoral, antinociceptive, larvicidal and insecticidal activities. There were 87 research works on EOs rich in alpha-phellandrene, which were summarized with a focus on additional data concerning potential biological activities. We believe this data is a useful starting point to start new research on the pure molecule, and, in particular, to distinguish between the synergistic effects of the different components of the OEs and those due to alpha-phellandrene itself. Toxicological data are still lacking, requiring further investigation on the threshold values to distinguish the boundary between beneficial and toxic effects, i.e., mutagenic, carcinogenic and allergenic. All these findings offer inspiration for potential applications of alpha-phellandrene as a new biopesticide, antimicrobial and antitumoral agent. In particular, we believe our work is of interest as a starting point for further studies on the food application of alpha-phellandrene.
PubMed: 36295037
DOI: 10.3390/life12101602 -
Clinical and Experimental Rheumatology May 2022Relapsing polychondritis (RP) evolves with variable and intermittent involvement of cartilage and proteoglycan-rich structures. Ocular manifestations are present in up... (Review)
Review
OBJECTIVES
Relapsing polychondritis (RP) evolves with variable and intermittent involvement of cartilage and proteoglycan-rich structures. Ocular manifestations are present in up to two-thirds of RP patients. Necrotising scleritis (NS) and peripheral ulcerative keratitis (PUK) may be inaugural and may lead to eye perforation and vision loss. We aimed to review NS and PUK in RP, in order to characterise them, to identify successful treatment options and unmet needs.
METHODS
A systematic review of the currently available evidence in PubMed, EMBASE and Scopus was performed according to PRISMA, including observational studies, single case reports and case series of NS/PUK in RP. Study design, number of patients, age, gender, treatment and outcome, were extracted. Two RP patients also provided their opinion.
RESULTS
Five case reports and two case series were eligible for inclusion. We identified 10 RP patients with eye-threatening complications (NS and/or PUK), 9 adults (2 males, 7 females, aged 35-72, median age 57.6 years) and one paediatric patient (F, 11 years). Apart from glucocorticoids, cyclophosphamide was effective in 4 patients; infliximab, high-dose immunoglobulins, dapsone, or cyclosporine were also successfully employed in a case each. Surgical repair was reported in 2 cases.
CONCLUSIONS
Ocular inflammation is often bilateral and recurring in RP; NS/PUK are rare complications. All patients who develop NS/PUK should be specifically questioned for RP signs and symptoms. Early institution of immunosuppressive therapies is mandatory. Increasing awareness, physicians' and patients' education and a multidisciplinary approach may help improve the prognosis of these serious complications of RP.
Topics: Adult; Child; Corneal Ulcer; Cyclophosphamide; Female; Humans; Infliximab; Male; Middle Aged; Polychondritis, Relapsing; Scleritis
PubMed: 35238768
DOI: 10.55563/clinexprheumatol/27n7im -
Journal of Oral and Maxillofacial... 2022Waterpipe tobacco smoking (WTS) is an issue all over the world, although it is particularly prevalent in the Middle East, and Southeast Asia. The genotoxic effects of... (Review)
Review
BACKGROUND
Waterpipe tobacco smoking (WTS) is an issue all over the world, although it is particularly prevalent in the Middle East, and Southeast Asia. The genotoxic effects of smoking were reported to be associated with nucleus abnormalities such as micronuclei (MN), karyorrhexis (KR), karyolysis, pyknosis, binucleates, broken eggs, condensed chromatin in exfoliated buccal mucosal cells, and was believed to be associated with apoptosis of cells and was not correlated to the exposure time.
AIM
The aim of this study was to evaluate and compare the cytotoxic and genotoxic effects of cigarette and WTS on buccal mucosa.
MATERIALS AND METHODS
The pertinent search was done through the computerized literature on MEDLINE, EMBASE, and PUBMED databases, which included case-control, clinical and observational studies regarding the mutagenic effects of cigarettes and WTS in oral tissues. The retraction of data in this study was undertaken from May 2010 to May 2022. A total of 60 articles from the search data were retrieved. This investigation was registered with the research center of Riyadh Elm University for institution review board approval (IRB) and obtained the IRB number "FRP/2021/448/733/707 and the systematic review registration number with respect to PROSPERO is 345417.
RESULTS
After the removal of duplicates, 32 were evaluated for the inclusion and exclusion criteria. Out of 32 articles, twenty studies were evaluated for cytogenetic abnormalities in buccal mucosal cells of waterpipe tobacco smokers (WTS) and cigarette smokers, and 12 were excluded. The mean MN levels in the oral tissues of WTS were more (1.94 ± 0.39) than in non-smokers (1.68 ± 0.35).
