Impact of COVID-19 on posttraumatic stress disorder in ICU survivors: a prospective observational comparative cohort study.

BACKGROUND: Posttraumatic stress disorder (PTSD) after a stay in the intensive care unit (ICU) can affect one in five ICU survivors. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, admission to the ICU for COVID-19 was stressful due to the severity of this disease. This study assessed whether admission to the ICU for COVID-19 was associated with a higher prevalence of PTSD compared with other causes of ICU admission after adjustment for pre-ICU psychological factors. METHODS: This prospective observational comparative cohort study included 31 ICUs. Eligible patients were adult ICU survivors hospitalized during the first wave of COVID-19 pandemic in France, regardless of the reason for admission. The prevalence of presumptive diagnosis of PTSD at 6 months was assessed using the PTSD Checklist for DSM-5 (PCL-5). Sociodemographics, clinical data, history of childhood trauma (Childhood Trauma Questionnaire [CTQ]), and exposure to potentially traumatic events (Life Events Checklist for DSM-5 [LEC-5]) were assessed. RESULTS: Of the 778 ICU survivors included during the first wave of COVID-19 pandemic in France, 417 and 361 were assigned to the COVID-19 and non-COVID-19 cohorts, respectively. Fourteen (4.9%) and 11 (4.9%), respectively, presented with presumptive diagnosis of PTSD at 6 months (p = 0.976). After adjusting for age, sex, severity score at admission, use of invasive mechanical ventilation, ICU duration, CTQ and LEC-5, COVID-19 status was not associated with presumptive diagnosis of PTSD using the PCL-5. Only female sex was associated with presumptive diagnosis of PTSD. However, COVID-19 patients reported significantly more intrusion and avoidance symptoms than non-COVID patients (39% vs. 29%, p = 0.015 and 27% vs. 19%, p = 0.030), respectively. The median PCL-5 score was higher in the COVID-19 than non-COVID-19 cohort (9 [3, 20] vs. 4 [2, 16], p = 0.034). CONCLUSION: Admission to the ICU for COVID-19 was not associated with a higher prevalence of PTSD compared with admission for another cause during the first wave of the COVID-19 pandemic in France. However, intrusion and avoidance symptoms were more frequent in COVID-19 patients than in non-COVID-19 patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT03991611, registered on June 19, 2019.

Oesophageal pressure monitoring in intubated patients by intensive care units' nurses: An educational study.

BACKGROUND: Trained ICU nurses may perform oesophageal pressure measurements which may help facilitate its implementation in the usual patient care to better assess lung and chest wall mechanics and easily detect patient-ventilator asynchronies. AIM AND STUDY DESIGN: We thus conducted a prospective educational study aiming to assess the ability of ICU nurses to perform reliable oesophageal pressure measurements after a short dedicated training program. RESULTS: All the 11 nurses who completed the program succeeded their practical evaluation (nine (82%) at the first evaluation and two (18%) at their second attempt). CONCLUSION: These results show that this training program is feasible and that trained ICU nurses can perform accurate oesophageal pressure measurements in mechanically ventilated patients. RELEVANCE TO CLINICAL PRACTICE: Such training program may help to implement this technique in routine ICU care.

Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome.

BACKGROUND: Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients' respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients. METHODS: All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg-1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation. RESULTS: Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics. CONCLUSIONS: Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients. Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).

177Lu-PSMA Treatment Monitoring Through Serial Fast Whole-Body Tomoscintigraphies Recorded With a Latest-Generation CZT-Camera.

ABSTRACT: The tomoscintigraphy monitoring of 177Lu-prostate-specific membrane antigen (PSMA) treatment may be helpful for quality control and predicting therapeutic response. Furthermore, the drawbacks of relatively low image quality and extended recording times can be overcome by new CZT-cameras providing fast, high-quality, whole-body recordings. Although still requiring further larger-scale confirmation, the current case report demonstrates that these CZT-cameras have the potential to provide straightforward and comprehensive 177Lu-PSMA treatment monitoring, that is, <20-minute whole-body tomoscintigraphy recording, tumor activities concordant with those from 68Ga-PSMA PET, and no requirement for any additional tracer injection.

