Multidrug Therapy Research Articles

Fuyuan decoction prevents nasopharyngeal carcinoma metastasis by inhibiting circulating tumor cells/ endothelial cells interplay and enhancing anti-cancer immune response.

Distant metastasis is a major cause of treatment failure in cancer patients and a key challenge to improving cancer care today. We hypothesized that enhancing anti-cancer immune response and inhibiting circulating tumor cells (CTCs) adhesion and transendothelial migration through synergistic multi-target approaches may effectively prevent cancer metastasis. "Fuyuan Decoction" (FYD) is a traditional Chinese medicine compound that is widely used to prevent postoperative metastasis in cancer patients, but its underlying mechanism remains unclear. In this work, we systematically elucidated the underlying molecular mechanism by which FYD prevents cancer metastasis through multi-compound and multi-target synergies in vitro and in vivo. FYD significantly prevented cancer metastasis at non-cytotoxic concentrations by suppressing the adhesion of CTCs to endothelial cells and their subsequent transendothelial migration, as well as enhancing anti-cancer immune response. Mechanistically, FYD interrupts adhesion of CTCs to vascular endothelium by inhibiting TNF-α-induced CAMs expression via regulation of the NF-κB signaling pathway in endothelial cells. FYD inhibits invasion and migration of CTCs by suppressing EMT, PI3K/AKT and FAK signaling pathways. Moreover, FYD enhances the anti-cancer immune response by significantly increasing the population of Tc and NK cells in the peripheral immune system. In addition, the chemical composition of FYD was determined by UPLC-HRMS, and the results indicated that multiple compounds in FYD prevents cancer metastasis through multi-target synergistic treatment. This study provides a modern medical basis for the application of FYD in the prevention of cancer metastasis, and suggesting that multi-drug and multi-target synergistic therapy may be one of the most effective ways to prevent cancer metastasis.

Nucleus-targeting DNase I self-assembly delivery system guided by pirarubicin for programmed multi-drugs release and combined anticancer therapy

The cell nucleus serves as the pivotal command center of living cells, and delivering therapeutic agents directly into the nucleus can result in highly efficient anti-tumor eradication of cancer cells. However, nucleus-targeting drug delivery is very difficult due to the presence of numerous biological barriers. Here, three antitumor drugs (DNase I, ICG: indocyanine green, and THP: pirarubicin) were sequentially triggered protein self-assembly to produce a nucleus-targeting and programmed responsive multi-drugs delivery system (DIT). DIT consisted of uniform spherical particles with a size of 282 ± 7.7 nm. The acidic microenvironment of tumors and near-infrared light could successively trigger DIT for the programmed release of three drugs, enabling targeted delivery to the tumor. THP served as a nucleus-guiding molecule and a chemotherapy drug. Through THP-guided DIT, DNase I was successfully delivered to the nucleus of tumor cells and killed them by degrading their DNA. Tumor acidic microenvironment had the ability to induce DIT, leading to the aggregation of sufficient ICG in the tumor tissues. This provided an opportunity for the photothermal therapy of ICG. Hence, three drugs were cleverly combined using a simple method to achieve multi-drugs targeted delivery and highly effective combined anticancer therapy.

Mixture of Doxycycline, ML-7 and L-NAME Restores the Pro- and Antioxidant Balance during Myocardial Infarction-In Vivo Pig Model Study.

The restoration of blood flow to the ischemic myocardium inflicts ischemia/reperfusion (I/R) heart injury (IRI). The main contributors to IRI are increased oxidative stress and subsequent excessive production of ROS, increased expression of NOS and peroxinitate, activation of MMPs, and enhanced posttranslational modifications of contractile proteins, which make them more susceptible to proteolytic degradation. Since the pathophysiology of IRI is a complex issue, and thus, various therapeutic strategies are required to prevent or reduce IRI and microvascular dysfunction, in the current study we proposed an innovative multi-drug therapy using low concentrations of drugs applied intracoronary to reach microvessels in order to stabilize the pro- and antioxidant balance during a MI in an in vivo pig model. The ability of a mixture of doxycycline (1 μM), ML-7 (0.5 μM), and L-NAME (2 μM) to modulate the pro- and antioxidative balance was tested in the left ventricle tissue and blood samples. Data showed that infusion of a MIX reduced the total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA). It also increased the total antioxidant capacity, confirming its antioxidative properties. MIX administration also reduced the activity of MMP-2 and MMP-9, and then decreased the release of MLC1 and BNP-26 into plasma. This study demonstrated that intracoronary administration of low concentrations of doxycycline in combination with ML-7 and L-NAME is incredibly efficient in regulating pro- and antioxidant balance during MI.

