Combination Of Hydroxychloroquine Research Articles

Inhibitory effect of hydroxychloroquine on glucocorticoid‐induced osteoporosis in lupus therapy

AbstractObjectivesSystemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease characterised by persistent inflammation. Hydroxychloroquine (HCQ) and glucocorticoids (GCs) are the primary agents commonly used in combination as the first‐line treatment for SLE. Nevertheless, the specific mechanisms responsible for the effectiveness of this combined therapy with HCQ and GCs have not been fully elucidated. This study aimed to reveal the mechanism behind combined HCQ and GC treatment in lupus.MethodsAn SLE IgG‐induced inflammation model was used to investigate the anti‐inflammatory effects of HCQ and dexamethasone (DXM). A glucocorticoid‐induced osteoporosis (GIOP) model was used to investigate the inhibitory effect of HCQ on osteoclastogenesis. Inflammation was assessed by haematoxylin and eosin staining. Bone metabolism was determined structurally via microcomputer tomography and in bone marrow‐derived osteoclast cultures.ResultsAn SLE IgG‐induced inflammation model demonstrated that HCQ could not ameliorate inflammation alone but could enhance the anti‐inflammatory effect of GCs by decreasing the expression of FcγRI on macrophages. HCQ inhibited osteoclastogenesis induced by GCs and RANKL by upregulating nuclear factor erythroid 2‐related factor 2 and limiting reactive oxygen species formation, which mitigated GC‐induced bone loss.ConclusionThe results indicate that HCQ improved the anti‐inflammatory effects of GCs and inhibits the osteoclastogenesis in experimental lupus. This study offers valuable insights into the mechanisms underlying the combined treatment of lupus with HCQ and GCs.

Efficacy and safety of methotrexate plus hydroxychloroquine combination therapy vs. methotrexate monotherapy in the treatment of rheumatoid arthritis: A randomized controlled clinical trial.

To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study. At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05). In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

The evaluation of the short-term and long-term hydroxychloroquine therapy on ECG parameters.

Amidst the COVID-19 pandemic, hydroxychloroquine (HCQ) was widely administered despite limited data on its safety and efficacy. This study assesses the acute and chronic impacts of HCQ on electrocardiography (ECG) parameters alongside the effects of azithromycin and levofloxacin coadministration in patients with COVID-19. A comprehensive analysis was conducted on 109 COVID-19 patients receiving HCQ, with or without Azithromycin and/or Levofloxacin, and 51 long-term HCQ-treated Sjogren's syndrome (SS) patients. ECG parameters, including QTc interval, were meticulously evaluated against a control group of 109 COVID-19 patients without HCQ treatment. HCQ monotherapy, in combination with Levofloxacin, significantly prolonged the QTc interval in COVID-19 patients compared to controls. Notably, the combination of HCQ and Azithromycin demonstrated a mitigated impact on QTc prolongation. Long-term HCQ use in SS patients did not significantly affect QTc intervals, illustrating a distinct safety profile from short-term use in COVID-19 treatment. HCQ's impact on QTc prolongation is influenced by therapeutic context, coadministered drugs, and patient demographics. The findings underscore the necessity of cautious HCQ use, particularly in acute settings like COVID-19, where monitoring and consideration of drug interactions and patient-specific factors are critical.

Effective Treatment of COVID-19 Infection with Repurposed Drugs: Case Reports.

The COVID-19 pandemic response has been hindered by the absence of an efficient antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The reason why the previous preventative approach to COVID-19 solely through vaccines has failed could be a lack of understanding of how quickly the SARS-CoV-2 virus evolves. Given the absence of specific treatments for the virus, efforts have been underway to explore treatment options. Drug repurposing involves identifying new therapeutic uses for approved drugs, proving to be a time-saving strategy with minimal risk of failure. In this study, we report the successful use of a multidrug approach in patients with COVID-19. Successful administration of multidrug therapy, such as combinations of hydroxychloroquine and azithromycin, doxycycline and ivermectin, or ivermectin, doxycycline, and azithromycin, has been reported. Multidrug therapy is effective because of the differing mechanisms of action of these drugs, and it may also mitigate the emergence of drug-resistant SARS-CoV-2 strains. The medicines were lopinavir/ritonavir (Kaletra), bamlanivimab (monoclonal antibody), glycopyrrolate-formoterol (Bevespi), ciclesonide (Alvesco), famotidine (Pepcid), and diphenhydramine (Benadryl).

