The Unusual Adverse Effects of Antituberculosis Therapy in Kidney Patients.

BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of tuberculosis (TB), with a relative risk of developing active TB of 10%-25%. Similarly, glomerular disease increases the risk of TB due to diminished glomerular filtration rate, proteinuria, and immunosuppression use. Further, the first-line anti-TB drugs are associated with acute kidney injury (AKI) even in patients with normal kidney functions. METHODS: We retrospectively identified 10 patients hospitalized with unusual adverse effects of antituberculosis therapy (ATT) from 2013 to 2022. RESULTS: We found three cases of AKI caused by rifampicin: acute interstitial nephritis, crescentic glomerulonephritis, and heme pigment-induced acute tubular necrosis. We observed rifampicin-induced accelerated hypertension and thrombocytopenia in two patients on maintenance hemodialysis. Isoniazid caused pancreatitis and cerebellitis in two CKD patients, respectively. In a CKD patient, we detected acute gout secondary to pyrazinamide-induced reduced uric acid excretion. We also observed cases of drug rash with eosinophilia and systemic symptoms and hypercalcemia due to immune reconstitution inflammatory syndrome in patients with glomerular disease on ATT. Immediate discontinuation of the offending drug, along with specific and supportive management, led to a recovery in all cases. CONCLUSION: The adverse effects of ATT may be unusually severe and varied in kidney patients due to decreased renal elimination. Early recognition of these adverse effects and timely discontinuation of the offending drug is essential to limit morbidity and mortality.

Effect of Formulation Parameters on Enalapril Maleate Mucoadhesive Buccal Tablet Using Quality by Design (QbD) Approach.

The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising the buccal tablet formulation of Enalapril Maleate (EM) by using the QbD approach. We prepared the EM buccal tablets using the dry granulation method. In the QTPP profile, the CQAs for EM buccal tablets are Mucoadhesive strength, swelling index and drug release (dependent variables); the CMAs identified for EM buccal tablets were Carbopol 934P, HPMC-K100M and chitosan (independent variables). Diluent quantity, blending time and compression force were selected as CPPs; the Box-Behnkentdesign was used to evaluate the relationship between the CMAs and CPPs. Based on the DoE, the composition of the optimised formulation of EM BT-18 consists of 20mg of EM, 15 mg of carbopol 934p, 17 mg of HPMC-K100M, 10mg of chitosan, 30 mg of PVP K-30, 1 mg of magnesium stearate, 16 mg of Mannitol, 1 mg of aspartame, and 50 mg of Ethyl cellulose. The optimised formulation of EM BT 18 was found to have a Mucoadhesive strength of 24.32±0.30g. The swelling index was 90.74±0.25% and drug release was sustained up to 10 hours 98.4±3.62% compared to the marketed product, whose release was up to 8 hours. We attempted to design a buccal tablet of Enalapril Maleate for sustained drug release in the treatment of hypertension. Patients who cannot take oral medication due to trauma or unconscious conditions could receive the formulation. Development of a newly P.ceutical product is very time-consuming, extremely costly and high-risk, with very little chance of a successful outcome. Hence, this study showed EM tablets are already available on the market but we have chosen a buccal drug delivery system using a novel approach using QbD tools to target the quality of the product accurately.

Mucoadhesive Microspheres: A Promising Delivery System for Helicobacter Pylori (H. pylori) Treatment.

A major worldwide health problem, Helicobacter Pylori (H. pylori) infection is associated with a number of gastrointestinal disorders, such as gastric cancer and peptic ulcers. The shortcomings of traditional treatment plans often include adverse effects, low patient compliance, and the emergence of antibiotic resistance. Investigating different delivery methods is thus necessary to improve the effectiveness of treatment. Mucoadhesive microspheres show promise as a method for delivering anti H. pylori drugs in a targeted and sustained manner. With their ability to stick to the stomach mucosa, these microspheres increase the local concentration of the medication and guarantee a more thorough removal of the pathogen. The potential of Mucoadhesive microspheres in the management of H. pylori infection is examined in this review. We explore the properties and benefits of Mucoadhesive polymers, the production techniques for microspheres, and the variables affecting their functionality. To provide a thorough grasp of this delivery system, a variety of drug-loading strategies, release mechanisms, and in vitro and in vivo assessment methodologies are covered. The potential of Mucoadhesive microspheres to overcome the drawbacks of traditional therapy is shown by highlighting recent developments in their formulation and their therapeutic consequences. Mucoadhesive microspheres constitute an important advancement in the treatment of Helicobacter pylori because they guarantee a regulated release of antibiotics and improve medication absorption at the site of infection. In order to fully appreciate the advantages of this novel delivery method, further study is necessary. Future research paths and the difficulties in the clinical translation of this technology are also discussed.