CONCLUSION
Therefore, we conclude that the MN count can be employed as a biomarker and preliminary signal for the identification of changes in oral mucosa among smokers, which develop towards cancer formation.
PubMed: 37082081
DOI: 10.4103/jomfp.jomfp_292_22 -
Particle and Fibre Toxicology Sep 2022The number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union... (Review)
Review
The number of publications in the field of nanogenotoxicology and the amount of genotoxicity data on nanomaterials (NMs) in several databases generated by European Union (EU) funded projects have increased during the last decade. In parallel, large research efforts have contributed to both our understanding of key physico-chemical (PC) parameters regarding NM characterization as well as the limitations of toxicological assays originally designed for soluble chemicals. Hence, it is becoming increasingly clear that not all of these data are reliable or relevant from the regulatory perspective. The aim of this systematic review is to investigate the extent of studies on genotoxicity of NMs that can be considered reliable and relevant by current standards and bring focus to what is needed for a study to be useful from the regulatory point of view. Due to the vast number of studies available, we chose to limit our search to two large groups, which have raised substantial interest in recent years: nanofibers (including nanotubes) and metal-containing nanoparticles. Focusing on peer-reviewed publications, we evaluated the completeness of PC characterization of the tested NMs, documentation of the model system, study design, and results according to the quality assessment approach developed in the EU FP-7 GUIDEnano project. Further, building on recently published recommendations for best practices in nanogenotoxicology research, we created a set of criteria that address assay-specific reliability and relevance for risk assessment purposes. Articles were then reviewed, the qualifying publications discussed, and the most common shortcomings in NM genotoxicity studies highlighted. Moreover, several EU projects under the FP7 and H2020 framework set the aim to collectively feed the information they produced into the eNanoMapper database. As a result, and over the years, the eNanoMapper database has been extended with data of various quality depending on the existing knowledge at the time of entry. These activities are highly relevant since negative results are often not published. Here, we have reviewed the NanoInformaTIX instance under the eNanoMapper database, which hosts data from nine EU initiatives. We evaluated the data quality and the feasibility of use of the data from a regulatory perspective for each experimental entry.
Topics: DNA Damage; Databases, Factual; Metal Nanoparticles; Nanostructures; Reproducibility of Results
PubMed: 36104711
DOI: 10.1186/s12989-022-00499-2 -
Heliyon Mar 2023The genus is traditionally used in folk medicine in Brazil and other tropical American countries and is represented by 282 species in this region. It is a multifaceted... (Review)
Review
The genus is traditionally used in folk medicine in Brazil and other tropical American countries and is represented by 282 species in this region. It is a multifaceted genus of medicinal plants widely used to treat rheumatoid arthritis (RA), pain, inflammatory diseases, and many more therapeutic applications. In the present study, we systematically identify and discuss the literature on and studies focusing on the therapeutic potentials and related molecular mechanisms of the genus. The review also assessed phytochemicals and their pharmacological properties and considered safety concerns related to the genus. Literature searches to identify studies on the genus were carried out through four main electronic databases, namely PubMed, Embase, Scopus, and Web of Science limited to Medical Subjects Headings (MeSH) and Descriptores en Ciencias de la Salud (DCS) (Health Sciences Descriptors) to identify studies published up to December 2022. The relevant information about the genus was gathered using the keywords ', 'biological activities', 'therapeutic mechanisms', 'animal model, 'cell-line model', 'antinociceptive', 'hyperalgesia', 'anti-inflammatory', and 'inflammation'. The therapeutic potentials and mechanisms of action of 14 species from genus were examined in 18 studies and included their anti-inflammatory, anticancer, analgesic, antibacterial, cytotoxic, mutagenic, antioxidant, anti-leishmanial, antinociceptive, schistosomicidal, and anti-osteoarthritis potentials, and in eight studies, assessing their analgesic, antioxidant, antinociceptive, and anti-osteoarthritis activities. Some of the main related molecular mechanisms identified are the modulation of cytokines such as IL-1β, IL-6, and TNF-α, as well as the inhibition of inflammatory mediators and prostaglandin synthesis. The limited number of studies showed that commonly available species from the genus are safe for consumption. Sw.Triana and (Bonpl.) DC was the most frequently used species and showed significant efficacy and potential for developing safe drugs to treat pain and inflammation.
PubMed: 36967930
DOI: 10.1016/j.heliyon.2023.e14609 -
Parasitology Nov 2022From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease... (Review)
Review
From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day, 200 mg day, 150 mg day and 2.5 mg kg) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
Topics: Humans; Trypanosoma cruzi; Trypanocidal Agents; Allopurinol; Randomized Controlled Trials as Topic; Chagas Disease; Nitroimidazoles; Drug Therapy, Combination; Treatment Outcome
PubMed: 35957576
DOI: 10.1017/S0031182022001081