Testosterone recovery after androgen deprivation therapy in localised prostate cancer: Long-term data from two randomised trials.

BACKGROUND AND PURPOSE: To determine the rate and time of testosterone (T) recovery in patients (pts) with localised prostate cancer treated with radiotherapy plus 0-, 6-, 18- or 36-month of androgen deprivation therapy (ADT). MATERIALS AND METHODS: In 1230 pts with prostate cancer randomised into two phase III trials, serum T was measured at baseline, then regularly. T recovery rate was compared between normal vs. abnormal baseline T and with ADT duration with Chi-square test or Fisher's exact test. A multivariable logistic regression model to predict the probability of recovering normal T was performed. RESULTS: Overall, 87.4 % (167/191), 75.9 % (293/386), 54.8 % (181/330) and 43.2 % (80/185) of pts, recovered normal T on the 0-, 6-, 18- or 36-month schedule, respectively (p < 0.001). In patients recovering normal T, the median time to T recovery increased with ADT duration ranging from 0.31, 1.64, 3.06 to 5.0 years for the 0-, 6-, 18- or 36-month schedules, respectively (p < 0.001) and was significantly faster for those with a normal T at baseline (p < 0.001). On multivariable analysis, older age and longer ADT duration are associated with a lower T recovery. CONCLUSIONS: Testosterone recovery rate after ADT depends on several factors including hormonal duration, normal baseline T, age and medical comorbidities. A longer ADT duration is the most important variable affecting T recovery. The data from this report might be a valuable tool to help physicians and patients in evaluating risks and benefits of ADT.

Third-line treatment patterns in HER2-positive metastatic breast cancer: a retrospective analysis of real-world data in Canada.

There is an increasing demand for real-world data pertaining to the usage of cancer treatments, especially in settings where no standard treatment is specifically recommended. This study presents the first real-world analysis of third-line treatment patterns in HER2-positive metastatic breast cancer (mBC) patients in Canada. The purpose was to assess evolution of clinical practice and identify unmet needs in post-second-line therapy. Retrospective data from medical records of 66 patients who received third-line treatment before 31st October 2018, and data from 56 patients who received third-line treatment after this date, extracted from the Personalize My Treatment (PMT) cancer patient registry, were analyzed. In the first cohort, the study revealed heterogeneity in the third-line setting, with trastuzumab, lapatinib, and T-DM1 being the main treatment options. Even though data were collected before the wide availability of tucatinib, neratinib and trastuzumab deruxtecan in Canada, the PMT cohort revealed the emergence of new therapeutic combinations and a shift from lapatinib usage to T-DM1 choice was observed. These findings underscore the evolving nature of third-line treatment strategies in Canada, a facet that is intrinsically tied to the availability of new drugs. The absence of a consensus on post-second-line treatment highlights the pressing need for more efficient therapeutic alternatives beyond the currently available options. This study not only offers valuable insights into the present landscape of third-line treatment in Canada but validates the significance and effectiveness of the PMT registry as a tool for generating pan-Canadian real-world evidence in oncology and its capacity to provide information on evolution of therapeutic practices.

Predictive factors for severe long-term chronic kidney disease after acute kidney injury requiring renal replacement therapy in critically ill patients: an ancillary study of the ELVIS randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown. METHODS: We performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD. RESULTS: Of the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (ORM12 = 1.03 95% CI [1.02-1.05] per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (ORM60 = 0.85 95% CI [0.77-0.93] per point). CONCLUSION: Severe long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT. Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017).

Performance of renal Doppler to predict the occurrence of acute kidney injury in patients without acute kidney injury at admission.