A systematic review on diabetic retinopathy detection and classification based on deep learning techniques using fundus images.

Diabetic retinopathy (DR) is the leading cause of visual impairment globally. It occurs due to long-term diabetes with fluctuating blood glucose levels. It has become a significant concern for people in the working age group as it can lead to vision loss in the future. Manual examination of fundus images is time-consuming and requires much effort and expertise to determine the severity of the retinopathy. To diagnose and evaluate the disease, deep learning-based technologies have been used, which analyze blood vessels, microaneurysms, exudates, macula, optic discs, and hemorrhages also used for initial detection and grading of DR. This study examines the fundamentals of diabetes, its prevalence, complications, and treatment strategies that use artificial intelligence methods such as machine learning (ML), deep learning (DL), and federated learning (FL). The research covers future studies, performance assessments, biomarkers, screening methods, and current datasets. Various neural network designs, including recurrent neural networks (RNNs), generative adversarial networks (GANs), and applications of ML, DL, and FL in the processing of fundus images, such as convolutional neural networks (CNNs) and their variations, are thoroughly examined. The potential research methods, such as developing DL models and incorporating heterogeneous data sources, are also outlined. Finally, the challenges and future directions of this research are discussed.

Prevalence, Predictors, and Prognosis of Serious Infections in Takayasu Arteritis: A Cohort Study.

OBJECTIVE: To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TA). METHODS: Serious infections, defined as infections resulting in hospitalization or death or unusual infections like tuberculosis, were identified from a cohort of patients with TA. Corticosteroid and disease-modifying antirheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation, and the use of DMARDs during follow-up were compared between patients with TA with or without serious infections. Mortality in patients with TA who developed serious infections was compared to those who did not using hazard ratios (HR; with 95% CI). RESULTS: Of 238 patients with TA, 38 (16%) had developed serious infections (50 episodes, multiple episodes in 8; 3 episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n = 19) was the most common infection, followed by tuberculosis (n = 12). Patients with TA who developed serious infections vs those who did not had higher disease activity at presentation (active disease 97.4% vs 69.5%, mean Indian Takayasu Arteritis Activity Score 2010 12.7 (SD 7.3) vs 10.2 (SD 7.0), mean Disease Extent Index in Takayasu Arteritis 11.2 (SD 6.1) vs 8.8 (SD 6.1) and were more frequently initiated on corticosteroids or DMARDs. HRs calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TA who developed serious infections (HR 5.52, 95% CI 1.75-17.39). CONCLUSION: Serious infections, which occurred in the absence of immunosuppressive treatment in approximately one-fifth of patients with TA, were associated with increased mortality in patients with TA.

Clinico-epidemiological characteristics of early- versus late-onset cytomegalovirus disease among renal transplant recipients: A two-decade experience.

BACKGROUND: Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients. METHODS: A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes. RESULTS: Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection. CONCLUSIONS: Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease.

Exploring the Potential of Natural Products as FoxO1 Inhibitors: an In Silico Approach.

