Development of the Lémann index to assess digestive tract damage in patients with Crohn's disease.

BACKGROUND & AIMS: There is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, for measuring disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohn's disease (CD). METHODS: We performed a prospective, multicenter, international, cross-sectional study of patients with CD evaluated at 24 centers in 15 countries. Inclusions were stratified based on CD location and duration. All patients underwent clinical examination and abdominal magnetic resonance imaging analyses. Upper endoscopy, colonoscopy, and pelvic magnetic resonance imaging analyses were performed according to suspected disease locations. The digestive tract was divided into 4 organs and subsequently into segments. For each segment, investigators collected information on previous operations, predefined strictures, and/or penetrating lesions of maximal severity (grades 1-3), and then provided damage evaluations ranging from 0.0 (no lesion) to 10.0 (complete resection). Overall level of organ damage was calculated from the average of segmental damage. Investigators provided a global damage evaluation (from 0.0 to 10.0) using calculated organ damage evaluations. Predicted organ indexes and Lémann Index were constructed using a multiple linear mixed model, showing the best fit with investigator organ and global damage evaluations, respectively. An internal cross-validation was performed using bootstrap methods. RESULTS: Data from 138 patients (24, 115, 92, and 59 with upper tract, small bowel, colon/rectum, and anus CD location, respectively) were analyzed. According to validation, the unbiased correlation coefficients between predicted indexes and investigator damage evaluations were 0.85, 0.98, 0.90, 0.82 for upper tract, small bowel, colon/rectum, anus, respectively, and 0.84 overall. CONCLUSIONS: In a cross-sectional study, we assessed the ability of the Lémann Index to measure cumulative structural bowel damage in patients with CD. Provided further successful validation and good sensitivity to change, the index should be used to evaluate progression of CD and efficacy of treatment.

Daily urinary urea excretion to guide intermittent hemodialysis weaning in critically ill patients.

BACKGROUND: There are no easily available markers of renal recovery to guide intermittent hemodialysis (IHD) weaning. The aim of this study was to identify markers for IHD weaning in critically ill patients with acute kidney injury (AKI). METHODS: We performed a retrospective single-center cohort study of patients treated with IHD for at least 7 days and four dialysis sessions for AKI between 2006 and 2011 in an intensive care unit (ICU) of a French university hospital. Blood and urinary markers were recorded on the day of the last IHD in the ICU for unweaned patients and 2 days after the last IHD for weaned patients. Factors associated with IHD weaning were identified by multiple logistic regression. The areas under the receiver operating characteristic curve (AUROC) and the characteristics of the best diagnostic thresholds were compared. RESULTS: Sixty-seven patients were analyzed, including thirty-seven IHD-weaned patients. Urine output [odds ratio (OR) 1.59, 95% confidence interval (CI) 1.20-2.10 (per ml/kg/24 h increase); P = 0.01] and urinary urea concentration [OR 1.29, 95% CI 1.01-1.64 (per 10 mmol/L increase); P = 0.04] were both associated with IHD weaning. The optimal diagnostic thresholds for IHD weaning were urine output greater than 8.5 ml/kg/24 h, urinary urea concentration greater than 148 mmol/L, and daily urea excretion greater than 1.35 mmol/kg/24 h, with accuracy of 82.1%, 76.1%, and 92.5% (P = 0.03), respectively. The AUROC of daily urinary urea excretion (0.96) was greater than the AUROC of urine output (0.86) or the AUROC of urinary urea concentration (0.83) (P < 0.001). CONCLUSIONS: A daily urinary urea excretion greater than 1.35 mmol/kg/24 h was found to be the best marker for weaning ICU patients with AKI from IHD.

Predictive factors for longer length of stay in an emergency department: a prospective multicentre study evaluating the impact of age, patient's clinical acuity and complexity, and care pathways.

