Colchicine Treatment Research Articles

Drug metabolism and inflammation related distinct miRNA signature of colchicine resistant familial Mediterranean fever patients

ObjectiveColchicine is the primary treatment for familial Mediterranean fever (FMF). Although colchicine is safe and effective in FMF patients, around 5–10% of patients show resistance to the drug. This study investigates the possibility of a link between colchicine resistance and the distinct miRNA profiles in colchicine resistant FMF patients. MethodsDifferentially expressed miRNAs in colchicine resistant FMF patients were detected by Affymetrix 4.0 miRNA array analysis. These miRNAs were then categorized based on the role of their target genes in drug metabolism and inflammation related pathways. qRT-PCR was used to validate candidate miRNAs selected by Enrichr, a gene enrichment analysis system based on the relevance of possible target genes in drug metabolism pathways. Expression levels of these miRNAs’ potential target genes were investigated by qRT-PCR. Then, a colchicine resistant hepatoblastoma cell line (HEPG2) was established, and the differentially expressed miRNAs and genes identified in patients were also analyzed in this colchicine-resistant cell line. Results25 differentially expressed miRNAs were detected in colchicine resistant FMF patients. miR-183-5p, miR-15b-5p, miR-505-5p, and miR-125a-5p were identified to be associated with drug resistance and inflammatory pathways and thus chosen for further validation. miR-183-5p, miR-15b-5p, miR-505-5p miRNAs showed significantly differential expression in qRT-PCR.NFKB1, NR3C1, PPARα – drug absorption, distribution, metabolism, and excretion (ADME) genes were predicted to be targeted by these miRNAs. Among these targets, NFKB1 and NR3C1 were differentially over expressed in colchicine resistant FMF patients. These findings were validated in the colchicine resistant hepatoblastoma cell line (HEPG2). ConclusionThis is the first study evaluating the role of miRNAs in colchicine resistant patients with FMF. Their differential expression may result in resistance to standard colchicine treatment by affecting the expression of genes that take place in drug absorption, distribution, metabolism, and excretion (ADME) or nuclear receptors that regulate ADME genes, thus potentially playing a role in both drug metabolism and inflammation.

Induction of Synthetic Polyploids of Porang (<i>Amorphophallus muelerri</i> Blume) and Assessment of Its Genetic Variability Using Morphological Data and RAPD Molecular Marker

This study uses morphological characteristics and RAPD markers to evaluate the polyploidization of synthetic porang. Seeds of triploid porang (2n=2x=26) were soaked in the different colchicine concentrations for 24 hours. After colchicine treatment, the porang seeds were planted to an MS medium that contained 2.2 µM of 6-benzylaminopurine (BAP), then, 40 days after planting in the MS media, the morphology and molecular of synthetic polyploid porang were characterized. For DNA extraction, a total of 100 mg of young leaves of porang plantlet was collected. One way Anova followed by the Duncan test (95%) was performed for phenotypic characterization. The number of different alleles, number of effective alleles, Shannon's information index, diversity, and unbiased diversity were assessed for genetic diversity. Synthetic polyploid porang has a higher total shoot, root, and wider leaves than normal porang. Polyploidy induction also successfully increased the genetic diversity of porang, and the genetic diversity will increase porang adaptability and sustainability of porang cultivation.

Colchicine Intoxication Subsequent to an Autolytic Attempt with Positive Evolution