PURPOSE: This study aimed at evaluating the performance of Doppler-based resistive index (RI) and semi-quantitative evaluation of renal perfusion using color-Doppler (SQP) to predict de novo AKI in the subgroup of critically ill patients without AKI at admission. METHODS: This study is an ancillary analysis of a prospective multicenter cohort study. Consecutive ICU patients requiring mechanical ventilation were included. Renal Doppler was performed at ICU admission. The diagnostic performance of RI and SQP to predict de novo AKI at day 3 was evaluated. RESULTS: Among the 371 patients of the prospective cohort, 118 without AKI at study inclusion were included. Thirty-four patients (29%) developed an AKI. Neither RI (0.64 UI [0.57-0.70] vs 0.67 [0.62-0.70] in no AKI and de novo AKI group respectively, p = 0.177) nor SQP (2 [2, 3] vs 2 [1-3] in no AKI and de novo AKI group respectively, p = 0.061) were associated with AKI occurrence. Overall performance in predicting de novo AKI was null to poor with area under ROC curve of respectively 0.60 (95% CI 0.49-0.65) and 0.58 (95% CI 0.47-0.60) for RI and SQP. Similar results were obtained after adjustment for confounders. CONCLUSIONS: These results confirm the poor performance of Doppler-based indices in predicting renal prognosis of ICU patients.

Can the Six-Minute Walk Test Be Used to Individualize Physical Activity Intensity in Patients with Breast Cancer?

BACKGROUND: Adapted physical activity (APA) aids breast cancer patients. It is necessary to use an adapted target heart rate (HR) when prescribing exercise intensity. METHODS: In total, 138 patients previously included in two published randomized clinical trials underwent the CPET and 6MWT before and after adjuvant therapy. Of these patients, 85 had performed APA, and 53 had received only the usual therapy. HRs were recorded during the two tests. RESULTS: Before starting chemotherapy, good agreement (intraclass correlation (ICC) 0.69; confidence interval at 95% IC0.95 (0.591-0.769); p < 0.001) and a moderate correlation were evident between the 6MWT-HR and ventilatory threshold HR of the CPET (r = 0.70; p < 0.001). Good agreement and a high positive correlation were noted only in the group who engaged in APA (ICC 0.77; IC0.95 (0.659-0.848); p < 0.001; r = 0.8; p < 0.01); moderate agreement and a moderate positive correlation were apparent in the control group (ICC 0.57; IC0.95 (0.329-0.74); p < 0.001; r = 0.6; p < 0.01). The correlations were independent of age and body mass index. CONCLUSIONS: The 6MWT-HR can be used to prescribe exercise intensity for breast cancer patients both before and after specific treatment with concomitant APA.

Outcomes of ICU patients with and without perceptions of excessive care: a comparison between cancer and non-cancer patients.

BACKGROUND: Whether Intensive Care Unit (ICU) clinicians display unconscious bias towards cancer patients is unknown. The aim of this study was to compare the outcomes of critically ill patients with and without perceptions of excessive care (PECs) by ICU clinicians in patients with and without cancer. METHODS: This study is a sub-analysis of the large multicentre DISPROPRICUS study. Clinicians of 56 ICUs in Europe and the United States completed a daily questionnaire about the appropriateness of care during a 28-day period. We compared the cumulative incidence of patients with concordant PECs, treatment limitation decisions (TLDs) and death between patients with uncontrolled and controlled cancer, and patients without cancer. RESULTS: Of the 1641 patients, 117 (7.1%) had uncontrolled cancer and 270 (16.4%) had controlled cancer. The cumulative incidence of concordant PECs in patients with uncontrolled and controlled cancer versus patients without cancer was 20.5%, 8.1%, and 9.1% (p < 0.001 and p = 0.62, respectively). In patients with concordant PECs, we found no evidence for a difference in time from admission until death (HR 1.02, 95% CI 0.60-1.72 and HR 0.87, 95% CI 0.49-1.54) and TLDs (HR 0.81, 95% CI 0.33-1.99 and HR 0.70, 95% CI 0.27-1.81) across subgroups. In patients without concordant PECs, we found differences between the time from admission until death (HR 2.23, 95% CI 1.58-3.15 and 1.66, 95% CI 1.28-2.15), without a corresponding increase in time until TLDs (NA, p = 0.3 and 0.7) across subgroups. CONCLUSIONS: The absence of a difference in time from admission until TLDs and death in patients with concordant PECs makes bias by ICU clinicians towards cancer patients unlikely. However, the differences between the time from admission until death, without a corresponding increase in time until TLDs, suggest prognostic unawareness, uncertainty or optimism in ICU clinicians who did not provide PECs, more specifically in patients with uncontrolled cancer. This study highlights the need to improve intra- and interdisciplinary ethical reflection and subsequent decision-making at the ICU.

