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PURPOSE/HYPOTHESIS: Coronavirus disease 2019 (COVID-19) may result in hypoxemic respiratory failure and death similar to acute respiratory distress syndrome (ARDS). Based on its known efficacy in ARDS, prone positioning (PP) was used to manage intubated patients with severe COVID-19 lung disease. Though less supported by evidence, awake prone positioning (APP) was also trialed in non-intubated patients with COVID-19 to preserve resources and optimize outcomes. The primary available evidence included in recent reviews on APP in COVID-19 were the resultant retrospective single group studies that showed mixed findings. While such designs expedite results, a risk of bias weakens their application. With emerging research, this focused review evaluated APP in COVID-19 based on prospective trials that included a comparison group. NUMBER OF SUBJECTS: Not applicable. MATERIALS AND METHODS: PubMed and CINAHL databases were searched through June 10, 2022 with the following strategy: [(SARS-COV-2) OR (COVID-19) OR (coronavirus)] AND [(prone) OR (proning) OR (prone positioning)]. Prospective studies investigating APP in non-intubated adults with COVID-19 compared to usual care were included. Quality of evidence was determined by the Cochrane Risk of Bias tool with recommendations made using the GRADE approach. RESULT(S): Seven articles evaluating APP in a combined total of 2604 participants (66% male, mean age: 59.8 yrs, BMI: 29.0) with mild to moderate hypoxemic respiratory failure were included. Participant characteristics were heterogeneous and the duration of proning ranged from 4 to 16 hrs/d. APP was associated with improved oxygenation;however, only one study reported a lower incidence of intubation. No effect was noted on mortality or length of stay (LOS). Adverse events were rare but APP was associated an initial worsening outcome in one instance. Lack of blinding and protocol heterogeneity were identified risks of bias. CONCLUSION(S): APP may improve oxygenation in non-intubated individuals with mild to moderate COVID-19 lung disease as compared to usual care;however, prospective controlled trials do not support a positive effect on intubation, LOS, or mortality. The lack of transference in contrast to PP in intubated patients suggests that the primary benefit of PP may be minimizing ventilator-induced lung injury. Alternatively, benefits of APP may be reserved in select individuals as patient characteristics and proning protocols may influence the response. Though serious adverse events were not reported, the potential for skin breakdown and brachial plexus injuries are noted in ventilated patients with the proning times necessary for benefit. Given these findings, the value of immobilizing awake patients in prone should be questioned and alternate active interventions investigated. CLINICAL RELEVANCE: The routine application of APP in COVID-19 lung disease to improve clinical outcomes is not supported by current literature. Based on the GRADE approach, a weak recommendation against using APP was determined. Future studies should investigate if optimal protocols matched to potential responders improve the value of APP in COVID-19.
ABSTRACT
Background: Prior studies have demonstrated improved accuracy and efficacy when Intra-articular (IA) therapeutics are injected using ultrasound (US) guidance. There is also growing evidence that many patients with knee oste-oarthritis (OA) exhibit a pro-infammatory catabolic synovial fuid (SF) profile. However, it is not known if temporary clinical improvement in pain and function after IA Hyaluronic acid (HA) injections is associated with changes in SF volumes. Objectives: The purpose of this study was to determine if IA HA injections delivered using US directed needle visualization with an external pneumatic compression device would result in improved clinical outcomes for knee OA at 3 and 6 months, and if this was associated with a reduction in the amount of knee synovial fuid (SF) measured on US. Methods: 49 eligible subjects with symptomatic Knee OA, BMI < 40 and KL radiographic rating of II or III OA were consented for this open label prospective IRB approved Investigator Initiated SF OA biomarker study (HS 3179, NCT 04093232). All standing radiographs were reviewed by a fellowship-trained MSK radiologist. 36 subjects had adequate aspirated SF volumes of > 500 mcl for biomarker analysis and therefore were eligible to receive two IA injections of HYADD4, 24 mg/3ml (Fidia Farmaceutici S.p.A. Italy) 7 days apart by a MSK US certifed Rheumatologist. An external pneumatic compression device and US visualized needle insertion ensured injections were delivered into the intra-syn-ovial space. Despite COVID-19 restrictions, 34 patients (17 women and 17 men) between 35 and 78 years of age returned for 3 month evaluations and 30 had evaluations at 6 months. The following clinical variables were measured: Western Ontario and McMaster Universities Index (WOMAC) total scores, Visual Analog Pain Scale (VAS, 0-10), PCS scores on the SF-36 health survey questionnaires (physical function/bodily pain and general health), 6-min-ute walking distance in meters (6 MWD), and measured SF depth before and after an external pneumatic compression device was infated to 100 mmHg to facilitate aspiration by increasing available SF volumes under positive presure. The SF depth was measured on the recorded US image (GE logiq e) as the largest anechoic region selected for aspiration on either the lateral (n= 30) or medial (n=4) compartment. SF and simultaneous peripheral blood samples were centrifuged and cryopreserved at-80 o C within 45 minutes of aspiration for future analysis. Statistical differences between baseline values compared to those levels at 3 and 6 months were determined using a paired ANOVA test with p <0.05 signifcance. Results: Improvements over baseline values were observed at 3 and 6 months respectively, after IA HA injections in WOMAC (40%, 40%), VAS (45%, 51%) and PCS (15%, 18%) all p< 0.0001. The 6 WWD improved by 7 % at 3 months (p< 0.007) but was not statistically improved at 6 months. US measured SF depth at baseline was 3.2 ± 2.2 mm before infation and 6.4 + 3.7 mm after infation of the pneumatic external compressioin device but statistical differences in SF depth were not observed at 3 and 6 months. Conclusion: Despite improvements in WOMAC, VAS scores, and PCS scores on the SF 36 at 3 and 6 months after US guided knee injections with an HA product, a statistically signifcant reduction in the amount of US measured SF was not observed. The 6 MWD improved at 3 months but was not statistically different from the baseline distance by 6 months. IA injections using US needle visualization confrmed that the product was delivered into the synovial space with 100 % accuracy which might have resulted in improved efficacy results in this study compared to prior IA HA studies injected without US or using different HA products. In the future, we hope SF biomarkers may identify which individual OA patients will likely achieve the greatest beneft with IA HA injections and to determine if this is associated with a reduction in catabolic pro-infammatory proteins.