BACKGROUND: It has been reported that emergency department length of stay (ED-LOS) for older patients is longer than average. Our objective was to determine the effect of age, patient's clinical acuity and complexity, and care pathways on ED-LOS and ED plus observation unit (EDOU) LOS (EDOU-LOS). METHODS: This was a prospective, multicentre, observational study including all patients attending in 2011. Age groups were: I, <50; II, ≥50-64; III, ≥65-74; IV, ≥75-84; V, ≥85 years. Univariate and multivariate analyses were performed. RESULTS: Of 125 478 attendances, 20 845(16.6%) were of patients aged ≥65 years. Multivariate analysis found significant predictors for ED-LOS (C-statistics 0.79, p<0.0000001) to be: arrival mode (ambulance, OR 1.13 (95% CI 1.08 to 1.18)); acuity level (level 4, OR 1.24 (95% CI 1.21 to 1.28); level 1-3, OR 1.54 (95% CI 1.5 to 1.59)); haematological examinations (OR 3.34 (95% CI 3.15 to 3.56)); intravenous treatment (OR 1.58 (95% CI 1.47 to 1.69)); monitoring of vital signs (OR 1.89 (95% CI 1.69 to 2.10)); x-ray examinations (OR 1.53 (95% CI 1.45 to 1.61)); CT/MRI/ultrasound (OR 2.60 (95% CI 2.39 to 2.82)); and specialist advice (OR 1.39 (95% CI 1.30 to 1.48)). For EDOU-LOS (C-statistics 0.81, p<0.0000001) we found: age group (II, OR 1.19 (95% CI 1.16 to 1.22); III, OR 1.42 (95% CI 1.38 to 1.46); IV, OR 1.69 (95% CI 1.65 to 1.74); V, 2.01 (95% CI 1.96 to 2.07)); acuity level (level 4, OR 1.31 (95% CI 1.27 to 1.35); level 1-3, OR 1.71 (95% CI 1.66 to 1.77)); haematological examinations (OR 7.81 (95% CI 7.23 to 8.43)); intravenous treatment (OR 1.95 (95% CI 1.8 to 2.12)); x-ray examinations (OR 1.95 (95% CI 1.85 to 2.06)); CT/MRI/ultrasound (OR 6.74 (95% CI 5.98 to 7.6)); specialist advice (OR 2.24 (95% CI 2.07 to 2.42)); admission to a medical or surgical ward (OR 0.61 (95% CI 0.54 to 0.68)); and transfer (OR 1.79 (95% CI 1.54 to 2.07)). CONCLUSIONS: Whereas ED-LOS and EDOU-LOS seem to be directly related to patients' acuity and complexity, notably the need for diagnostic and therapeutic interventions, only EDOU-LOS was significantly associated with age and proposed care pathways. We propose that EDOU-LOS measurement should be made in EDs with an OU.

Emergency management of patients with Glanzmann thrombasthenia: consensus recommendations from the French reference center for inherited platelet disorders.

Glanzmann thrombasthenia (GT) is a genetic bleeding disorder characterised by severely reduced/absent platelet aggregation in response to multiple physiological agonists. The severity of bleeding in GT varies markedly, as does the emergency situations and complications encountered in patients. A number of emergency situations may occur in the context of GT, including spontaneous or provoked bleeding, such as surgery or childbirth. While general management principles apply in each of these settings, specific considerations are essential for the management of GT to avoid escalating minor bleeding events. These recommendations have been developed from a literature review and consensus from experts of the French Network for Inherited Platelet Disorders, the French Society of Emergency Medicine, representatives of patients' associations, and Orphanet to aid decision making and optimise clinical care by non-GT expert health professionals who encounter emergency situations in patients with GT.

Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

BACKGROUND: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets. METHODS: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed. FINDINGS: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032). INTERPRETATION: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications. FUNDING: French Ministry of Health.

Laparoscopic spleen-preserving distal pancreatectomy followed by intramuscular autologous islet transplantation for traumatic pancreatic transection in a young adult.

CONTEXT: Pancreatic injuries caused by blunt trauma are often treated conservatively, except for the highest grades of these. CASE REPORT: We report a case of complete transection of the distal pancreas in a young adult which was successfully managed by spleen-preserving laparoscopic distal pancreatectomy followed by an islet autotransplantation in the patient's forearm striated muscle. CONCLUSION: We describe a mini-invasive approach for pancreatectomy with restoration of resected islets to the patient.

Serum sodium abnormalities during nonexertional heatstroke: incidence and prognostic values.

