Rapid identification of inflammatory arthritis and associated adverse events following immune checkpoint therapy: a machine learning approach.

Introduction: Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) poses a major clinical challenge to ICI therapy for cancer, with 13% of cases halting ICI therapy and ICI-IA being difficult to identify for timely referral to a rheumatologist. The objective of this study was to rapidly identify ICI-IA patients in clinical data and assess associated immune-related adverse events (irAEs) and risk factors. Methods: We conducted a retrospective study of the electronic health records (EHRs) of 89 patients who developed ICI-IA out of 2451 cancer patients who received ICI therapy at Northwestern University between March 2011 to January 2021. Logistic regression and random forest machine learning models were trained on all EHR diagnoses, labs, medications, and procedures to identify ICI-IA patients and EHR codes indicating ICI-IA. Multivariate logistic regression was then used to test associations between ICI-IA and cancer type, ICI regimen, and comorbid irAEs. Results: Logistic regression and random forest models identified ICI-IA patients with accuracies of 0.79 and 0.80, respectively. Key EHR features from the random forest model included ICI-IA relevant features (joint pain, steroid prescription, rheumatoid factor tests) and features suggesting comorbid irAEs (thyroid function tests, pruritus, triamcinolone prescription). Compared to 871 adjudicated ICI patients who did not develop arthritis, ICI-IA patients had higher odds of developing cutaneous (odds ratio [OR]=2.66; 95% Confidence Interval [CI] 1.63-4.35), endocrine (OR=2.09; 95% CI 1.15-3.80), or gastrointestinal (OR=2.88; 95% CI 1.76-4.72) irAEs adjusting for demographics, cancer type, and ICI regimen. Melanoma (OR=1.99; 95% CI 1.08-3.65) and renal cell carcinoma (OR=2.03; 95% CI 1.06-3.84) patients were more likely to develop ICI-IA compared to lung cancer patients. Patients on nivolumab+ipilimumab were more likely to develop ICI-IA compared to patients on pembrolizumab (OR=1.86; 95% CI 1.01-3.43). Discussion: Our machine learning models rapidly identified patients with ICI-IA in EHR data and elucidated clinical features indicative of comorbid irAEs. Patients with ICI-IA were significantly more likely to also develop cutaneous, endocrine, and gastrointestinal irAEs during their clinical course compared to ICI therapy patients without ICI-IA.

Triterpenes G-A and G-E from Galphimia glauca with anti-inflammatory and anti-arthritic activity in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Galphimia glauca is a medicinal plant that treats inflammatory and anti-rheumatic problems. Its anti-inflammatory capacity has been reported pharmacologically, attributed to the triterpenes G-A and G-E. AIM: The objective of the present work was to measure the anti-inflammatory and immunomodulatory effect of the methanolic extract (GgMeOH) of Galphimia glauca and the isolated galphimines G-A and G-E, first in an acute test of plantar edema with carrageenan, and later in the model of experimental-induced arthritis with CFA. The effect was measured by quantifying joint inflammation, the concentration of pro- (TNF-α, IL-6, IL-17) and anti-inflammatory (IL-10, and IL-4) cytokines, and the ADA enzyme in joints, kidneys, and spleen from mice with experimental arthritis. METHOD: The extract and the active triterpenes were obtained according to established methods using different chromatographic techniques. Female ICR strain mice were subjected to intraplantar administration with carrageenan and treated with different doses of GgMeOH, G-A, and G-E; edema was monitored at different times. Subsequently, the concentration of TNF-a and IL-10 in the spleen and swollen paw was quantified. Meloxicam (MEL) was used as an anti-inflammatory control drug. The most effective doses of each treatment were analyzed using a complete Freunds adjuvant (CFA)-induced experimental arthritis model. Joint inflammation was followed throughout the experiment. Ultimately, the concentration of inflammation markers, oxidant stress, and ADA activity was quantified. In this experimental stage, methotrexate (MTX) was used as an antiarthritic drug. RESULTS: Treatments derived from G. glauca, GgMeOH (DE50 = 158 mg/kg), G-A (DE50 = 2 mg/kg), and G-E (DE50 = 1.5 mg/kg) caused an anti-inflammatory effect in the plantar edema test with carrageenan. In the CFA model, joint inflammation decreased with all natural treatments; GgMeOH and G-A inhibited the ADA enzyme in all organs analyzed (joints, serum, spleen, left and right kidneys), while G-E inhibited the enzyme in joints, serum, and left kidney. CFA caused an increase in the weight index of the organs, an effect that was counteracted by the administration of G. glauca treatments, which also modulate the response to the cytokines analyzed in the different organs (IL-4, IL-10, IL-17, IL-6, and TNF- α). CONCLUSION: It is shown, for the first time, that the GgMeOH extract and the triterpenes G-A and G-E of Galphimia glauca have an anti-arthritic effect (anti-inflammatory, immunomodulatory, antioxidant, and ADA inhibitor), using an experimental arthritis model with CFA. Therefore, knowledge of the plant as a possible therapeutic agent for this rheumatic condition is expanding.