FoxO1, a member of the Forkhead transcription factor family subgroup O (FoxO), is expressed in a range of cell types and is crucial for various pathophysiological processes, such as apoptosis and inflammation. While FoxO1's roles in multiple diseases have been recognized, the target has remained largely unexplored due to the absence of cost-effective and efficient inhibitors. Therefore, there is a need for natural FoxO1 inhibitors with minimal adverse effects. In this study, docking, MMGBSA, and ADMET analyses were performed to identify natural compounds that exhibit strong binding affinity to FoxO1. The top candidates were then subjected to molecular dynamics (MD) simulations. A natural product library was screened for interaction with FoxO1 (PDB ID- 3CO6) using the Glide module of the Schrödinger suite. In silico ADMET profiling was conducted using SwissADME and pkCSM web servers. Binding free energies of the selected compounds were assessed with the Prime-MMGBSA module, while the dynamics of the top hits were analyzed using the Desmond module of the Schrödinger suite. Several natural products demonstrated high docking scores with FoxO1, indicating their potential as FoxO1 inhibitors. Specifically, the docking scores of neochlorogenic acid and fraxin were both below -6.0. These compounds also exhibit favorable drug-like properties, and a 25 ns MD study revealed a stable interaction between fraxin and FoxO1. Our findings highlight the potential of various natural products, particularly fraxin, as effective FoxO1 inhibitors with strong binding affinity, dynamic stability, and suitable ADMET profiles.

Renal artery involvement is associated with increased morbidity but not mortality in Takayasu arteritis: a matched cohort study of 215 patients.

BACKGROUND: We analyzed differences in presentation and survival of Takayasu arteritis (TAK) with or without renal artery involvement (RAI) from a large monocentric cohort of patients with TAK. METHODS: Clinical and angiographic features were compared between TAK with versus without RAI, with bilateral versus unilateral RAI, and with bilateral RAI versus without RAI using multivariable-adjusted logistic regression. Inter-group differences in survival were analyzed [hazard ratios (HR) with 95% confidence intervals (95%CI)] adjusted for gender, age at disease onset, diagnostic delay, baseline disease activity, and significant clinical/angiographic inter-group differences after multivariable-adjustment/propensity score matching (PSM). RESULTS: Of 215 TAK, 117(54.42%) had RAI [66(56.41%) bilateral]. TAK with RAI or with bilateral RAI had earlier disease onset than without RAI (p < 0.001). Chronic renal failure (CRF) was exclusively seen in TAK with RAI. TAK with RAI (vs without RAI) had more frequent hypertension (p = 0.001), heart failure (p = 0.047), abdominal aorta (p = 0.001) or superior mesenteric artery involvement (p = 0.018). TAK with bilateral RAI (vs unilateral RAI) more often had hypertension (p = 0.011) and blurring of vision (p = 0.049). TAK with bilateral RAI (vs without RAI) more frequently had hypertension (p = 0.002), heart failure (p = 0.036), abdominal aorta (p < 0.001), superior mesenteric artery (p = 0.002), or left subclavian artery involvement (p = 0.041). Despite higher morbidity (hypertension, CRF), mortality risk was not increased with RAI vs without RAI (HR 2.32, 95%CI 0.61-8.78), with bilateral RAI vs unilateral RAI (HR 2.65, 95%CI 0.52-13.42) or without RAI (HR 3.16, 95%CI 0.79-12.70) even after multivariable adjustment or PSM. CONCLUSION: RAI is associated with increased morbidity (CRF, hypertension, heart failure) but does not adversely affect survival in TAK. Key Points •Renal artery involvement in TAK is associated with chronic renal failure. •TAK with renal artery involvement more often have heart failure and hypertension. •Bilateral renal artery involvement (compared with unilateral) is more often associated with hypertension and visual symptoms. •Renal artery involvement is not associated with an increased risk of mortality in TAK.

Increased mortality rate in Takayasu arteritis is largely driven by cardiovascular disease-a cohort study.