Treatment of persistent focalized Q fever: time has come for an international randomized controlled trial.

Q fever is a worldwide zoonosis due to Coxiella burnetii, responsible for endocarditis and endovascular infections. Since the 1990s, the combination hydroxychloroquine + doxycycline has constituted the curative and prophylactic treatment in persistent focalized Q fever. This combination appears to have significantly reduced the treatment's duration (from 60 to 26 months), yet substantial evidence of effectiveness remains lacking. Data are mostly based on in vitro and observational studies. We conducted a literature review to assess the effectiveness of this therapy, along with potential alternatives. The proposed in vitro mechanism of action describes the inhibition of Coxiella replication by doxycycline through the restoration of its bactericidal activity (inhibited in acidic environment) by alkalinization of phagolysosome-like vacuoles with hydroxychloroquine. So far, the rarity and heterogeneous presentation of cases have made it challenging to design prospective studies with statistical power. The main studies supporting this treatment are retrospective cohorts, dating back to the 1990s-2000s. Retrospective studies from the large Dutch outbreak of Q fever (>4000 cases between 2007 and 2010) did not corroborate a clear benefit of this combination, notably in comparison with other regimens. Thus, there is still no consensus among the medical community on this issue. However insufficient the evidence, today the doxycycline + hydroxychloroquine combination remains the regimen with the largest clinical experience in the treatment of 'chronic' Q fever. Reinforcing the guidelines' level of evidence is critical. We herein propose the creation of an extensive international registry, followed by a prospective cohort or ideally a randomized controlled trial.

Acute Coxiella burnetii Infection: A 10-Year Clinical Experience at a Tertiary Care Center in the United States.

Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In this study, we share our decade-long clinical experience with acute Q fever, highlighting the challenges that clinicians encounter from making an initial diagnosis and performing risk stratification to determining the appropriate prophylaxis regimen and duration. We retrieved records of adult Mayo Clinic patients (≥18 years) with positive Coxiella burnetii serology results between 1 January 2012 and 31 March 2022. Patients with Q fever anti-phase II immunoglobulin G ≥1:256 by indirect immunofluorescence were further analyzed. Thirty-one patients were included. Their median age was 58 years (IQR, 50-64), and the majority were men (84%). Acute hepatitis (29%), flu-like illness (25.8%), and pneumonia (16%) were the most common presentations. Thirteen patients (42%) received antibiotic prophylaxis to prevent disease progression, with significant variation in the indications and duration across physicians. The combination of doxycycline and hydroxychloroquine was the preferred regimen. Prophylaxis was administered for a median 333 days (IQR, 168-414). Four patients (13%) progressed to Q fever native valve infective endocarditis, with elevated anticardiolipin immunoglobulin G levels being the sole risk factor in 2 cases. The small sample size precluded drawing conclusions on the impact of prophylaxis in preventing disease progression. Management of acute Q fever is complicated by the lack of comprehensive clinical guidelines leading to varied clinical practices. There is a critical need for randomized trials to establish robust evidence-based protocols for management.

Complex connective tissue convergence: A case report of scleroderma, systemic lupus erythematosus, and Sjögren's Syndrome overlap syndrome in an adolescent female

This case report illustrates the uncommon occurrence of an overlap syndrome involving systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Sjögren's syndrome in a 16-year-old female patient. Despite their distinct pathophysiological mechanisms and clinical manifestations, these connective tissue diseases converged in this patient, presenting a diagnostic challenge. The clinical presentation included features such as Raynaud's phenomenon, mouth and digit ulcers, alopecia, photosensitivity, and positive autoantibodies. Diagnostic workup revealed positive findings on antinuclear antibodies (ANA) and extractable nuclear antigen (ENA) panel, confirming the presence of autoantibodies associated with all three conditions. The patient was managed with a combination of symptomatic treatment, hydroxychloroquine, and prednisolone. This case underscores the complexity of overlapping autoimmune diseases and emphasizes the importance of a thorough clinical evaluation, appropriate diagnostic testing, and timely initiation of management to optimize patient outcomes.

