Association of autoimmunity and cancer: An emphasis on proteolytic enzymes.

Cancer and autoimmune diseases are the two devastating conditions that together constitute a leading health problem worldwide. The rising burden of these disorders in the developing world demands a multifaceted approach to address the challenges it poses. Understanding the root causes and specific molecular mechanisms by which the progression of the diseases takes place is need of the hour. A strong inflammatory background and common developmental pathways, such as activation of immune cells, proliferation, increased cell survival and migration which are controlled by growth factors and inflammatory cytokines have been considered as the critical culprits in the progression and complications of these disorders. Enzymes are the potential immune modulators which regulate various inflammatory events and can break the circulating immune complexes via macrophages production. In the current manuscript, we have uncovered the possible role of proteolytic enzymes in the pathogenesis and progression of cancer and autoimmune diseases. In the light of the available scientific literature, we advocate in-depth comprehensive studies which will shed light towards the role of proteolytic enzymes in the modulation of inflammatory responses in cancer and autoimmune diseases together.

Impact of metformin therapy on health-related quality of life outcomes in tuberculosis patients with diabetes mellitus in India: A prospective study.

OBJECTIVE: To assess the impact of metformin use on health-related quality of life (HRQoL) in tuberculosis (TB) patients who are presented with type 2 diabetes mellitus (T2DM). METHODOLOGY: In this community-based prospective study, TB patients attending Hakeem Abdul Hameed Centenary Hospital, New Delhi (India) and had comorbidity of T2DM between April 2018 and July 2019 were enrolled. Patients were divided into metformin users and metformin non-users on the basis of the presence of metformin in their routine as antidiabetic drug(s). HRQoL was determined using a validated TB-specific tool (Dhingra and Rajpal-12 scale ie, DR-12) consists of symptom and socio-psychological and exercise adaptation domains. The HRQoL scores were compared at pretreatment (1st visit), end of intensive phase (2nd visit) and end of treatment (3rd visit) between the two groups. RESULTS: A total of 120 patients were enrolled, of which 24 were excluded as they did not respond at follow-up visits. Among the metformin users (n = 48) the mean age of patients was 47.56 years and 62.50% was males. Among the metformin non-users (n = 48), the mean age of patients was 49.02 years and 54.10% was males. The baseline characteristics were similar in both groups except for the substance used history (P = .025), literacy level (P = .048) and BMI (P = .028). Metformin users demonstrated significant improvement in symptom scores (2nd visit: P < .001; 3rd visit: P = .001) and socio-psychological and exercise adaptation scores (2nd visit: P < .0001; 3rd visit: P < .0001) as compared with metformin non-users at 2nd visit and 3rd visit. Overall, scores were also found to be significantly improved in metformin users (2nd visit: P < .001; 3rd visit: P = .001). CONCLUSION: Metformin therapy exerted favourable effects on HRQoL in patients with TB and T2DM and can be recommended as an adjuvant antitubercular drug in TB patients with co-morbidity of T2DM, unless contraindicated.

Warfarin use increases bleeding risk in hemodialysis patients with atrial fibrillation: A meta-analysis of cohort studies.

BACKGROUND AND AIM: Atrial fibrillation is one of the most common comorbid conditions in hemodialysis patients, and warfarin is widely prescribed anticoagulant to prevent thromboembolic complications in such patients. In the last decade, several epidemiological studies pointed out the risk of bleeding with the use of warfarin. So, this meta-analysis is aimed to assess the bleeding risk associated with the use of warfarin. METHODS: This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. PubMed, Embase, Scopus, and Cochrane central databases were searched from inception to June 10, 2018. The primary outcome was to quantify the bleeding risk associated with warfarin use. The secondary outcome was to assess the bleeding risk based on different subgroups. Review Manager (RevMan) version 5.3 was used for performing statistical analysis. RESULTS: A total of 15 studies, constituting a pooled sample of 53 581 patients (37.14% female), were included. Of these, 17 469 were warfarin users. We found that warfarin use had a significant association with the bleeding risk. The pooled relative risk (RR) of bleeding was estimated to be 1.35 (95% CI: 1.18-1.53, P = < 0.00001), and the pooled RR of major bleeding (five studies) was estimated to be 1.32 (95% CI: 1.07-1.63, P = 0.009). Subgroup analysis revealed a significant association of warfarin use with the intracranial hemorrhage/hemorrhagic stroke (nine studies) (pooled RR: 1.43 [95% CI: 1.20-1.71, P = < 0.0001]). CONCLUSIONS: The results indicate that warfarin use increases the risk of bleeding in hemodialysis patients with atrial fibrillation.

Proton pump inhibitors' use and risk of hip fracture: a systematic review and meta-analysis.