IJCM_276A: Determinants of Delayed Sputum Conversion among Tuberculosis Patients in Malappuram District: A Case Control Study

Background: Treatment of drug-sensitive TB consists of an intensive phase of 2 months followed by a continuation phase of 4 months. After completion of intensive phase of therapy, sputum AFB smear microscopy is repeated and presence of smear conversion is suggested as a significant early predictor of treatment effectiveness. Delay in sputum conversion will lead to prolongation of the period of time that patients remain contagious. Objectives: To study the determinants of delayed sputum conversion among Tuberculosis patients in Malappuram district Methodology: A Case control study was conducted among tuberculosis patients residing in Malappuram district of Kerala and registered under NTEP in District Tuberculosis Centre (DTC), Manjeri, Malappuram. After satisfying inclusion and exclusion criteria, 90 tuberculosis patients who failed to achieve sputum smear negativity after completion of 2 months of intensive phase multi drug therapy were taken as cases. Another 90 tuberculosis patients those who achieved sputum smear negativity after completion of 2 months of intensive phase therapy were selected as control group. Data was collected by interview method. Results: Patients with lower socio-economic status (OR = 3.59, 95% CI 1.92- 6.73), low BMI or underweight (OR = 1.98, 95% CI 1.1 - 3.6), multiple symptoms (OR= 5.50, 95% CI 1.98 - 15.28), increased duration of symptoms (OR=4.54, 95% 2.24-9.19), co-morbid condition of diabetes mellitus (OR = 2.25, 95% CI 1.24 - 4.09) are at statistically significant risk of delay in sputum smear conversion after intensive phase of anti-tubercular therapy. Conclusion: Patients with lower socio-economic status, low BMI or underweight, multiple symptoms, increased duration of symptoms, co-morbid condition of diabetes mellitus are at statistically significant risk of delay in sputum smear conversion after intensive phase of anti-tubercular therapy. Treating physicians and public health experts should give special attention to TB patients with these risk factors.

Zero Leprosy Strategic Plans: Global and National Level: A Short Communication

Since the launch of multidrug therapy in 1982, the global leprosy situation has undergone significant changes, with the prevalence falling from over 5 million cases in the mid-1980s to <200,000 by the end of 2016. In India, the program reduced the prevalence rate from 57.8/10,000 in 1983 to <1/10,000 by the end of 2005, marking the achievement of the World Health Organizations (WHOs) target of eliminating leprosy as a public health issue. The WHO has recently introduced a new global leprosy plan called “Towards Zero Leprosy” as part of the disease-specific strategies outlined in the WHO's roadmap for neglected tropical diseases (NTDs) 2021–2030. This strategy aims to achieve interruption of leprosy transmission by 2030 and provides a framework for direction, objectives, challenges, and strategic pillars at a global level. In India, a committee of over 80 experts in the field of leprosy developed the National Strategic Plan and Roadmap for Leprosy 2023–2027, which was published on January 30, 2023. This policy is aligned with the WHO's NTDs roadmap 2021–2030 and the Global Leprosy Strategy 2021–2030, both of which aim to interrupt leprosy transmission by 2030. In this article, we have discussed the strategic plans of both the National leprosy eradication programme (NLEP) and the WHO.

Coinfection with Leprosy and Tuberculosis: A Case Series in Malagasy Patients.