Background and objectives: Colchicine is a drug that has been used to treat gout for several centuries, it is also indicated in certain autoimmune diseases and has been tested as a chemotherapeutic. Only a few cases of intoxication by this drug have been described, but it is known that it has a narrow therapeutic margin (0.5 to 0.8 mg/kg), almost always resulting in fatal results above these limits. Regarding therapeutic management, the initiation of supportive measures is essential. Initial strategies are gastric lavage, administration of activated charcoal and fluid resuscitation aimed at preventing renal failure. Case report: A 63-year-old man with a history of spondylodiscitis and gouty arthropathy, receiving colchicine treatment. He reported abdominal symptoms with nausea, vomiting, watery stools, and diffuse pain after taking 36 tablets of 1 mg of colchicine due to exacerbation of arthralgias (the patient later recognized the autolytic ideation). He was hospitalized in the ICU due to hemodynamic instability, severe pancytopenia, respiratory failure requiring mechanical ventilation and non-oliguric acute renal failure. The patient improved and was discharged from the ICU after 14 days. Conclusions: Colchicine poisoning is rare and has high mortality despite the favorable evolution of our patient. There is no specific treatment at the moment and management should emphasize early admission to the ICU, close monitoring and organ support measures.

Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.

Despite the advanced knowledge concerning autoinflammatory diseases (AID), more data regarding the optimal treatment options and outcomes of the children who met the criteria of more than one AID are required. This study aimed to describe the demographic and clinical characteristics of children from familial Mediterranean fever (FMF)-endemic countries who meet both the FMF and the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome criteria. Moreover, we aimed to measure the response rates to colchicine and tonsillectomy and evaluate the factors affecting the colchicine response in these patients. The study was conducted at pediatric rheumatology tertiary centre. A total of 131 patients (58 females; 73 males) who met both the modified Marshall and pediatric FMF criteria were included. The median age at onset was 18months (1-77months), and the mean age at diagnosis was 47 ± 21.88months. The median interval between episodes was 21 (7-90) days. The median disease duration was 46 (6-128) months. Consanguineous marriage was detected in 17 (13%) of the patients. The most common clinical finding was fever (100%), followed by exudative pharyngitis (88.5%), abdominal pain (86.3%), arthralgia (61.8%), stomatitis (51.1%), adenitis (42%), myalgia (28.7%), chest pain (16%), maculopapular rash (12.2%), arthritis (8.4%), and erysipelas-like rash (4.6%). MEFV gene variants were identified in 106 (80.9%) patients. The most common variants were M694V heterozygous (29%). We found that patients with tonsillopharyngitis, aphthous stomatitis, and PFAPA family history were more likely to be colchicine-resistant and tonsillectomy responsive, while those with exon 10 MEFV gene mutations were more prone to have a favorable response to colchicine. Conclusion: PFAPA syndrome patients with exon 10 MEFV gene mutation, showing typical FMF symptoms, should be treated with colchicine, even after tonsillectomy. In multivariate analysis, PFAPA family history and lack of exon 10 MEFV gene mutations were independent risk factors for colchicine resistance. Thus, tonsillectomy may be recommended as a possible treatment option for these patients. It has yet to be clarified when colchicine treatment will be discontinued in patients whose attacks ceased after tonsillectomy that was performed due to colchicine unresponsiveness. What is Known: • A certain number of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome concomitantly fulfill the familial Mediterranean fever (FMF) criteria. • While colchicine is proposed as a first treatment choice in familial Mediterranean fever (FMF), corticosteroids are recommended as a first-line treatment in PFAPA syndrome patients. What is New: • In patients with concomitant PFAPA syndrome and FMF, PFAPA family history and lack of exon 10 MEFV gene mutation are predictive factors of colchicineresistance. • The presence of exon 10 MEFV gene mutations in patients with concomitant FMF and PFAPA syndrome has a favourable effect on response to colchicine treatment.

