The clinical significance of neopterin and NT-pro BNP in chronic heart failure: a systematic review.

BACKGROUND: Biomarkers emerged as powerful adjuncts to conventional clinical care in heart failure (HF). The aim of this study is to evaluate neopterin and NT-pro BNP as diagnostic and prognostic biomarkers in HF. METHODS: A systematic search was conducted in six electronic databases from inception to July 24th, 2022. Independent reviewers screened the title, abstract and full text then data extraction and critical appraisal of included studies were performed. RESULTS: A total of eleven studies were included. Neopterin and NT-pro BNP levels were elevated in HF patients as compared to control. Moreover, within HF patients, levels of biomarkers were significantly higher in patients with advanced HF and more severe disease state. Patients who suffered cardiovascular adverse events had high levels of biomarkers. Two studies assessed the effect of treatment on biomarkers levels, showed that levels of neopterin and/or NT-pro BNP decreased with treatment. Studies confirmed the potential of relying on neopterin and NT-pro BNP as diagnostic and prognostic biomarkers in HF in addition to assessing disease severity. CONCLUSION: Biomarkers levels correlate with disease severity and could be used as diagnostic and prognostic biomarkers in HF. Further research is needed for a definitive conclusion about using these biomarkers to determine the efficacy of therapy.

Drug Utilization Evaluation Study of Ciprofloxacin Use and Adverse Events Occurrence: Role of Community Pharmacists.

Background: Antimicrobial resistance is a global health crisis threatening optimal management of infectious diseases. Ciprofloxacin is a widely used fluoroquinolone in various disease conditions. Resistance against ciprofloxacin is increasing, leading to nonoptimal management of patients. Thus, the aim of this study was to assess ciprofloxacin use in the community setting in terms of appropriate prescribing, dosing, frequency, and duration of use. Methods: A cross-sectional, retrospective study was conducted by community pharmacists in 5 community pharmacies in Egypt from September 2021 to February 2022. Patients prescribed oral ciprofloxacin during the period of the study were included. Data on demographics, indications for ciprofloxacin, dosing regimen, adverse events, and drug interactions were collected. Results: A total of 151 patients' record indicated for ciprofloxacin were included in the study, of whom 44.4% were men and 55.6% were women who were neither pregnant nor lactating. Based on international guidelines, 96.69% ciprofloxacin prescriptions were appropriate; 96.03% contained correct ciprofloxacin dosing whereas 3.97% were overdose. A total of 90. 73% had correct frequency of administration and 96.03% records had correct durations. Only 1.99% of patients were ≤18 years of age, which is an absolute contraindication. Interacting drugs with ciprofloxacin were 28.5% with acetaminophen, 31.1% with ibuprofen, 16.6% with antacids, 21.2% with chlorpheniramine, and 7.9% with prednisolone. Adverse events included 1.32% hypoglycemia, 0.66% hyperglycemia, 3.97% tendinitis, and 2.65% QTc (heart rate-corrected QT interval) prolongation. Conclusion and relevance: Ciprofloxacin use in community pharmacies is appropriate according to international guidelines. Ongoing drug utilization evaluation is necessary to ensure rational drug use, which in turn can decrease resistance rates.

Nanomedicines as enhancers of tumor immunogenicity to augment cancer immunotherapy.

The potential of cancer immunotherapy is hampered by the poor immunogenicity of cancer cells. Strategies to enhance tumor immunogenicity are imperative to enhance T cell-mediated anti-tumor immunity. Although conventional therapeutics can increase tumor antigen expression or stimulate the release of danger signals to promote immunogenic cell death (ICD), they face challenges relating to efficacy and tumor-specific delivery. Nanomedicines can efficiently deliver tumor antigens, immune adjuvants, epigenetic modulators, or ICD inducers through targeted drug delivery with minimal off-target effects. Collectively, nanomedicines can overcome biological barriers to immunotherapy through targeted antigen delivery, induction of ICD, or epigenetic remodeling, resulting in increased tumor immunogenicity.

Proteolysis Targeting Chimera (PROTAC) as a promising novel therapeutic modality for the treatment of triple-negative breast cancer (TNBC).

