AI-driven drug discovery: Exploring Abaucin as a promising treatment against multidrug-resistant Acinetobacter baumannii.

Background and Aims: This study presents a comprehensive overview of a well-recognized critical pathogen Acinetobacter baumannii and demonstrates the potential of artificial intelligence (AI) in discovering new antibiotics. It is well-known for causing serious infections, especially in patients admitted to intensive care units, which is further compromised by bacterium's resistance to even last-resort antibiotics like carbapenems, posing critical challenges in its treatment and eradication. This article discusses Abaucin, a revolutionary antibiotic created from artificial intelligence, as a creative and potential treatment for A. baumannii. Methods: A comprehensive literature search was conducted using various databases including PubMed, Google Scholar, Cochrane, Science Direct, MEDLINE. Only articles written in English were considered. This correspondence was written after a thorough evaluation of all the articles that discussed Abaucin's discovery, potency against A. baumannii, and the potential of AI in discovering new antibiotics. In addition, references from the selected articles were also examined to ensure a comprehensive review of the literature. Results: This article highlights the discovery of a novel AI-derived antibiotic, Abaucin that offers a promising solution for A. baumannii infections. Abaucin has a narrow range of action that minimizes the risk of inter-pathogen spread of resistance, making the drug more appealing and effective. Its potential to suppress wound infections caused by multidrug-resistant A. baumannii paves a hope for the eradication of superbugs. Further investigation and trials are needed to determine its effectiveness in human subjects and its integrity in the clinical workflow. machine learning (ML) and precision approach could revolutionize treatment strategies. Conclusion: The discovery of Abaucin as an antibiotic to combat drug-resistant A. baumannii bacteria showcases AI and ML's potential to uncover novel antibiotics, thereby offering alternative treatment options. This novel inception of the AI-derived antibiotic, Abaucin marks the first step in introducing an innovative treatment option and represents a substantial leap in the treatment of drug-resistant illnesses and the use of AI in medical advancements.

The efficacy and safety of the novel combination lenvatinib and pembrolizumab in endometrial cancer: A systematic review and single-arm meta-analysis.

Objective: Endometrial carcinoma is the most widespread gynecological cancer, with increasing morbidity and mortality. Pembrolizumab, a monoclonal antibody that targets PD1 receptor tumors, is approved for patients with microsatellite instability-high (MSI-H) solid tumors. Many clinical trials and observational studies have been conducted to assess the safety and efficacy of Lenvatinib and Pembrolizumab combination therapy in the setting of endometrial cancer. However, results have been inconsistent, and current data is based on a heterogeneous population. The primary objective was to assess the safety and efficacy of Lenvatinib plus Pembrolizumab for endometrial cancer. Data sources: The search was conducted from inception from four databases; PubMed, Google Scholar, the Cochrane Library, and ClinicalTrials.gov. The electronic database search was conducted from inception to August 20, 2023. Study eligibility criteria: We considered randomized controlled trials and single-arm observational studies, i.e. cohort, case-control and cross-sectional studies. Methodology: We performed a single-arm meta-analysis, involving 7 studies having a total of 495 patients with endometrial cancer were eventually included which had the following outcomes: Complete response, Partial response, Progression-free survival, stable disease, progressive disease, safety outcomes, Adverse events, and the total number of deaths. Results: Our results showed that 88.6 % of the patients were positive for non-MSI-H/pMMR tumors (95 % CI = 0.825-0.927) whereas 6.5 % (95 % CI = 3.8-9.8 %) of the patients for MSI-H/dMMR tumors. The pooled objective response of endometrial cancer patients treated with Lenvatinib and Pembrolizumab was 36.5 % (95 % CI = 0.258-0.471), the pooled estimate of complete and partial response was 47 % (95 % CI = 0.024-0.070) and 31.3 % (95 % CI = 0.230-0.396). 38.2 % patients had stable disease (95 % CI = 0.329-0.435) and 24.0 % patients had progressive disease (95 % CI = 0.103-0.378). The pooled median progression-free survival was 5.97 (95 % CI 5.43-7.63) months and, whereas the median overall survival was 17.19 months (95 % CI 15.34-19.31). All grade adverse events occurred in 85 % and Grade 3 or worse adverse events occurred in 39 % of patients during the therapy whereas death occurred in 23.8 % during the treatment. Conclusion: The results of this meta-analysis concludes that although the combined treatment of a Lenvatinib and Pembrolizumab had a PFS and OS that was inferior to the standard therapy used to treat advanced and recurrent endometrial cancer, it is still a novel treatment and shows potential for further research with a greater sample size.