Pharmacological Approaches in Rheumatoid Arthritis- An In-depth Analysis of Prescribed Medications

Inflammation, pain, swelling, and stability of the joints are some of the symptoms associated with rheumatoid arthritis (RA). A variety of treatment options are available to manage symptoms and slow the progression of RA, despite the fact that there is no cure. This cross-sectional study, which was conducted in a tertiary care hospital in Kerala, India, aimed to evaluate medication prescribing practices and therapeutic strategies in RA patients. The study included 280 RA patients and data on demographics, medications prescribed, dosage, and mode of administration were collected. The findings revealed that disease-modifying anti-rheumatic drugs (DMARDs) were the cornerstone of RA treatment, with hydroxychloroquine (HCQ), methotrexate (MTX), and sulfasalazine (SAAZ) being the most frequently prescribed DMARDs. Combination DMARD therapy, particularly the triple combination of HCQ + Folitrax + SAAZ, was prevalent among patients. Furthermore, the study highlighted the use of biologic DMARDs, such as rituximab and tofacitinib, albeit at a relatively lower rate due to the outpatient population’s milder disease severity. Supplement therapy, including vitamin D3 and folic acid, was commonly prescribed to address deficiencies and mitigate the side effects of medications like MTX. The prescription patterns also encompassed analgesics, anti-anxiety, and antidepressant medications to manage pain and psychological symptoms associated with RA. Steroids were administered initially to control inflammation, with a focus on minimizing long-term usage. The study underscores the complexity of RA management and the importance of individualized treatment approaches. It highlights the evolving landscape of RA therapeutics, emphasizing the need for clinicians to stay updated on emerging evidence and guidelines. Future research should focus on evaluating the long-term efficacy, safety, and cost-effectiveness of different treatment regimens to optimize patient outcomes in RA management.

Abstract C078: Inhibiting the autophagy-lysosomal pathway in pancreatic ductal adenocarcinoma using novel small molecules

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with a 5-year survival rate of 11.5% due to poor early detection and a lack of effective therapies. To meet the energetic demands, PDAC relies on autophagy to sustain growth and proliferation. Autophagy inhibitors such as hydroxychloroquine (HCQ) only showed limited autophagy inhibition in vivo and failed to provide clinical benefit to patients. However, studies have shown that the combination of HCQ and the MEK/ERK inhibitors can render better therapeutic results with stronger cytotoxicity. Our lab has designed and developed a class of small molecules (GN compounds) that target the autophagy-lysosomal pathway (ALP). Our GN compounds show autophagy inhibition and induction of extrinsic apoptosis markers by Western blot. Furthermore, GN64 affects the function of endosomes and lysosomes by immunofluorescence (IF). The combination treatment of GN79 and Binimetinib, a MEKi, inhibits the ALP and confers enhanced cytotoxicity in a panel of human PDAC cell lines. Future directions are aimed at determining the protein target and mechanism of GN compounds that leads to ALP inhibition. Completion of this project will advance the therapeutic development of novel ALP inhibitors and advance our understanding of the ALP with the possibility to imrpove the current therapeutic regimen for PDAC patients. Citation Format: Yangjingyi Ruan, Daniel W. Worroll, Grady Nelson, Yue-Ming Li. Inhibiting the autophagy-lysosomal pathway in pancreatic ductal adenocarcinoma using novel small molecules [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C078.

Inducing Melanoma Cell Apoptosis by ERp57/PDIA3 Antibody in the Presence of CPI-613 and Hydroxychloroquine.