In-vitro Induction of Polyploidy in Niger (Guizotia abyssinica L.f. Cass) through Colchicine Treatment

The present study was conducted to induce polyploidy through colchicine treatment to obtain better yield by enhancing the vigour, improving morphological and yield attributing traits. The Niger seeds were exposed to four different colchicine concentrations (0.025,0.05,0.1 and 0.2%) at different time duration (6, 16, 24 and 48 hrs.). The experiment was carried out in two different conditions i.e., ex-vitro and in-vitro. The survival percentage of treated plants was found better under in-vitro conditions while the mortality rate was found higher in ex-vitro condition. The germination percentage was found higher in control as compared to colchicine treated except the 16 hrs treatment at 0.05% and 0.1% which showed similar germination as control. On assessing the morphological parameters including plant height, number of branches per plant, capitulum size, number of capitulum per plant and seed yield per plant, the treated plantlets with 0.05% and 0.1% colchicine at 16 hrs.showed increment compared to control. Stomatal length and width were found increased whereas stomatal density per microscopic area was found higher in control plants. The size of the cell and nucleus was also found increased in the above treatment as compared to control. Comparing the morphological and cytological results it can be anticipated that the plants treated for 16 hrs at 0.05% and 0.1% colchicine concentration may show the putative polyploidy.

In Vivo and In Vitro Chromosome Doubling of ‘I3’ Hemp

Cannabis sativa L. is a diploid (2x) herbaceous plant that provides a wide variety of products such as essential oils, fiber, and medicine. Hemp was defined in the 2018 Farm Bill as a Cannabis plant with a delta-9 tetrahydrocannabinol concentration of not more than 0.3% on a dry-weight basis. Polyploidy is frequently used in plant breeding to manipulate vigor, reproductive fertility, and biochemistry. By inducing polyploidy/chromosome doubling, we may increase the compounds of interest, principally CBD (cannabidiol), produced by hemp. The purpose of this experiment was to evaluate the efficacy of different treatments of colchicine and oryzalin applied in vivo and in vitro to induce polyploidy in ‘I3’ hemp. After treating vegetative cuttings with colchicine or oryzalin, we had a 31% survival rate. Of the 85 survivors, we recovered two tetraploids: one from the 12-h 0.05% colchicine treatment group and the other from the 12-h 0.2% colchicine treatment group. For the in vitro portion of the experiment, the 12-h 50-µM oryzalin treatment yielded one tetraploid and the 36 h 50 µM oryzalin treatment yielded one cytochimera (mixoploid). The relative efficiency of some treatments showed potential for a simple method to induce tetraploids in clonal hemp for breeding.

Genotype Mutations in Palestinian Children with Familial Mediterranean Fever: Clinical Profile, and Response to Colchicine Treatment: A Retrospective Cohort Study

Genotype Mutations in Palestinian Children with Familial Mediterranean Fever: Clinical Profile, and Response to Colchicine Treatment: A Retrospective Cohort Study

First and second-trimester biochemical serum markers in maternal familial Mediterranean fever: The impact of colchicine use

IntroductionWe aimed to investigate the effects of colchicine use on first and second trimester screening markers in pregnancies complicated with familial Mediterranean fever (FMF) and to evaluate the overall impact of these effects on perinatal outcomes. MethodsA retrospective case-control study was conducted in pregnancies complicated with FMF using colchicine and healthy pregnancies as controls without any defined risk factors and medication use. Biochemical markers for the aneuploidy screening, including free ß-hCG and PAPP-A in the first trimester, and AFP, HCG, and unconjugated estriol (uE3) in the second trimester, were recorded, and MoM levels of these markers were compared between the FMF and control groups. Obstetric history and outcomes were also compared between groups. We used propensity score matching to form a cohort in which patients had similar baseline characteristics. ResultsAmong 93 eligible pregnant women, 31 women in FMF group and 31 in control group had similar propensity scores and were included in the analyses. Levels of serum-free ß-hCG, PAPP-A and AFP were similar between FMF and control groups (p = 0.671, p = 0.387 and p = 0.963, respectively). For the second-trimester markers, maternal serum uE3 MoM level were significantly lower in the FMF group using colchicine than in the controls (p = 0.045). We also compared these markers according to the daily colchicine dose between FMF subgroups. We did not detect significant difference between the different colchicine treatment modalities (0.5–1 mg/day vs. 1.5–2 mg/day, p > 0.05). ConclusionMaternal biochemical serum markers of an aneuploidy screening test in the second trimester may be affected by FMF with colchicine use, leading to misinterpretation of the risk level of tests. For these tests with decreased uE3 levels, FMF and colchicine use should be considered as a causative etiology after ruling out common etiologies and confounding factors before recommending invasive diagnostic testing.

