Single-dose of integrated bilayer microneedles for enhanced hypertrophic scar therapy with rapid anti-inflammatory and sustained inhibition of myofibroblasts.

Hypertrophic scar (HS) tends to raised above skin level with high inflammatory microenvironment and excessive proliferation of myofibroblasts. The HS therapy remains challenging due to dense scar tissue which makes it hard to penetrate, and the side effects resulting from intralesional corticosteroid injection which is the mainstay treatment in clinic. Herein, bilayer microneedle patches combined with dexamethasone and colchicine (DC-MNs) with differential dual-release pattern is designed. Two drugs loaded in commercially available materials HA and PLGA, respectively. Specifically, after administration, outer layer rapidly releases the anti-inflammatory drug dexamethasone, which inhibits macrophage polarization to pro-inflammatory phenotype in scar tissue. Subsequently, inner layer degrades sustainedly, releasing antimicrotubular agent colchicine, which suppresses the overproliferation of myofibroblasts with extremely narrow therapeutic window, and inhibits the overexpression of collagen, as well as promotes the regular arrangement of collagen. Only applied once, DC-MNs directly delivered drugs to the scar tissue. Compared to traditional treatment regimen, DC-MNs significantly suppressed HS at lower dosage and frequency by differential dual-release design. Therefore, this study put forward the idea of integrated DC-MNs accompany the development of HS, providing a non-invasive, self-applicable, more efficient and secure strategy for treatment of HS.

Factors Associated With Successful Withdrawal of Biologic Agents in Children With Colchicine-Resistant Familial Mediterranean Fever.

BACKGROUND: Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease, and colchicine is the mainstay of treatment. Approximately 5%-10% of patients may respond inadequately to colchicine, and anti-interleukin-1 (anti-IL-1) agents are important treatment options in these patients. The aim of this study was to see whether there is any factor associated with the withdrawal of these anti-IL-1 agents and to investigate the characteristics of colchicine-resistant FMF patients who needed biological therapy. METHODS: Demographic, clinical characteristics, and disease severity of patients, at 2 referral centers, between 2012 and 2022, in whom anti-IL-1 treatment was continued and discontinued, were compared in this study. The international severity scoring system for FMF (ISSF) was used for disease severity assessment. RESULTS: In 64 colchicine-resistant FMF patients, the median (interquartile range) duration of biological treatment was 39 (45) months. Treatment of 26 patients (40.6%) was started with anakinra and 38 (59.4%) with canakinumab. During follow-up, anti-IL-1 treatment was discontinued in 23 patients (35.9%). High ISSF scores before biological treatment, presence of exertional leg pain, subclinical inflammation, and comorbidities were found to be statistically more frequent in the group whose biological therapy could not be discontinued ( p = 0.009, p = 0.006, p = 0.026, p = 0.001, respectively). CONCLUSIONS: Low ISSF scores before biological treatment with no accompanying exertional leg pain, subclinical inflammation, and comorbidities may be stated as an associated factors in terms of the discontinuation of biological agents in colchicine-resistant pediatric FMF patients.

Colchicine, Caffeine, Gramine, and Their Derivatives as Potential Herbicides, Fungicides, and Insecticides.

A preliminary in silico screening of 94 compounds, including colchicine, caffeine, gramine, and their derivatives, was conducted to identify potential herbicides, insecticides, and fungicides. Among the compounds tested, only gramine and its 13 derivatives exhibited potential activity. These compounds were further tested against eight species of insects, three species of weeds, and four species of fungi. All of the tested alkaloids were found to be ineffective as herbicides and insecticides, but they did exhibit some fungicidal activity. Four gramine derivatives showed some activity against Phytophthora infestans, Botrytis cinerea, Zymoseptoria tritici, and Fusarium culmorum.

Colchicine Prevents Cardiac Rupture in Mice with Myocardial Infarction by Inhibiting P53-Dependent Apoptosis.