The combination of the cancer mitochondrial metabolic inhibitor CPI-613 and hydroxychloroquine has tumor-suppressive effects on clear cell sarcoma, which shares pathobiological properties with melanoma. Therefore, we intended to examine the effects of a combination of CPI-613 and hydroxychloroquine on the growth of melanoma cells in the present study. However, cell death was not induced in melanoma cells. Therefore, a monoclonal antibody, ICT, that induced apoptosis in melanoma cells in combination with CPI-613 and hydroxychloroquine was developed. Immunoprecipitation, mass spectrometry, and small interfering RNA (siRNA)-mediated gene silencing demonstrated that ICT targeted Endoplasmic Reticulum Resident Protein 57/ Protein Disulfide Isomerase Family A Member 3 (ERp57/PDIA3), which was first identified as being upregulated by metabolic depletion stress and is localized on the cell surface during immunogenic cell death. The combination of CPI-613 and hydroxychloroquine enhanced the localization of ERp57/PDIA3 to the surface of melanoma cells. siRNA-mediated downregulation of ERp57/PDIA3 did not significantly induce ICT-mediated apoptosis in melanoma cells in the presence of CPI-613 and hydroxychloroquine. Therefore, the ICT antibody acts as a tumor suppressor in melanoma cells by targeting the cell membrane ERp57/PDIA3, expression of which was enhanced by the combination of CPI-613 and hydroxychloroquine.

Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review.

Hydroxychloroquine and Azithromycin combination was used rampantly in management of COVID-19 patients in different countries. Present review was conducted to evaluate the efficacy of Hydroxychloroquine and Azithromycin combination compared to the control (standard care) and any adverse effect following this combination use in COVID-19 patients if any. We included all the systematic review with or without meta-analysis reporting the effect of Hydroxychloroquine (HCQ) and Azithromycin (AZM) combination use in COVID-19 patient using three databases namely PubMed, medline, CINHAL, Web of Science from July 2020 till Jan 2022. The systematic search strategy has identified 104 studies in total, after removal of duplicates only 4 systematic reviews were included in the qualitative synthesis. The various tools for assessing and reporting the data in the reviews were PRISMA, ROBINS-I, Robs2, AMSTAR, MASTER checklists. Mortality among the hydroxychloroquine with azithromycin combination group was significantly higher than among the Standard Care group. The duration of hospital stay in days was shorter in the Standard Care group in comparison with the hydroxychloroquine group or the hydroxychloroquine and azithromycin combination group. Of the 4 systematic reviews included, 3 had low risk of bias and one had unclear risk of bias using the ROBIS tool. Chloroquine or Hydroxychloroquine combination did not shorten the duration of hospital stay. Rampant use of Chloroquine or Hydroxychloroquine alone or with Azithromycin combination caused adverse effects like QT prolongation. Finally, there is no evidence to support use of either Hydroxychloroquine with or without Azithromycin, for the treatment of COVID-19.

Clinical signs, symptoms, and severity of COVID-19 in patients with rheumatic diseases during the COVID-19 epidemic

Introduction: Recent studies have shown that patients with rheumatic diseases are more likely to experience severe cases of COVID-19. Additionally, certain anti-inflammatory medications have been linked to a reduction in the severity of COVID-19 symptoms. Objectives: This cross-sectional study aimed to determine the frequency of clinical signs, symptoms, and severity of COVID-19 in outpatients with rheumatic diseases. Patients and Methods: A total of 77 patients with rheumatic disorders who were diagnosed with COVID-19 and referred to Isfahan rheumatology clinics in 2020 were selected for this study. The study investigated their clinical signs, symptoms, severity of COVID-19, type of rheumatic disease, and the medications they were using. Furthermore, the study examined the relationship between the severity of COVID-19 and the type of rheumatic disease. Results: Among the 77 patients, 79.2% had rheumatoid arthritis (RA), 9.1% had systemic lupus erythematosus (SLE), 9.1% had Sjogren’s syndrome, and 2.6% had other rheumatic disorders. The severity of COVID-19 was classified as mild in 40.3% of cases, moderate in 44.2%, and severe in 15.6%. There was no statistically significant relationship between the type of rheumatic disease and the severity of COVID-19 (P=0.093). Conclusion: The findings suggest that patients with rheumatic diseases are more likely to experience severe cases of COVID-19. Conversely, the combination of hydroxychloroquine, sulfasalazine, and prednisolone has been associated with a lower prevalence of severe cases of COVID-19. In contrast, the administration of methotrexate and prednisolone has been linked to a higher prevalence of severe cases of COVID-19.

Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.

Metformin ameliorates valve interstitial cell calcification by promoting autophagic flux

Calcific aortic valve disease (CAVD) is the most common heart disease of the developed world. It has previously been established that metformin administration reduces arterial calcification via autophagy; however, whether metformin directly regulates CAVD has yet to be elucidated. In the present study we investigated whether metformin alleviates valvular calcification through the autophagy-mediated recycling of Runx2. Calcification was reduced in rat valve interstitial cells (RVICs) by metformin treatment (0.5–1.5 mM) (P < 0.01), with a marked decrease in Runx2 protein expression compared to control cells (P < 0.05). Additionally, upregulated expression of Atg3 and Atg7 (key proteins required for autophagosome formation), was observed following metformin treatment (1 mM). Blocking autophagic flux using Bafilomycin-A1 revealed colocalisation of Runx2 with LC3 puncta in metformin treated RVICs (P < 0.001). Comparable Runx2 accumulation was seen in LC3 positive autolysosomes present within cells that had been treated with both metformin and hydroxychloroquine in combination (P < 0.001). Mechanistic studies employing three-way co-immunoprecipitation with Runx2, p62 and LC3 suggested that Runx2 binds to LC3-II upon metformin treatment in VICs. Together these studies suggest that the utilisation of metformin may represent a novel strategy for the treatment of CAVD.

Impact of COVID-19 Medication (Favipiravir and Hydroxychloroquine) on High Frequency Hearing.

During the initial phase of the COVID-19 pandemic, there was ongoing investigation into potentially effective treatments. Antiviral medications such as Favipiravir and Hydroxychloroquine were employed to treat COVID-19 infections. However, limited studies have examined the adverse effects of these medications on hearing, particularly at extended high frequencies. This study included 10 subjects who had received medications like Azithromycin, a combination of Favipiravir and Hydroxychloroquine, and Hydroxychloroquine alone as part of their COVID-19 treatment. These subjects had previously undergone extended high-frequency audiometry testing (from 8 to 20kHz) as part of another project conducted by the same department before contracting COVID-19. Post-COVID-19 extended high-frequency audiometry was performed 1 month after the patients received a negative RT-PCR report. The results were then compared using a Paired t-test. A significant shift in the thresholds of high frequencies above 8-20kHz is found in subjects who had received Favipiravir and Hydroxychloroquine medications. We observed a significant impact of COVID-19 medications on high-frequency hearing, which tends to go unnoticed in regular pure-tone audiometry evaluations. Therefore, our study emphasizes the need for regular follow-ups, including detailed audiological assessments that incorporate extended high-frequency testing, at least once every 3 months for patients who have taken medications for COVID-19 treatment.

Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model.

Effective therapy for COVID-19 remains limited. Hydroxychloroquine (HCQ) has been considered, but safety and efficacy concerns remain. Chitosan exhibits antiviral and immunomodulatory effects, yet how the combination of HCQ and chitosan performs in treating COVID-19 is unknown. Male Syrian hamsters were inoculated intranasally with standardized stocks of the SARS-CoV-2 virus. Hamsters were allocated to saline (PBS), chitosan oligosaccharide (COS), HCQ, or COS+HCQ groups and received corresponding drugs. On days 1, 7, and 14 post-infection, two animals from each group were euthanized for sample collection. Viral loads were measured in lung homogenates. Biochemistry markers, cytokines, and immunoglobulins were analyzed from hamster sera. HCQ concentrations were compared between the blood, bronchoalveolar lavage, and lung tissues. All groups underwent histopathology exams of the lungs. Additional hamsters were treated with the same drugs to assess for toxicities to the heart and liver. Among all groups, viral loads in the COS+HCQ group were the lowest by day 8. The COS+HCQ group produced the highest interleukin (IL)-6 levels on day 4, and the highest IL-10, IgA and IgG levels on day 8. HCQ concentrations were higher in the COS+HCQ group's lungs than the HCQ group, despite having received half the dose of HCQ. Histopathology demonstrated earlier inflammation resolution and swifter viral clearance in the COS+HCQ group. There was no evidence of cardiac or hepatic injury in hamsters that received HCQ. In hamsters infected with the SARS-CoV-2 virus, the combination of intranasal COS and HCQ was associated with increased HCQ absorption in the lungs, more effective immune responses, without increasing the risk of hepatic or cardiac injuries.