Dysphoric milk ejection reflex - call for future trials.

Dysphoric milk ejection reflex is a condition that causes an abrupt emotional downturn during the initial moments of milk ejection in a breastfeeding mother. Depression, anxiety, hopelessness, anger, irritability, homesickness, and stomach hollowness are all possible symptoms. The exact cause of D-MER remains unknown. However, it is proposed that it is caused by an alteration in oxytocin signaling response where secretion of oxytocin upregulates the stress response instead of its downregulation. Activation of the defensive response of the mother by oxytocin during breastfeeding, disruption in dopamine levels, and activation of vasopressin-regulated pathways are other probable causes. Due to a lack of awareness, this phenomenon is easily misdiagnosed as postpartum depression and aversion by many healthcare professionals. Its prevalence in various populations of the world remains unknown due to the lack of research studies conducted in these populations. While no medically approved therapeutic strategy is available, supportive techniques such as maintaining a healthy diet, mental distraction, relaxation methods, and increasing skin-to-skin contact can help alleviate dysphoria during breastfeeding. However, due to a lack of D-MER research, specific challenges exist regarding early withdrawal from breastfeeding and women's help-seeking attitude toward perinatal mental health.

Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace. METHODS: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes. RESULTS: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo. CONCLUSION: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Re-emergence of polio in Pakistan: Can the nation achieve the WPV1 eradication goal?

Background and Aims: Poliomyelitis is an acute neurologic condition that causes muscle weakness, permanent flaccid paralysis, and even death. The world has seen a drastic fall in the number of poliovirus cases owing to effective immunization programs and preventive measures. Pakistan and Afghanistan still remain the two endemic countries for poliovirus, particularly, the WPV1 strain. Global Polio Eradication Initiative (GPEI) has set a target to eradicate all WPV1 cases by the end of 2023. However, the re-emergence of WPV1 cases has posed a serious setback for the achievement of this target. This article aims to discuss the public health challenges that contribute to resurgence of poliovirus cases. Methods: A comprehensive literature search was conducted using various databases including Cochrane, Google Scholar, PubMed, Science Direct, MEDLINE. Only articles written in English were considered. All the articles reporting the incidence of poliovirus and WPV1 cases in Pakistan, surveillance data and global context of poliovirus outbreak were evaluated to write this correspondence. In addition, references from the selected articles were also examined to ensure a comprehensive review of the literature. Results: This article highlights the factors contributing to the re-emergence of WPV1 cases in Pakistan. Low vaccine coverage, attacks on frontline polio health workers, misinformation, and reluctance to vaccine acceptance pose a daunting challenge for polio eradication. Further, gaps in AFP surveillance and sensitivity may underestimate the true extent of the emerging genetic clusters. The Covid-19 pandemic and subsequent flooding in the affected area have further worsened the underdeveloped public health infrastructure. Conclusion: Despite the challenges, the country has observed a significant decline in the number of cases in the past 2 years. It is high time to capitalize on the decrease in WPV1 cases by intensifying the efforts to mitigate and limit the spread of the disease.

White Matter Stroke Masquerading as Subarachnoid Hemorrhage After High-Risk Percutaneous Coronary Intervention: A Case Report.

Considering the context of percutaneous coronary artery angiography (PCI), stroke is a rare but severe complication and is associated with high morbidity and mortality. A computed tomography (CT) scan of the brain is an indispensable imaging modality to diagnose ischemic stroke changes following PCI. A 75-year-old female who presented with sudden onset chest pain was diagnosed with anterior-wall myocardial infarction which required primary PCI. However, an hour following the procedure, she suddenly developed drowsiness, confusion, and hemiparesis. Non-contrast CT showed hyperdense signals in posterior falx and tentorium cerebelli suggesting subarachnoid hemorrhage (SAH) as well as low attenuation signals in bilateral periventricular region suggestive of microvascular ischemic changes. It was critical to decide about the continuation of dual antiplatelet therapy (DAPT), aspirin and P2Y12 inhibitor, as soon as possible. Based on the clinical presentation and mixed picture on the CT scan, a second opinion was sought by a multidisciplinary team, which concluded that the findings were consistent with white matter stroke and DAPT was resumed. The hemiparesis improved gradually with the reversal of CT scan findings. There is a lack of reported literature about ischemic stroke and SAH following high-risk PCI and what should be the best approach in ambiguous cases. The management of white matter stroke and SAH is contrasting, particularly in deciding whether to continue the DAPT after PCI; hence it is critical to diagnose them promptly. Thus, this case highlights the importance of differentiating SAH from white matter stroke for prompt treatment of post-PCI complications to ensure positive outcomes.

