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.

A Unique Presentation of Bacterial Group G Streptococcus Myopericarditis.

Perimyocarditis and myopericarditis are inflammatory conditions of the pericardium and myocardium, often of idiopathic or infectious etiology, with viral infections being the most common. Nonrheumatic streptococcal myopericarditis (NSM) is a rare condition that can mimic acute myocardial infarction. This case report presents a 22-year-old male with no prior medical history who developed NSM following a streptococcal pharyngitis infection. The patient presented with pleuritic chest pain, tightness, and decreased exercise tolerance. Laboratory studies revealed elevated troponin levels and positive Streptococcus G antigen. Treatment included ampicillin-sulbactam, colchicine, ibuprofen, and dexamethasone. The patient's symptoms resolved, and he was discharged with amoxicillin-clavulanate, colchicine, and ibuprofen.

Neutrophil Activation and Adhesiveness in Coronary Artery Disease: Results From the COLCHICINE-PCI Biomarker Substudy.

Registration URL: https://clinicaltrials.gov. Unique identifier: NCT02594111.

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.

Diagnosis, Risk Stratification, and Treatment of Pericarditis: A Review.

Importance: Pericarditis accounts for up to 5% of emergency department visits for nonischemic chest pain in North America and Western Europe. With appropriate treatment, 70% to 85% of these patients have a benign course. In acute pericarditis, the development of constrictive pericarditis (<0.5%) and pericardial tamponade (<3%) can be life-threatening. Observations: Acute pericarditis is diagnosed with presence of 2 or more of the following: sharp, pleuritic chest pain that worsens when supine (≈90%); new widespread electrocardiographic ST-segment elevation and PR depression (≈25%-50%); a new or increased pericardial effusion that is most often small (≈60%); or a pericardial friction rub (<30%). In North America and Western Europe, the most common causes of acute pericarditis are idiopathic or viral, followed by pericarditis after cardiac procedures or operations. Tuberculosis is the most common cause in endemic areas and is treated with antituberculosis therapy, with corticosteroids considered for associated constrictive pericarditis. Treatment of acute idiopathic and pericarditis after cardiac procedures or operations involves use of high-dose nonsteroidal anti-inflammatory drugs (NSAIDs), with doses tapered once chest pain has resolved and C-reactive protein level has normalized, typically over several weeks. These patients should receive a 3-month course of colchicine to relieve symptoms and reduce the risk of recurrence (37.5% vs 16.7%; absolute risk reduction, 20.8%). With a first recurrence of pericarditis, colchicine should be continued for at least 6 months. Corticosteroids are often used if pericarditis does not improve with NSAIDs and colchicine. In certain patients with multiple recurrences, which can occur for several years, interleukin 1 (IL-1) blockers have demonstrated efficacy and may be preferred to corticosteroids. Conclusions: Acute pericarditis is a common cause of nonischemic chest pain. Tuberculosis is the leading cause of pericarditis in endemic areas and is treated with antitubercular therapy. In North America and Western Europe, pericarditis is typically idiopathic, develops after a viral infection, or develops following cardiac procedures or surgery. Treatment with NSAIDs and colchicine leads to a favorable prognosis in most patients, although 15% to 30% of patients develop recurrence. Patients with multiple recurrent pericarditis can have a disease duration of several years or more, are often treated with corticosteroids, and IL-1 blockers may be used for selected patients as steroid-sparing therapy.

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.

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.

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).

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.

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.

The Effect of Low-Dose Colchicine on the Phenotype and Function of Neutrophils and Monocytes in Patients with Chronic Coronary Artery Disease: A Double-Blind Randomized Placebo-Controlled Cross-Over Study.

Recent landmark trials showed that colchicine provides a substantial benefit in reducing major cardiovascular events in patients with coronary artery disease. Yet, its exact mechanism of action is still poorly understood. This study aimed to unravel the effect of colchicine on monocyte and neutrophil phenotype and function. A randomized double-blind placebo-controlled cross-over intervention study was executed in patients with a history of myocardial infarction. In neutrophils, colchicine treatment decreased CD62L expression and NGAL release upon ex vivo stimulation and increased PMA-induced ROS production. The effects of colchicine on monocytes were limited to a decrease in HLA-DR expression in the intermediate and nonclassical monocytes. Also, on the level of RNA expression, colchicine did not affect monocyte phenotype, while affecting various immunomodulating genes in neutrophils. Overall, our study suggests that treatment with colchicine affects neutrophil function, particularly by reducing neutrophil recruitment, lowering concentrations of NGAL, and changing the expression of various genes with immunomodulatory potential, whereas the effect on monocytes is limited.

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.

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.

Challenging chest pain: salmonella myopericarditis.

Salmonella infections have been associated with cardiovascular complications, including myocarditis and myopericarditis. This presentation of Salmonella myopericarditis highlights key clinical features to aid in diagnosis and the importance of prompt treatment with antibiotics, colchicine and non-steroidal anti-inflammatory drugs (NSAIDs).

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.

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.