Immune-mediated polyarthritis and anterior uveitis secondary to zonisamide administration in a dog with refractory epilepsy.

The objective of this article is to describe a case of suspected zonisamide-induced immune-mediated polyarthritis (IMPA) and anterior uveitis in a dog. A 7-year-old male neutered Siberian Husky with a history of refractory idiopathic epilepsy was presented for cluster seizures. Following the addition of zonisamide to the antiepileptic regime, the dog developed new IMPA and anterior uveitis. Within a few weeks of discontinuation of the zonisamide, the dog's IMPA and anterior uveitis resolved. These immune-mediated conditions were thus presumed to be an idiosyncratic reaction to zonisamide. To our knowledge, this is the first report of IMPA and anterior uveitis in dogs associated with zonisamide administration at its recommended dose.

Pragmatic targets for moderate/severe SLE and their implications for clinical care and trial design: sustained DORIS or LLDAS for at least 6 months is sufficient while their attainment for at least 24 months ensures high specificity for damage-free progression.

OBJECTIVES: Treatment targets in systemic lupus erythematosus (SLE) have been validated in unselected-in terms of severity-cohorts, which limits their generalisability. We assessed remission (Definition of Remission in SLE (DORIS)) and Lupus Low Disease Activity State (LLDAS) in a historical cohort of 348 patients with active moderate-to-severe disease and median follow-up of 5 years. METHODS: Active SLE was defined as Physician Global Assessment ≥1.5 and/or SLE Disease Activity Index 2000 ≥6, requiring therapy intensification. DORIS/LLDAS, organ damage, flares and adverse events were monitored. Shared frailty survival, generalised linear models and K-means clustering were applied. RESULTS: Sustained DORIS and LLDAS for ≥6 months occurred in 41.1% and 80.4%, respectively, and resulted in reduced damage accrual (HR: 0.58; 95% CI 0.36 to 0.93 and 0.61; 0.43 to 0.86) and severe flares (HR: 0.14; 0.08 to 0.27 and 0.19; 0.13 to 0.27). LLDAS without DORIS was also protective (HR: 0.65; 0.43 to 0.98 for damage, 0.49; 0.36 to 0.67 for flares). Models fitting increasing duration of targets showed that DORIS ≥50% and LLDAS ≥60% of time, or alternatively, ≥24 and ≥36 months, achieved optimal balance between feasibility (20.2-41.7%) and specificity (73.3-86.1%) for damage-free outcome. These targets were linked to reduced serious adverse events (risk ratio (RR): 0.56-0.71), hospitalisation (RR: 0.70) and mortality (RR: 0.06-0.13). Patients with predominant arthritis and mucocutaneous disease experienced reduced DORIS/LLDAS, compared with counterparts with major organ involvement. Conventional drugs were more frequently used in the former group, whereas potent immunosuppressive/biological agents in the latter. CONCLUSIONS: In moderate-to-severe SLE, sustained DORIS/LLDAS for at least 6 months is sufficient, while attainment for at least 24 months ensures higher specificity for damage-free progression, thus facilitating treat-to-target strategies and clinical trials. Arthritis and skin disease represent unmet therapeutic needs that could benefit from novel biologics.

