Prognostic role of suPAR in acute pancreatitis: A protocol for systematic review.

BACKGROUND: Acute pancreatitis (AP) is a common emergency condition with high morbidity, mortality, and socio-economic impact. Soluble urokinase plasminogen activator receptor (suPAR) is a potential biomarker for AP prognosis. This study systematically reviews the literature on suPAR's prognostic roles in assessing AP severity, organ failure, mortality, and other pathological markers. METHODS: A comprehensive search of 5 databases up to March 19, 2023, was conducted, selecting cohort studies that examined suPAR's relationship with AP outcomes. Outcome variables included AP severity, organ failure, mortality, hospital stay length, and suPAR's association with other inflammatory markers. Our paper has been registered on Prospero (ID: CRD42023410628). RESULTS: Nine prospective observational studies with 1033 AP patients were included. Seven of eight studies found suPAR significantly elevated in severe acute pancreatitis (P < .05). Four studies showed suPAR effectively predicted organ failure risk, and 4 studies concluded suPAR significantly predicted mortality (P < .05). The review had no high-risk studies, enhancing credibility. CONCLUSION: suPAR is a valuable prognostic marker in AP, significantly predicting severity, organ failure, hospital stay length, and mortality. Further large-scale studies are needed to explore suPAR's role in other clinical outcomes related to AP disease course, to establish it as a mainstay of AP prognosis.

Exploring the clinical potentials of zuranolone in managing postpartum depression: A new therapeutic horizon.

Postpartum depression (PPD) poses a major threat to maternal mental health and wellbeing while also adversely affecting the mother's relationship with her baby, leading to significant repercussions that may hinder the growth and cognitive development of the child. For decades, antidepressants have been the mainstay of treating PPD; however, recent evidence suggests that antidepressants are not as effective as they are believed to be and there is a dire need to explore new treatment options. In 2023, a breakthrough in treating PPD emerged with the recent FDA approval of zuranolone, a gamma-aminobutyric acid (GABAA) receptor selective positive allosteric modulator. The implementation of zuranolone in treating PPD can prove to be revolutionary, considering it is the first oral medication available for PPD. Our review aims to discuss the various clinical trials that have been conducted to validate the efficacy of zuranolone in mitigating the symptoms of PPD, hence, leading to better outcomes for mothers.

Unleashing the power of retatrutide: A possible triumph over obesity and overweight: A correspondence.

Background and Aims: Overweight and obesity have become global health challenges with increasing prevalence. Several drugs have received Food and Drug Administration approval for nonsyndromic obesity treatment, but most have limitations, including gastrointestinal side effects and limited weight loss efficacy. Body: Retatrutide, a novel incretin mimetic agent, has shown promise in clinical trials for significant weight reduction. It has demonstrated dosage-dependent pharmacokinetics with favorable safety profiles. The primary focus of this paper is to explore retatrutide and critically assess its clinical trials to justify its use and feasibility while highlighting its shortcomings. This paper also delves into the subject of obesity and its health manifestations. Conclusion: It is expected that the use of retatrutide, a triple agonist, will result in significant weight loss among individuals who are obese or overweight.

The Role of Anticoagulants and Antiplatelets in Reducing Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis of Studies Reporting Adjusted Data.

The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels. Therefore, we aim to investigate if anticoagulants (AC) and antiplatelet (AP) therapy play a role in mitigating COVID-19 and its associated thrombosis along with its effect on the mortality rate, the need for mechanical ventilation, and the risk of hospital admission. Electronic databases were searched from their inception to July 19, 2022. The studies were divided into two groups: Group A (any dose of AC/AP versus no AC/AP) and Group B (therapeutic dose of AC (tAC)/AP versus prophylactic dose of AC (pAC)/AP). Review Manager (RevMan) version 5.4.1 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used for all statistical analyses. Adjusted data ratios were extracted from all included studies and pooled using the random effects model. A total of 33 studies were taken for the analysis of two groups (Group A: 285,065 COVID-19-positive patients, Group B: 2,421 COVID-19-positive patients). Overall analysis in Group A showed that the AC/AP group had a low risk of mortality in COVID-19 patients compared to the control group (risk ratio (RR): 0.77, 95% confidence interval (CI): 0.69-0.86). There was no significant difference in the need for mechanical ventilation (RR: 0.80, 95% CI: 0.60-1.08) and hospital admission (RR: 1.12, 95% CI: 0.78-1.59) between the AC/AP and no AC/AP group. Alongside, in Group B, tAC/AP did not demonstrate a significant decrease in mortality as compared to pAC/AP (RR: 0.62, 95% CI: 0.37-1.06). Treatment with AC and AP drugs can significantly decrease the mortality rate in COVID-19-infected patients, while AC also significantly reduces the need for mechanical ventilation.