In Vitro Induction of Interspecific Hybrid and Polyploidy Derived from Oryza officinalis Wall.

Oryza officinalis Wall is a potential genetic resource for rice breeding; however, its distant genome limits its crossing ability with cultivated rice. The interspecific hybridization of O. officinalis and cultivated rice, establishment of its tissue culture, and induction of polyploidy are ways to improve O. officinalis's poor crossability. We developed an interspecific hybrid and studied its reproductive pollen development process in this work, and the results showed that abortive pollens (81.94%) and embryo sac abnormalities (91.04%) were the key causes of its high sterility. In order to induce callus formation in interspecific hybrid explants, two different culture media, namely Chu's N-6 medium (N6) and 1/2 Murashig and Skoog medium (1/2 MS), were employed. Additionally, two plant growth regulators (PGRs), namely 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BA), along with L-proline (Pro) and acid hydrolyzed casein, were utilized in the experiment. The optimal N6 medium, supplemented with 2.0 mg·L-1 2,4-D, produced the highest induction rate (80.56 ± 5.44)%. For callus differentiation and proliferation, the MS medium supplemented with 2.0 mg·L-1 BA + 0.2 mg·L-1 NAA produced the highest differentiation rate (75.00 ± 4.97)% and seedling emergence ratio (28.97 ± 4.67)%. The optimal combination for seedling rooting was the 1/2 MS medium supplemented with 2.0 mg L-1 NAA and 0.2 mg L-1 BA, which produced an average of 13.95 roots per plant. For polyploidy induction in the interspecific hybrid, the concentration of colchicine treatment at 400 mg·L-1 for three days is an ideal protocol. We devised tissue culture and interspecific hybrid polyploidy induction to overcome O. officinalis' poor crossability and introduce its favorable features into cultivated rice.

Variables fordifferential diagnosis offamilial Mediterranean fever: Multiple correspondence analysis ofa large Japanese cohort.

We investigated differential diagnoses that should be noted with familial Mediterranean fever (FMF) and useful variables for differentiation in a large Japanese cohort. Patients aged ≥13 years who were clinically suspected of having FMF by Livneh criteria were studied 1 year after MEFV genetic testing. Patients ultimately diagnosed with other diseases were studied, and the association among each disease, patient characteristics, and clinical variables were analysed using multiple correspondence analysis. In total, 504 patients were included in this study; 34 (6.7%) were diagnosed with a disease other than FMF. The most common diagnosis was Behçet's disease, followed by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome, inflammatory bowel disease, myelodysplastic syndromes (MDS), and infectious diseases. Although none of the non-FMF patients had exon 10 variants, some responded to colchicine treatment. Multiple correspondence analysis suggested that atypical symptoms such as stomatitis were associated with Behçet's disease and PFAPA syndrome, whereas characteristic situations such as disease onset ≥40 years were associated with MDS and infectious diseases. Careful follow-ups and reanalysis of the diagnosis should be performed for patients with atypical findings and no exon 10 variants, even if their symptoms meet the clinical criteria for FMF.

The Clinical Characteristics and Prognosis of Exon 2 Mutations in Familial Mediterranean Fever