Cardiac rupture is a fatal complication following myocardial infarction (MI) and there are currently no effective pharmacological strategies for preventing this condition. In this study, we investigated the effect of colchicine on post-infarct cardiac rupture in mice and its underlying mechanisms.We induced MI in mice by permanently ligating the left anterior descending artery. Oral colchicine or vehicle was administered at a dose of 0.1 mg/kg/day from day 1 to day 7 after MI. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with colchicine.Colchicine significantly improved the survival rate (colchicine, n = 46: 82.6% versus vehicle, n = 42: 61.9%, P < 0.05) at 1 week after MI. Histological analysis revealed colchicine significantly reduced the infarct size and the number of macrophages around the infarct area. Colchicine decreased apoptosis in the myocardium of the border zone and cultured cardiomyocytes and fibroblasts as assessed by TUNEL assay. Colchicine also attenuated the activation of p53 and decreased the expression of cleaved-caspase 3 and bax, as assessed by Western blotting.Colchicine prevents cardiac rupture via inhibition of apoptosis, which is attributable to the downregulation of p53 activity. Our findings suggest that colchicine may be a prospective preventive medicine for cardiac rupture, however, large clinical trials are required.

Differential diagnosis of pseudogout of the lumbar spine.

This case report details a rare instance of calcium pyrophosphate dihydrate crystal deposition disease (CPPD), commonly known as pseudogout, affecting the lumbar spine. A man in his mid-50s of age presented with severe low-back pain and fever, initially suspected as a spinal infection. Elevated erythrocyte sedimentation rate and leucocytosis were observed, while the initial imaging showed only lumbar spondylosis with arthritic changes in the right L4-L5 facet joint. However, an MRI revealed a cystic lesion at the right L5-S1 facet joint without signs of spondylodiscitis. Ultrasound-guided needle aspiration and synovial fluid analysis, including polarised light microscopy, identified calcium pyrophosphate crystals. Treatment with intravenous pain management was initially ineffective. Confirmation of CPPD led to successful treatment with oral colchicine, resulting in rapid pain alleviation and fever reduction. The patient reported significant improvement at a 2-week follow-up. This case emphasises the importance of thorough investigation in differentiating common symptoms and avoiding unnecessary treatments, highlighting the role of histological examination in diagnosing rare conditions like spinal CPPD.

Drug-Drug Interactions and the Clinical Tolerability of Colchicine Among Patients With COVID-19: A Secondary Analysis of the COLCORONA Randomized Clinical Trial.

Importance: Colchicine has many drug-drug interactions with commonly prescribed medications. Only pharmacokinetic studies have provided data on colchicine drug-drug interactions. Objective: To evaluate the clinical tolerability of colchicine according to the presence or absence of a drug-drug interaction. Design, Setting, and Participants: A secondary analysis of the COLCORONA trial was performed. The COLCORONA trial was a randomized, double-blind, placebo-controlled trial conducted in Brazil, Canada, Greece, South Africa, Spain, and the US between March 23, 2020, and January 20, 2021. The COLCORONA trial included ambulatory patients with COVID-19 with at least 1 high-risk characteristic and compared the effects of colchicine (0.5 mg twice daily for 3 days, then 0.5 mg daily thereafter) with placebo for 27 days. Data analysis was performed from February 24, 2023, to June 20, 2024. Exposure: In this secondary analysis, baseline medications that had interactions with colchicine were identified using a previously published expert classification. Main Outcomes and Measures: The primary outcome for this analysis was the composite of serious and nonserious treatment-related and treatment-unrelated gastrointestinal adverse events. The secondary outcomes were other adverse events and the composite of death or hospital admission due to COVID-19 infection. Logistic regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, heart failure, and myocardial infarction were assessed for effect modification of the association between the randomization arm and the outcomes of interest by drug-drug interaction status. Results: The cohort included 2205 participants in the colchicine arm and 2227 in the placebo arm (median age, 54 [IQR, 47-61] years; 2389 [54%] women). The most common colchicine drug-drug interactions were rosuvastatin (12%) and atorvastatin (10%). In fully adjusted models, the odds of any gastrointestinal adverse event were 1.80 (95% CI, 1.51-2.15) times higher in the colchicine arm than the placebo arm among people without a drug-drug interaction and 1.68 (95% CI, 1.24-2.26) times higher in the colchicine arm than the placebo arm among people with a drug-drug interaction (P = .69 for interaction). Drug-drug interaction status did not significantly modify the effect of colchicine on the composite of COVID-19 hospitalization or death (odds ratio, 0.91; 95% CI, 0.59-1.40 for drug-drug interaction and 0.84; 95% CI, 0.60-1.19 for no drug-drug interaction; P = .80 for interaction). Conclusions and Relevance: In this secondary analysis of the COLCORONA trial, operational classification of drug interactions system class 3 or 4 drug-drug interactions did not appear to significantly increase the risk of colchicine-related adverse effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04322682.