Leprosy and tuberculosis are two of the oldest and most common mycobacterial infections, caused by Mycobacterium leprae and Mycobacteium lepramatosis for leprosy and Mycobacterium tuberculosis for tuberculosis. Dual infections have been known since ancient times; however, cases remain rarely reported in the literature, even in countries where both diseases are endemic, such as Madagascar. We report a case series of simultaneous occurrence of leprosy and tuberculosis. In this retrospective study, we reviewed the medical records of patients with leprosy registered at the Department of Dermatology, University Hospital Befelatanana, Antananarivo, Madagascar, between January 2012 and June 2021. Patients with leprosy and diagnosed as coinfected by tuberculosis were included in the study. Of the 120 leprosy cases observed during the study period, coinfection with leprosy and tuberculosis was found in five patients. The mean age was 43.4 (SD 13.2) ranging, 21-59 years. Male gender was predominant (4/5). Four patients presented with lepromatous leprosy, and one with borderline lepromatous leprosy. Three patients experienced leprosy reaction. Four cases of pulmonary tuberculosis and one case of multifocal tuberculosis were observed. The diagnosis of leprosy preceded tuberculosis in four cases, and a coinfection diagnosis was made simultaneously in one case. The average time to develop tuberculosis was 38.8 (SD 10.2) months. HIV infection, malnutrition, alcohol consumption, and long-term corticosteroid therapy were the immunosuppressive factors reported in our patients. Three patients received concomitant multidrug therapy for leprosy and tuberculosis. Dermatologists should be aware of the importance of screening patients affected by leprosy for latent or active tuberculosis to prevent morbidity and mortality due to coinfection and to reduce the risk of acquired resistance to rifampicin, which is the greatest risk of this association.

Joint-related manifestations of leprosy: A case report

Leprosy is a chronic granulomatous disease in which the musculoskeletal system has been described as the third most commonly affected system. Leprosy infections may manifest with various autoimmune phenomena reminiscent of classic autoimmune diseases. Among the leprosy factors affecting the prognosis of the disease, early diagnosis was reported to be the most effective. A 46-year-old married woman was referred to the hospital with initial articular symptoms. The patient also had deep folds, increased thickness of the skin in the forehead area, and dryness of the skin with a progressive course. The finger deformities and swelling are certainly misleading, but they may constitute an unsuspected inaugural form of leprosy, especially in its lepromatous form. The skin smear and biopsy confirmed leprosy, and treatment consisting of multi-drug therapy, as suggested by the WHO, was prescribed for the patient. According to these findings, it seems that one of the major symptoms of leprosy is musculoskeletal involvement and rheumatological manifestations, which may obscure and mislead diagnostic and treatment plans.

Leprosy- Atypical Presentation with Reaction

Leprosy is a chronic granulomatous disease affecting mainly the skin and nerves caused by the obligate intracellular pathogen Mycobacterium leprae. Patient not always present with typical skin lesion with loss of sensation or muscle weakness rather may present with atypical skin lesion with swelling of the affected area like cellulites or lymphangitis as reactional state. A 25- years-old male patient presented with linear erythematous verrucous plaque along with multiple nodules and pain and swelling of left upper extremity. Local examination revealed sensory loss on inner aspect of left hand and finger and ulner nerve found enlarged, thickened and tender. Slit skin smear showed numerous lepra bacilli. Skin biopsy for histopathology showed collection of foamy histocytes forming granuloma within the upper dermis and wade fite staining, moderate number of lepra bacilli was seen. Patient was diagnosed as a case of borderline leprosy with type 1 lepra reaction. Patient was getting treatment with MDT (multi drug therapy) and systemic steroid and responded very well. His skin lesions are almost subsided and weakness of hand was recovering gradually. JAFMC Bangladesh. Vol 19, No 1 (June) 2023: 76-79

The potential role of artificial intelligence in the clinical management of Hansen's disease (leprosy).

Missed and delayed diagnoses of Hansen's disease (HD) are making the battle against it even more complex, increasing its transmission and significantly impacting those affected and their families. This strains public health systems and raises the risk of lifelong impairments and disabilities. Worryingly, the three countries most affected by HD witnessed a growth in new cases in 2022, jeopardizing the World Health Organization's targets to interrupt transmission. Artificial intelligence (AI) can help address these challenges by offering the potential for rapid case detection, customized treatment, and solutions for accessibility challenges-especially in regions with a shortage of trained healthcare professionals. This perspective article explores how AI can significantly impact the clinical management of HD, focusing on therapeutic strategies. AI can help classify cases, ensure multidrug therapy compliance, monitor geographical treatment coverage, and detect adverse drug reactions and antimicrobial resistance. In addition, AI can assist in the early detection of nerve damage, which aids in disability prevention and planning rehabilitation. Incorporating AI into mental health counseling is also a promising contribution to combating the stigma associated with HD. By revolutionizing therapeutic approaches, AI offers a holistic solution to reduce the burden of HD and improve patient outcomes.