Objective: It is unclear whether exon 2 mutations are variations or a mutations that causes the disease. This study aimed to evaluate the clinical features and prognosis exon 2 mutations in Familial Mediterranean Fever. Methods: The clinical features, disease severity and prognosis of all patients with at least one exon 2 mutations were evaluated retrospectively. These data were compared seperately for homozygous (Group 1), heterozygous (Group 2), compound heterozygous (Group 3), and complex alleles (Group 4), and the data were compared by grouping patients into those with and without exon 10 mutations. Results: There were a total of 119 patients with exon 2 mutations, including 11.7% in Group 1, 36.1% in Group 2, 21.8% in Group 3, and 30.2% in Group 4 were similar in terms of demographic data, clinical characteristics, and disease course. When compared patients with exon 10 mutations (+) to those with exon 10 mutations (-), the exon 10 mutations (+) group had a higher presence of chest pain (100%, p=0.02) and a significantly higher mean Pras severity score (6.66±1.87, 6.01±1.40; p=0.02). Additionally, a higher number of patients with exon 10 mutation (-) achieved remission with treatment (76 (67.9%), 36 (32.1%); p=0.03). Conclusion: Exon 2 mutations have a milder course and higher remission rates but they should be considered as Familial Mediterranean Fever disease because of their similar clinical presentation and response to colchicine treatment with exon 10 mutations. Early treatment and close follow-up should be performed.

Abstract P2038: Role Of The Microtubule Network In Right Ventricle Passive Viscoelasticity With Pulmonary Hypertension Development

Microtubule (MT) polymerization is a key contributor to myocardium viscoelasticity, which describes elastic and viscous resistance under stress and impacts the contractile function. MT de- or hyper-polymerization has been shown to decrease or increase healthy cardiomyocyte viscoelasticity, but the responses of hypertrophied cells to these modifications are unknown. Moreover, the ventricular free wall is a complex tissue composed of myofibers, collagen and vasculature, and it exhibits anisotropic mechanical behavior. To fully understand the role of MT in the tissue-level anisotropic viscoelasticity of myocardium, we investigated the responses of healthy and failing rat right ventricles (RV) to alterations in MT network. All procedures were approved by Colorado State University IACUC. Adult male rats were treated with monocrotaline to induce pulmonary hypertension and RV failure. After euthanasia, the RV free wall underwent equibiaxial stress relaxation in intact state (baseline) and under the treatment of colchicine and deuterium oxide (D 2 O) to remove and enhance MT network, respectively. Viscoelastic parameters were quantified as previously described. As expected, the diseased RV had greater viscoelasticity than the healthy RV. Depolymerization of MT in healthy RVs reduced tissue viscosity (relaxation rate) and elasticity (relaxation modulus), and the changes were more significant in the longitudinal (outflow tract) direction. MT hyper-polymerization increased tissue elasticity and decreased viscosity, with the changes stronger in the circumferential direction. In diseased RVs, MT depolymerization reduced viscosity in both directions and elasticity only in the circumferential direction. However, MT hyper-polymerization unexpectedly decreased tissue elasticity and tended to decrease viscosity, as well. The altered MT polymerization dynamics after D 2 O treatment in a fibrotic environment may explain these heterogeneous responses This is the first report of distinct impacts of MT polymerization on the tissue mechanical behavior between the hypertrophied and healthy myocardium. The exact molecular mechanisms involving MT polymerization dynamics and the interactions with collagen await further investigation.

Adult-onset chronic recurrent multifocal osteomyelitis: a case report.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease predominantly affecting the metaphyses of long bones and is usually seen in children. Although CRMO is generally a pediatric disease, it may also occur in adults. This may result in a delay in the diagnosis of adult-onset CRMO. This report presents an adult-onset female patient who presented with left leg pain followed by swelling in the right knee. The patient was initially started on colchicine treatment, but, due to unresponsiveness in the follow-up the patient, the treatment was switched to a combination of methotrexate and prednisolone. A satisfactory clinical recovery was achieved with these drugs. CRMO could be considered in the differential diagnosis of patients presenting with bone pain and joint complaints. Considering that the disease progresses with clinical flare-ups and remission periods, it should be kept in mind that patients should be followed closely and treatment can be changed.