In the last decade, epidemiological studies presented inconsistent findings concerning the proton pump inhibitors (PPI) use and the risk of hip fracture. So, this systematic review and meta-analysis were performed with the aim to quantify the risk of hip fracture associated with PPI use. PubMed® and Cochrane Central databases were searched from inception to January 2018. The quality of included studies in meta-analysis was assessed using Newcastle-Ottawa scale. Primary outcome of this study was to assess the risk of hip fracture among PPI user. Secondary outcomes include subgroup analysis based on study design, study quality, duration of PPI use, calcium intake, and geographical region. Sensitivity analysis was also performed. Review Manager (RevMan) was used to perform statistical analysis. This meta-analysis was based on seventeen studies. Pooled risk ratio showed a statistically significant association between PPI use and hip fracture risk (RR 1.26 [95% CI 1.17-1.35], p < 0.00001). Subgroup analysis, based on the study design, showed a highly significant association between PPI use and risk of hip fracture (p < 0.0001). The risk of hip fracture persisted even when stratified by calcium adjustment and the duration of PPI use (p < 0.0001). This meta-analysis suggests that PPI user have a 26% increased risk of hip fracture as compared to non-PPI user. Physicians should take caution in prescribing PPI to patients who are at increased risk of hip fracture.

Diabetes prevalence and its impact on health-related quality of life in tuberculosis patients.

OBJECTIVE: To determine the prevalence of diabetes mellitus (DM), assess its influence on health-related quality of life (HRQoL) among patients with TB. METHODS: In this prospective study, eligible patients at three primary healthcare centres in urban slum region of south Delhi, India, underwent blood glucose screening at treatment initiation. HRQoL scores were determined by conducting face-to-face interviews using Dhingra and Rajpal (DR-12) scale at pre-treatment, end of intensive phase and end of the treatment. RESULTS: In 316 patients, the overall DM prevalence was 15.8%, of whom 9.5% were known to have diabetes, and 6.3% were diagnosed at TB treatment initiation. DM was more common among patients of older age (P < 0.001), with higher BMI (P < 0.001), with PTB (P = 0.02) and with poor psychological status. HRQoL was significantly poor in the socio-psychological & exercise adaptation domain in patients with DM ˃50 years of age at each visit. Older age, poor literacy, loss in workdays, alcohol use and socio-economic status significantly predict poor HRQoL scores in patients with DM. Uncontrolled DM patients demonstrated poor HRQoL at the end of the intensive phase (P = 0.04) of treatment and at its completion (P = 0.03) compared to those with controlled DM. CONCLUSION: Addressing screening measures and glycaemic control along with social determinants such as literacy level and alcohol consumption could be an important means of improving the HRQoL of TB with DM patients.

Impact of Bariatric Surgery in Reducing Macrovascular Complications in Severely Obese T2DM Patients.

BACKGROUND: Evidence from real-world studies have suggested a reduced rate of macrovascular complications following bariatric surgery. We undertook this meta-analysis to investigate the impact of bariatric surgery on macrovascular disease outcomes in severely obese type 2 diabetes mellitus (T2DM) patients. METHODS: An extensive literature search was performed in PubMed from inception until March 2020. All cohort studies assessing the association between bariatric surgery and macrovascular complications in severely obese T2DM patients were included. Two independent reviewers screened the articles, extracted data, and assessed the quality using the Newcastle-Ottawa Scale. The primary outcome was to assess the impact of bariatric surgery and the risk of macrovascular complications. Statistical analysis was performed using Review Manager 5.3. RESULTS: This meta-analysis comprised of five studies including 49,211 participants (75% female), of which 14,434 underwent bariatric surgery and 34,777 underwent usual care. Participants who underwent bariatric surgery had a significantly lower risk of macrovascular complications as compared to those with non-surgical interventions (RR: 0.50 [95% CI: 0.35-0.73], p = 0.0003). In the subgroup analysis, based on the geographical regions, studies conducted in the USA showed a higher reduction (RR: 0.41 [95% CI: 0.32-0.53], p < 0.00001) in macrovascular complications as compared to other parts of the world. The risk of all-cause mortality was also significantly lower in patients with bariatric surgery (RR 0.39 [95% CI: 0.30-0.50], p < 0.00001). CONCLUSION: Bariatric surgery was associated with a 50% reduction in macrovascular complications along with 61% reduction in risk of all-cause mortality in morbidly obese T2DM patients.

Cannabis, a Miracle Drug with Polyvalent Therapeutic Utility: Preclinical and Clinical-Based Evidence.

Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, various parts of the plant like leaf, flower, and seed were used for recreational as well as therapeutic purposes. The main chemical components of Cannabis sativa are termed as cannabinoids, among them the key psychoactive constituent is Δ-9-tetrahydrocannabinol and cannabidiol (CBD) as active nonpsychotic constituent. Upon doing extensive literature review, it was found that cannabis has been widely studied for a number of disorders. Very recently, a pure CBD formulation, named Epidiolex, got a green flag from both United States Food and Drug Administration and Drug Enforcement Administration for 2 rare types of epilepsies. This laid a milestone in medical cannabis research. This review intends to give a basic and extensive assessment, from past till present, of the ethnological, plant, chemical, pharmacological, and legal aspects of C. sativa. Further, this review contemplates the evidence the studies obtained of cannabis components on Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, multiple sclerosis, emesis, epilepsy, chronic pain, and cancer as a cytotoxic agent as well as a palliative therapy. The assessment in this study was done by reviewing in extensive details from studies on historical importance, ethnopharmacological aspects, and legal grounds of C. sativa from extensive literature available on the scientific databases, with a vision for elevating further pharmaceutical research to investigate its total potential as a therapeutic agent.