[18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study.

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells.

The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P<0.001) than patients with low TMTV. Multivariable analyses identified baseline elevated lactate dehydrogenase, DS-5, CAR T cells at M1 for PFS and baseline elevated lactate dehydrogenase, TMTV >80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.

Phase III Study of 18F-PSMA-1007 Versus 18F-Fluorocholine PET/CT for Localization of Prostate Cancer Biochemical Recurrence: A Prospective, Randomized, Crossover Multicenter Study.

The objective of this study was to compare 18F-PSMA-1007 PET/CT and 18F-fluorocholine PET/CT for the localization of prostate cancer (PCa) biochemical recurrence. Methods: This prospective, open-label, randomized, crossover multicenter study included PCa patients with prior definitive therapy and suspected PCa recurrence. All men underwent both 18F-PSMA-1007 PET/CT and 18F-fluorocholine PET/CT (102 received 18F-PSMA-1007 PET/CT first and 88 received 18F-fluorocholine PET/CT first). All images were assessed independently by 3 readers masked to all clinical information using a 3-point qualitative scale (0 = no recurrence, 1 = undetermined, and 2 = recurrence). Patients were monitored for approximately 6 mo. An independent panel with a urologist, radiologist, and nuclear physician reviewed all clinical data, including imaging and response to therapy, but were masked regarding PET/CT information; acting in consensus, they determined a patient-based and region-based composite standard of truth for PCa lesions. The "correct detection rates" for PCa lesions on a patient basis for each radiopharmaceutical were compared for the 3 readers individually and for the "average reader." Secondary objectives included determining whether PET/CT findings affected diagnostic thinking (impact of a test result on posttest vs. pretest probability of a correct diagnosis), therapeutic decision making (description and quantification of impact of diagnostic information gained with both radiopharmaceuticals on patient management), and adequacy of management changes. Results: A total of 190 patients were included. The primary endpoint was met. The overall correct detection rates were 0.82 for 18F-PSMA-1007 and 0.65 for 18F-fluorocholine (P < 0.0001) when undetermined findings were considered positive for malignancy and 0.77 and 0.57, respectively (P < 0.0001), when undetermined findings were considered negative for malignancy. A change in diagnostic thinking due to PET/CT was reported in 149 patients; 18F-PSMA-1007 contributed more than 18F-fluorocholine in 93 of these patients. In 122 patients, PET/CT led to an adequate diagnosis that benefited the patient; 18F-PSMA-1007 contributed more than 18F-fluorocholine in 88 of these patients. Conclusion: 18F-PSMA-1007 PET/CT is superior to 18F-fluorocholine PET/CT for the localization of PCa recurrence. Decision making was more beneficial when based on 18F-PSMA-1007 PET/CT results.

Bothrops lanceolatus snake venom impairs mitochondrial respiration and induces DNA release in human heart preparation.

INTRODUCTION: Envenomations by Bothrops snakebites can induce overwhelming systemic inflammation ultimately leading to multiple organ system failure and death. Release of damage-associated molecular pattern molecules (DAMPs), in particular of mitochondrial origin, has been implicated in the pathophysiology of the deregulated innate immune response. OBJECTIVE: To test whether whole Bothrops lanceolatus venom would induce mitochondrial dysfunction and DAMPs release in human heart preparations. METHODS: Human atrial trabeculae were obtained during cannulation for cardiopulmonary bypass from patients who were undergoing routine coronary artery bypass surgery. Cardiac fibers were incubated with vehicle and whole Bothrops lanceolatus venom for 24hr before high-resolution respirometry, mitochondrial membrane permeability evaluation and quantification of mitochondrial DNA. RESULTS: Compared with vehicle, incubation of human cardiac muscle with whole Bothrops lanceolatus venom for 24hr impaired respiratory control ratio and mitochondrial membrane permeability. Levels of mitochondrial DNA increased in the medium of cardiac cell preparation incubated with venom of Bothrops lanceolatus. CONCLUSION: Our study suggests that whole venom of Bothrops lanceolatus impairs mitochondrial oxidative phosphorylation capacity and increases mitochondrial membrane permeability. Cardiac mitochondrial dysfunction associated with mitochondrial DAMPs release may alter myocardium function and engage the innate immune response, which may both participate to the cardiotoxicity occurring in patients with severe envenomation.