Optimizing Treatment in Intermediate-Risk Prostate Cancer: Secondary Analysis of a Randomized Phase 3 Trial.

PURPOSE: To identify patients with intermediate-risk prostate cancer (IRPC) benefiting from de-escalation of androgen deprivation therapy (ADT) and/or dose escalated radiation therapy (DERT), we performed a secondary analysis of a phase 3 trial by measuring biochemical failure (BF), distant metastases, prostate cancer-specific mortality, overall survival (OS), and distant metastases-free survival (DMFS) rates according to prognostic intermediate risk factors (IRF). METHODS AND MATERIALS: The initial trial randomized 600 patients with IRPC to a 3-arm trial with 200 patients per arm, consisting of 6 months of ADT plus 70 Gy radiation therapy (ADT + RT70) versus ADT plus a DERT of 76 Gy (ADT + DERT76) versus DERT of 76 Gy alone (DERT76). We performed an analysis based on IRF: clinical stage, prostate-specific antigen level, Gleason score, percentage of positive biopsy cores (PBC) ≥50%, and Gleason pattern. Patients were allocated to 2 groups: favorable intermediate risk (FIR), defined as patients with only 1 IRF without Gleason pattern 4 + 3 or PBC ≥50%; and unfavorable intermediate risk (UIR), defined as all other patients. BF, distant metastases, prostate cancer-specific mortality, OS, and DMFS were compared between FIR and UIR. RESULTS: The median follow-up was 11.3 years (interquartile range, 10.9-11.7). In the FIR cohort, BF and OS were not significantly different between arms. UIR patients had significantly worse DMFS (hazard ratio [95% confidence interval], 1.61 [1.20-2.15]; P = .026) and OS (1.51 [1.12-2.04]; P = .0495) and a nonsignificant higher cumulative incidence of BF rate (1.55 [0.98-2.47]; P = .08). In UIR patients, a significant improvement in BF was seen in the arms receiving ADT compared to DERT76 alone. On multivariable analysis, Gleason pattern 4 + 3 and prostate-specific antigen >10 ng/mL independently affected BF and OS, regardless of the treatment arm. CONCLUSIONS: In IRPC, therapeutic optimization appears possible. To avoid ADT side effects, DERT76 alone appears sufficient in patients harboring only 1 risk factor without Gleason pattern 4 + 3 and PBC ≥50% (FIR). All other UIR patients seem to benefit from ADT + DERT76.

Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial.