Late relapses in leprosy patients in Brazil: 10-year post-trial of uniform multidrug therapy (U-MDT/CT-BR)

BackgroundLeprosy is a neglected dermato-neurologic, infectious disease caused by Mycobacterium leprae or M. lepromatosis. Leprosy is treatable and curable by multidrug therapy/MDT, consisting of 12 months rifampicin, dapsone and clofazimine for multibacillary/MB patients and for 6 months for paucibacillary/PB patients. The relapse rate is considered a crucial treatment outcome. A randomized Controlled Clinical Trial (U-MDT/CT-BR) conducted from 2007‒2012 compared clinical outcomes in MB patients after 12 months regular MDT/R-MDT and 6 months uniform MDT/U-MDT in two highly endemic Brazilian areas. ObjectivesTo estimate the 10 years relapse rate of MB patients treated with 6 months U-MDT. MethodsThe statistical analyses treated the data as a case-control study, sampled from the cohort generated for the randomized trial. Analyses estimated univariate odds ratio and applied logistic regression for multivariate analysis, controlling the confounding variables. ResultsThe overall relapse rate was 4.08 %: 4.95 % (16 out of 323) in the U-MDT group and 3.10 % (9 out of 290) in the regular/R-MDT group. The difference in relapse proportion between U-MDT and R-MDT groups was 1.85 %, not statistically significant (Odds Ratio = 1.63, 95 % CI 0.71 to 3.74). However, misdiagnosis of relapses, may have introduced bias, underestimating the force of the association represented by the odds ratio. ConclusionsThe relapse estimate of 10 years follow-up study of the first randomized, controlled study on U-MDT/CT-BR was similar to the R-MDT group, supporting strong evidence that 6 months U-MDT for MB patients is an acceptable option to be adopted by leprosy endemic countries worldwide. Trial registrationClinicalTrials.gov: NCT00669643.

Primary Mandibular Tuberculous Osteomyelitis Mimicking Ameloblastoma: A Case Report and Literature Review of Mandibular Tuberculous Osteomyelitis.

Primary tuberculous osteomyelitis involving the mandible represents less than 2% of skeletal locations. In this paper, we report a case of mandibular tuberculosis (TB) detected after histopathological analysis of the surgically resected specimen during surgical management of a suspected case of ameloblastoma. A 14-year-old male patient presented to us with history of right-sided chin swelling. The clinical examination revealed a swelling, involving right body and parasymphysis of mandible, measuring approximately 6 cm in length and 2 cm in width, extending from right lateral incisor till the first molar. Radiological scans revealed a large multiloculated osteolytic expansive lesion measuring 52 × 20 × 18 mm. Excision of the lesion was performed and reconstruction was done with iliac bone grafting. The histopathological findings revealed a granulomatous lesion, suggestive of tuberculous osteomyelitis. The patient was successfully treated with standard multidrug therapy. One year after completion of therapy, there were no signs of recurrence. Primary mandibular TB is an extremely rare entity. Its clinical presentation is not specific. Radiologically, TB has no characteristic appearance. The positive diagnosis is based on histology. Primary mandibular TB is rare and should be kept among differential diagnoses in susceptible population and in endemic areas.

Type II Reaction Erythema Nodosum Leprosum: A Case Report

Leprosy, or Hansen's disease, is a chronic granulomatous infectious disease caused by Mycobacterium leprae. This is a case of a 25-year-old male from Micronesia who presented to a hospital in the Midwest with a two-week history of a widespread, nodular, erythematous, painful rash most severe on his lower extremities and sparing only his hands and feet. In addition to the cutaneous manifestations, the patient met the criteria for Systemic Inflammatory Response Syndrome (SIRS) due to his presentation of tachycardia, tachypnea, leukocytosis, and elevated inflammatory markers. A short course of antibiotics, including Piperacillin-Tazobactam and Vancomycin, and IV steroids were started on admission. A skin biopsy taken from the center and edge of a lesion on the patient’s right arm demonstrated acute and chronic granulomatous superficial and deep inflammation with abundant acid-fast bacilli consistent with lepromatous leprosy from a Mycobacterium leprae infection. Once the National Hansen's Disease Center was contacted previous therapies were stopped and a multidrug therapy, consisting of Rifampin, Moxifloxacin, Minocycline, Methotrexate, and Prednisone was started. The multidrug therapy promptly resulting in substantial clinical improvement over the subsequent months. This case emphasizes the significance of early recognition, accurate diagnosis, and timely initiation of appropriate treatment in leprosy management, even in unlikely regions such as the Midwestern United States.