High flow nasal cannula improves breathing efficiency and ventilatory ratio in COPD patients recovering from an exacerbation.

BACKGROUND AND STUDY PURPOSE: High flow nasal cannula (HFNC) may improve CO2 elimination by washing out CO2 from the upper airways. This study aimed at assessing the effect of HFNC on minute ventilation and ventilatory ratio (VR), a surrogate of dead space, in patients hospitalized for acute hypercapnic COPD exacerbation. METHODS: Physiological study comparing HFNC at 40 L/min to low flow oxygen. Variations of tidal volume (VT) and minute ventilation between the two treatments were estimated from chest plethysmography. Respiratory rate (RR) and arterial blood gases were measured. Variations in VR were calculated. Data were compared using Wilcoxon tests. RESULTS: Recordings performed in 10 patients. Minute ventilation was reduced with HFNC by -16.2 [-30.9-0.4] % (p = 0.049). VT was not different but RR was lower during HFNC. PaCO2 was lower with HFNC compared to standard oxygen: 48.7 [46.4-58.1] vs 50.7 [48.4-57.5] mmHg (p = 0.020). VR decreased by -18.0 [-34.7 - -4.0] % (p = 0.020) with HFNC. CONCLUSIONS: In patients recovering from acute COPD exacerbation, the use of HFNC reduced RR, minute ventilation, PaCO2 and VR compared to standard oxygen. These changes are consistent with a decrease in physiologic dead space with HFNC.

Disentangling temporal food web dynamics facilitates understanding of ecosystem functioning.

Studying how food web structure and function vary through time represents an opportunity to better comprehend and anticipate ecosystem changes. Yet, temporal studies of highly resolved food web structure are scarce. With few exceptions, most temporal food web studies are either too simplified, preventing a detailed assessment of structural properties or binary, missing the temporal dynamics of energy fluxes among species. Using long-term, multi-trophic biomass data coupled with highly resolved information on species feeding relationships, we analysed food web dynamics in the Gulf of Riga (Baltic Sea) over more than three decades (1981-2014). We combined unweighted (topology-based) and weighted (biomass- and flux-based) food web approaches, first, to unravel how distinct descriptors can highlight differences (or similarities) in food web dynamics through time, and second, to compare temporal dynamics of food web structure and function. We find that food web descriptors vary substantially and distinctively through time, likely reflecting different underlying ecosystem processes. While node- and link-weighted metrics reflect changes related to alterations in species dominance and fluxes, unweighted metrics are more sensitive to changes in species and link richness. Comparing unweighted, topology-based metrics and flux-based functions further indicates that temporal changes in functions cannot be predicted using unweighted food web structure. Rather, information on species population dynamics and weighted, flux-based networks should be included to better comprehend temporal food web dynamics. By integrating unweighted, node- and link-weighted metrics, we here demonstrate how different approaches can be used to compare food web structure and function, and identify complementary patterns of change in temporal food web dynamics, which enables a more complete understanding of the ecological processes at play in ecosystems undergoing change.

Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).

Recruitability and effect of PEEP in SARS-Cov-2-associated acute respiratory distress syndrome.