Colchicine in patients with heart failure and preserved left ventricular ejection fraction: rationale and design of a prospective, randomised, open-label, crossover clinical trial

IntroductionSystemic low-grade inflammation is a fundamental pathophysiological mechanism of heart failure with preserved left ventricular ejection fraction (HFpEF). The efficacy of anti-inflammatory therapy in HFpEF is largely understudied. The aim...

ANMCO Position paper: Colchicine as a therapeutic agent in coronary syndromes

With the growing knowledge about the role of inflammatory processes in the pathogenesis of atherosclerotic lesions, inflammation has been identified as a cardiovascular risk factor and therapeutic target to reduce the residual risk in patients with atherosclerotic disease. Several therapeutic agents with anti-inflammatory action have been tested to evaluate their efficacy and safety in the context of atherosclerotic cardiovascular diseases. Among these, colchicine, a drug with multiple therapeutic effects including anti-inflammatory action, in randomized clinical trials conducted in the setting of atherosclerotic cardiovascular disease secondary prevention, significantly reduced the risk of adverse cardiovascular events.This position paper of the Italian Association of Hospital Cardiologists (ANMCO) summarizes the main biological mechanisms through which colchicine contributes to the inhibition of inflammatory processes that increase the atherosclerotic cardiovascular risk. Furthermore, the document reports the available evidence on clinical impact of colchicine treatment in the reduction of residual cardiovascular risk in chronic and acute coronary syndromes. Finally, practical information is provided regarding the use of this drug in this specific clinical setting, emphasizing precautions and possible side effects.

Resveratrol alleviates MSU-induced gouty arthritis in rats through inhibition of HIF-1α- and NLRP3-derived IL-1β secretion in macrophages.

Gouty arthritis is an acute and chronic joint inflammatory joint disease characterized by the deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. Resveratrol (3, 5, 4-trihydroxy-trans-stilbene, RV), a natural polyphenolic compound, has anti-inflammatory and antioxidant properties. The purpose of this study was to investigate the effect of resveratrol on rats with gouty arthritis and its molecular mechanism. THP-1-derived macrophages were induced by lipopolysaccharide (LPS) and MSU to create an in vitro gout cell inflammation model, and rats were injected with MSU crystals into the right ankle joint for an in vivo acute gouty arthritis model. We investigated the anti-inflammatory properties of resveratrol using these in vitro and in vitro models. Our findings suggested that resveratrol effectively reduced ankle swelling and synovial inflammation in a dose-dependent manner in rats with acute gouty arthritis, with almost the same effect as colchicine treatment. In MSU-treated THP-1-derived macrophages, resveratrol inhibited NLRP3 inflammasome activation and IL-1β secretion. Furthermore, resveratrol and the HIF-1α inhibitor PX478 both inhibited the expression of the NLRP3 inflammasome, IL-1β, and HIF-1α. This study demonstrated that resveratrol significantly improved the symptoms of acute gouty arthritis and its potential mechanism may be IL-1β reduction via HIF-1α modulation and inhibition of NLRP3 inflammasome activation. Our study might offer a novel sight for the treatment of gouty arthritis.

NLRP12-associated autoinflammatory disease: much more than the FCAS phenotype.