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Rationale The pulmonary vasculature is critical for gas exchange, impacts both pulmonary and cardiac function, and has renewed importance due to COVID-19. Pulmonary blood volume is, however, technically difficult to assess, generally requiring invasive methodology for quantification. Prior studies are limited in size and participant enrollment was selective;therefore, variation in the general population is largely unknown. We performed contrast-enhanced dual-energy computed tomography (DECT) in a multicenter, community-based cohort to describe variation in pulmonary perfused blood volume (PBV) in the community. MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) recruited adults from six sites. The MESA Lung Study invited all MESA participants attending Exam 6 (2017-18), excluding those with kidney disease and contrast allergy, to undergo DECT at functional residual capacity via Siemens Flash or Force scanner: CareDose on, pitch 0.55, 0.25 sec exposure, 0.5mm slice thickness, iterative reconstruction (Admire) with Qr40 Kernel. Half concentration 370mg/ml Iopamidol was delivered at 4ml/s for the full scan, starting 17 seconds prior to scanning, including a ∼4 sec breath hold. PBV was calculated by material decomposition and normalized with iodine concentration in the pulmonary trunk. Generalized linear regression models included age, sex, race/ethnicity, height, weight, smoking status, site, and education.ResultsDECT scans were acquired for 714 participants, 36 of which were excluded due to image quality. Mean age of the remaining 678 participants was 71 years (range 63 - 79), 55% were male, 51% were ever smokers, and the race/ethnic distribution was 41% White, 29% Black, 17% Hispanic, and 13% Asian. Mean PBV was 468 + 151mL. The strongest demographic correlate was lower PBV with greater age (-30 mL per 10 years, 95% CI: -43, -18, p<0.001). Pulmonary PBV was positively associated with height, weight, and male sex (all P<0.001). PBV was lower in former compared to never smokers (p =0.04) and in Black than White participants (p=0.002), but not in Hispanic or Asian participants. There were no consistent differences across education or study site. Results were similar after adjustment for lung function and percent emphysema on CT.ConclusionsTo our knowledge, this is the first assessment of pulmonary PBV in a large, multiethnic, general community sample. Pulmonary PBV assessed by contrast-enhanced DECT was substantially reduced with advancing age and varied with body size, sex, former smoking, and, to a lesser extent, Black race. Understanding variation in pulmonary PBV in the general population may elucidate risk of cardiopulmonary disease and physical function.
ABSTRACT
Accurate phenotyping of patients with pulmonary hypertension (PH) is an integral part of informing disease classification, treatment, and prognosis. The impact of lung disease on PH outcomes and response to treatment remains a challenging area with limited progress. Imaging with computed tomography (CT) plays an important role in patients with suspected PH when assessing for parenchymal lung disease, however, current assessments are limited by their semi-qualitative nature. Quantitative chest-CT (QCT) allows numerical quantification of lung parenchymal disease beyond subjective visual assessment. This has facilitated advances in radiological assessment and clinical correlation of a range of lung diseases including emphysema, interstitial lung disease, and coronavirus disease 2019 (COVID-19). Artificial Intelligence approaches have the potential to facilitate rapid quantitative assessments. Benefits of cross-sectional imaging include ease and speed of scan acquisition, repeatability and the potential for novel insights beyond visual assessment alone. Potential clinical benefits include improved phenotyping and prediction of treatment response and survival. Artificial intelligence approaches also have the potential to aid more focused study of pulmonary arterial hypertension (PAH) therapies by identifying more homogeneous subgroups of patients with lung disease. This state-of-the-art review summarizes recent QCT developments and potential applications in patients with PH with a focus on lung disease.