BACKGROUND: The role of androgen deprivation therapy (ADT) in combination with radiotherapy (RT) in intermediate-risk prostate cancer (IRPC) remains controversial, particularly in patients receiving dose-escalated RT (DERT). We compared outcomes between patients with IRPC treated with ADT and two different doses of RT vs. RT alone. METHODS: From December 2000 to September 2010, 600 patients with IRPC were randomised to a three-arm trial consisting of 6 months of ADT plus RT 70 Gy (ADT + RT70) vs. ADT plus a DERT of 76 Gy (ADT + DERT76) vs. DERT of 76 Gy alone (DERT76). Primary end-point was biochemical failure (BF), and secondary end-points were overall survival (OS) and toxicity. RT toxicity was assessed by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria. FINDINGS: With a median follow-up of 11.3 years (interquartile range: 10.9-11.7), patients receiving DERT76 alone, compared with patients receiving ADT + RT70 and ADT + DERT76, had higher rates of BF (32%, 18% and 14%, respectively, p < 0.001), higher rates of prostate cancer progression (12%, 4.5% and 3.3%, respectively, p = 0.001) and more deaths due to prostate cancer (6.5%, 3.0% and 1.5%, respectively, p = 0.03) with no significant difference seen between ADT + RT70 and ADT + DERT76. There was no significant difference in OS between the 3 arms. A higher dose of RT (76 Gy) increased late gastrointestinal (GI) toxicity grade ≥ II compared with lower dose (70 Gy) (16% vs 5.3%, p < 0.001) with no statistical difference for late genitourinary toxicity. INTERPRETATION: In IRPC, the addition of 6 months of ADT to RT70 or DERT76 significantly improves BF and appears to decrease the risk of death from prostate cancer compared with DERT76 alone with no difference in OS. In the setting of IRPC, ADT plus RT 70 Gy yields effective disease control with a better GI toxicity profile. Clinicaltrials.gov#NCT00223145.

Hepatic dysfunction impairs prognosis in critically ill patients with hematological malignancies: A post-hoc analysis of a prospective multicenter multinational dataset.

PURPOSE: Hyperbilirubinemia is frequent in patients with hematological malignancies admitted to the intensive care unit (ICU). Literature about hepatic dysfunction (HD) in this context is scarce. METHODS: We investigated the prognostic impact of HD analyzing a prospective multicenter cohort of 893 critically ill hematology patients. Two groups were defined: patients with HD (total bilirubin ≥33 µmol/L at ICU admission) and patients without HD. RESULTS: Twenty one percent of patients were found to have HD at ICU admission. Cyclosporine, antimicrobials before ICU admission, abdominal symptoms, ascites, history of liver disease, neutropenia, increased serum creatinine and myeloma were independently associated with HD. Etiology remained undetermined in 73% of patients. Hospital mortality was 56.3% and 36.3% respectively in patients with and without HD (p < 0.0001). Prognostic factors independently associated with hospital mortality in HD group were, performance status >1 (OR = 2.07, 95% CI = 1.49-2.87, p < 0.0001), invasive mechanical ventilation (OR = 3.92, 95% CI = 2.69-5.71, p < 0.0001), renal replacement therapy (OR = 1.74, 95% CI = 1.22-2.47, p = 0.002), vasoactive drug (OR = 1.81, 95% CI = 1.21-2.71, p = 0.004) and SOFA score without bilirubin level at ICU admission (OR = 1.09, 95% CI = 1.04-1.14, p < 0.0001). CONCLUSIONS: HD is common, underestimated, infrequently investigated, and is associated with impaired outcome in critically ill hematology patients. HD should be considered upon ICU admission and managed as other organ dysfunctions.

Home-Based Physical Activity in Patients With Breast Cancer: During and/or After Chemotherapy? Impact on Cardiorespiratory Fitness. A 3-Arm Randomized Controlled Trial (APAC).

OBJECTIVES: Physical activity (PA) programs are recommended for breast cancer care. However, their modalities remain to be discussed. This study determined the best time to begin a personalized or adapted program based on cardiopulmonary exercise test function. This randomized controlled trial evaluated the effect of home-based adapted PA (APA) performed during or after treatment on cardiorespiratory fitness (CRF) at 12 months. METHOD: The primary endpoint was the peak oxygen consumption (VO2peak) at 12 months (group A vs C and B vs C). Secondary endpoints included the 6-minute walking test, assessment of muscle strength, fatigue, quality of life, anxiety, and depression, and a questionnaire on PA levels. All tests were evaluated at baseline and at 6 and 12 months. A total of 94 patients with breast cancer were randomized to 3 different groups: group A, performing 6 months of APA during adjuvant care; group B, 6 months of APA after adjuvant care; and group C, 12 months of APA during and after specific care. The program combined 1 resistance session and 2 aerobic sessions per week. Analysis of variance was used for repeated measures, Student's t-test or the Mann-Whitney U-test for continuous variables, and χ2 test for binary or categorical variables. RESULTS: The study assessed 81 participants at 6 months and 73 at 12 months. The majority of patients completed more than 85% of the exercise sessions. The baseline for VO2peak and secondary outcomes did not differ among the groups. VO2peak increased during the exercise period and decreased during the chemotherapy period without APA, but at 12 months no significant difference was observed. The same variation was observed in the 6-minute walking test, with significance at 6 months between A+C versus B (P = .04), but no difference among the groups at 12 months. In the 3 groups, no decreases in other studied parameters were noted, except at 6 months in group B without APA. CONCLUSION: Home-based APA in breast cancer patients has a positive effect on CRF and physical functions, with no differences based on the timing of this program based on specific cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gouv.fr (NCT01795612). Registered 20 February 2013.