Breast cancer (BC) is considered one of the most prevalent malignancies impacting women worldwide, constituting 15% of all new cancer cases. It is classified according to its molecular targets into three subtypes; HR+/ERBB2-, ERBB2+/HR+, or HR- and triple-negative breast cancer (TNBC). TNBC is considered aggressive cancer with bad prognosis and poor clinical outcomes. It lacks estrogen, progesterone, and ERBB2 receptors rendering its treatment more challenging. Owing to its unresponsiveness to hormonal therapy, quick tumor growth, and the high probability to have spread at the time of discovery, it is more likely to recur following therapy. Proteolysis Targeting Chimeric molecules (PROTACs) are hetero-bifunctional molecules that are able to hijack the ubiquitin-proteasome system, a major physiological proteolytic mechanism. This leads to ubiquitination through endogenous E3 ligases and subsequent degradation through 26-S proteasome. Since its discovery in 2001, PROTACs have been considered an important therapeutic modality due to their ability to target and degrade undruggable proteins. In vitro studies have been conducted to investigate the possibility of using PROTACs as a therapeutic modality in TNBC. Data available propose great potential of PROTACs technology as a major candidate in TNBC management. Further in vitro and in vivo clinical trials are required to establish a definitive decision. In this review, we aim to give a brief overview of TNBC and PROTACs and highlight the rationale behind using PROTACs as a therapeutic modality in patients with TNBC.

Role of neopterin as an inflammatory biomarker in congestive heart failure with insights on effect of drug therapies on its level.

Inflammation has a major role in the pathogenesis of heart failure (HF). It triggers a cascade that leads to the release of pro-inflammatory cytokines which in turn cause cardiac hypertrophy, fibrosis, apoptosis, negative inotorpy and leukocyte recruitment which worsen the condition. Neopterin is an inflammatory biomarker which is released as a response to macrophage activation. Levels of neopterin are elevated in conditions which has an immunological component such as autoimmune disease, viral and bacterial infections and malignancy. Neopterin levels were found to be elevated in patients with HF. This is due to the fact that inflammation takes place during the development of the condition. Studies demonstrated that neopterin can be used as a biomarker for diagnosing HF, determining severity of the disease and monitoring its progression. Neopterin levels were higher in patients with New York Heart Association classification (NYHA) III-IV more than class I-II. Moreover, neopterin levels correlated well with morbidity and mortality. It has been suggested that neopterin be monitored levels to determine effectiveness of HF treatment options.

Clinical comparative study assessing the effect of ivabradine on neopterin and NT-Pro BNP against standard treatment in chronic heart failure patients.

PURPOSE: Heart rate reduction (HR) is a cornerstone in heart failure therapy as it improves patient outcomes. The aim of this study is to evaluate short-term effect of ivabradine on NT-Pro BNP and neopterin in heart failure patients and assess the association between HR and these biomarkers. METHODS: Sixty patients on standard heart failure therapy were randomly allocated into ivabradine group (n = 30) and non-ivabradine group (n = 30). Ivabradine 5 mg twice daily was given for 3 months. Lipid profile and kidney functions were performed and blood samples for NT-Pro BNP and neopterin were analysed at baseline and after 3 months of intervention in both groups. RESULTS: There was a significant improvement in NYHA class in ivabradine group (p < 0.001). Ejection fraction was improved in ivabradine and non-ivabradine groups after intervention (p < 0.001), with a greater improvement in ivabradine group (p = 0.026). Heart rate was reduced in ivabradine group (p < 0.001) and non-ivabradine group (p < 0.001) yet greater reduction was seen in ivabradine group (p < 0.001). Serum creatinine and blood urea nitrogen were reduced in ivabradine group (Scr: p = 0.001, BUN: p = 0.001). NT-Pro BNP and neopterin levels significantly decreased in ivabradine group (NT-Pro BNP: p < 0.001, neopterin p < 0.001). Significant positive correlation was found between HR and biomarker levels after intervention (NT-Pro BNP: r = 0.475, p < 0.001, neopterin: r = 0.384, p = 0.002). CONCLUSION: Ivabradine therapy reduced levels of both biomarkers which correlated well with HR. Biomarker levels might provide a tool for assessing ivabradine effectiveness in HF. Trial registration Date: June 26, 2020. Identifier: NCT04448899. Link: Ivabradine in Patients with Congestive Heart Failure-Full Text View-ClinicalTrials.gov.