Perioperative selenium administration in cardiac surgery patients, a way out to reduce post surgical adversities? A meta analysis.

Introduction: The oxidative damage suffered in cardiac surgery is associated with declining trace elements which lead to the development of multi organ dysfunction (MOD), acute kidney injury (AKI), or increased length of hospital stay (LOS). Recent evidence shows the cardioprotective role of the trace element selenium as it mitigates worsening outcomes post cardiac surgery. Hence, this meta analysis aims to investigate the role of selenium in lowering cardiac surgery related adverse outcomes. Methods: Literature search of five electronic databases was performed from the inception of the paper till 29th July, 2023. Eligibility criteria included; (a) randomized clinical trials with Adult patients (≥18 years) undergoing cardiac surgery (b) intervention with selenium pre or/and postoperatively; (c) a control group of a placebo, normal saline, or no selenium. Outcomes of interest include postoperative mortality, LOS in the hospital and Intensive Care Unit (ICU), AKI, troponin I, and Creatinine Kinase-MB (CK-MB). The Cochrane bias assessment tool was used to evaluate the risk of bias. Outcomes were pooled with the Mantel-Haenszel Random-effects model using Review Manager. Results: Seven RCTs with 2,521 patients and 65% of males were included in this paper. No noticable differences were observed between selenium and control groups in terms of postoperative AKI, mortality, LOS in hospital and ICU, troponin I, and CK-MB levels. All studies had a low risk of bias on quality assessment. Discussion: Our meta analysis demonstrated no discernible effects of selenium infusion on post operative complications among patients undergoing cardiac surgery. Further large scale multi centered studies comparing the protective role of selenium with combined therapy of other bioactive agents are needed to provide convincing explanations. Systematic Review Registration: PROSPERO Identifier: 424920.

Comment on: Electrocardiographic findings and mortality in covid-19 patients hospitalized in different clinical settings.

We have diligently reviewed the article presented by Marco Mele et al., titled "Electrocardiographic findings and mortality in covid-19 patients hospitalized in different clinical settings"1 It was a concise and informative paper, and we acknowledge the authors for presenting an exceptional article that expanded our knowledge. Although we concur with the study's conclusion that Covid-19 patients' electrocardiograms (ECGs) differ at admission depending on the intensity of their care and the clinical setting, the stratification of risk for in-hospital mortality may be aided by a simplified score based on various clinical and ECG variables. However, we would like to highlight a few areas that would further strengthen the conclusion.

Therapeutic and safety outcomes of intracoronary nicardipine in coronary artery disease patients: a systematic review.

Aim: This systematic review aimed to shed light on the efficacy of intracoronary (IC) nicardipine in treating no reflow with CAD undergoing revascularization. Methods: Literature search was performed on databases with following eligibility criteria: adult patients with CAD; clinical trials or observational studies; IC nicardipine as intervention; therapeutic and safety outcome reported. Results: A total of 1249 papers were yielded during the literature search. Of these, 11 studies were finalized for this systematic review. Complete restoration of TIMI 3 flow was observed in 98.6% of the patients receiving IC nicardipine. A significant increase in the CBF after infusion of IC nicardipine (p < 0.05) was also observed. Conclusion: IC nicardipine significantly increases CBF and decreases coronary vascular resistance.

Coronary artery disease (CAD) is a condition that results in the narrowing or blockage of heart arteries. Arteries are blood vessels that bring oxygen-rich blood from your heart to the rest of your body's cells. We aimed to evaluate the effects of intracoronary (IC) nicardipine, a drug that blocks calcium from entering the muscle cells and blood vessels of the heart, which causes the vessels to relax and widen, allowing for blood to flow more easily, on a phenomenon known as coronary slow flow (CSF). CSF is defined as a delayed widening of the blood vessels of the heart. CSF or the no reflow phenomenon is a major negative complication associated with surgical procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), both of which are used to open up blocked arteries. The systematic search identified studies that evaluated the effect of IC nicardipine in patient during CAD treatment, undergoing PCI, CABG, or having confirmed or suspected narrowing of the aortic valve or one of the four valves of the heart, which results in restricted blood flow from the heart to the body. From the results of studies discussed in the review, it can be concluded that IC nicardipine significantly increases blood flow to the heart and can help prevent the no reflow phenomenon in patients undergoing PCI. Nicardipine proved to be a safe and effective option in the management of complications such as no reflow in patients receiving therapies to restore blood flow following CAD.