Outcomes in 886 Critically Ill Patients After Near-Hanging Injury.

BACKGROUND: Near-hanging experiences are life-threatening events about which few data are available. RESEARCH QUESTION: What are the outcomes and early predictors of hospital mortality in critically ill patients who have undergone a near-hanging experience? STUDY DESIGN AND METHODS: Adult patients who were resuscitated successfully after suicidal near-hanging injury admitted to 31 university or university-affiliated ICUs in France and Belgium between 1992 and 2014 were studied retrospectively. Patients were identified by searching the hospital databases for International Statistical Classification of Diseases and Related Health Problems, 9th and 10th revisions, codes and hospital charts for hanging. Logistic multivariate regression was performed to identify factors associated vital and functional outcomes at hospital discharge as the primary end points. Secondary outcomes were evaluation of temporal trends and identification of predictors of hospital mortality. RESULTS: Of the 886 patients (181 women and 705 men; median age, 43 years; interquartile range, 34-52 years), 266 (30.0%) had attempted suicide previously, 600 (67.7%) had a diagnosed mental illness, and 55 (6.2%) attempted hanging while hospitalized. Median time from hanging awareness to unhanging was 0 min (interquartile range [IQR], 0-0; range, 0-82 min). Median Glasgow Coma Scale score was 3 (IQR, 3-5) at ICU admission. Hanging induced cardiac arrest in 450 of 886 patients (50.8%). Overall, 497 of 886 patients (56.1%) were alive at hospital discharge, including 479 of 497 patients (96.4%) with a favorable neurocognitive outcome (defined as a Glasgow Outcome Scale score of 4 or 5). By multivariate analysis, factors associated with hospital mortality were hanging-induced cardiac arrest (OR, 19.50; 95% CI, 7.21-60.90; P < .00001) and findings at ICU admission of glycemia level > 1.4 g/L (OR, 4.34; 95% CI, 1.82-10.81; P = .0007) and of lactate level > 3.5 mmol/L (OR, 9.98; 95% CI, 4.17-25.36; P < .00001). INTERPRETATION: The findings from this large multicenter retrospective cohort emphasize the very high mortality after hanging injury chiefly because of hanging-induced cardiac arrest. However, patients who survive near-hanging experiences achieve excellent neurocognitive recovery. Studies of early neuroprotective strategies for patients who have undergone near-hanging experiences are warranted. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04096976; URL: www.clinicaltrials.gov.

Positioning Performance Limits of GNSS Meta-Signals and HO-BOC Signals.