Effect of multidrug therapy on the prognosis of Mycobacterium avium complex pulmonary disease

Multidrug therapy for Mycobacterium avium complex pulmonary disease (MAC-PD) results in negative sputum cultures. However, the prognostic value of this treatment approach remains unclear. This study aimed to clarify whether multidrug therapy reduces the incidence of events related to MAC-PD and improves the mortality rate. Patients who met the diagnostic criteria for MAC-PD at our hospital between 2003 and 2019 were retrospectively evaluated using medical records. Events related to MAC-PD were defined as hospitalisation for haemoptysis or respiratory infection and the development of chronic respiratory failure. There were 90 and 108 patients in the multidrug and observation groups, respectively. The median observation period was 86 months. Intergroup differences in body mass index, proportion of patients with cavities, and erythrocyte sedimentation rate were not significant. However, the observation group was older with a higher mean age (multidrug group: 62 years, observation group: 69 years; P < 0.001) and had a higher proportion of male patients (multidrug group: 13/90 [14.4%], observation group: 35/108 [32.4%]; P < 0.01). Furthermore, intergroup differences in the incidence of events related to MAC-PD (multidrug group: 26.69/1000 person-years, observation group: 25.49/1000 person-years), MAC-PD-associated mortality rate (multidrug group: 12.13/1000 person-years, observation group: 12.74/1000 person-years), and total mortality (multidrug group: 24.26/1000 person-years, observation group: 29.50/1000 person-years) were not significant. Many patients relapse even after multidrug therapy, and our findings suggest that multidrug therapy has no effect in preventing the onset of respiratory events or prolonging life expectancy.

Leprosy: treatment, prevention, immune response and gene function.

Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.

Development of a rapid detection method for the macrolide resistance gene in Mycobacterium avium using the amplification refractory mutation system-loop-mediated isothermal amplification method.

Macrolide antibiotics such as clarithromycin (CLR) and azithromycin are the key drugs used in multidrug therapy for Mycobacterium avium complex (MAC) diseases. For these antibacterial drugs, drug susceptibility has been correlated with clinical response in MAC diseases. We have previously demonstrated the correlation between drug susceptibility and mutations in the 23S rRNA gene, which confers resistance to macrolides. Herein, we developed a rapid detection method using the amplification refractory mutation system (ARMS)-loop-mediated isothermal amplification (LAMP) technique to identify mutations in the 23S rRNA gene of M. avium. We examined the applicability of the ARMS-LAMP method to genomic DNA extracted from six genotypes of M. avium clinical isolates. The M. avium isolates were classified into 21 CLR-resistant and 9 CLR-susceptible strains based on the results of drug susceptibility tests; the 23S rRNA genes of these strains were sequenced and analyzed using the ARMS-LAMP method. Sequence analysis revealed that the 9 CLR-sensitive strains were wild-type strains, whereas the 21 CLR-resistant strains comprised 20 mutant-type strains and one wild-type strain. Using ARMS-LAMP, no amplification from genomic DNAs of the 10 wild-type strains was observed using the mutant-type mismatch primer sets (MTPSs); however, amplification from the 20 mutant-type strain DNAs was observed using the MTPSs. The rapid detection method developed by us integrates ARMS-LAMP with a real-time turbidimeter, which can help determine drug resistance in a few hours. In conclusion, ARMS-LAMP might be a new clinically beneficial technology for rapid detection of mutations.IMPORTANCEMultidrug therapy for pulmonary Mycobacterium avium complex disease is centered on the macrolide antibiotics clarithromycin and azithromycin, and resistance to macrolides is an important prognosticator for clinical aggravation. Therefore, it is important to develop a quick and easy method for detecting resistance to macrolides. Drug resistance is known to be correlated with mutations in macrolide resistance genes. We developed a rapid detection method using amplification refractory mutation system (ARMS)-loop-mediated isothermal amplification (LAMP) to identify a mutation in the 23S rRNA gene, which is a macrolide resistance gene. Furthermore, we examined the applicability of this method using M. avium clinical isolates. The rapid method developed by us for detection of the macrolide resistance gene by integrating ARMS-LAMP and a real-time turbidimeter can help in detection of drug resistance within a few hours. Since this method does not require expensive equipment or special techniques and shows high analytical speed, it would be very useful in clinical practice.

Complementary supramolecular drug associates in perfecting the multidrug therapy against multidrug resistant bacteria.