Erythema Nodosum Triggered by a Bite From a Copperhead Snake.

Erythema nodosum (EN) is a form of septal panniculitis that can occur secondary to multiple etiologies including inflammatory disorders, infections, or medications. We describe a 42-year-old woman who developed tender, erythematous, subcutaneous nodules persisting for 4 months following a copperhead snakebite. The diagnosis of EN was confirmed via histopathology, and the patient was treated with colchicine. Physicians should be aware of possible etiologies of EN to evaluate patients who present with new-onset tender subcutaneous nodules. Additionally, physicians should understand the various complications that can result from snakebites, with the potential for lingering cutaneous manifestations weeks to months following the initial bite.

Anti-inflammatory effect of colchicine on organ damage during the perioperative period of cardiac surgery: a study protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial.

INTRODUCTION: The systemic inflammatory response syndrome during the perioperative period of cardiac surgery can lead to serious postoperative complications and significantly increase the hospital mortality rate. Colchicine, a widely used traditional anti-inflammatory drug, has good clinical value in cardiovascular anti-inflammatory therapy. Our preliminary single-centre study had confirmed the protective value of colchicine in patients undergoing cardiac surgery with cardiopulmonary bypass. For this multicentre investigation, we aim to further validate the anti-inflammatory and organ-protective effects of low-dose colchicine during the perioperative period in a low-risk population. METHODS AND ANALYSIS: This study is a multicentre, randomised, double-blind, placebo-controlled clinical trial. A total of 768 patients undergoing elective cardiac surgery will be enrolled from eight heart centres in China. The participants will be randomly assigned to two groups: the colchicine group will receive low-dose colchicine (0.5 mg once-a-day dosing regimen (QD) orally for 3 days before the surgery and 0.5 mg dosing frequency of every other day (QOD) continuously for 10 days after the surgery), whereas the placebo group will be given starch tablets for the same time and dosage. Primary endpoints are the occurrence of postoperative inflammatory diseases, including postoperative atrial fibrillation, acute respiratory distress syndrome, preoperative myocardial injury and post-pericardiotomy syndrome. Secondary endpoints included laboratory tests on postoperative days 1, 3, 5, 7 and 10, intensive care unit data, APACHE II score, Murray lung injury score, medication-related gastrointestinal reactions, 30-day and 90-day all-cause mortality, surgical data, chest radiograph on postoperative days 1, 2 and 3, and chest CT within 14 days after surgery. ETHICS AND DISSEMINATION: This research has received approval from the Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (approval number 2023-366-01). The study findings will be made available by publishing them in an open access journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT06118034).

Clinical profiling, treatment characteristics and outcome in Behcet's Disease (BD)-A retrospective cohort study from Karnataka Rheumatology Association (KRA).

BACKGROUND: Behcet's disease (BD) has a heterogeneous and unpredictable phenotype that differs in various geographical areas. OBJECTIVE: To describe the clinical phenotype & outcome of Behcet's disease(BD) from Karnataka, India and compare them with large cohorts from endemic regions. METHODS: Databases of practising rheumatologists from Karnataka were reviewed to retrieve clinical characteristics, course of illness, prescribing information and outcome at last follow-up of patients clinically diagnosed as BD. The classification criteria, namely revised International criteria for Behcet's disease (rICBD) and International study group (ISG) criteria were applied. Outcome was defined as complete or partial remission, persistent disease or relapse. RESULTS: We included 72 patients, equal gender distribution and mean age 37.4 ± 12.8 years from 8 rheumatology centres. Commonest presentations were recurrent oral aphthosis 58(80.6%), genital ulcers 36(50%) and ocular manifestations 40(55.6%). Three-quarters [51/72(70.8%)] fulfilled rICBD criteria whereas only half [36/72(50%)] fulfilled ISG criteria. Apart from glucocorticoids [53/72(73.6%)], frequently prescribed therapies were colchicine 39(54.2%) and azathioprine 35(48.6%). Eleven-patients received biologics(anti-TNF-α) and JAK inhibitors to treat severe organ involvement. HLA-B*51 and pathergy tests were positive in 27/45(60%) and 12/34(35.3%) patients respectively. Outcomes were documented in 94.4%(68/72) patients at median follow-up of 24 (12;36) months. Majority [46/68(67.6%)] had complete remission, 17/68(25%) had partial remission, 4/68(5.9%) had persistent while 1/68(1.5%) had relapsing course. CONCLUSION: Majority of BD patients had orogenital aphthosis and ocular manifestations and an excellent response to treatment. Key Points • In our region, Behçet's Disease primarily manifests with recurrent oral aphthae and ocular involvement, with comparatively lower incidence of severe genital ulcers and neurological involvement than in endemic regions. • Apart from glucocorticoids, colchicine and azathioprine are the most commonly used agents. Biologics and JAK inhibitors are prescribed infrequently, primarily in cases of severe organ involvement. • A significant proportion of patients achieved either complete or partial remission during follow-up, with no observed mortality suggesting a milder disease course and better outcome compared to endemic regions. • Gender, HLA-B*51 status, and pathergy response did not exert any significant influence on the clinical profile or outcome in BD patients in Karnataka.