Global Navigation Satellite Systems (GNSS) are the main source of position, navigation, and timing (PNT) information and will be a key player in the next-generation intelligent transportation systems and safety-critical applications, but several limitations need to be overcome to meet the stringent performance requirements. One of the open issues is how to provide precise PNT solutions in harsh propagation environments. Under nominal conditions, the former is typically achieved by exploiting carrier phase information through precise positioning techniques, but these methods are very sensitive to the quality of phase observables. Another option that is gaining interest in the scientific community is the use of large bandwidth signals, which allow obtaining a better baseband resolution, and therefore more precise code-based observables. Two options may be considered: (i) high-order binary offset carrier (HO-BOC) modulations or (ii) the concept of GNSS meta-signals. In this contribution, we assess the time-delay and phase maximum likelihood (ML) estimation performance limits of such signals, together with the performance translation into the position domain, considering single point positioning (SPP) and RTK solutions, being an important missing point in the literature. A comprehensive discussion is provided on the estimators' behavior, the corresponding ML threshold regions, the impact of good and bad satellite constellation geometries, and final conclusions on the best candidates, which may lead to precise solutions under harsh conditions. It is found that if the receiver is constrained by the receiver bandwidth, the best choices are the L1-M or E6-Public Regulated Service (PRS) signals. If the receiver is able to operate at 60 MHz, it is recommended to exploit the full-bandwidth Galileo E5 signal. In terms of robustness and performance, if the receiver can operate at 135 MHz, the best choice is to use the GNSS meta-signals E5 + E6 or B2 + B3, which provide the best overall performances regardless of the positioning method used, the satellite constellation geometry, or the propagation conditions.

Performance Limits of GNSS Code-based Precise Positioning: GPS, Galileo & Meta-Signals.

This contribution analyzes the fundamental performance limits of traditional two-step Global Navigation Satellite System (GNSS) receiver architectures, which are directly linked to the achievable time-delay estimation performance. In turn, this is related to the GNSS baseband signal resolution, i.e., bandwidth, modulation, autocorrelation function, and the receiver sampling rate. To provide a comprehensive analysis of standard point positioning techniques, we consider the different GPS and Galileo signals available, as well as the signal combinations arising in the so-called GNSS meta-signal paradigm. The goal is to determine: (i) the ultimate achievable performance of GNSS code-based positioning systems; and (ii) whether we can obtain a GNSS code-only precise positioning solution and under which conditions. In this article, we provide clear answers to such fundamental questions, leveraging on the analysis of the Cramér-Rao bound (CRB) and the corresponding Maximum Likelihood Estimator (MLE). To determine such performance limits, we assume no external ionospheric, tropospheric, orbital, clock, or multipath-induced errors. The time-delay CRB and the corresponding MLE are obtained for the GPS L1 C/A, L1C, and L5 signals; the Galileo E1 OS, E6B, E5b-I, and E5 signals; and the Galileo E5b-E6 and E5a-E6 meta-signals. The results show that AltBOC-type signals (Galileo E5 and meta-signals) can be used for code-based precise positioning, being a promising real-time alternative to carrier phase-based techniques.

Severe toxicity from checkpoint protein inhibitors: What intensive care physicians need to know?

Checkpoint protein inhibitor antibodies (CPI), including cytotoxic T-lymphocyte-associated antigen 4 inhibitors (ipilimumab, tremelimumab) and the programmed cell death protein 1 pathway/programmed cell death protein 1 ligand inhibitors (pembrolizumab, nivolumab, durvalumab, atezolizumab), have entered routine practice for the treatment of many cancers. They improve the outcome for many cancers, and more patients will be treated with CPI in the future. Although CPI can lead to adverse events (AE) less frequently than for chemotherapy, their use can require intensive care unit admission in case of severe immune-related adverse events (IrAE). Moreover, some of these events, particularly late events, are poorly documented, so a high level of suspicion should be maintained for patients receiving CPI. Intensivists should be aware in general of the known complications and appropriate management of these AE. Nevertheless, a multidisciplinary collaboration remains essential for their diagnosis and management. This review described the most severe complications related to CPI.

Long-term health-related quality of life of critically ill patients with haematological malignancies: a prospective observational multicenter study.