Medication Adherence Support Applications for Chronic Arthritis Patients: Healthcare Providers' Perspective in Saudi Arabia.

Mobile health applications provide chronic disease patients with different capabilities and resources to support medication adherence. The study aims to understand the health care providers' (HCP) perceptions and recommendations about the design features and content of medication adherence support apps for individuals with chronic arthritis conditions in Saudi Arabia. Individual interviews were conducted with ten participants, such as rheumatologists, health educators, pharmacists, informaticians, and representatives from the Saudi Arthritis Association. The thematic analysis is utilised to code data and develop themes that help researchers in the design process. Four themes are identified: informational content, utilitarian, motivational, and socialisation features. The app content should improve arthritis patient awareness about medication management and adherence. Provide features that enable patients to set medication management and self-monitoring goals. The application design should be trustworthy, usable, enjoyable, and accessible for a diverse group of patients and respect patient privacy.

Steroid-dependent polyarthritis induced by immune checkpoint inhibitor therapy successfully treated with bimekizumab.

Immune checkpoint inhibitors (ICIs) are an integral part of modern-day cancer therapy. Along with a greatly improved antitumor response come a number of immune-related adverse events (irAEs), musculoskeletal irAEs rank among the less frequent manifestations. The mechanisms behind these events are poorly understood, and so far clear guidelines for therapeutic management beyond treatment with glucocorticosteroids are lacking. We present the case of a 72-year-old patient who developed a severe ICI-induced polyarthritis that could not be controlled by glucocorticosteroids. We initiated an immunomodulating therapy with the IL-17A/F/AF-inhibitor bimekizumab, which lead to a full clinical and sonographic remission.

In advanced stages, melanoma requires systemic therapy. Immune checkpoint inhibitors (ICIs) allow the body's own defense system to fight the cancer. They are an important part of this therapy. As a downside, they can cause immune-related side effects such as pain and inflammation in the joints. These are often chronic and have a great effect on the patient's quality of life. We therefore need long-term treatments that do not interfere with the intended antitumor response and allow the patients to live a nearly normal life. Corticosteroids often offer short-term relief. Patients whose symptoms cannot be steadily controlled by corticosteroids alone often need further medication. These substances aim to change the activity of the immune system. We present the case of a 72-year-old patient with a melanoma that had spread to other parts of the body. He suffered from great pain caused by inflammation of many of his joints. We could not control his symptoms using corticosteroids, so we decided to use the IL-17 blocker bimekizumab. This treatment is approved for psoriasis associated joint inflammation, inflammations of the spinal joints and psoriasis. This led to a rapid relief of joint pain and stiffness and allowed us to continue the melanoma therapy. The patient further continued to show a good antitumor response. As of this writing, the scans show no signs of cancer.

Emulgels: a promising topical drug delivery system for arthritis management and care.