Artificial tears: Promising treatment or silent threat to public health?

Background and Aims: Dry Eye Disease (DED) is a multifactorial chronic inflammatory condition of the corneal surface, attributed to insufficient or low-quality production of tears, accounting for 5-50% of the cases globally. Artificial tears are the first line of treatment as they reduce ocular surface tension, and improve film stability and optical quality. EzriCare Artificial Tears are preservative-free, multi-dose, readily accessible eye drops containing carboxymethylcellulose sodium solution (10 mg in 1 ml) aiming for relief against DED. This article discusses the public health challenges faced by the use of EzriCare Artificial Tears and emphasizes the need for alternative therapies for the effective management of DED. Methods: We searched for articles documenting the incidence of the current multi-drug resistant P. aeruginosa strain outbreak caused by the use of preservative-free artificial tears and the challenges faced through the use of artificial tears on PubMed, and Google Scholar. Results: EzriCare and other preservative-free artificial tears have been reported to pose a serious public health risk as they have been found to be the commonly used product among the people infected with the current multi-state outbreak of the multi-drug resistant P. aeruginosa strain. Conclusion: The current multi-state outbreak of the multi-drug resistant P. aeruginosa strain has raised concerns about the safe use of other artificial products. It is high time that further trials should be conducted on other alternative strategies and evaluate the safety and efficacy of nanotechnology in the treatment of dry eye disease.

Revolutionising Impacts of Artificial Intelligence on Health Care System and Its Related Medical In-Transparencies.

The application of artificial intelligence (AI) in the field of medicine has revolutionised various sectors of the health care system, including robotics surgery, biotechnology, pharmaceutical, evidence-based medicine and advanced research and transplantation techniques. By offering improved 3D imagery of the various organs involved in surgery and perfectly minimising the chances of error, AI aid made complicated surgical procedures more efficient and highly effective, requiring less hands-on. Further, the AI tool helps plastic surgery and aesthetic surgeons in anticipating prognostic surgical markers and post-operative consequences. In addition to enhancing accurate and rapid diagnosis, AI has played a pivotal role in the development and discovery of new drugs. Nevertheless, the application of AI in health care also raises significant challenges and concerns. Incorrect drug recommendations, failure to identify tumours and lesions on imaging modalities and potential bias in data entry and its automatic can risk the life of patients on a large scale. Additionally, breaching patient data privacy may raise concerns about cybersecurity issues, further compromised by growing dependency on AI which can result in massive unemployment. In short, AI has played a pivotal role in health care; however, addressing the in-transparencies is critical to ensure safe, ethical and more effective implementation in the dynamic field of medicine.

Ritonavir-boosted Nirmatrelvir and COVID-19 outcomes in the age of Omicron variant.

Nirmatrelvir boosted with Ritonavir is the recommended and preferred treatment for COVID-19. Because real-world evidence of Nirmatrelvir's antiviral activity against the Omicron variation is minimal, our study focuses on recent papers suggesting the use of Ritonavir-boosted Nirmatrelvir in the real world against the most frequent SARS coronavirus variant circulating worldwide (Omicron). Despite sparse clinical evidence, we discovered that Ritonavir-boosted Nirmatrelvir reduced COVID-19-related hospitalization and mortality during the onset of the Omicron variant. Furthermore, this study discusses the main limitations and offers recommendations for administering this drug in non-hospitalized COVID-19 patients at high risk for severe infection.

Exploring the Efficacy of ZB-06 Vaginal Biofilm as a Novel Treatment for Recurrent Bacterial Vaginosis.

The purpose of this research was to investigate the efficacy of ZB-06 vaginal biofilm as a novel treatment for recurrent bacterial vaginosis (BV). BV is a prevalent vaginal infection that primarily affects women of reproductive age and is linked to adverse health outcomes. Biofilm production allows bacteria to cling to the vaginal epithelium, making antibiotics harder to penetrate and treat the illness efficiently. ZB-06 is a vaginal biofilm inhibitor that may dissolve the biofilm generated by the bacteria causing BV, enhancing antibiotic therapy efficacy and lowering the risk of recurrence. The current literature on BV, biofilm formation, and the possible function of ZB-06 as a therapy option for recurrent BV is reviewed in this article. More research is needed to determine ZB-06's safety and efficacy.