BACKGROUND: Although outcomes of critically ill patients with haematological malignancies (HMs) have been fully investigated in terms of organ failure and mortality, data are scarce on health-related quality of life (HRQOL) in this population. We aim to assess post-intensive care unit (ICU) burden and HRQOL of critically ill patients with HMs and to identify risk factors for quality-of-life (QOL) impairment. RESULTS: In total, 1011 patients with HMs who required ICU admission in 17 ICUs in France and Belgium were included in the study; 278 and 117 patients were evaluated for QOL at 3 months and 1 year, respectively, after ICU discharge. HRQOL was determined by applying the interview form of the Short Form 36 (SF-36) questionnaire. Psychological distress symptoms were evaluated using the Hospital Anxiety Depression Score (HADS) and the Impact of Event Scale (IES). In-hospital mortality rates at 3 months and 1 year were, respectively, 39.1, 50.7 and 57.2%, respectively. At 3 months, median [IQR] physical and mental component summary scores (PCS and MCS) (SF-36) were 37 [28-46] and 51 [45-58], respectively. PCS was lower in ICU patients with HMs when compared to general ICU septic patients (52 [5-13], p = 0.00001). The median combined HAD score was 8 [5-13], and the median IES score was 8 [3-16]. However, recovery during the first year after ICU discharge was not consistent in all dimensions of HRQOL. Three months after ICU discharge, the maximum daily Sequential Organ Failure Assessment score and status of the underlying malignancy at ICU admission were significantly associated with MCS impairment (- 0.54 points [95% CI - 0.99; - 0.1], p = 0.018 and - 4.83 points [95% CI - 8.44; - 1.22], p = 0.009, respectively). CONCLUSION: HRQOL is strongly impaired in critically ill patients with HMs at 3 months and 1 year after ICU discharge. Organ failure and disease status are strongly associated with QOL. The kinetic evaluation of QOL at 3 months and 1 year offers the opportunity to focus on QOL aspects that may be improved by therapeutic interventions during the first year after ICU discharge.

Granulocyte colony-stimulating factor and respiratory status of critically ill neutropenic patients with hematologic malignancies.

In patients with hematologic malignancies, respiratory status may deteriorate during neutropenia recovery. This multicenter, observational study aims to evaluate granulocyte colony-stimulating factor (G-CSF) impact on respiratory status in critically ill neutropenic patients. Among 1011 critically ill patients with hematologic malignancies, 288 were neutropenic and included in this study. 201 (70%) did not receive G-CSF at day 1 or 2. After propensity score matching for the probability of receiving G-CSF at day 1 or 2, there was no association between G-CSF and respiratory deterioration at day 14 (OR =1.19; 95%CI (0.57-2.51); p = .64). Additional sensitivity analysis in patients admitted for acute respiratory failure showed similar results (OR =1.34; 95%CI (0.5-3.59); p = .57). Among patients who recovered from neutropenia, 75% experienced respiratory deterioration during neutropenia recovery. This study confirms that neutropenia recovery is a situation at risk of respiratory deterioration. However, whether G-CSF is an aggravating factor cannot be supported by our results.

Clinical Significance of Upper Airway Virus Detection in Critically Ill Hematology Patients.

RATIONALE: Noninvasive diagnostic multiplex molecular tests may enable the early identification and treatment of viral infections in critically ill immunocompromised patients. OBJECTIVES: To assess the association between viral detection in nasopharyngeal swabs and ICU mortality in critically ill hematology patients. METHODS: This was a post hoc analysis of a prospective cohort of critically ill hematology patients admitted to 17 ICUs. Nasal swabs sampled and frozen at ICU admission were tested using a multiplex PCR assay. Predictors of ICU mortality and assay positivity were identified. MEASUREMENTS AND MAIN RESULTS: Of the 747 patients (447 with acute respiratory failure [ARF]), 21.3% had a virus detected (56.4% rhinovirus/enterovirus and 30.7% influenza/parainfluenza/respiratory syncytial viruses). Overall ICU and hospital mortality rates were 26% and 37%, respectively. Assay positivity was associated with lymphoproliferative disorders, hematopoietic stem cell transplantation, treatment with steroids or other immunosuppressants, ARF (25.5% vs. 16.3%; P = 0.004), and death in the ICU (28.9% vs. 19.3%; P = 0.008). The association with ICU mortality was significant for all viruses and was strongest for influenza/parainfluenza/respiratory syncytial viruses. In patients with ARF, detection of any respiratory virus was independently associated with ICU mortality (odds ratio, 2.07; 95% confidence interval, 1.22-3.50). CONCLUSIONS: Respiratory virus detection in the upper airway by multiplex PCR assay is common in critically ill hematology patients. In patients with ARF, respiratory virus detection was independently associated with ICU mortality. Multiplex PCR assay may prove helpful for the risk stratification of hematology patients with ARF. Studies to understand whether respiratory tract viruses play a causal role in outcomes are warranted.