BACKGROUND: Emulgels, hybrid formulations of emulsions and gels, offer distinct benefits viz. extended release, enhanced bioavailability, and targeted drug delivery to inflamed joints, thereby minimizing systemic side effects, and maximizing therapeutic efficacy in targeting the diseases. Oral medications and topical creams have limitations viz. limited permeation, efficacy, and side effects. Arthritis is a prevalent chronic inflammatory disorder affecting a substantial global population of about 350 million necessitating the exploration of innovative and effective treatment approaches. Inflammation of one or more joints in the body is referred to generally as arthritis, associated with joint discomfort, edema, stiffness, and decreased motion in the joints. MAIN PART: Emulgels further improve drug solubility and penetration into the affected tissues, augmenting the potential for disease-modifying effects. This review article comprehensively examines recent research for the potential of emulgels (micro- and nanoemulgels) as a potential therapeutic approach for arthritis management, thus showcasing their promising potential in precise treatment regimens. Despite the considerable progress in emulgel-based arthritis therapies, the review emphasizes the need for additional research and translation to clinical trials, thus ascertaining their long-term safety, efficacy, and cost-effectiveness compared to conventional treatments. CONCLUSION: With ongoing advancements in drug delivery, emulgels present an exciting frontier in arthritis-associated conditions, with the potential to revolutionize arthritis treatment and significantly enhance patient life's quality.

Management of Blau syndrome: review and proposal of a treatment algorithm.

Blau syndrome is a rare genetic granulomatosis affecting children. It could be responsible for vision-threatening complications and articular deformation. Due to the rarity of this disease, there are no standardized guidelines for its management. This work aimed to provide an updated overview of the different therapeutic options for Blau syndrome. We conducted research in the PubMed database for the different treatments used in Blau syndrome patients, and we proposed a therapeutic algorithm for disease management. High doses of corticosteroids are considered as a bridging therapy in Blau syndrome. Methotrexate should be initiated if the patient has articular or ocular involvement. An anti-tumor necrosis factor α should be added for patients with uveitis or residual arthritis. If the patient remains symptomatic, a switch to another anti-tumor necrosis factor α is the best option. In non-responders to the first- and second-line biotherapies, a switch to an anti-interleukin 1, an anti-interleukin 6, or tofacitinib is necessary. CONCLUSION: This article suggested an algorithm for the treatment of Blau syndrome. Other studies are necessary to confirm the efficacy of these treatments. WHAT IS KNOWN: • Blau syndrome is a rare but severe granulomatosis that could be responsible for vision-threatening complications and articular deformation. • Blau syndrome seems to be refractory to treatments. WHAT IS NEW: • High doses of corticosteroids are usually insufficient and should be considered only as a bridging therapy. • Blau syndrome could be considered as a poor factor for uveitis, thus, an anti-tumor necrosis factor α should be initiated for patients with uveitis or with residual arthritis.

Retention, safety and efficacy of off-label conventional treatments and biologics for chronic calcium pyrophosphate crystal inflammatory arthritis.

OBJECTIVES: Very little is known on the efficacy and safety of drugs for the management of chronic calcium pyrophosphate (CPP) crystal inflammatory arthritis. The objectives of this work were to describe the drugs used in the management of chronic CPP crystal inflammatory arthritis in expert European centres, and to examine treatment retention. METHODS: This was a retrospective cohort study. Charts from patients with a diagnosis of persistent inflammatory and/or recurrent acute CPP crystal arthritis were reviewed in seven European centres. Baseline characteristics were collected, and visits at months 3, 6, 12 and 24 included an assessment of treatment response and safety. RESULTS: One hundred and ninety-four treatments were initiated in 129 patients. Colchicine (used first-line in n = 73/86), methotrexate (used first-line in n = 14/36), anakinra (n = 27) and tocilizumab (n = 25) were the most prescribed treatments, while long-term corticosteroids, hydroxychloroquine, canakinumab and sarilumab were used occasionally. The 24-month on-drug retention was higher for tocilizumab (40%) than anakinra (18.5%) (P < 0.05), while the difference between colchicine (29.1%) and methotrexate (44.4%) was not statistically significant (P = 0.10). Adverse events led to 14.1% of colchicine discontinuations (100% of diarrhoea), 4.3% for methotrexate, 31.8% for anakinra and 20% for tocilizumab; all other discontinuations were related to insufficient response or losses to follow-up. Efficacy outcomes did not differ significantly between treatments throughout follow-up. CONCLUSION: Daily colchicine is the first-line therapy used in chronic CPP crystal inflammatory arthritis, which is considered efficient in a third to half of cases. Second-line treatments include methotrexate and tocilizumab, which have higher retention than anakinra.