NLRP12-associated autoinflammatory disease (NLRP12-AID) is a rarely seen periodic fever syndrome also known as familial cold autoinflammatory syndrome-2 (FCAS2), caused by autosomal dominant inherited mutations in the NLRP12 gene. We aimed to present our clinical experience constituting one of the largest paediatric NLRP12-AID cohort. The patients with preliminary diagnosis of systemic autoinflammatory disease (SAID) other than familial Mediterranean fever (FMF) and PFAPA syndrome were evaluated with the next-generation-sequence (NGS) genetic-panel analysis between January-2016 and January-2022. Among children carrying NLRP12-variant, patients with recurrent episodes of autoinflammatory disease manifestations were diagnosed with NLRP12-AID. Demographic, clinical and laboratory data, treatments and outcomes of patients were presented. Seventeen patients were diagnosed with NLRP12-AID. The mean age at diagnosis was 114.7±69.5 months. The most frequently seen clinical manifestations were respectively; fever (100%), arthritis/arthralgia (58.8%), rash (52.9%), abdominal pain (52.9%), diarrhoea (41.2%), myalgia/fatigue (53.2%) and, conjunctivitis (11.7%). Clinical manifestations were triggered by cold exposure in three patients (17.6%). Seven patients had pathogenic, one had likely pathogenic, seven had VUS, and two had novel heterozygous variants. The most common defined variant in the NLRP12 gene was R352C. Complete response was achieved in 5 patients and partial response was in 6 with colchicine treatment. Attacks were prevented with anti-IL-1 treatments in 6 patients unresponsive to colchicine. In conclusion, the disease can cause effects on various tissues, especially the musculoskeletal and gastrointestinal systems, apart from FCAS symptoms. We think that a patient who can be defined as syndrome of undifferentiated recurrent fever should also be evaluated genetically in terms of NLRP12 previously.

Systemic inflammatory response in cardiac surgery: possibilities of using colchicine

To evaluate manifestations of systemic inflammatory response (SIR) and the effect of the colchicine therapy on SIR severity in patients with ischemic heart disease (IHD) after coronary artery bypass grafting (CABG) with extracorporeal circulation (EC). This study included 100 patients aged 62+6.3 years with stable IHD and multivessel coronary atherosclerosis scheduled for CABG with EC. Patients of group 1 (n=50) were administered with a single dose of colchicine (Colchicum-Dispert) 500 µg 4 hours before surgery followed by 500 µg twice a day for 10 days after surgery. Patients of group 2 (n=50) received a standard treatment, including nonsteroid anti-inflammatory drugs after surgery. Severity of the inflammatory response was evaluated by measuring blood cytokines. In the postoperative period, patient of group 1 showed a tendency toward a lower incidence of pleurisy and heart rhythm disorders in the form of paroxysmal atrial fibrillation (AF) (p=0.18). Levels of the anti-inflammatory cytokines, interleukin-10 (IL-10) and interleukin-6 (IL-6), were significantly increased in both groups at 6 hours after surgery (p<0.05); at the same time, in group 1, IL-10 remained increased also at 10 days after surgery (р=0.0002). No significant time-related changes in the proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), were observed. At 3 days post-CABG, there were significant increases in tissue inhibitors of matrix metalloprotease 1 (TIMP-1) (р<0.0001) and matrix metalloproteinase 9 (MMP-9) (р<0.001); at the same time, patients of group 1 had lower MMP-9 concentrations than patients of group 2 (p<0.05). At 10 days of postoperative period, these values were comparable with the background values. Increases in neopterin compared to preoperative values were found in both groups on days 3 and 10 after surgery (р <0.0001). CABG with EC is associated with the activation of SIR. The colchicine therapy at a dose of 500 µg 4 hours prior to surgery and 500 µg twice a day for 10 days after surgery reduces manifestations of SIR, which is clinically evident as a tendency to reduced incidence of pleurisy and arrhythmias, and does not result in the development of serious complications. The dynamics of matrix metalloproteinases indicates that the colchicine treatment is promising for decreasing the risk of CHF progression and myocardial remodeling in patients with IHD.

A meta-analysis evaluating efficacy and safety of colchicine for prevention of major cardiovascular events in patients with coronary artery disease.