Potential role of adjuvant drugs on efficacy of first line oral antitubercular therapy: Drug repurposing.

Despite the availability of potent antitubercular drugs, tuberculosis (TB) still remains one of the world's leading causes of death. The current antitubercular therapy (ATT) suffers from a drawback of longer duration that imposes a major challenge of patient non compliance and resistance development. The current scenario necessitates alternative strategies with potential to shorten treatment duration that could pave the way for improved clinical outcomes. In recent years, host directed adjunctive therapies have raised considerable attention and emerged as a promising intervention which targets clinically relevant biological pathways in hosts to modulate pathological immune responses. Few of the approved drugs namely statins, metformin, ibuprofen, aspirin, valproic acid, adalimumab, bevacizumab, zileuton and vitamin D3 have shown promising results in clinical outcomes during their preliminary screening in TB patients and can be potentially repurposed as antitubercular drugs. This review highlights clinical and non clinical evidences of some already existing drug and their targets in hosts that could help in shortening treatment duration and reducing bacterial burden at minimal doses.

Materiovigilance: Concept, Structure and Emerging Perspective for Patient's Safety in India.

There has been an escalation in the number, diversity, and complexity of medical devices. Regulation of these devices has also advanced due to the requirement of better regulatory perspective induced due to elevation in the number of adverse events associated with medical devices. All over the globe, various measures are undertaken to provide better safety to the patients along with attempts to improve the standard of medical devices. The initial and ultimate objective of the concept happens to be unfailingly to ensure patient safety as well as impart required guidance for both manufacturers and adept authorities enabling them to superintend cases coherently and appropriately. Materiovigilance programme of India (MvPI) was launched by the Drug Controller General of India at the Indian Pharmacopoeia commission (IPC) in Ghaziabad in 2015. The main purpose of this initiative is to monitor adverse events associated with medical devices in order to generate safety data, create awareness among the various stakeholders, and prescribe best practices for patient safety. Whilst the reforms in regulations have proposed policies and designs to elucidate, consolidate and accelerate the processes involved in manufacturing and importing medical devices to India, they consistently carry their challenges and limitations. To eliminate such complications the guidelines and regulations are anticipated to be implemented appropriately with the efficacious conclusion. India has been evident in matching with advancements in the World Medical Device regulation scenario, the current review at hand takes upon the question of 'how successful has it been so far'?

Detrimental association between diabetes and tuberculosis: An unresolved double trouble.

Despite significant efforts made to control tuberculosis (TB) through DOTS program, the increasing burden of diabetes mellitus (DM) threatens the progress in reducing TB-related mortality, particularly in developing countries. In recent years, TB-DM comorbidity continues to remain high in countries where DM is on rampant. DM increases the risk of TB, reactivates the dormant TB and worsens the TB treatment outcome. The present review highlights the current findings regarding the prevalence and association of TB-DM comorbidity along with their public health implications. This review will increase the awareness among researchers, policymakers and clinicians, regarding the current scenario of TB-DM association.

Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study.

Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539-2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; 0.310-4.457) at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114-11.494, p = 0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence.

Neuroprotective Role of Steroidal Sex Hormones: An Overview.

Progesterone, estrogens, and testosterone are the well-known steroidal sex hormones, which have been reported to have "nonreproductive "effects in the brain, specifically in the neuroprotection and neurotrophy. In the last one decade, there has been a surge in the research on the role of these hormones in neuroprotection and their positive impact on different brain injuries. The said interest has been sparked by a desire to understand the action and mechanisms of these steroidal sex hormones throughout the body. The aim of this article was to highlight the potential outcome of the steroidal hormones, viz. progesterone, estrogens, and testosterone in terms of their role in neuroprotection and other brain injuries. Their possible mechanism of action at both genomic and nongenomic level will be also discussed. As far as our knowledge goes, we are for the first time reporting neuroprotective effect and possible mechanism of action of these hormones in a single article.

Current Updates on Therapeutic Advances in the Management of Cardiovascular Diseases.

Despite the significant advances in the medical research and treatment methods, the rate of mortality associated with cardiovascular disease (CVD) is continuously rising and it remains the leading cause of death worldwide. There are several treatment methods for CVD and associated complications that have been considered till now. The current treatment methods cannot produce rapid cure, but could prevent or reduce the progression of this devastating disease. In the current article, we have summarized the use of various pharmacological agents viz. HMG-CoA reductase inhibitors (statins), antihypertensive, thrombolytic and anticoagulation agents that are currently being used for the management of CVD which targets different biochemical or molecular events. Based on our article, more research in this field is advocated which will provide the rapid and effective treatment methods in order to avoid fatal complications associated with CVD.