A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis.

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (- 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.

Current knowledge of TNF-α monoclonal antibody infliximab in treating Kawasaki disease: a comprehensive review.

Kawasaki disease (KD), an autoinflammatory disease primarily affecting young children, characterized by consisting of acute systemic vasculitis and coronary artery involvement in severe cases. Intravenous immunoglobulin gamma (IVIG) combined with aspirin therapy is the first-line regimen for the prevention of coronary aneurysms in the acute phase of KD. The etiology and pathogenesis of KD are unclear, but its incidence is increasing gradually, especially in the cases of IVIG-naïve KD and refractory KD. Conventional therapies for refractory KD have unsatisfactory results. At present, infliximab (IFX), a human-murine chimeric monoclonal antibody that specifically blocks tumor necrosis factor-α (TNF-α), has made great progress in the treatment of KD. This review revealed that IFX infusion (5 mg/kg) could effectively modulate fever, reduce inflammation, improve arthritis, diminish the number of plasma exchange, decrease hospitalizations, and prevent the progression of coronary artery lesions. The adverse effects of IFX administration included skin rash, arthritis, respiratory disease, infusion reaction, hepatomegaly, and vaccination-associated complications. But the incidence of these adverse effects is low. The clear optimal application protocol of the application of IFX for either initial combination therapy or salvage therapy in KD is still under investigation. In addition, there are no effective biomarkers to predict IFX resistance. Further multicenter trials with large sample size and long-term follow-up are still needed to validate the clinical efficacy and safety of IFX for IVIG-resistant KD or refractory KD.

Three doses of COVID-19 mRNA vaccine induce class-switched antibody responses in inflammatory arthritis patients on immunomodulatory therapies.

Patients with inflammatory arthritis (IA) are at increased risk of severe COVID-19 due to medication-induced immunosuppression that impairs host defenses. The aim of this study was to assess antibody and B cell responses to COVID-19 mRNA vaccination in IA patients receiving immunomodulatory therapies. Adults with IA were enrolled through the Johns Hopkins Arthritis Center and compared with healthy controls (HC). Paired plasma and peripheral blood mononuclear cell (PBMC) samples were collected prior to and 30 days or 6 months following the first two doses of mRNA vaccines (D2; HC=77 and IA=31 patients), or 30 days following a third dose of mRNA vaccines (D3; HC=11 and IA=96 patients). Neutralizing antibody titers, total binding antibody titers, and B cell responses to vaccine and Omicron variants were analyzed. Anti-Spike (S) IgG and S-specific B cells developed appropriately in most IA patients following D3, with reduced responses to Omicron variants, and negligible effects of medication type or drug withholding. Neutralizing antibody responses were lower compared to healthy controls after both D2 and D3, with a small number of individuals demonstrating persistently undetectable neutralizing antibody levels. Most IA patients respond as well to mRNA COVID-19 vaccines as immunocompetent individuals by the third dose, with no evidence of improved responses following medication withholding. These data suggest that IA-associated immune impairment may not hinder immunity to COVID-19 mRNA vaccines in most individuals.

COVID-associated arthritis after severe and non-severe COVID-19: A systematic review.