OBJECTIVES: To analyze the risk, causes, and predictors of mortality in Takayasu arteritis (TAK). METHODS: Survival was assessed in a cohort of patients with TAK using Kaplan-Meier curves. Age- and sex-standardized mortality ratio (SMR = observed: expected deaths) for TAK were calculated by applying age- and sex-specific mortality rates for the local population to calculate expected deaths. Hazard ratios (HR with 95%CI) for predictors of mortality based on demographic characteristics, presenting features, baseline angiographic involvement, disease activity, number of immunosuppressive medications used, procedures related to TAK, and any serious infection were calculated using Cox regression or exponential parametric regression models. RESULTS: Among 224 patients with TAK (159 females, mean follow-up duration 44.36 months), survival at 1, 2, 5, and 10 years was 97.34%, 96.05%, 93.93%, and 89.23%, respectively. Twelve deaths were observed, most of which were due to cardiovascular disease (heart failure, myocardial infarction, stroke). Mortality risk was significantly higher with TAK (SMR 17.29, 95%CI 8.95-30.11) than the general population. Earlier age at disease onset (HR 0.90, 95%CI 0.83-0.98; or pediatric-onset vs adult-onset disease, HR 5.51, 95%CI 1.57-19.32), higher disease activity scores (ITAS2010: HR 1.15, 95%CI 1.05-1.25, DEI.TAK: HR 1.18, 95%CI 1.08-1.29), any serious infections (HR 5.43, 95%CI 1.72-17.12), heart failure (HR 7.83, 95%CI 2.17-28.16), or coeliac trunk involvement at baseline (HR 4.01, 95%CI 1.26-12.75) were associated with elevated mortality risk. CONCLUSION: Patients with TAK had an elevated risk of mortality as compared with the general population. Cardiovascular disease was the leading cause of death in TAK.

Paediatric-onset Takayasu's arteritis associates with worse survival than adult-onset Takayasu's arteritis. A matched retrospective cohort study.

OBJECTIVES: A subset of Takayasu's arteritis (TAK) begins in the paediatric age group (≤18 years). Differences in prognosis between paediatric-onset and adult-onset TAK are unclear. We compared the differences in the presentation and survival between paediatric-onset and adult-onset TAK in our cohort of TAK. METHODS: From a retrospective cohort of TAK, clinical presentation, angiographic features, treatments received, disease activity, and survival were compared between paediatric-onset and adult-onset TAK. Multivariable-adjusted logistic regression models were used to compute adjusted odds ratio (aOR) with 95% confidence intervals (95%CI) for paediatric-onset vs. adult-onset TAK. Hazard ratios (HR, with 95%CI) for mortality with paediatric-onset vs adult-onset TAK (crude, adjusted for prognostic covariates or differences in presentation) and propensity score-matched survival analyses were estimated. RESULTS: Among 56 paediatric-onset and 135 adult-onset TAK, chest pain (aOR 3.21, 95%CI 1.06-9.74), heart failure (aOR 3.16, 95%CI 1.05-9.53), headache (aOR 2.60, 95%CI 1.01-6.74), ascending aorta (aOR 3.02, 95%CI 1.04-8.80) and left renal artery involvement (aOR 2.45, 95%CI 1.04-5.80) were more frequent in paediatric-onset TAK. Despite similar longitudinal patterns of disease activity and glucocorticoid or disease-modifying antirheumatic drug (DMARD) use, mortality was higher for paediatric-onset TAK (HR, unadjusted 6.13, 95%CI 1.51-24.91; adjusted for prognostic covariates gender, diagnostic delay, baseline disease activity, number of conventional and biologic/targeted synthetic DMARDs used, 4.97, 95%CI 1.20-20.58; adjusted for differences between groups 5.54, 95%CI 1.22-25.09; after propensity-score matching for prognostic covariates, 54 pairs, log-rank p-value 0.026). CONCLUSIONS: Considering the greater mortality risk, greater vigilance is required while managing paediatric-onset TAK.

Antibody response to ChAdOx1 nCoV-19 (Covishield®) vaccine in people on maintenance hemodialysis.