BACKGROUND: A large proportion of patients with a SARS-Cov-2-associated respiratory failure develop an acute respiratory distress syndrome (ARDS). It has been recently suggested that SARS-Cov-2-associated ARDS may differ from usual non-SARS-Cov-2-associated ARDS by higher respiratory system compliance (CRS), lower potential for recruitment with positive end-expiratory pressure (PEEP) contrasting with severe shunt fraction. The purpose of the study was to systematically assess respiratory mechanics and recruitability in SARS-Cov-2-associated ARDS. METHODS: Gas exchanges, CRS and hemodynamics were assessed at 2 levels of PEEP (15 cmH2O and 5 cmH2O) within 36 h (day1) and from 4 to 6 days (day 5) after intubation. The recruited volume was computed as the difference between the volume expired from PEEP 15 to 5 cmH2O and the volume predicted by compliance at PEEP 5 cmH2O (or above airway opening pressure). The recruitment-to-inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and CRS at PEEP 5 cmH2O) was used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruitable patients. RESULTS: The R/I ratio was calculated in 25 of the 26 enrolled patients at day 1 and in 15 patients at day 5. At day 1, 16 (64%) were considered as highly recruitable (R/I ratio median [interquartile range] 0.7 [0.55-0.94]) and 9 (36%) were considered as poorly recruitable (R/I ratio 0.41 [0.31-0.48]). The PaO2/FiO2 ratio at PEEP 15 cmH2O was higher compared to PEEP 5 cmH2O only in highly recruitable patients (173 [139-236] vs 135 [89-167] mmHg; p < 0.01). Neither PaO2/FiO2 or CRS measured at PEEP 15 cmH2O or at PEEP 5 cmH2O nor changes in PaO2/FiO2 or CRS in response to PEEP changes allowed to identify highly or poorly recruitable patients. CONCLUSION: In this series of 25 patients with SARS-Cov-2 associated ARDS, 64% were considered as highly recruitable and only 36% as poorly recruitable based on the R/I ratio performed on the day of intubation. This observation suggests that a systematic R/I ratio assessment may help to guide initial PEEP titration to limit harmful effect of unnecessary high PEEP in the context of Covid-19 crisis.

Head-to-head comparison between digital and analog PET of human and phantom images when optimized for maximizing the signal-to-noise ratio from small lesions.

BACKGROUND: Routine PET exams are increasingly performed with reduced injected activities, leading to the use of different image reconstruction parameters than the NEMA parameters, in order to prevent from any deleterious decrease in signal-to-noise ratio (SNR) and thus, in lesion detectability. This study aimed to provide a global head-to-head comparison between digital (Vereos, Philips®) and analog (Ingenuity TF, Philips®) PET cameras of the trade-off between SNR and contrast through a wide-ranging number of reconstruction iterations, and with a further reconstruction optimization based on the SNR of small lesions. METHODS: Image quality parameters were compared between the two cameras on human and phantom images for a number of OSEM reconstruction iterations ranging from 1 to 10, the number of subsets being fixed at 10, and with the further identification of reconstruction parameters maximizing the SNR of spheres and adenopathies nearing 10 mm in diameter. These reconstructions were additionally obtained with and without time-of-flight (TOF) information (TOF and noTOF images, respectively) for further comparisons. RESULTS: On both human and phantom TOF images, the compromise between SNR and contrast was consistently more advantageous for digital than analog PET, with the difference being particularly pronounced for the lowest numbers of iterations and the smallest spheres. SNR was maximized with 1 and 2 OSEM iterations for the TOF images from digital and analog PET, respectively, whereas 4 OSEM iterations were required for the corresponding noTOF images from both cameras. On the TOF images obtained with this SNR optimization, digital PET exhibited a 37% to 44% higher SNR as compared with analog PET, depending on sphere size. These relative differences were however much lower for the noTOF images optimized for SNR (- 4 to + 18%), as well as for images reconstructed according to NEMA standards (- 4 to + 12%). CONCLUSION: SNR may be dramatically higher for digital PET than for analog PET, especially when optimized for small lesions. This superiority is mostly attributable to enhanced TOF resolution and is significantly underestimated in NEMA-based analyses.