AIM: Since the coronavirus outbreak became a global health emergency in 2020, various immune-based effects, such as inflammatory arthritis (IA), have been recorded. This study aimed to determine the role of COVID-19 severity on post-COVID arthritis. METHODS: We systematically reviewed 95 patients who developed arthritis after severe and non-severe COVID-19 infection by searching the databases, including PubMed, SCOPUS, and EMBASE. We used the term "COVID-associated arthritis" because there was no definite diagnostic method for classifying arthritides after COVID-19 infection, and the diagnosed arthritis types were based on the authors' viewpoints. RESULTS: After evaluating the data between the two severe and non-severe COVID-19-infected groups of patients, the results showed that the COVID-19 severity may affect the pattern of joint involvement in IA. In both groups, combination therapy, including oral nonsteroidal anti-inflammatory drugs with different types of corticosteroids, was the most common treatment. In addition, the mean age and comorbidities rate was higher in the severe COVID-19 group. Even though the patients in the severe COVID-19 group developed more serious COVID-19 symptoms, they experienced milder arthritis with better outcomes and more delayed onsets that required less aggressive therapy. CONCLUSION: We conclude that there may be an inverse relationship between COVID-19 severity and arthritis severity, possibly due to weaker immunity conditions following immunosuppressant treatments in patients with severe COVID-19.

Case Report: Methotrexate and hydroxychloroquine in combination for the treatment of NOD2-mutation-associated Blau syndrome.

Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)-a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the clinical triad of arthritis, granulomatous dermatitis, and recurrent uveitis. Here, we report a case of NOD2-mutation-associated early-onset sarcoidosis in which a combination of methotrexate and hydroxychloroquine was used to achieve improvement in arthritis, granulomatous dermatitis, and uveitis. A 13-month-old boy presented with a sudden-onset cutaneous eruption affecting the face, trunk, and extremities that initially mimicked papular atopic dermatitis but progressively worsened despite topical steroid therapy. The patient had no other known medical comorbidities or abnormalities except for heterochromia of the right eye. However, prior to presentation to dermatology, the patient began experiencing frequent falls, conjunctival injection, and apparent eye and joint pain. Skin biopsy from the right shoulder demonstrated rounded aggregates of epithelioid histiocytes and multinucleated giant cells without a significant lymphocytic component ("naked granulomas"), consistent with sarcoidal granulomatous dermatitis. Given the concern for Blau syndrome, the patient was sent for evaluation by ophthalmology and was found to have bilateral subconjunctival nodules. Our patient underwent genetic testing and was found to have a mutation in codon 1000 C > T (protein R334W) in the NOD2 gene. The patient responded to oral prednisolone 2 mg/kg/day for 8 weeks, but quickly relapsed, requiring a second 8-week course with taper upon starting methotrexate 7.5 mg subcutaneously weekly with 1 mg folic acid orally daily. After 8 weeks on methotrexate, due to persistent arthritis, conjunctival injection, and pruritus, and in consultation with rheumatology, the patient was started on hydroxychloroquine 75 mg orally daily along with continuation of 7.5 mg methotrexate subcutaneously weekly for 8 weeks, achieving significant reduction in arthritis, pruritus, and uveitis. After 8 weeks of this combination therapy, due to concerns of long-term macular toxicity, hydroxychloroquine was discontinued in favor of continuing methotrexate alone. The patient has remained free of significant side effects and stable with good disease control on 7.5 mg methotrexate weekly injected subcutaneously.

Therapeutic Importance and Pharmacological Activities of Norisoboldine in Medicine for the Treatment of Human Disorders.

