Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide () is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning into membrane conductance (diffusing capacity) for carbon monoxide () and alveolar capillary blood volume () through combined measurement of and transfer factor of the lung for nitric oxide () is more effective to identify pulmonary hypertension in SSc patients compared with alone. Here, the objective was to determine whether combined- partitioned with recently refined equations could more accurately detect pulmonary hypertension than alone in SSc.For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres.Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients., and were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for (0.82, 95% CI 0.79-0.85) and (0.80, 95% CI 0.76-0.83), but lower for (0.75, 95% CI 0.71-0.78) and (0.66, 95% CI 0.62-0.70).Compared with alone, combined- does not add capability to detect pulmonary hypertension in unselected SSc patients.

Background: During this pandemic situation, some studies have led to hasty conclusions about Corona Virus Disease-19 (COVID-19) treatment, due to a lack of methodology. This pedagogic study aimed to highlight potential biases in research on COVID-19 treatment. Methods: We evaluate the effect of coffee’s active part, 1,3,7-trimethylxanthine (TMX) on patients with COVID-19. A cohort of 93 patients, with a diagnosis of COVID-19 is analyzed. Results: TMX group and control group included, respectively, 26 and 67 patients. In the TMX group, patients had a median length of stay in hospital of 5.5 days shorter than in the control group (9.5 vs. 15 days, p < 0.05). Patients in the control group were more severe than patients in the TMX group with a significantly higher National Early Warning Score 2 (NEWS-2 score) (8 vs. 6, p = 0.002). Conclusions: Multiple biases prevents us from concluding to an effect of coffee on COVID-19. Despite an important social pressure during this crisis, methodology and conscientiousness are the best way to avoid hasty conclusions that can be deleterious for patients. Identifier: NCT04395742.

BackgroundSeverity and antimicrobial resistance of P. aeruginosa (PA) hospital-acquired pneumonia led the FDA to encourage the development of animal models for preclinical evaluation of new therapeutic strategies. We present here the validation of a rabbit model of PA acute pneumonia.MethodsRabbits were infected by endotracheal instillation of 1.8 mL of a standardized inoculum containing 9 × 107 CFU of PA clinical strain 6206 (predetermined 100% lethal dose). The natural history of the disease was described by the following parameters evaluated at 3, 4, 5, 6, 10 hours post-infection (hpi) and at the time of spontaneous death (6 rabbits/group): lung-to-body weight ratio (LW/BW), pulmonary, splenic and renal bacterial counts, pulmonary histology and blood markers (blood cell counts, blood gas and IL-8). Three groups of 12 rabbits were then treated with saline (controls), tobramycin or meropenem at doses determined by PK/PD analysis to confirm the efficacy of a human-equivalent dosing regimen.ResultsPA strain 6,206 caused fatal pneumonia in 13–23 hours by acute respiratory distress syndrome (pulmonary edema and necrosis with LW/BW > 10, pO2 <40 mmHg) and/or sepsis (hyperlactatemia, hypoglycemia, cytopenias). LW/BW and pulmonary bacterial counts increased significantly over time. The splenic and renal bacterial spread was constant after 6 hpi. Hypoxemia <60 mmHg appeared at 5 hpi for 4/6 rabbits, associated with elevated plasma IL-8 concentration, massive neutrophilic influx into the airspace, lung necrosis, hemorrhage, and pulmonary edema formation. Consequently, 5 hpi appeared as the most appropriate time to trigger a therapeutic intervention. Meropenem (80 mg/kg/q2h) or tobramycin (1 injection of 2.5 mg/kg, then saline/q2h) showed superiority over saline, with a mortality rate of 33% and 17% vs. 100%, and an LW/BW ratio of 8.53 and 8.54 vs. 13.9, respectively. Tobramycin was less effective than meropenem in clearing bacteria, with, respectively, 1 and 9 out of 12 rabbits having sterile samples.ConclusionThis rabbit model of PA acute pneumonia is a reliable evaluation tool for new therapeutic strategies. Our study also provides guidance for the development of animal models by describing the natural history of disease and therapeutic validation. Disclosures All authors: No reported disclosures.

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IntroductionPositive urine sample is a frequent nding in post-chemotherapy febrile neutropenia (FN) and can lead to prolonged antibiotic therapy. The aim of this study was to assess the outcome of bacteriuria episodes in FN patients receiving targeted antibiotic therapy. Materials and methodsA multicentric retrospective study was conducted over a four-year period (2014)(2015)(2016)(2017)(2018)(2019). All consecutive rst bacteriuria episodes (≤2 bacteria with at least ≥10 3 CFU/mL) during FN in hospitalized adult patients for hematological malignancies were included. Relapse and recurrence were de ned by fever or urinary tract symptoms (UTS) with the same bacterial subspecies in urine occurring ≤ 7 days and ≤30 days, respectively, after antibiotic discontinuation. Mortality rate was determined at 30 days. Targeted antibiotic therapy ≤10 days for women and ≤14 for men was considered as short course. ResultsAmong 97 patients, 105 episodes were analyzed; 67.6% occurred in women, 41.9% in AML patients, 17.1% were bacteremic, 14.2% presented with UTS, and 61.9% were treated with short-course antibiotic treatment. One death was reported. In men, no relapse/recurrence was noted, even in the short-course antibiotic group. In women, 2.8% of episodes treated with short-course antibiotic led to relapse or recurrence. ConclusionsRelapse, recurrence, and mortality were uncommon events in FN patients experiencing bacteriuria episode, whatever the antibiotic duration. To distinguish asymptomatic bacteriuria from infection remained challenging in women. In men, the withdrawal of systematic urinalysis at onset of FN could lead to insu cient bacteriuria diagnosis and treatment.