The inappropriate and inconsistent use of antibiotics in combating multidrug-resistant bacteria exacerbates their drug resistance through a few distinct pathways. Firstly, these bacteria can accumulate multiple genes, each conferring resistance to a specific drug, within a single cell. This accumulation usually takes place on resistance plasmids (R). Secondly, multidrug resistance can arise from the heightened expression of genes encoding multidrug efflux pumps, which expel a broad spectrum of drugs from the bacterial cells. Additionally, bacteria can also eliminate or destroy antibiotic molecules by modifying enzymes or cell walls and removing porins. A significant limitation of traditional multidrug therapy lies in its inability to guarantee the simultaneous delivery of various drug molecules to a specific bacterial cell, thereby fostering incremental drug resistance in either of these paths. Consequently, this approach prolongs the treatment duration. Rather than using a biologically unimportant coformer in forming cocrystals, another drug molecule can be selected either for protecting another drug molecule or, can be selected for its complementary activities to kill a bacteria cell synergistically. The development of a multidrug cocrystal not only improves tabletability and plasticity but also enables the simultaneous delivery of multiple drugs to a specific bacterial cell, philosophically perfecting multidrug therapy. By adhering to the fundamental tenets of multidrug therapy, the synergistic effects of these drug molecules can effectively eradicate bacteria, even before they have the chance to develop resistance. This approach has the potential to shorten treatment periods, reduce costs, and mitigate drug resistance. Herein, four hypotheses are presented to create complementary drug cocrystals capable of simultaneously reaching bacterial cells, effectively destroying them before multidrug resistance can develop. The ongoing surge in the development of novel drugs provides another opportunity in the fight against bacteria that are constantly gaining resistance to existing treatments. This endeavour holds the potential to combat a wide array of multidrug-resistant bacteria.

Bilateral Ocular Leprosy An Effect By Erythema Nodusum Leprosum : A Case Report

Introduction : Leprosy or Hansen’s disease is an infection caused by Mycobacterium leprae that primarily affects the skin, the peripheral nerves and the eyes, causing chronic granulomatous inflammation.&#x0D; Case Illustration : We present a case of lepromatous leprosy with erythema nodosum leprosum of a 47 years old man with bilateral and asymmetrical ocular complications. One year ago patient consumed multidrug therapy for leprosy for one year but didn’t finish the medication. On the right eye diagnose with chronic anterior and intermediate uveitis, on the left eye with panuveitis. Best corrected visual acuity (BCVA) was 2/60 for right eye and light perception for left eye. Intraocular pressure were within normal limits. Madarosis and corneal hypoesthesia were found on both eyes. On the right eye was found cells, synechia anterior and posterior, iris pearls and vitreous haze. On the left eye was found plasmoid iridocyclitis and vitreous opacities from USG. Slit skin smear (SSS) result positif acid fast bacilli (AFB) dan granular. Patients were treated with multidrug therapy for leprosy, topical antibiotics, atropine and steroids, oral antibiotics and treatment from a dermatologist.&#x0D; Discussion : The diagnosis of lepromatous uveitis (LU) in this patient is made through skin tissue biopsy and ophthalmological examination. The effective management of ocular leprosy depends on early diagnosis and appropriate treatment. Hence it is imperative for ophthalmologist to recognize the ocular clinical signs associated with leprosy.&#x0D; Conclusion : Most blindness and impaired vision resulting from leprosy is preventable. A multidisciplinary approach is to be taken in order to improve the prognosis.

Efficacy and safety of eszopiclone combined with drug therapy in the treatment of insomnia after stroke: A network meta-analysis and systematic review.