Efficacy of colchicine and melatonin in the treatment of rat endometriosis model: An animal study.

OBJECTIVE: This study investigates the therapeutic effects of colchicine and melatonin on endometriotic implants in an experimentally created endometriosis model in rats. STUDY DESIGN: Forty-four adult female Wistar albino rats weighing between 260 and 300 g, 8 weeks old, were selected for the study. The unilateral uterine horn of rats with a bicornuate uterus was excised for 1 cm, washed with sterile saline, incised longitudinally, and the endometrium was exposed. A 0.5*0.5 cm endometrial tissue sample taken with a scalpel was implanted with suturing (4/0 Vicryl) to the abdominal wall. Forty-four rats were divided into four groups. Group 1 was randomized as the endometriosis group (control), Group 2 as endometriosis + colchicine treatment, Group 3 as endometriosis + melatonin treatment, and Group 4 as the endometriosis + melatonin + colchicine treatment group. The colchicine (Sigma Chemical Co., St Louis, Missouri) group was administered orally at a dose of 0.1 mg/kg, and the Melatonin group orally at a dose of melatonin (20 mg/kg per day). Treatment continued daily for 30 days. RESULTS: In the post-treatment focal diameter measurements, the endometrial focal diameter in the colchicine and colchicine + melatonin group was significantly lower than the control group (p=0.026). Bcl-2 levels of the colchicine group were lower than the control group and the melatonin group (p=0.021). CONCLUSION: Colchicine and melatonin reduce adhesion to the peritoneal surface in ectopic endometrial cells. It also acts by increasing apoptosis and decreasing cell survival.

Adult-Onset PFAPA Syndrome: Successful Management with Colchicine.

BACKGROUND Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory fever syndrome primarily seen in children under age 5 years, and its etiology is unknown. Most cases are resolved by the age of 10 years, and it is rare in adults. PFAPA is characterized by recurrent episodes of fever associated with pharyngitis, stomatitis, and cervical adenitis, although not all clinical features are present at initial evaluation. Diagnosis is made clinically, as there are no specific biomarkers available. Treatment includes prednisone, colchicine, interleukin-1 blockers, and tonsillectomy. We report a case of adult-onset PFAPA syndrome that responded to colchicine. CASE REPORT A 22-year-old woman presented to the Rheumatology Clinic for evaluation of recurrent fevers associated with sore throat and enlarged painful cervical lymph nodes. She was symptom-free between the episodes. Workup for infectious causes and autoinflammatory/autoimmune diseases was unremarkable. Various differential diagnoses were considered, due to her unusual presentation. After all were ruled out, PFAPA was diagnosed based on her symptoms, and she started steroids, to which she had a dramatic response and resolution of symptoms. She was then transitioned to oral colchicine, which significantly decreased flare frequency. CONCLUSIONS Being aware of PFAPA syndrome in adults is vital. A timely diagnosis can significantly improve a patient's quality of life. This case highlights the importance of considering PFAPA syndrome in the differential diagnosis of periodic febrile illnesses in adults and the role of Colchicine as prophylaxis. Larger studies are needed to understand etiopathogenesis better and develop other effective therapeutics.

Effects of Colchicine on Major Adverse Limb and Cardiovascular Events in Patients With Peripheral Artery Disease.

