BackgroundPleural fluid cytology is an important diagnostic test used for the investigation of pleural effusions. There is considerable variability in the reported sensitivity for the diagnosis of malignant pleural effusions (MPE) in the literature.ObjectiveThe purpose of this review is to determine the diagnostic sensitivity of pleural fluid cytology for MPE, both overall and by tumour type, to better inform the decision-making process when investigating pleural effusions.Data sourcesA literature search of EMBASE and MEDLINE was performed by four reviewers. Articles satisfying inclusion criteria were evaluated for bias using the QUADAS-2 tool.Data extractionFor quantitative analysis, we performed a metaanalysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on primary cancer site and meta-regression by year of publication.SynthesisThirty-six studies with 6057 patients with MPE were included in the meta-analysis. The overall diagnostic sensitivity of pleural fluid cytology for MPE was 58.2% (95% CI 52.5% to 63.9%; range 20.5%–86.0%). There was substantial heterogeneity present among studies (I2 95.5%). For primary thoracic malignancies, sensitivity was highest in lung adenocarcinoma (83.6%; 95% CI 77.7% to 89.6%) and lowest in lung squamous cell carcinoma (24.2%; 95% CI 17.0% to 31.5%) and mesothelioma (28.9%; 95% CI 16.2% to 41.5%). For malignancies with extrathoracic origin, sensitivity was high for ovarian cancer (85.2%; 95% CI 74.2% to 96.1%) and modest for breast cancer (65.3%; 95% CI 49.8% to 80.8%).ConclusionsPleural fluid cytology has an overall sensitivity of 58.2% for the diagnosis of MPE. Clinicians should be aware of the high variability in diagnostic sensitivity by primary tumour type as well as the potential reasons for false-negative cytology results.PROSPERO registration numberCRD42021231473.

IntroductionInhaled volatile anaesthetics have a long tradition of use as hypnotic agents in operating rooms and are gaining traction as sedatives in intensive care units (ICUs). However, uptake is impeded by low familiarity with volatiles, unique equipment and education needs. Inhaled anaesthetics are often reserved in ICUs as therapies for refractory and life threatening status asthmaticus, status epilepticus, high and difficult sedation need scenarios given they possess unique pharmacological properties to manage these medical conditions while providing sedation to acutely ill patients. The objective of this systematic review is to collate evidence regarding the efficacy, safety and feasibility of volatile anaesthetics in adult and paediatric ICU patients for these three emergency conditions.Methods and analysisWe will conduct a systematic review of the primary studies in adult and paediatric ICU patients with status asthmaticus, status epilepticus and high/difficult sedation needs. We will include observational and interventional studies published from 1970 to 2021 in English or French investigating patients who have received a volatile inhalational agent for the above indications. We will evaluate the efficacy, safety, feasibility and implementation barriers for the volatile anaesthetics for each of three specified indications. Included studies will not be limited by necessity of a comparator arm. We will also evaluate clinical characteristics, patient demographics and provider attitudes towards volatile anaesthetic administration in defined critical care scenarios. Data will be extracted and analysed across these domains. The databases MEDLINE, EMBASE, the Science Citation Index as well as the Cochrane Central Controlled Trials Register will be queried with our search strategy.Descriptive and statistical analysis will be employed where appropriate. Data extraction and quality assessment will be performed in duplicate using a standardised tool. A narrative approach and statistical analyses will be used to describe patient characteristics, volatile efficacy, safety concerns, technical administration, attitudes towards administration and other implementation barriers.Ethics and disseminationNo ethics board approval will be necessary for this systematic review. This research is independently funded. Results will be disseminated in a peer-reviewed journal and conference presentation.PROSPERO numberCRD42021233083.

Background: Since the identification of JAK2 mutations in polycythemia vera (PV) in 2005 (Kralovics et al., NEJM 2005), molecular testing of JAK2 in patients with erythrocytosis has become part of routine clinical practice. We hypothesized that changes in the World Health Organization (WHO) diagnostic criteria for PV in 2016, which lowered the hemoglobin threshold to >165 g/L for men and >160 g/L for women, may have resulted in increased molecular testing. This study examines changing patterns of utilization of molecular diagnostics in patients referred for erythrocytosis at a tertiary care center. Methods: We examined all patients with erythrocytosis who underwent JAK2 testing, which included testing for JAK2 V617F with PCR between 2015 and 2017, and JAK2 V617F and exon 12 mutations with Next-Generation Sequencing (NGS) between 2018 and 2020 at London Health Sciences Centre in Ontario, Canada. We performed a retrospective chart review to extract laboratory and clinical data, including information on medical comorbidities and medications, with a focus on known secondary causes of erythrocytosis. Results: A total of 668 patients with erythrocytosis underwent JAK2 testing at our institution between August 1, 2015 and December 31, 2020. There was an overall increase in testing over the five-year study period, with a decline in the positive detection rate: 8/29 (28%) in 2015, 15/94 (16%) in 2016, 15/100 (15%) in 2017, 19/136 (14%) in 2018, 17/162 (10%) in 2019, and 14/147 (10%) in 2020 (Figure 1). The average hemoglobin levels in patients with erythrocytosis who underwent testing remained similar across all years (range 170-173 g/L for women, 179-181 g/L for men). In our cohort, there was a high proportion of patients with known or suspected secondary causes of erythrocytosis who underwent molecular testing. Between 2018 and 2020, 324/445 (73%) of patients who underwent molecular testing had either chronic obstructive pulmonary disease, obstructive sleep apnea, other hypoxic lung disease, smoking history, erythropoietin-secreting tumor, or potential drug-induced erythrocytosis. Specifically, we observed an increase in proportion of patients who underwent molecular testing on sodium-glucose cotransporter-2 (SGLT-2) inhibitors, a known secondary cause of erythrocytosis, with 15/136 (11%) in 2018, 17/162 (10%) in 2019, and 25/147 (17%) in 2020. In contrast, the proportion of patients on testosterone was relatively constant at 15/136 (11%) in 2018, 11/162 (6.8%) in 2019, and 11/147 (7.5%) in 2020. Conclusion: This study revealed that a high proportion of patients with known or suspected secondary causes of erythrocytosis underwent JAK2 testing, resulting in increase in molecular testing over time and a decline in positive detection rate. In particular, we observed a number of patients on SGLT-2 inhibitors who had investigation, suggesting that this class of medications may be an underrecognized cause of drug-induced erythrocytosis (Chin-Yee et al., CMAJ 2020). Our findings underscore the importance of careful medical history and medication review to support more judicious use of molecular testing. Similarity in average hemoglobin levels across the five-year study period suggests that other factors, such as increased availability of 'routine' molecular testing, rather than changes in the WHO diagnostic criteria may explain increases in JAK2 testing. Our study indicates a need to develop an effective clinical prediction rule for JAK2 positivity to better risk stratify patients with suspected PV based on clinical and laboratory parameters to optimize utilization of molecular diagnostics. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Highlights Acetaminophen toxicity can be associated with a metabolic acidosis and treated with Renal Replacement Therapy. Metabolic acidosis refractory to renal replacement therapy likely leads to worse outcomes. Cystatin C should be used as a marker of renal function in acetaminophen toxicity.