Efficacy and safety of in-hospital treatment of Covid-19 infection with low-dose hydroxychloroquine and azithromycin in hospitalized patients: A retrospective controlled cohort study

ObjectivesIn this study we evaluate the efficacy and safety of a treatment protocol with standard dose of hydroxychloroquine plus azithromycin in patients hospitalized with COVID-19 infection. MethodsWe conducted a retrospective analysis to compare the 28-day mortality rate in 352 patients treated with hydroxychloroquine with or without azithromycin (HCQ-group) in our hospital with a contemporary control group of 3533 patients receiving standard of care from the Belgian Collaborative Group on COVID-19 Hospital Surveillance. ResultsAll patients who received at least one dose of treatment were included in the analysis. A statistically significant reduction in crude mortality rate at 28 days was observed in the HCQ-group compared to standard of care (16.8% vs 25.9%,p ​= ​0.001).Patients in the treatment group were on average younger (69,7 vs73,1 years, p ​= ​0,0002), were less likely to smoke or to have malignancy and more likely to be male. Patients in the treatment group were more likely to be obese, immunocompromised or to have arterial hypertension, liver disease and lung disease.After adjustment for these variables the OR for mortality was 0.635 (95%CI 0.464–0.875). Patients who did not receive HCQ had a 57% higher risk of mortality. A survival benefit in the treatment group was consistent across all age groups. 13 patients discontinued treatment due to side effects (4 with QTc-prolongation>60msec (1.1%) and 9 because of gastro-intestinal symptoms (2.55%)). No episodes of ventricular arrhythmia or torsade de pointes were recorded during treatment. ConclusionTreatment of COVID-19 using a combination of hydroxychloroquine plus azithromycin was safe and was associated with a statistically significant mortality benefit in the treatment of COVID-19 infection in hospitalized patients. Our findings do not support the current negative recommendations regarding this treatment.

Glucocorticoid Receptors and Disease Activity in Systemic Lupus Erythematosus Patients

Glucocorticoids (GC) have been widely used to treat patients with systemic lupus erythematosus (SLE). However, GC-insensitivity remains a major barrier in achieving remission. Therefore, understanding its mechanism is crucial to enhance the efficacy of GC treatment. Our study aimed to explore the association of the nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, which encodes GC receptors GRα and GRβ, the histone deacetylase2 (HDAC2), the histone acetyltransferase-1 (HAT1), and the interleukin- 23 receptor (IL-23R), with the response to treatment in SLE patients. Methods: Quantitative real-time PCR (qPCR) was used to determine the expression levels of NR3C1 isoforms, HDAC2, HAT1, and IL23R in peripheral blood mononuclear cells (PBMC) from 30 SLE patients and 6 healthy controls (HC). Immunohistochemical (IHC) staining was used to analyze the protein expression level of GRα in 19 SLE patients’ 8 controls renal biopsies. Results: GRα mRNA expression level was associated with SLE disease (p=0.018) and correlated with the SLEDAI score (p=0,038). HDAC2 was up-regulated in patients during remission phase compared to active phase (p=0.015). The IL23R mRNA expression was associated with anemia (p=0.037) and lymphopenia (p=0.028). It was up-regulated in treated patients with the combination of hydroxychloroquine, cyclophosphamide, and methylprednisolone (p=0,028) compared to other treatments. Tubular GRα expression showed a positive correlation with the chronicity index (rs=0.607, p=0.016). Conclusion: The GRα may be involved in the pathogenesis of SLE. It appears that HDAC2 contributes to the remission phase in SLE. IL23R expression could be affected by treatments in SLE patients.