INTRODUCTION: People on renal replacement therapy (RRT) have a high risk of COVID-19 infection and subsequent death. COVID-19 vaccination is strongly recommended for those on RRT. Data are limited on the immune response of the ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine in patients on RRT. METHODS: A prospective cohort of adult (age > 18 years), on RRT in the form of hemodialysis were included and received two intramuscular doses of Covishield®. A blood specimen of 5.0 mL was collected at two time points, within a few days before administering the first dose of the vaccine and at 4-16 weeks after the second dose. According to their prior COVID-19 infection status, the participants were grouped as (i) prior symptomatic COVID-19 infection, (ii) prior asymptomatic COVID-19 infection, and (iii) no prior COVID-19 infection. RESULTS: A large proportion (81%) of participants had anti-spike antibodies (ASAb) before vaccination, and a reasonable proportion (30%) also had neutralizing antibodies (NAb). The titer of ASAb was relatively low (207 U/mL) before vaccination. The ASAb titer (9405 [1635-25,000] U/mL) and percentage of NAb (96.4% [59.6-98.1%]) were markedly increased following the administration of two doses of the vaccine. The participants' prior COVID-19 exposure status did not influence the rise in ASAb titer and NAb percentage. Further, administering two doses of the Covishield vaccine helps them achieve a high ASAb titer. CONCLUSION: Two doses of ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine, given 12 weeks apart, achieve a high titer of ASAb and a high percentage of NAb in people on hemodialysis.

Phytochemical Screening and Evaluation of Pesticidal Efficacy in the Oleoresins of Globba sessiliflora Sims and In Silico Study.

Globba sessiliflora Sims is an aromatic rhizomatous herb of family Zingiberaceae which is endemic to Peninsular India. This study first reports the phytochemical profile and pesticidal potential of oleoresins obtained from the aerial and rhizome parts of Globba sessiliflora Sims. The oleoresins were prepared by the cold percolation method and were analyzed by a gas chromatography-mass spectrometry (GC-MS) method. Both the oleoresins varied greatly in composition, the major compounds identified in aerial part oleoresin (GSAO) were methyl linoleate, methyl palmitate, and phytol, while the major compounds present in rhizome part oleoresin (GSRO) were γ-sitosterol, 8 (17),12-labdadiene-15, 16-dial, methyl linoleate, and methyl palmitate. In order to evaluate the biological activities, the oleoresins were tested under laboratory conditions for nematicidal action and inhibition of egg hatching potential against root knot nematode, where GSRO was more effective. Insecticidal activity was performed against mustard aphid, Lipaphis erysimi and castor hairy caterpillar, Selepa celtis. In case of mustard aphid, GSRO (LC50 = 154.8 ppm) was more effective than GSAO (LC50 = 263.0 ppm), while GSAO (LC50 = 346.7.0 ppm) was more effective against castor hairy caterpillar than GSRO (LC50 = 398.1 ppm). The herbicidal activity was performed in the receptor species Raphanus raphanistrum subsp. sativus, and the oleoresins showed different intensities for seed germination inhibition and coleoptile and radical length inhibition. Molecular docking studies were conducted to screen the in vitro activities and through molecular docking, it was found that the major oleoresins components were able to interact with the binding pocket of HPPD and AChE with γ-sitosterol showing the best binding affinity.

A Comprehensive Review on Phytochemistry, Ethnopharmacology, and Pharmacological Properties of Zingiber roseum (Roxb.) Roscoe.

Medicinal and aromatic plants are known to have a number of biologically active compounds. Since ancient times, such plants have been used in ethnopharmacology. A number of medicines have been developed from plant origin by researchers and researchers continue to be interested in plant-based medicines. Zingiberaceae is a well-known plant family for such types of medicinal and aromatic plants. Zingiber is the third largest genus of this family and Zingiber roseum (Roxb.) Roscoe is a medicinal and aromatic Z. roseum is a rhizomatous perennial herbaceous plant of this genus, popularly known as "Rosy Ginger" and "Jangli Adrak," utilized in the Siddha arrangement of medication, and its rhizomes have been used to treat injury, cough, asthma, skin illnesses, gastric ulcers, liver diseases, and heartburn in tradition. It also has ethnopharmacological uses, such as the rhizome of Z. roseum is used for digestion, relieving giddiness, and as a stimulant. Apart from this, it has been reported for several pharmacological activities such as antispasmodic, hepatoprotective, antimicrobial, and anticancer activities, etc. Z. roseum is a reservoir of several chemical constituents such as terpenes and terpenoids such as linalool, α-pinene, ß-pinene, limonene, terpinen-4-ol, α- terpineol, etc., phenols, flavonoids, alkaloids, saponins, and ascorbic acid along with important unique constituents such as zerumbone which are responsible for its medicinal and other biological activities. In this review article, we discussed the thorough knowledge published by researchers regarding the phytochemistry, ethnopharmacological, and mediational properties of Z. roseum and its botanical descriptions.