Performance of Doppler-based resistive index and semi-quantitative renal perfusion in predicting persistent AKI: results of a prospective multicenter study.

PURPOSE: The Doppler-based resistive index (RI) and semi-quantitative evaluation of renal perfusion using color Doppler (SQP) have shown promising results for predicting persistent acute kidney injury (AKI) in preliminary studies. This study aimed at evaluating the performance of RI and SQP to predict short-term renal prognosis in critically ill patients. METHODS: Prospective multicenter cohort study including unselected critically ill patients. Renal Doppler was performed at admission to the intensive care unit. The diagnostic performance of RI and SQP to predict persistent AKI at day 3 was evaluated. RESULTS: Overall, 371 patients were included, of whom 351 could be assessed for short-term renal recovery. Two thirds of the included patients had AKI (n = 233; 66.3%), of whom 136 had persistent AKI (58.4%). Doppler-based RI was higher and SQP lower in AKI patients and according to AKI recovery. Overall performance in predicting persistent AKI was however poor with area under ROC curve of respectively 0.58 (95% CI 0.52-0.64) and 0.59 (95% CI 0.54-0.65) for RI and SQP. Optimal cutoff was respectively 0.71 and 2 for RI and SQP. At optimal cutoff, sensitivity and specificity were 50% (95% CI 41-58%) and 68% (62-74%) for RI and 39% (32-45%) and 75% (66-82%) for SQP. CONCLUSION: Although statistically associated with AKI occurrence, RI and SQP perform poorly in predicting persistent AKI at day 3. Further studies are needed to adequately describe factors influencing Doppler-based assessment of renal perfusion and to delineate whether these indicators may be useful at the bedside. CLINICALTRIAL.GOV: NCT02355314.

Oxygenation/non-invasive ventilation strategy and risk for intubation in immunocompromised patients with hypoxemic acute respiratory failure.

We investigated how the initial ventilation/oxygenation management may influence the need for intubation on the coming day in a cohort of immunocompromised patients with acute hypoxemic respiratory failure (ARF). Data from 847 immunocompromised patients with ARF were used to estimate the probability of intubation at day+1 within the first 3 days of ICU admission, according to oxygenation management. First, noninvasive ventilation (NIV) was compared to oxygen therapy whatever the administration device; then standard oxygen was compared to High Flow Nasal Cannula therapy alone (HFNC), NIV alone or NIV+HFNC. To take into account the oxygenation regimens over time and to handle confounders, propensity score weighting models were used. In the original sample, the probability of intubation at day+1 was higher in the NIV group vs oxygenation therapy (OR = 1.64, 95CI, 1.09-2.48) or vs the standard oxygen group (OR = 2.05, 95CI: 1.29-3.29); it was also increased in the HFNC group compared to standard oxygen (OR = 2.85, 95CI: 1.37-5.67). However, all these differences disappeared by handling confounding-by-indication in the weighted samples, as well as in the pooled model. Note that adjusted OR for day-28 mortality increased with the day of intubation. In this large cohort of immunocompromised patients, ventilation/oxygenation management had no impact on the probability of intubation on the coming day.