Childhood-onset rheumatoid arthritis at a tertiary hospital in Senegal, West Africa

BackgroundChildhood-onset rheumatoid arthritis (CORA), known as rheumatoid factor (RF)-positive juvenile idiopathic arthritis is a type of juvenile idiopathic arthritis that shares the same genetic factors and clinical features as adult-onset rheumatoid arthritis. In Africa, CORA hasn’t been the subject of a specific study.ObjectivesThe aim of this study is to describe the clinical features, disease activity, functional disability, and treatment of CORA at diagnosis in Senegal and compare the findings to other CORA populations.MethodsWe conducted a mixed cohort study by reviewing the medical records of patients diagnosed with CORA with an age of symptom onset < 18 years according to the 2019 PRINTO provisional criteria for RF-positive JIA from January 2020 to December 2022 at rheumatology department of Aristide Le Dantec Hospital in Dakar, Senegal. We collected demographic, clinical, paraclinical and therapeutic data. Disease activity score was assessed by DAS28-ESR and DAS28-CRP. Functional disability was assessed using Health Assessment Questionnaire (HAQ) or Childhood HAQ.ResultsA total of 21 patients were included. Eighteen (85.7%) were Females. The mean age at symptom onset was 13.0 ± 3.0 years, and at diagnosis was 16.4 ± 4.2 years. Morning stiffness, joint swelling, and joint deformities were found in 20, 18 and 13 patients respectively. Four patients had a family history of rheumatoid arthritis. Five patients had extra-articular involvement such as rheumatoid nodules. Two patients had interstitial lung disease. The biological inflammatory syndrome was found in 90% of cases. 16 of 21 (76.2%) patients had positive RF, and 18 of 20 (90%) patients had positive Anti-CCP. Seven of 12 (58.3%) patients had positive anti-nuclear antibodies. The mean DAS28-ESR was 5.7 ± 1.0. Fifteen (71.4%) patients had high disease activity (DAS28-ESR > 5.1). The mean DAS28-CRP was 5.4 ± 1.1. The median HAQ was 2.12 with a mean HAQ of 1.9. Nineteen (90.5%) patients were treated with methotrexate, while 17 (81%) had a combination of methotrexate and hydroxychloroquine. Oral prednisone was used in 17 (81%) cases. Non-steroidal anti-inflammatory drugs were used in 4 cases (19%). After 6 months of treatment, mean DAS28-CRP was 2.9.ConclusionIn our study, CORA mainly affects 13-year-old girls, characterised by high disease activity with joint deformity and significant functional impairment. Treatment is mainly based on methotrexate, prednisone and hydroxychloroquine. Further studies are needed to determine the exact clinical phenotype of this disease.

Zinc's protective role against hydroxychloroquine-induced cardiac effects in adult male albino rats

BackgroundLong exposure to Hydroxychloroquine (HCQ) has been complicated by some dangerous though infrequent cardiotoxicity. MethodsA total of 40 normal adult male albino rats dispersed into 4 groups were used. Group 1 (Control group), Group II (HCQ treated group), Group III (zinc [Zn]-treated group), and Group IV (HCQ and Zn treated group). Once the experimentation ended, rats were sacrificed and cardiac soft tissue sections were processed twenty-four hours at the end of the experiment for histological study. ResultsCardiac-stained sections revealed that HCQ induced widespread necrosis, dilatation, and vacuolar degeneration. However, the combination of HCQ with Zn ameliorated these damaging effects. Cardiac enzyme parameters were also studied in the 4 groups and revealed CK-MB and troponin were considerably elevated in groups II associated to the control group. ConclusionIt was concluded that Zn revealed a protective role against HCQ cardiomyopathy in adult male albino rats. This might signify an appreciated means for Zn-based treatment in the upcoming subsequent clinical records to adjust doses and guarantee patient safeguard.