Pre-Pulseless Takayasu Arteritis is Associated with Distinct Clinical and Angiographic Features but Similar Outcomes - A Cohort Study.

Objectives: To compare the presentation, angiographic features, evolution, and prognosis of prepulseless Takayasu arteritis (TAK) with TAK with pulse loss. Methods: Pre-pulseless TAK (defined as without pulse loss in the upper limbs, lower limb, carotid, or subclavian arteries) were identified from a cohort of TAK. Demographic characteristics, clinical features, angiographic involvement, baseline and longitudinal patterns of disease activity, medication use, and mortality rates were compared between pre-pulseless TAK and TAK with pulse loss. Adjusted odds ratios (aOR, with 95%CI) for categorical variables between pre-pulseless TAK and TAK with pulse loss were computed using multivariable-adjusted logistic regression models. Time-to-event data was compared using hazard ratios (HR) with 95%CI. Results: Compared with TAK with pulse loss, pre-pulseless TAK (91/238, 38.24%) more frequently had deranged renal function (aOR 4.43, 95%CI 1.58-12.37) and Hata's type IV disease (aOR 8.02, 95%CI 2.61-24.65), and less often had pulse or blood pressure asymmetry (aOR 0.34, 95%CI 0.18-0.63), limb claudication (aOR for upper limb 0.38, 95%CI 0.18-0.82, for lower limb 0.28, 95%CI 0.12-0.68), right subclavian (aOR 0.45, 95%CI 0.23-0.90) or left carotid artery involvement (aOR 0.42, 95%CI 0.21-0.84). Only two patients with pre-pulseless TAK developed pulse loss on follow-up. Despite fewer pre-pulseless TAK having active disease at presentation, similar proportions of patients in both groups had active disease on follow-up. Survival was similar in both groups (HR for mortality 0.41, 95%CI 0.09-1.90). Conclusion: Pulse loss on follow-up is uncommon in those with prepulseless TAK. Pre-pulseless TAK is associated with similar long-term outcomes to TAK with pulse loss.

A Comprehensive Review: Personalized Medicine for Rare Disease Cancer Treatment.

In the United States, cancer is one of the major causes of death. In 2010 alone, over 1.5 million fresh instances were recorded and over 0.5 billion died. After the completion of human genome sequence, significant progress in characterizing human epigenomes, proteomes and metabolomes has been made; a stronger knowledge of pharmacogenomics has been established and the capacity for individual personalization of health care has grown considerably. Personalized medicine has recently been primarily used to systematically select or optimize the prevention and therapeutic care of the patient through genetic or other data about the particular patient. Molecular profiling in healthy samples and cancer patients can allow for more personalized medications than is currently available. Patient protein, genetic and metabolic information may be used for adapting medical attention to the needs of that individual. The development of complementary diagnostics is a key attribute of this medicinal model. Molecular tests measuring the level of proteins, genes or specific mutations are used to provide a specific treatment for a particular individual by stratify the status of a disease, selecting the right drugs and tailoring dosages to the particular needs of the patient. These methods are also available for assessing risk factors for a patient for a number of conditions and for tailoring individual preventive therapies. Recent advances of personalized cancer medicine, challenges and futures perspectives are discussed.

Mucoadhesive Drug Delivery System and There Future Prospective: Are a Promising Approach for Effective Treatment?