Dual time point [18F]FLT-PET for differentiating proliferating tissues vs non-proliferating tissues.

PURPOSE: For differentiating tumor from inflammation and normal tissues, fluorodeoxyglucose ([18F]FDG) dual time point PET could be helpful. Albeit [18F]FLT is more specific for tumors than [18F]FDG; we explored the role of dual time point [18F]FLT-PET for discriminating benign from malignant tissues. METHODS: Before any treatment, 85 womens with de novo unifocal breast cancer underwent three PET acquisitions at 33.94 ± 8.01 min (PET30), 61.45 ± 8.30 min (PET60), and 81.06 ± 12.12 min (PET80) after [18F]FLT injection. Semiquantitative analyses of [18F]FLT uptake (SUV) were carried out on tumors, liver, bone marrow (4th thoracic vertebra (T4) and humeral head), descending thoracic aorta, muscle (deltoid), and contralateral normal breast. Repeated measures ANOVA tests and Tukey's posttests were used to compare SUVmax of each site at the three time points. RESULTS: There was a significant increase in SUVmax over time for breast lesions (5.58 ± 3.80; 5.97 ± 4.56; 6.19 ± 4.42; p < 0.0001) (m ± SD for PET30, PET60, and PET80, respectively), and bone marrow (for T4, 8.21 ± 3.17, 9.64 ± 3.66, 10.85 ± 3.63, p < 0.0001; for humeral head, 3.36 ± 1.79, 3.87 ± 1.89, 4.39 ± 2.00, p < 0.0001). A significant decrease in SUVmax over time was observed for liver (6.79 ± 2.03; 6.24 ± 1.99; 5.57 ± 1.74; p < 0.0001), muscle (0.95 ± 0.28; 0.93 ± 0.29; 0.86 ± 0.20; p < 0.027), and aorta (1.18 ± 0.34; 1.01 ± 0.32; 0.97 ± 0.30; p < 0.0001). No significant difference was observed for SUVmax in contralateral breast (0.8364 ± 0.40; 0.78 ± 0.38; 0.80 ± 0.35). CONCLUSION: [18F]FLT-SUVmax increased between 30 and 80 min only in proliferating tissues. This could be helpful for discriminating between residual tumor and scar tissue.

Major bleeding events in octagenarians associated with drug interactions between dabigatran and P-gp inhibitors.

BACKGROUND: The direct oral anticoagulant dabigatran does not require any routine therapeutic drug monitoring. Yet, concerns about possible drug interactions susceptible to increase its inherent bleeding risk, especially in very elderly patients, have been raised recently. The aim of our study was to evaluate to what extent the co-prescription of P-gp inhibitors with dabigatran may increase its plasma levels and lead to bleeding complications, in usual conditions of care of the very elderly. METHODS: Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective cohort. Prescriptions were screened for the presence of P-gp inhibitors (Group A) or not (Group B). RESULTS: Patients from Group A had increased dabigatran mean plasma concentrations as compared with patients from Group B (A vs. B: 182.2 ± 147.3 vs. 93.7 ± 64.9 ng/mL). One third of the patients from Group A had dabigatran concentrations that were deemed "out of range" versus none in Group B (P = 0.05). This was associated with more frequent bleeding complications in Group A (A: 30.4%, B: 8.6%, P = 0.04). CONCLUSION: In our cohort of very elderly patients, at least, the co-prescription of dabigatran with P-gp inhibitors in usual conditions of care resulted in higher dabigatran plasma concentrations and more frequent bleeding occurrences.

Accuracy of P0.1 measurements performed by ICU ventilators: a bench study.