BACKGROUND: Natural products constitute a unique source of chemical compounds with multi-target potential for the treatment of complex human disorders. Phytochemicals are pure phytoconstituents of plants, mainly responsible for their therapeutic potential and pharmacological activities. Natural products isolated from medicinal plants have been used as a lead source of drug. Norisoboldine is an important isoquinoline alkaloid found to be present in the dry root of Lindera aggregate. METHODS: In the present paper, scientific data of norisoboldine have been collected from Google, Google Scholar, PubMed, Science Direct and Scopus and analyzed in order to know the biological potential and therapeutic effectiveness of norisoboldine in medicine. Scientific data of medicinal importance and therapeutic potential of norisoboldine has been collected and analyzed in the present work. Moreover, all the collected scientific data have been separated into different sub-section i.e. Medicinal importance, pharmacological activities and analytical aspects. Detailed pharmacological activity data of norisoboldine have been analyzed in the present work to know the therapeutic effectiveness of norisoboldine in medicine. Analytical data of norisoboldine have also been collected and analyzed in the present work. RESULTS: Scientific data analysis revealed the biological importance of isoquinoline alkaloids in medicine. Isoquinoline alkaloids are pure, active phytochemical present in several natural edible products including vegetables, plants, and fruits. Norisoboldine has a biological effect on arthritis, colitis, apoptosis, osteoclast differentiation, inflammatory pain, renal ischemia-reperfusion injury, acute lung injury, pro-inflammatory cytokines, tumor, regulatory T cells, and endothelial cell migration. However nanoemulsifying drug delivery system of norisoboldine has also been prepared in order to get better therapeutic value. Further analytical parameters of norisoboldine were also discussed in the present work in order to get the scientific information of separation, isolation and identification parameter of norisoboldine. CONCLUSION: Present work revealed the therapeutic potential of norisoboldine in medicine.

A randomized interventional clinical trial assessing the safety and effectiveness of PeaNoc XL tablets in managing joint pain and inflammation in arthritis patients.

Background: Globally, alternative medicine is used widely by most patients for several health challenges. To evaluate the effectiveness and safety of PeaNoc XL Tablet in managing pain and inflammation, a randomized clinical trial and systematic study was designed. PeaNoc XL Tablet has been widely utilized for pain and inflammation management, but no previous studies have examined its efficacy and safety. The aim of this study was to determine the clinical effectiveness and safety profile of PeaNoc XL in patients with arthritis experiencing joint pain and inflammation. Methods: A randomized, controlled, and an open-label trial was conducted. A total of 155 patients (18 to 60 years) with arthritis were enrolled for participation. Using computer-generated random sequences, the study population was divided into two groups in a randomized manner. Group A received Standard therapy and Group B received Standard therapy with PeaNoc XL Tablet 400mg (two tablets OD after food). Results: Out of 155 patients, a total of 83 individuals were excluded from the study, leaving 72 patients who were randomly assigned to either Group A (n=36) or Group B (n=36). The administration of PeaNoc XL as an adjunct to standard therapy resulted in a significant reduction in levels of TNF-α (P<0.01), IL-1ß (P<0.001), IL-6 (P<0.01), and CRP (P<0.01) in arthritis patients experiencing joint pain and inflammation. Conversely, no notable differences were observed from the baseline in the standard therapy group. Conclusions: After 12 weeks of supplementation of PeaNoc XL tablets, as an add-on therapy helps in the reduction of pain score, joint stiffness, and physical stiffness. Trial registration:  CTRI/2022/10/046693.

Pancreatitis, panniculitis and polyarthritis (PPP) syndrome.

A young male presented with intermittent high-grade fever, asymmetric polyarthritis and erythematous, tender nodules over left shin for 2 months duration. He had a history of alcohol dependence with multiple episodes of acute pancreatitis. With polyarthritis progressing relentlessly, unresponsive to non-steroidal anti-inflammatory drugs and steroids, a provisional diagnosis of sarcoidosis was considered. Indeed, he was treated with azathioprine and rituximab with no effect. Biopsy of the skin nodule revealed subcutaneous fat necrosis, foam cells, deposition of eosinophilic amorphous material and calcification. Synovial fluid aspiration from the arthritic knee obtained purulent but surprisingly culture-negative material, rich in triglycerides. Abdominal CT confirmed chronic pancreatitis. Final diagnosis of pancreatitis, panniculitis and polyarthritis (PPP) syndrome was made. He underwent surgical pancreatic ductal drainage leading to complete remission of symptoms. PPP syndrome triad occurs due to leakage of pancreatic enzymes into systemic circulation and subsequent fat necrosis. Surgical drainage of pancreatic duct is often curative.