Gender differences in pulmonology and critical care authorship and editorial boards.

OBJECTIVE: This study aims to characterize the gender distribution of first authors, senior authors, and editorial board members across several high-impact factor journals in PCCM. METHODS: In this cross-sectional study, we analysed gender disparities in critical care authorship and editorial boards, based on publications from 1 January 2019 to 31 December 2021 from the top 20 high impact journals based on the Journal of Citation Reports. RESULTS: Among 20 journals (median impact factor of 6.66), 25% of editors-in-chief and 28.8% of editorial board members were female. From 2019 to 2021, a total of 23,994 articles were published. Female first authors and last authors made up 29.1% and 21.2% of the authorship, respectively (n = 6637 articles). CONCLUSIONS: Our study demonstrates significant gender disparities in critical care authorship and editorial boards, with males predominantly filling the roles of editors in chief, editorial members, and first and senior authors. Despite this significant difference in gender distribution, there was no statistically significant correlation between authorship and editor gender.

Phenazopyridine-Induced Methaemoglobinaemia The Aftermath of Dysuria Treatment.

Introduction: Phenazopyridine is an over-the-counter urinary analgesic commonly used to alleviate the burning and urgency associated with lower urinary tract infections. Methaemoglobinaemia is an uncommon adverse effect of phenazopyridine use. We report a case of methaemoglobinaemia in a patient prescribed daily phenazopyridine to treat urethral and bladder irritation caused by a chronic indwelling Foley catheter. Case description: A 55-year-old female resident of a long-term acute care facility with a chronic Foley, tracheostomy and ventilator-dependent respiratory failure was observed to have generalized dusky skin and hypoxia. Pulse oximetry was reading in the high 80s despite administration of 100% FiO2. ABG revealed paO2 of 451, oxyhaemoglobin level 75% and methaemoglobin level 22%. Medication review indicated that the patient was prescribed phenazopyridine 400 mg TID for the previous 2 months. This medication was discontinued. Considering she was chronically taking mirtazapine, she can increase risk of serotonin syndrome should she be administered first-line treatment with methylene blue. Vitamin C was thus instead administered as a second-line agent. Serial ABGs showed a rapid decline in methaemoglobin levels and an increase in oxyhaemoglobin within 2 days. Discussion: Acquired methaemoglobinaemia is a rare adverse effect of treatment with phenazopyridine. This risk increases when drug dosage and duration exceed manufacturer specifications. Treatment typically includes cessation of the offending drug and administration of methylene blue in severe cases. A thorough medication reconciliation should be performed prior to methylene blue initiation, as patients taking serotonergic medications (for example, MAOIs, SSRIs, SNRIs, TCAs) are at increased risk of serotonin toxicity with co-administration of methylene blue. In these instances, ascorbic acid/vitamin C can be chosen as an alternative treatment agent. Conclusion: Work-up of refractory hypoxia should involve a thorough review of medications as even some over-the-counter drugs can cause the fatal side effect of methaemoglobinaemia. Treatment with vitamin C should be considered over methylene blue if serotonergic medications have been recently prescribed in order to avoid risk of serotonin syndrome. LEARNING POINTS: Methaemoglobinaemia is an uncommon, life-threatening adverse effect of phenazopyridine use. Presentation depends on the severity of the disorder, ranging from headache, weakness, lightheadedness and dyspnoea, to arrhythmias, confusion, seizures and multiorgan failure.Workup of refractory hypoxia should involve a comprehensive medication review as even some over-the-counter drugs can cause methaemoglobinaemia.Management of methaemoglobinaemia involves cessation of the offending drug, administration of supplemental oxygen and treatment with methylene blue (1-2 mg/kg) if MetHb >30%, or for symptomatic patients with MetHb >20%. Vitamin C can be used as an alternative agent if there is a contraindication to methylene blue (for example, with patients simultaneously receiving serotonergic medications and/or those with G6PD deficiency).

Pseudoshock: A Challenging Presentation of Bilateral Subclavian Artery Stenosis.