To evaluate the efficacy and safety of multi-drug therapy based on eszopiclone in the treatment of insomnia after stroke using a network meta-analysis method and to provide evidence for clinical practice. Computer searches of PubMed, Excerpt Medica Database (Embase), Cochrane Library Central Register of Controlled Trials, APA PsycInfo, CNKI, WanFang, Sinomed and other databases were performed to search for clinical randomized controlled studies (RCTs) on multi-drug therapy based on eszopiclone in the treatment of insomnia patients after stroke. The search time was from the establishment of each database until July 2023. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. Stata 14.0 was applied to perform network meta-analysis using Review Manager 5.3 software for traditional meta-analysis. Eighteen RCTs and 1646 patients were ultimately included, involving 11 treatment options. The results of the network meta-analysis showed that the ranking of Pittsburgh Sleep Quality Index (PSQI) decline was eszopiclone combined with sweet dream oral liquid (ESZ+SDOL)>eszopiclone combined with a shugan jieyu capsule (ESZ+SGJYC)>eszopiclone combined with agomelatine (ESZ+AGO)>eszopiclone combined with flupentixol and melitracen tablets (ESZ+FMT)>eszopiclone combined with yangxue qingnao granules (ESZ+YXQNG)>eszopiclone combined with mirtazapine (ESZ+MIR)>ESZ>FMT; the modified Edinburgh Scandinavia Stroke Scale (MESSS) decline ranking was ESZ+SDOL>ESZ+AGO>ESZ; and the clinical total effective rate ranking was eszopiclone combined with a xuefu zhuyu capsule (ESZ+XFZYC)>ESZ+MIR>ESZ+SGJYC>ESZ+SDOL> ESZ+FMT>ESZ+YXQNG>ESZ>FMT. In terms of clinical adverse reactions, in addition to ESZ therapy, ESZ+ESC had the highest number of adverse reactions, with abdominal pain being the most common. ESZ+YXQNG had the most types of adverse reactions, with 8 types. Multi-drug therapy based on eszopiclone can effectively improve the sleep quality of patients with insomnia after stroke, and ESZ+SDOL has significant efficacy and safety. However, due to the limitations of this study, efficacy ranking cannot fully explain the superiority or inferiority of clinical efficacy. In the future, more multicentre, large sample, double-blind randomized controlled trials are needed to supplement and demonstrate the results of this study.

Transmission dynamics and optimal control strategies in a multi-pathways delayed HIV infection model with multi-drug therapy

Transmission dynamics and optimal control strategies in a multi-pathways delayed HIV infection model with multi-drug therapy

Abstract PR003: Multi-drug adaptive therapy protocol in vitro: An exercise in optimization for neuroblastoma

Abstract From initiation, invasion, dissemination to local and distant progression, relapse, recurrence to metastasis – clinico-pathological development of cancer follows the ecological processes of a multi-species niche construction. Ecological interactions result in adaptive changes that are driven by Darwinian evolution. This can be observed in the heterogeneity of tumor cells and their differential response to therapy. Some tumor cells are sensitive to treatment and can be eliminated by therapy, while others are resistant and can survive and proliferate under therapy. Adaptive therapy is a novel approach that leverages the competitive dynamics between sensitive and resistant cells, by dynamically adjusting the therapy dose and schedule based on biomarkers of tumor burden. In this study, we propose a multi-drug adaptive therapy protocol that uses two drugs with orthogonal mechanisms of action, meaning that they target different pathways or processes in the cancer cells. We investigate how to optimize the switching time between the two drugs, based on the personalized response to therapy and the evolutionary trade-offs between resistance and fitness and describe a corresponding real-time in vitro protocol. We performed experiments using two human neuroblastoma cell lines, sknbe2c and lan1, which exhibit distinct resistance profiles to different therapies, have different genetic profiles and show different growth patterns. We chose the combination of cisplatin and vincristine as the drugs of interest, since they are part of the Rapid COJEC protocol, which is a standard multidrug regimen for treating high-risk neuroblastomas in children. We monitored the drug treatment effects using noninvasive real-time microscopy based on cellular holography, which allows us to capture the morphological and behavioral changes of the cells. We fitted the treatment response curves with a stochastic diffusion equation that incorporates evolutionary mechanisms such as speciation, cost-dependent predator-prey interaction and drift, to model the dynamics of drug resistance and sensitivity. Unlike conventional therapy, which follows a fixed schedule and dose, adaptive therapy uses biomarkers of tumor burden, such as imaging or circulating tumor cells, to guide the timing and intensity of treatment. We propose a stochastic model that predicts the optimal switching time between two drugs based on the personalized response to therapy, which is inferred from Bayesian updating of the model parameters. This results in a patient-specific response model that accounts for the uncertainty and variability in the data. Assuming that a reliable and sensitive measure of tumor burden is available, we demonstrate how our model can be used to design a customized multi-drug adaptive therapy protocol for each patient. We are currently testing the efficacy of our protocol over other conventional protocols, and we plan to translate it to patient derived xenograft mouse models of neuroblastoma in the future. Citation Format: Subhayan Chattopadhyay, Jenny Karlsson, David Gisselsson. Multi-drug adaptive therapy protocol in vitro: An exercise in optimization for neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr PR003.