OBJECTIVE: To assess the effects of colchicine, which has been shown to reduce the risks of coronary artery disease but scarcely studied in peripheral artery disease (PAD), on major adverse limb events (MALE) in patients with PAD. METHODS: This is a retrospective study based on a nationwide database. Patients who were diagnosed with PAD between 2010 and 2020 and prescribed with colchicine after the diagnosis of PAD were identified. Patients were then categorized into the colchicine or the control group according to drug use. Propensity score matching was performed to mitigate selection bias. Risks of MALE (including lower limb revascularization and nontraumatic amputation) and major adverse cardiovascular events were compared between the two groups. RESULTS: After patient selection and propensity score matching, there were 60,219 patients in both colchicine and control groups. After a mean follow-up of 4.5 years, the risk of MALE was significantly lower in the colchicine group compared with control (subdistribution HR, 0.75; 95% CI, 0.71 to 0.80), as were the incidence of both components of MALE, lower limb revascularization and major amputations. Colchicine treatment was also associated with lower risk of cardiovascular death. The lower risk of MALE observed with colchicine therapy was accentuated in the subgroup of patients receiving concomitant urate-lowering medications. CONCLUSION: In patients diagnosed with PAD, the use of colchicine is associated with lower risks of MALE and cardiovascular death. Anti-inflammatory therapy with colchicine may provide benefits in vascular beds beyond the coronary arteries.

[Challenges in diagnosing familial Mediterranean fever: exploring atypical clinical features. Clinical case].

This clinical case series presents descriptions of 3 patients with familial Mediterranean fever (FMF) who have atypical manifestations and abnormal inheritance mechanisms in terms of Gregor Mendel's laws. Although molecular genetic testing can help with disease diagnosis, it is not always conclusive. The primary need for genetic testing in atypical cases is to explain the mechanism of inflammation and to select the optimal therapy. These clinical observations demonstrate the changes in the spectrum of phenotypic manifestations of FMF in the context of the widespread introduction of molecular genetic methods.

Understanding lymphatic drug delivery through chylomicron blockade: A retrospective and prospective analysis.

Scientists have developed and employed various models to investigate intestinal lymphatic uptake. One approach involves using specific blocking agents to influence the chylomicron-mediated lymphatic absorption of drugs. Currently utilized models include pluronic L-81, puromycin, vinca alkaloids, colchicine, and cycloheximide. This review offers a thorough analysis of the diverse models utilized, evaluating existing reports while delineating the gaps in current research. It also explores pharmacokinetic related aspects of intestinal lymphatic uptake pathway and its blockage through the discussed models. Pluronic L-81 has a reversible effect, minimal toxicity, and unique mode of action. Yet, it lacks clinical reports on chylomicron pathway blockage, likely due to low concentrations used. Puromycin and vinca alkaloids, though documented for toxicity, lack information on their application in drug intestinal lymphatic uptake. Other vinca alkaloids show promise in affecting triglyceride profiles and represent possible agents to test as blockers. Colchicine and cycloheximide, widely used in pharmaceutical development, have demonstrated efficacy, with cycloheximide preferred for lower toxicity. However, further investigation into effective and toxic doses of colchicine in humans is needed to understand its clinical impact. The review additionally followed the complete journey of oral lymphatic targeting drugs from intake to excretion, provided a pharmacokinetic equation considering the intestinal lymphatic pathway for assessing bioavailability. Moreover, the possible application of urinary data as a non-invasive way to measure the uptake of drugs through intestinal lymphatics was illustrated, and the likelihood of drug interactions when specific blockers are employed in human subjects was underscored.

E148Q variant: a familial Mediterranean fever-causing mutation or a sequence variant?

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, linked to mutations in the MEFV gene. The p.E148Q variant, found on exon 2, has an uncertain role in FMF, with debates on whether it is a benign polymorphism or a pathogenic mutation. This study aimed to assess the clinical characteristics and severity of FMF in patients homozygous for the p.E148Q variant and to evaluate the impact of the p.V726A variant in these patients. This retrospective cohort study analyzed data from electronic medical records at Carmel Medical Center, Israel. Patients who underwent genetic testing for FMF from November 2004 to December 2019 and had p.E148Q/p.E148Q or p.E148Q/p.E148Q + p.V726A variants were included. Disease severity was assessed using the Tel Hashomer Key to Severity Score. Statistical analyses compared clinical characteristics and severity between genotype groups. The study included 61 FMF patients, with 24 (39%) having p.E148Q/p.E148Q and 37 (61%) having p.E148Q/p.E148Q + p.V726A variants. The majority (72%) were Druze. Most patients (65.5%) exhibited mild disease, while 31.1% had moderate disease, with no cases of severe disease. Colchicine treatment significantly reduced CRP levels in all patients. CONCLUSION: These findings suggest that the p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity, supporting its pathogenic role in particular ethnicity. These results contribute to understanding the clinical significance of the p.E148Q variant and considering the patient's need for Colchicine treatment. WHAT IS KNOWN: • The role of the p.E148Q variant in FMF is debated, with questions about whether it is a benign polymorphism or a pathogenic mutation. • The prevalence of MEFV variants can vary significantly among different ethnic groups. WHAT IS NEW: • The p.E148Q variant has clinical significance in particular ethnicities, as supported by a significant reduction in CRP levels following colchicine treatment. • The p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity.

Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial.

BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] µm versus 87.2 [95% CI, 69.9 to 104.5] µm; difference, 34.2 [95% CI, 9.7 to 58.6] µm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857.

Clinical Associations of E148Q Heterozygosity: What to Expect From E148Q?

OBJECTIVE: The exact effects of MEFV variants on inflammation are still under investigation, and reports on variants of unknown significance, particularly the E148Q variant, have been conflicting. Therefore, this study aims to investigate patients exhibiting E148Q heterozygosity, focusing on diagnoses and disease courses to assist physicians in interpreting the variant. METHODS: Data of pediatric patients presenting to the Pediatric Rheumatology clinic between November 2016 and September 2023, exhibiting only E148Q heterozygosity in MEFV gene analysis, were extracted. Patients who were lost before 9 months of follow-up have been excluded to ensure the completion of initial diagnostic tests and evaluations. RESULTS: Among the 119 patients with E148Q variant, the diagnoses were as follows: healthy, 51.3%; IgA vasculitis, 10.1%; Familial Mediterranean Fever (FMF), 7.6%; Periodic fever, Aphtous stomatitis, Pharyngitis, Adenitis (PFAPA), 6.7%; and other diagnoses, 19.3%. IgA vasculitis patients experienced articular, gastrointestinal, and renal involvement at rates of 91.7%, 58.3%, and 16.7%, respectively. Complete response, partial response, and no response to colchicine were 37.5%, 12.5%, and 50%, respectively, in PFAPA patients. All FMF patients responded to colchicine treatment resulting in reduced mean FMF episode counts in 6 months from 3.22 ± 0.92 to 0.56 ± 0.52. CONCLUSIONS: The E148Q variant may amplify inflammation and modify disease courses. Patients with the E148Q variant experiencing typical FMF episodes should receive colchicine, but clinicians should exercise caution regarding alternative diagnoses. Additionally, the E148Q variant may increase acute phase reactants and disease severity in IgA vasculitis. However, to reach definitive conclusions on its treatment-modifying role in PFAPA, universal diagnosis and treatment response criteria should be adopted.

Recurrent pericarditis and interleukin (IL)-1 inhibitors.

Recurrent pericarditis (RP) is defined by the European Society of Cardiology (ESC) as an instance of acute pericarditis (AP) that occurs at least 4-6 weeks after the resolution of a previous episode of the same ailment. To mitigate the risk of RP, it is advised to administer accurate and prolonged pharmacological treatment for both the initial AP and subsequent RP. ESC guidelines recommend commencing treatment for any single episode of AP, including those that contribute to RP, with non-steroidal anti-inflammatory drugs (NSAIDs) in conjunction with colchicine for several months, often followed by gradual tapering. If there is an inadequate response, corticosteroids (CS) may be introduced cautiously. However, in a minority of cases, even when NSAIDs, colchicine, and CS are administered together at the highest recommended dosages, they may prove ineffective. In such instances, treatment with immunosuppressive drugs or biologics is advised. Among biologics, interleukin (IL)-1 inhibitors have been extensively studied, although certain gaps remain. This narrative review delves into the rationale for employing IL-1 inhibitors and presents findings from existing studies regarding their efficacy, tolerability, and safety. Analysis of the literature indicates that there is currently insufficient data to ascertain the true therapeutic role of IL-1 inhibitors in managing and preventing RP. However, theoretically, drugs targeting both IL-1α and IL-1ß may offer superior efficacy compared to those solely targeting IL-1ß due to the significant involvement of both cytokines in inflammation. Further research is warranted to determine the comparative effectiveness of IL-1α and IL-1ß inhibitors.