BACKGROUND: Occlusion pressure at 100 ms (P0.1), defined as the negative pressure measured 100 ms after the initiation of an inspiratory effort performed against a closed respiratory circuit, has been shown to be well correlated with central respiratory drive and respiratory effort. Automated P0.1 measurement is available on modern ventilators. However, the reliability of this measurement has never been studied. This bench study aimed at assessing the accuracy of P0.1 measurements automatically performed by different ICU ventilators. METHODS: Five ventilators set in pressure support mode were tested using a two-chamber test lung model simulating spontaneous breathing. P0.1 automatically displayed on the ventilator screen (P0.1vent) was recorded at three levels of simulated inspiratory effort corresponding to P0.1 of 2.5, 5 and 10 cm H2O measured directly at the test lung and considered as the reference values of P0.1 (P0.1ref). The pressure drop after 100 ms was measured offline on the airway pressure-time curves recorded during the automated P0.1 measurements (P0.1aw). P0.1vent was compared to P0.1ref and to P0.1aw. To assess the potential impact of the circuit length, P0.1 were also measured with circuits of different lengths (P0.1circuit). RESULTS: Variations of P0.1vent correlated well with variations of P0.1ref. Overall, P0.1vent underestimated P0.1ref except for the Löwenstein® ventilator at P0.1ref 2.5 cm H2O and for the Getinge group® ventilator at P0.1ref 10 cm H2O. The agreement between P0.1vent and P0.1ref assessed with the Bland-Altman method gave a mean bias of - 1.3 cm H2O (limits of agreement: 1 and - 3.7 cm H2O). Analysis of airway pressure-time and flow-time curves showed that all the tested ventilators except the Getinge group® ventilator performed an occlusion of at least 100 ms to measure P0.1. The agreement between P0.1vent and P0.1aw assessed with the Bland-Altman method gave a mean bias of 0.5 cm H2O (limits of agreement: 2.4 and - 1.4 cm H2O). The circuit's length impacted P0.1 measurements' values. A longer circuit was associated with lower P0.1circuit values. CONCLUSION: P0.1vent relative changes are well correlated to P0.1ref changes in all the tested ventilators. Accuracy of absolute values of P0.1vent varies according to the ventilator model. Overall, P0.1vent underestimates P0.1ref. The length of the circuit may partially explain P0.1vent underestimation.

Performance of 18F-sodium fluoride positron emission tomography with computed tomography to assess inflammatory and structural sacroiliitis on magnetic resonance imaging and computed tomography, respectively, in axial spondyloarthritis.

PURPOSE: To assess increased sacroiliac joint (SIJ) uptake on 18F-NaF PET/CT and to compare with MRI for inflammation and with CT scan for structural damages in a population of 23 patients with spondyloarthritis (SpA). METHODS: Twenty-three patients with active SpA according to the Assessment of SpondyloArthritis international Society (ASAS) and/or modified NY criteria were included. All patients had a pelvic radiograph, MRI, and CT scan of the SIJ and 18F-NaF PET/CT examinations within a month, analyzed by three blinded readers. MRIs were assessed according to the ASAS criteria and SPARCC method. On CT scans, erosion and ankylosis were quantified using the same methodology. On the 18F-NaF PET, abnormal uptake was assessed using a qualitative method inspired by the ASAS criteria and two quantitative approaches (the PET-activity score according to the SPARCC method and Maximum Standardized Uptake Value (SUVmax)). RESULTS: Structural sacroiliitis was observed on 7 radiographs and 10 CT scans; 10 MRIs showed inflammatory sacroiliitis, and 20 patients had a positive PET. The inter-reader reliability was good for the PET activity score and good to excellent for the SUVmax. A positive PET was not correlated with a positive MRI or with a structural sacroiliitis on CT scan. The PET-activity score and SUVmax were correlated with the SPARCC inflammation score but not with erosion or ankylosis scores on CT scan. CONCLUSION: Abnormal uptake by the SIJ on 18F-NaF PET is more frequent than inflammatory and structural sacroiliitis in a population of SpA patients. The PET activity score and SUVmax had good correlations with inflammatory sacroiliitis but not with structural lesions on CT scan.