Mucoadhesive polymers are a new and exciting development in drug delivery systems that have the potential to significantly increase therapeutic efficacy. These polymers stick to mucosal surfaces, increasing the amount of time that medications stay at the site of absorption and improving their bioavailability. These mechanisms include longer contact times with the mucosal surface, better drug solubility, and defence against enzymatic degradation of pharmaceuticals. Mucoadhesive polymers also provide a number of benefits over traditional drug delivery methods, including less frequent dosage, better patient compliance, and fewer adverse effects. Due to their adaptability, Mucoadhesive polymers may be used in the rectal, vaginal, ophthalmic, nasal, and oral routes of drug delivery. Mucoadhesive polymers have advantages now, but they also have potential for the future of medication delivery. Mucoadhesion offers excellent possibilities for the delivery of a range of substances through the nasal, vaginal, buccal, and ocular routes of administration. Furthermore, mucoadhesion facilitates the achievement of an extended local or systemic pharmacological effect. In this study, we covered the mechanisms behind mucoadhesion, possible uses for Mucoadhesive polymers in drug administration, and techniques for assessing Mucoadhesive drug delivery systems. The goal of current research is to create innovative Mucoadhesive polymers that have better biodegradability, biocompatibility, and adhesive qualities. Moreover, it is anticipated that the effectiveness of Mucoadhesive polymers would be increased when combined with other cutting-edge drug delivery technologies, such as micro particles and nanoparticles.

Impact of Geographic Location on Diagnosis and Initial Management of Takayasu Arteritis: A Tale of Two Cohorts from Italy and India.

The present study compares disease characteristics, imaging modalities used, and patterns of treatment in two large cohorts of Takayasu arteritis (TAK) from Italy and India. Clinic files were retrospectively reviewed to retrieve information about initial choices of vascular imaging and immunosuppressive therapies. Unpaired t-tests compared means, and proportions were compared using Fisher's exact test or Chi square test [Odds ratios (OR) with 95% confidence intervals (95%CI) calculated where appropriate]. The cohorts comprised 318 patients [Italy (n = 127), India (n = 191)] with similar delays to diagnosis. Ultrasound (OR Italy vs. India 9.25, 95%CI 5.02−17.07) was more frequently used in Italy and CT angiography in India (OR 0.32, 95%CI 0.20−0.51). Corticosteroid use was more prevalent and for longer duration in Italy. TAK from Italy had been more often treated with methotrexate, leflunomide or azathioprine, as opposed to tacrolimus in TAK from India (p < 0.05). Biologic or targeted synthetic disease-modifying agents were almost exclusively used in Italy. Survival on first immunosuppressive agent was longer from Italy than from India (log rank test p value 0.041). Considerable differences in the choice of initial vascular imaging modality and therapies for TAK from Italy and India could relate to prevalent socio-economic disparities. These should be considered while developing treatment recommendations for TAK.

Comparison of Presentation and Prognosis of Takayasu Arteritis with or without Stroke or Transient Ischemic Attack-A Retrospective Cohort Study.

Takayasu arteritis (TAK) could cause a stroke or transient ischemic attack (TIA) in young individuals due to inflammatory vascular occlusion or intracerebral hemorrhage. We compared the clinical presentation, angiographic features, longitudinal patterns of disease activity, medical treatments, and survival in 34 TAK patients with stroke/TIA and 157 without stroke/TIA from a single-center retrospective cohort. TAK patients with stroke/TIA were older (p = 0.044) with a greater proportion of males (p = 0.022), more frequent vision loss (odds ratio (OR) for stroke/TIA vs. without stroke TIA 5.21, 95% CI 1.42-19.14), and less frequent pulse or blood pressure inequality (OR 0.43, 95% CI 0.19-0.96) than TAK patients without stroke/TIA. Hata's angiographic type IIa was more common in TAK patients with stroke/TIA (OR 11.00, 95%CI 2.60-46.58) and type V in TAK patients without stroke/TIA (OR 0.27, 95% CI 0.12-0.58). Cyclophosphamide was used more often in TAK patients with stroke/TIA (p = 0.018). Disease activity at baseline, 6, 12, and 24 months of follow-up was mostly similar for both groups. Risk of mortality was similar in TAK patients with or without stroke/TIA (hazard ratio unadjusted 0.76, 95% CI 0.15-3.99; adjusted for gender, age of disease onset, delay to diagnosis, baseline disease activity, and the number of conventional or biologic/targeted synthetic immunosuppressants used 1.38, 95% CI 0.19-10.20) even after propensity score-matched analyses. Stroke or TIA does not appear to affect survival in TAK patients adversely.