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.

Role of topical spironolactone in the treatment of acne: A systematic review of clinical trials-Does this therapy open a path towards favorable outcomes?

Acne vulgaris is the eighth most common disease worldwide and presents with inflammatory and noninflammatory skin lesions along with other dermal abnormalities. Oral spironolactone is used for treating acne vulgaris due to its antiandrogenic properties and inhibition of sebogenesis. Recent evidence shows that spironolactone in topical form has similar efficacy to its oral form with comparatively fewer adverse events associated with its use. However, to establish an evidence-based understanding, this systematic review aims to investigate the efficacy and safety of topical spironolactone in the treatment of acne vulgaris. PubMed, ClinicalTrials.gov, Cochrane library, and Google Scholar were comprehensively searched from the date of inception till March 18, 2022 All the clinical trials experimenting with the role of topical spironolactone in the treatment of acne were included. Articles examining the effects of oral spironolactone or other topical agents were excluded. The Cochrane risk of bias assessment tool (RoB 2.0, version 2019) was used to assess the risk of bias in each study. The study findings have been reported in line with PRISMA 2020 guidelines. The literature search yielded 600 articles. Five clinical trials with 195 patients were included in this review. Out of the five trials, two showed a high risk of bias while three had overall some concerns. Patients treated with topical spironolactone showed a significant decrease in the number of papules (p = 0.004), closed comedones (p < 0.05), and lesions (p < 0.05). Compared to placebo, treatment with 5% spironolactone showed a significant decrease in total lesion count (p = 0.007). In addition, 2% spironolactone showed efficacy over clindamycin and reduced the number of comedones (p < 0.0001), papules (p < 0.0001), and pustules (p < 0.0001) while the acne severity index was also considerably lowered (p < 0.0001). Spironolactone was not found to affect significant skin hydration, sebum, elasticity, melanin, and redness (p > 0.05). Topical spironolactone yields better results than other first-line treatments for acne and displays fewer side effects. However, further large-scale clinical trials are required before spironolactone can be used as the preferred treatment in the clinical management of acne.

Perinatal mental disorders associated with adverse childhood experiences in Asian countries; call to practice recommendations.

Perinatal depression (PND) is a major health risk to the mother and her unborn child and is linked to negative events. For example, PND has been related to a rise in suicides, a decline in a mother's quality of life, and a baby's stunted neurobiological development. In addition, recent research has shown that a mother's Adverse Childhood Experiences (ACEs) might predispose her to perinatal depression, with the prevalence of PND being comparably greater in Asian and lower-income nations. Our paper clarified the relationship between PND and ACEs and the steps Asian countries could take to combat the rising PND rates.

How Universal Health Coverage can curb the escalating antimicrobial resistance in Pakistan: a call to action for the country's healthcare system.

Antimicrobial resistance (AMR) has emerged as a major threat to the global healthcare economy during Coronavirus disease 2019 (COVID-19), especially in developing countries like Pakistan where the healthcare facilities are already substandard. To combat AMR, the World Health Organization (WHO) has taken several initiatives including the establishment of a sustainable Universal Health Coverage (UHC) system. The implementation of UHC could eliminate various factors that contribute to a high AMR rate including self-medication. Our commentary explores in depth the current UHC system in Pakistan and how UHC could be the answer to Pakistan's AMR crisis.

Effects of SARS-CoV-2 infection and COVID-19 pandemic on menstrual health of women: A systematic review.

Background: The menstrual cycle in women is the main indicator of their reproductive health which is affected by the ongoing coronavirus disease 2019 (COVID-19) pandemic. This review aims to summarize the effects of the COVID-19 infection and the global pandemic on the menstrual health of women. Methods: The literature search was conducted in PubMed, Cochrane library, and Google Scholar using keywords "COVID-19," "Menstrual Cycle," "Menstrual Cycle Irregularities," "Amenorrhea," "Polymenorrhea," and "Dysmenorrhea." The articles were selected according to the following inclusion criteria: (i) cross-sectional studies, (ii) cohort studies, (iii) surveys, and (iv) other observational studies observing the effects of SARS-CoV-2 infection or COVID-19 pandemic on menstrual health of women. Exclusion criteria included: case reports, gray literature, and website articles regarding menstrual health. Results: A total of 30,510 articles were shortlisted after a comprehensive search. Sixteen articles were included out of which 13 studies investigated the effects of the COVID-19 pandemic on the menstrual cycle while 3 evaluated the possible effects of COVID-19 infection on the menstrual health of women. Menstrual disorders or irregularities were a more common finding during the pandemic as compared to before (p = 0.008). Women affected by pandemic-related stress were more prone to changes in the duration of their menses (p = 0.0008), reported heavier bleeding (p = 0.028), and increased incidence of painful periods (p < 0.0001). COVID-19 infected women also reported changes in their menstrual cycle including irregular menstruation, increased symptoms of premenstrual syndrome, and infrequent menstruation. Conclusions: Women suffering from COVID-19 infection or pandemic-associated stress and anxiety were more likely to experience irregular menstruation, dysmenorrhea, amenorrhea, and other menstrual abnormalities compared to those who were less exposed.

Glycolysis: The Next Big Breakthrough in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by the death of dopaminergic neurons. Its pathogenesis comprises defects in the physiological pathway of mitophagy and mutations in the genes involved in this process's regulatory mechanism. PD manifests itself with multiple motor and non-motor symptoms, and currently, there are multiple pharmacological treatments, and unconventional non-drug treatments available. The mainstay of Parkinson's disease treatment has centered around directly manipulating neural mechanisms to retain high dopamine levels, either by exogenous administration, increasing intrinsic production, or inhibiting the breakdown of dopamine. In this review, we highlight a new potential biochemical modality of treatment, treating PD through glycolysis. We highlight how terazosin (TZ), via PGK1, increases ATP levels and how enhanced glycolysis serves a neuroprotective role in PD, and compensates for damage caused by mitophagy. We also discuss the role of quercetin, a bioactive flavonoid, in preventing the development of PD, and reversing mitochondrial dysfunction but only so in diabetic patients. Thus, further research should be conducted on glycolysis as a protective target in PD that can serve to not just prevent, but also alleviate the non-dopaminergic signs and symptoms of PD.

Poliovirus returns to Pakistan: A rising concern.

Poliomyelitis is a completely preventable but deadly virus causing paralysis in children and in some cases, death. Pakistan is one of the only two countries where polio is still prevalent despite relentless vaccination drives. In the past two months, four cases of polio have been documented in children no older than two years, condemning them to a life of disability. This commentary explores the reasons for the recent spike in polio cases and what measures can be taken to limit the spread of the disease, especially in high-risk areas where vaccine hesitancy poses a major problem. Unless drastic measures are taken by the healthcare sector, polio will continue to be a burden on the country's economy and countless more children will fall victim to the disease.

Samidorphan/olanzapine combination therapy for schizophrenia: Efficacy, tolerance and adverse outcomes of regimen, evidence-based review of clinical trials.

Introduction: Schizophrenia is a complex medical illness characterized by hallucinations, delusions, and cognitive issues. Olanzapine, a second-generation antipsychotic widely prescribed for schizophrenia has proven to be efficacious, however, its use is associated with major adverse effects such as weight gain, metabolic syndrome and diabetes mellitus. Recently, FDA approved a combination dose of olanzapine and samidorphan (OLZ/SAM) to mitigate the adverse outcomes associated with olanzapine use for the treatment of Schizophrenia. Objectives: The approval of olanzapine/samidorphan combination by FDA in treatment of schizophrenia and bipolar I disorder has been a milestone. This article summarizes the clinical trials reporting the clinical efficacy and adverse effects of olanzapine/samidorphan combination along with their bias assessment. Methods: Pubmed, science direct, Ovid SP and Google Scholar were comprehensively searched for data collection. Clinical trials reporting the efficacy and adverse outcomes of the OLZ/SAM regimen were included in the review and the Cochrane risk of bias assessment tool (RoB 2.0, version 2019) was used to assess the risk of bias in each study. Results: Five trials employed the use of Positive and Negative Syndrome Scales (PANSS) and Clinical Global Impression-Severity (CGI-S) scale to assess the efficacy of OLZ/SAM. Overall, OLZ/SAM showed a significant reduction in PANSS total scores and CGI-S scores and might be a viable option for long-term treatment. The safety of combined therapy is assessed by trials considering the factors of ECG parameters, suicidal events, and movement disorders. Major adverse events included nervous system disorders, changes in blood chemistry, and metabolic or nutritional disorders, with worsening of adverse outcomes observed in a total of nineteen cases in six studies. Conclusion: The FDA-approved drug recombination of OLZ/SAM for the treatment of schizophrenia revealed efficacious outcomes and was generally well tolerated by patients partaking in various trials. The potential of samidorphan in mimicking the efficacy of olanzapine while mitigating olanzapine-induced weight gain makes it a promising regimen for improving symptoms and health outcomes in schizophrenic patients.