Inflammatory plays a key role in the development of coronary artery disease (CAD). Colchicine as an anti-inflammatory treatment for CAD has attracted much attention, its efficacy and safety are controversial and deserved further exploration. To evaluate the efficacy and safety of colchicine for patients with CAD, relevant randomized controlled trials (RCTs) were identified by searching several databases including PubMed, Web of Science, and EMBASE from January 1992 to May 2022. Fourteen eligible trials of colchicine therapy include populations with chronic coronary syndrome (CCS) (N = 2), acute coronary syndrome (ACS) (N = 5), and percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) (N = 7), and involve a total of 13,235 patients which include 6654 subjects in colchicine group and 6581 subjects in the respective control arms. The outcome was reported as odds ratio (OR) and 95% confidence interval (CI), as the relative measure of association. Overall, the incidences of major adverse cardiovascular events (MACEs) (OR 0.65; 95% CI 0.54-0.77, p < 0.01), new ACS (OR 0.68; 95% CI 0.57-0.81, p < 0.01), coronary revascularization (OR 0.65; 95% CI 0.53-0.78, p < 0.01), and stroke (OR 0.51; 95% CI 0.32-0.82, p < 0.01), were lower in the colchicine group than in the placebo arm. We did not find a significant reduction in the incidence of atrial fibrillation (OR 0.84; 95% CI 0.68-1.04, p = 0.11), all-cause mortality (OR 1.06; 95% CI 0.83-1.35, p = 0.83), cardiovascular mortality (OR 0.77; 95% CI 0.52-1.15, p = 0.21). However, we found that colchicine did increase non-cardiovascular mortality (OR 1.44; 95% CI 1.04-2.01, p = 0.03). Although the incidence of gastrointestinal events in the colchicine treatment group was higher than that in the placebo arms (OR 2.08; 95% CI 1.39-3.12, p < 0.01), the symptoms disappeared rapidly after drug withdrawal and could be tolerated by most patients. Colchicine did not increase the incidence of infections (OR 1.42; 95% CI 0.82-2.46, p = 0.22), pneumonia (OR 1.55; 95% CI 0.58-4.18, p = 0.39), cancers (OR 0.98; 95% CI 0.79-1.22, p = 0.88), bleeding (OR 1.14; 95% CI 0.41-3.14, p = 0.80). Colchicine is an effective, relatively safe drug that could be considered for the treatment of CAD. However, we need to pay attention to the increasing occurrence of non-cardiovascular mortality and infection especially pneumonia possibly caused by colchicine. Efficacy and safety of colchicine for patients with CAD. CAD coronary artery disease; RCTs randomized controlled trials; OR odds ratio; MACEs major adverse cardiovascular events; ACS acute coronary syndrome; NNT number needed to treat; NNH number needed to harm.

Gut microbiota alterations are associated with phenotype and genotype in familial Mediterranean fever.

FMF is the most common monogenic autoinflammatory disease associated with MEFV mutations. Disease phenotype and response to treatment vary from one patient to another, despite similar genotype, suggesting the role of environmental factors. The objective of this study was to analyse the gut microbiota of a large cohort of FMF patients in relation to disease characteristics. The gut microbiotas of 119 FMF patients and 61 healthy controls were analysed using 16 s rRNA gene sequencing. Associations between bacterial taxa, clinical characteristics, and genotypes were evaluated using multivariable association with linear models (MaAslin2), adjusting on age, sex, genotype, presence of AA amyloidosis (n = 17), hepatopathy (n = 5), colchicine intake, colchicine resistance (n = 27), use of biotherapy (n = 10), CRP levels, and number of daily faeces. Bacterial network structures were also analysed. The gut microbiotas of FMF patients differ from those of controls in having increased pro-inflammatory bacteria, such as the Enterobacter, Klebsiella and Ruminococcus gnavus group. Disease characteristics and resistance to colchicine correlated with homozygous mutations and were associated with specific microbiota alteration. Colchicine treatment was associated with the expansion of anti-inflammatory taxa such as Faecalibacterium and Roseburia, while FMF severity was associated with expansion of the Ruminococcus gnavus group and Paracoccus. Colchicine-resistant patients exhibited an alteration of the bacterial network structure, with decreased intertaxa connectivity. The gut microbiota of FMF patients correlates with disease characteristics and severity, with an increase in pro-inflammatory taxa in the most severe patients. This suggests a specific role for the gut microbiota in shaping FMF outcomes and response to treatment.