Introduction: Subclavian artery stenosis (SAS) is a manifestation of peripheral artery disease (PAD). Presentation varies, ranging from arm claudication and muscle fatigue to symptoms which reflect vertebrobasilar hypoperfusion, among which are syncope, ataxia and dysphagia. Although rare, severe bilateral SAS can exist and present as refractory hypotension. We describe a case of bilateral SAS masquerading as circulatory shock, or rather 'pseudoshock'. Case Description: A 59-year-old female patient presented to the emergency department with complaints of dark stools. She was anaemic and hypotensive and therefore suspected to have an acute gastrointestinal bleed (GIB) with resultant haemorrhagic shock. Her hypotension was unresponsive to fluid resuscitation and blood transfusions. Bilateral upper extremity radial artery catheters confirmed low blood pressures. After her blood pressure failed to improve despite the addition of several vasopressors, a femoral artery catheter (FAC) was placed, which revealed significant hypertension discordant with the hypotension measured by the radial artery catheters. Review of CT angiography of the upper extremities revealed the presence of bilateral SAS which was deemed to be the aetiology of the falsely low blood pressure. Discussion: SAS should be suspected in patients with lower extremity PAD or a blood pressure (BP) differential of 15 mmHg or more between arms. When bilateral subclavian arteries are stenosed, this difference in BP may be concealed, making lower extremity BP measurements, as seen in non-invasive tests such as ankle brachial index (ABI) tests or through more invasive procedures such as FAC placement, critically important. Conclusion: Bilateral SAS may present as pseudo-hypotension. In cases of refractory shock of unclear aetiology, especially in patients with known PAD, a high index of suspicion is warranted for 'pseudoshock' secondary to severe vascular stenosis. Comparison of upper and lower extremity BP via invasive arterial catheters or non-invasive ABI tests can aid in the diagnosis of bilateral SAS. LEARNING POINTS: Bilateral subclavian artery stenosis (SAS) may present as pseudo-hypotension and shock of unclear aetiology.In patients with underlying peripheral arterial disease, pseudoshock should be considered in the differential diagnosis.Comparison of upper and lower extremity blood pressure via invasive arterial catheters or the non-invasive ankle brachial index (ABI) test has diagnostic value for bilateral SAS.Pseudoshock is managed via secondary prevention with antiplatelets and statins for asymptomatic patients, and revascularization for symptomatic patients.

Acute Respiratory Distress Syndrome and the Use of Inhaled Pulmonary Vasodilators in the COVID-19 Era: A Narrative Review.

The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. COVID-19-associated ARDS (CARDS) differs from the typical ARDS due to distinct pathology involving the pulmonary vasculature endothelium, resulting in diffuse thrombi in the pulmonary circulation and impaired gas exchange. The National Institute of Health and the Society of Critical Care Medicine recommend lung-protective ventilation, prone ventilation, and neuromuscular blockade as needed. Further, a trial of pulmonary vasodilators is suggested for those who develop refractory hypoxemia. A review of the prior literature on inhaled pulmonary vasodilators in ARDS suggests only a transient improvement in oxygenation, with no mortality benefit. This narrative review aims to highlight the fundamental principles in ARDS management, delineate the fundamental differences between CARDS and ARDS, and describe the comprehensive use of inhaled pulmonary vasodilators. In addition, with the differing pathophysiology of CARDS from the typical ARDS, we sought to evaluate the current evidence regarding the use of inhaled pulmonary vasodilators in CARDS.

(-)-Epigallocatechin-3-gallate reverses the expression of various tumor-suppressor genes by inhibiting DNA methyltransferases and histone deacetylases in human cervical cancer cells.

There has been increasing evidence that numerous bioactive dietary agents can hamper the process of carcinogenesis by targeting epigenetic alterations including DNA methylation. This therapeutic approach is considered as a significant goal for cancer therapy due to the reversible nature of epigenetic-mediated gene silencing and warrants further attention. One such dietary agent, green tea catechin, (-)-epigallocatechin-3-gallate (EGCG) has been shown to modulate many cancer-related pathways. Thus, the present study was designed to investigate the role of EGCG as an epigenetic modifier in HeLa cells. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibition assays were conducted, and the transcription levels of DNMT3B and HDAC1 were assessed by enzymatic activity assay and RT-PCR, respectively. Furthermore, we studied the binding interaction of EGCG with DNMT3B and HDAC1 by molecular modeling as well as promoter DNA methylation and expression of retinoic acid receptor-ß (RARß), cadherin 1 (CDH1) and death-associated protein kinase-1 (DAPK1) in EGCG-treated HeLa cells by RT-PCR and MS-PCR. In the present study, time-dependent EGCG-treated HeLa cells were found to have a significant reduction in the enzymatic activity of DNMT and HDAC. However, the expression of DNMT3B was significantly decreased in a time-dependent manner whereas there was no significant change in HDAC1 expression. Molecular modeling data also supported the EGCG-mediated DNMT3B and HDAC1 activity inhibition. Furthermore, time-dependent exposure to EGCG resulted in reactivation of known tumor-suppressor genes (TSGs) in HeLa cells due to marked changes in the methylation of the promoter regions of these genes. Overall, the present study suggests that EGCG may have a significant impact on the development of novel epigenetic-based therapy.

Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells.

Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 µM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARß, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy.