Comparing Renin-Angiotensin-Aldosterone Blockade Regimens for Long-Term Chemotherapy-Related Cardiac Dysfunction: A Network Meta-Analysis.

PURPOSE: Cancer therapies including trastuzumab and anthracyclines are cardiotoxic and cause cardiac dysfunction. To prevent cardiotoxicity, pharmacological agents used in heart failure have been administered concomitantly with cardiotoxic cancer therapy, but few studies to date have performed a head-to-head comparison of these different agents. This systematic review and network meta-analysis of randomized-controlled trials aims to evaluate the efficacy of renin-angiotensin-aldosterone system (RAAS) blockers, namely angiotensin-converting enzyme inhibitors (ACE-Is), aldosterone receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), in primary prevention against chemotherapy-related cardiac dysfunction in patients receiving anthracyclines and/or trastuzumab. METHODS: A systematic search was performed in major web databases for studies from inception to 15 September 2022. A Bayesian network meta-analysis model was used to assess the relative effects of competing treatments on the primary outcomes of risk of significant decline in left ventricular ejection fraction (LVEF) and mean LVEF decline. Secondary outcomes included left ventricular diastolic function, global longitudinal strain, and cardiac biomarkers. This study is registered with PROSPERO, CRD42022357980. RESULTS AND CONCLUSION: Nineteen studies reported the effects of 13 interventions (N = 1905 patients). Only enalapril (RR 0.05, 95% CI 0.00-0.20) was associated with reduced risk of patients developing significant decline in LVEF relative to placebo. Subgroup analysis showed that the beneficial effect of enalapril was driven by protection against anthracycline-associated toxicity. In addition, no RAAS-inhibiting agents showed efficacy in protection against treatment with both anthracycline and trastuzumab. The use of RAAS inhibition therapy did not conclusively impact on other markers of cardiac function, including left ventricular diastolic function and cardiac biomarkers.

Correction to: Epidemiology of patients presenting to a pediatric emergency department in Karachi, Pakistan.

An amendment to this paper has been published and can be accessed via the original article.

Epidemiology of patients presenting to a pediatric emergency department in Karachi, Pakistan.

BACKGROUND: There is little data describing pediatric emergencies in resource-poor countries, such as Pakistan. We studied the demographics, management, and outcomes of patients presenting to the highest-volume, public, pediatric emergency department (ED) in Karachi, Pakistan. METHODS: In this prospective, observational study, we approached all patients presenting to the 50-bed ED during 28 12-h study periods over four consecutive weeks (July 2013). Participants' chief complaints and medical care were documented. Patients were followed-up at 48-h and 14-days via telephone. RESULTS: Of 3115 participants, 1846 were triaged to the outpatient department and 1269 to the ED. Patients triaged to the ED had a median age of 2.0 years (IQR 0.5-4.0); 30% were neonates (< 28 days). Top chief complaints were fever (45.5%), diarrhea/vomiting (32.3%), respiratory (23.1%), abdominal (7.5%), and otolaryngological problems (5.8%). Temperature, pulse and respiratory rate, and blood glucose were documented for 66, 42, and 1.5% of patients, respectively. Interventions included medications (92%), IV fluids (83%), oxygen (35%), and advanced airway management (5%). Forty-five percent of patients were admitted; 11 % left against medical advice. Outcome data was available at time of ED disposition, 48-h, and 14 days for 83, 62, and 54% of patients, respectively. Of participants followed-up, 4.3% died in the ED, 11.5% within 48 h, and 19.6% within 14 days. CONCLUSIONS: This first epidemiological study at Pakistan's largest pediatric ED reveals dramatically high mortality, particularly among neonates. Future research in developing countries should focus on characterizing reasons for high mortality through pre-ED arrival tracking, ED care quality assessment, and post-ED follow-up.

Feasibility of awake craniotomy for brain arteriovenous malformations: A scoping review.

Background: Brain Arteriovenous Malformations (AVMs) located in proximity to eloquent brain regions are associated with poor surgical outcomes, which may be due to higher rates of postoperative neurological deterioration. Current treatment protocols include stereotactic radiosurgery, transarterial embolization, and surgical resection under general anesthesia. Awake Craniotomy (AC) allows intraoperative mapping of eloquent areas to improve post-operative neurologic outcomes. Objectives: We reviewed the current literature reporting surgical outcomes and assessed the feasibility of AC for AVM resection. Methods: The PRISMA guidelines were utilized as a template for the review. Three databases including PubMed, Scopus, and Cochrane Library were searched using a predefined search strategy. After removing duplicates and screening, full texts were analyzed. Outcomes including the extent of resection, intra-operative and post-operative complications, and long-term neurologic outcomes were assessed. Results: 12 studies were included with a total of 122 AVM cases. Spetzler-Martin grading was used for the classification of the AVMs. The asleep-awake-asleep protocol was most commonly used for AC. Complete resection was achieved in all cases except 5. Intraoperative complications included seizures (n = 2) and bleeding (n = 4). Short-term post-operative complications included hemorrhage (n = 3), neurologic dysfunctions including paresis (n = 3), hemiplegia (n = 10), dysphasia/aphasia (n = 6), cranial nerve dysfunction (n = 3), and pulmonary embolism (n = 1). Almost all neurological deficits after surgery gradually improved on subsequent follow-ups. Conclusion: AVMs may shift the anatomical location of eloquent brain areas which may be mapped during AC. All studies recommended AC for the resection of AVMs in close proximity to eloquent areas as mapping during AC identifies the eloquent cortex thus promoting careful tissue handling which may preserve neurologic function and/or predict the postoperative functional status of the patients We, therefore, conclude that AC is a viable modality for AVMs resection near eloquent language and motor areas.

Clinical efficacy and long-term immunogenicity of an early triple dose regimen of SARS-CoV-2 mRNA vaccination in cancer patients.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION: This study demonstrates the benefit of early administration of the third dose among cancer patients.

Disaggregating Asian Race Reveals COVID-19 Disparities Among Asian American Patients at New York City's Public Hospital System.

OBJECTIVES: Data on the health burden of COVID-19 among Asian American people of various ethnic subgroups remain limited. We examined COVID-19 outcomes of people of various Asian ethnic subgroups and other racial and ethnic groups in an urban safety net hospital system. METHODS: We conducted a retrospective analysis of 85 328 adults aged ≥18 tested for COVID-19 at New York City's public hospital system from March 1 through May 31, 2020. We examined COVID-19 positivity, hospitalization, and mortality, as well as demographic characteristics and comorbidities known to worsen COVID-19 outcomes. We conducted adjusted multivariable regression analyses examining racial and ethnic disparities in mortality. RESULTS: Of 9971 Asian patients (11.7% of patients overall), 48.2% were South Asian, 22.2% were Chinese, and 29.6% were in other Asian ethnic groups. South Asian patients had the highest rates of COVID-19 positivity (30.8%) and hospitalization (51.6%) among Asian patients, second overall only to Hispanic (32.1% and 45.8%, respectively) and non-Hispanic Black (27.5% and 57.5%, respectively) patients. Chinese patients had a mortality rate of 35.7%, highest of all racial and ethnic groups. After adjusting for demographic characteristics and comorbidities, only Chinese patients had significantly higher odds of mortality than non-Hispanic White patients (odds ratio = 1.44; 95% CI, 1.04-2.01). CONCLUSIONS: Asian American people, particularly those of South Asian and Chinese descent, bear a substantial and disproportionate health burden of COVID-19. These findings underscore the need for improved data collection and reporting and public health efforts to mitigate disparities in COVID-19 morbidity and mortality among these groups.

Vitamin E, Alpha-Tocopherol, and Its Effects on Depression and Anxiety: A Systematic Review and Meta-Analysis.

BACKGROUND: Recently, it has been discovered that anti-inflammatory and anti-oxidative pathways play a role in depression and anxiety. Lower serum levels of antioxidants, such as vitamin E, have been implicated in both depression and anxiety. METHODS: This PROSPERO-registered systematic review (Reference: CRD42021260058) is reported according to PRISMA guidelines. PubMed, EMBASE, CENTRAL, PsycINFO, and CINAHL were searched from inception to June 2021. RESULTS: Twelve studies were included in this systematic review, and nine in meta-analysis of vitamin E versus placebo. For depression, meta-analysis of 354 participants showed a standardised mean difference of -0.88 (95% CI: -1.54, -0.21; I2 = 87%) favouring vitamin E. For anxiety, meta-analysis of 306 participants showed a standardised mean difference of -0.86 (95% CI: -2.11, 0.40; I2 = 95%) favouring vitamin E. Three of the studies involved a pure comparison of vitamin E against placebo, while others included constituents such as omega-3 fatty acids. Nine of the studies were at low risk of bias, two had some concerns, and one was at high risk of bias. CONCLUSION: Vitamin E supplementation has shown inconclusive results in ameliorating both depression and anxiety. Containing a reassuring safety profile and low cost, future studies would be of promise, and they would benefit from both larger sample sizes and from excluding other constituents, such as omega-3 fatty acids, from experimental and comparator arms.

Defining Gas-Phase Fragmentation Propensities of Intact Proteins During Native Top-Down Mass Spectrometry.

Fragmentation of intact proteins in the gas phase is influenced by amino acid composition, the mass and charge of precursor ions, higher order structure, and the dissociation technique used. The likelihood of fragmentation occurring between a pair of residues is referred to as the fragmentation propensity and is calculated by dividing the total number of assigned fragmentation events by the total number of possible fragmentation events for each residue pair. Here, we describe general fragmentation propensities when performing top-down mass spectrometry (TDMS) using denaturing or native electrospray ionization. A total of 5311 matched fragmentation sites were collected for 131 proteoforms that were analyzed over 165 experiments using native top-down mass spectrometry (nTDMS). These data were used to determine the fragmentation propensities for 399 residue pairs. In comparison to denatured top-down mass spectrometry (dTDMS), the fragmentation pathways occurring either N-terminal to proline or C-terminal to aspartic acid were even more enhanced in nTDMS compared with other residues. More generally, 257/399 (64%) of the fragmentation propensities were significantly altered (P ≤ 0.05) when using nTDMS compared with dTDMS, and of these, 123 were altered by 2-fold or greater. The most notable enhancements of fragmentation propensities for TDMS in native versus denatured mode occurred (1) C-terminal to aspartic acid, (2) between phenylalanine and tryptophan (F|W), and (3) between tryptophan and alanine (W|A). The fragmentation propensities presented here will be of high value in the development of tailored scoring systems used in nTDMS of both intact proteins and protein complexes. Graphical Abstract ᅟ.