BackgroundPulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.Methodology497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.Principal FindingsSixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).SignificanceThese data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.

BackgroundOxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.Methodology165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.Principal FindingsThere was wide variation in SaO2 on air (78.5–99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.SignificanceHaemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses.

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Postural changes in 258 patients with pulmonary arteriovenous malformations (PAVMs) reviewed between 2005 and 2013 were evaluated prospectively using validated pulse oximetry methods. Of the 257 completing the test, 75 (29%) demonstrated orthodeoxia with an oxygen saturation fall of at least 2% on standing. None described platypnoea (dyspnoea on standing). The heart rate was consistently higher in the erect posture: 74 (29%) had a postural orthostatic tachycardia of ≥20 min . Orthostatic tachycardia was more pronounced in PAVM patients than controls without orthodeoxia (age-adjusted coefficient 5.5 (95% CIs 2.6, 8.4) min −1 , p<0.001). For PAVM patients, the age-adjusted pulse rise was 0.79 min −1 greater for every 1% greater drop in oxygen saturation on standing ( p<0.001). In contrast to the postural orthostatic tachycardia syndrome, in this population, there was a trend for more pronounced orthostatic tachycardia to be associated with better exercise tolerance. To the editorPulmonary arteriovenous malformations (PAVMs) result in hypoxaemia due to right-to-left shunting. 1Recent studies highlight that chronic hypoxaemia in ironreplete patients leads to secondary erythrocytosis which preserves arterial oxygen content (CaO 2 ).2 Both shunt fraction 3 and hypoxaemia severity 4 may increase acutely on standing, a phenomenon ascribed to basally situated PAVMs.3 4 Platypnoeaorthodeoxia (dyspnoea and arterial deoxygenation on standing) has been described, particularly in patients with patent foramen ovale.5 However, platypnoea was not our experience in the PAVM population, suggesting they may be able to compensate for acute falls in CaO 2 . The goal of the study was to quantify orthodeoxia and examine potential compensatory mechanisms to facilitate provision of appropriate information to PAVM patients.The study was ethically approved by the Hammersmith, Queen Charlotte's, Chelsea, and Acton Hospital Research Ethics Committee (LREC 2000/5764). Full methods are presented in the online supplementary data supplement. In all, 258 consecutive patients with CT-proven PAVMs were prospectively and newly recruited (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013) and evaluated as described. Research letter on 28 April 2019 by guest. Protected by copyright.

Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define—for the first time—the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries—who only made up 21% of the total attendees. Conclusions To track global progress towards timely access to quality SAO care, these indicators—at the basic level—should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.

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CL. Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations. QJM. 2019 In Press Exercise capacity reflects airflow limitation rather than hypoxaemia in patients with pulmonary arteriovenous malformations

Objectives: To assist with planning hospital resources, including critical care (CC) beds, for managing patients with COVID-19.Methods: An individual simulation was implemented in Microsoft Excel using a discretely integrated condition event simulation. Expected daily cases presented to the emergency department were modeled in terms of transitions to and from ward and CC and to discharge or death. The duration of stay in each location was selected from trajectory-specific distributions. Daily ward and CC bed occupancy and the number of discharges according to care needs were forecast for the period of interest. Face validity was ascertained by local experts and, for the case study, by comparing forecasts with actual data.Results: To illustrate the use of the model, a case study was developed for Guy's and St Thomas' Trust. They provided inputs for January 2020 to early April 2020, and local observed case numbers were fit to provide estimates of emergency department arrivals. A peak demand of 467 ward and 135 CC beds was forecast, with diminishing numbers through July. The model tended to predict higher occupancy in Level 1 than what was eventually observed, but the timing of peaks was quite close, especially for CC, where the model predicted at least 120 beds would be occupied from April 9, 2020, to April 17, 2020, compared with April 7, 2020, to April 19, 2020 reality. The care needs on discharge varied greatly from day to day. Conclusions:The DICE simulation of hospital trajectories of patients with COVID-19 provides forecasts of resources needed with only a few local inputs. This should help planners understand their expected resource needs.