BACKGROUND: Although heatstroke is often associated with dehydration, the clinical significance of serum sodium abnormalities in patients with heat-related illness during heat wave has been poorly documented. METHOD: We evaluated 1263 patients (age, 82±15 years; body temperature, 40.1°C+1.2°C) admitted to emergency departments during the August 2003 heat wave in Paris, having a core temperature greater than 38.5°C and measurement of serum sodium concentrations. Patients were classified according to our previously described risk score of death. RESULTS: Hyponatremia (<135 mmol/L) was reported in 409 (32%) and hypernatremia (>145 mmol/L) in 220 patients (17%). One-year survival was significantly decreased in patients with hypernatremia (45%; P=.004) but not in those with hyponatremia (58%; P=.86) as compared with patients with serum sodium concentration in the reference range (57%). Using Cox regression, only hypernatremia was an independent prognostic factor (hazard ratio, 1.35; 95% confidence interval, 1.09-1.36) when risk score was taken into account. Using logistic regression, 2 variables were independently associated with hyponatremia (heatstroke severity score and blood urea nitrogen-creatinine ratio<100). Conversely, 5 variables were independently associated with hypernatremia (living in an institution, dementia, serum creatinine>120 µmol/L, a blood urea nitrogen-creatinine ratio >100, and absence of long-term diuretic intake). CONCLUSIONS: Serum sodium abnormalities are frequently observed in patients with a nonexertional heatstroke during heat wave; however, only hypernatremia should be considered as an independent risk factor of death. Rapid measurement of serum sodium concentration is mandatory to appropriately guide electrolyte resuscitation.

Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy.

OBJECTIVE: Heated and humidified high flow nasal cannula oxygen therapy (HFNC) represents a new alternative to conventional oxygen therapy that has not been evaluated in the emergency department (ED). We aimed to study its feasibility and efficacy in patients exhibiting acute respiratory failure presenting to the ED. METHODS: Prospective, observational study in a university hospital's ED. Patients with acute respiratory failure requiring > 9 L/min oxygen or with ongoing clinical signs of respiratory distress despite oxygen therapy were included. The device of oxygen administration was then switched from non-rebreathing mask to HFNC. Dyspnea, rated by the Borg scale and a visual analog scale, respiratory rate, and S(pO(2)) were collected before and 15, 30, and 60 min after beginning HFNC. Feasibility was assessed through caregivers' acceptance of the device in terms of practicality and perceived effect on the subjects, evaluated by questionnaire. RESULTS: Seventeen subjects, median age 64 y (46-84.7 y), were studied. Pneumonia was the most common reason for oxygen therapy (n = 9). HFNC was associated with a significant decrease in both dyspnea scores: Borg scale from 6 (5-7) to 3 (2-4) (P < .001), and visual analog scale from 7 (5-8) to 3 (1-5) (P < .01). Respiratory rate decreased from 28 breaths/min (25-32 breaths/min) to 25 breaths/min (21-28 breaths/min) (P < .001), and S(pO(2)) increased from 90% (88.5-94%) to 97% (92.5-100%) (P < .001). Fewer subjects exhibited clinical signs of respiratory distress (10/17 vs 3/17, P = .03). HFNC was well tolerated and no adverse event was noted. Altogether, 76% of healthcare givers declared preferring HFNC, as compared to conventional oxygen therapy. CONCLUSIONS: HFNC is possible in the ED, and it alleviated dyspnea and improved respiratory parameters in subjects with acute hypoxemic respiratory failure.

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.

Senior-COVID-Rea Cohort Study: A Geriatric Prediction Model of 30-day Mortality in Patients Aged over 60 Years in ICU for Severe COVID-19.

The SARS-COV2 pandemic induces tensions on health systems and ethical dilemmas. Practitioners need help tools to define patients not candidate for ICU admission. A multicentre observational study was performed to evaluate the impact of age and geriatric parameters on 30-day mortality in patients aged ≥60 years of age. Patients or next of kin were asked to answer a phone questionnaire assessing geriatric covariates 1 month before ICU admission. Among 290 screened patients, 231 were included between March 7 and May 7, 2020. In univariate, factors associated with lower 30-day survival were: age (per 10 years increase; OR 3.43, [95%CI: 2.13-5.53]), ≥3 CIRS-G grade ≥2 comorbidities (OR 2.49 [95%CI: 1.36-4.56]), impaired ADL, (OR 4.86 [95%CI: 2.44-9.72]), impaired IADL8 (OR 6.33 [95%CI: 3.31-12.10], p<0.001), frailty according to the Fried score (OR 4.33 [95%CI: 2.03-9.24]) or the CFS ≥5 (OR 3.79 [95%CI: 1.76-8.15]), 6-month fall history (OR 3.46 [95%CI: 1.58-7.63]). The final multivariate model included age (per 10 years increase; 2.94 [95%CI:1.78-5.04], p<0.001) and impaired IADL8 (OR 5.69 [95%CI: 2.90-11.47], p<0.001)). Considered as continuous variables, the model led to an AUC of 0.78 [95% CI: 0.72, 0.85]. Age and IADL8 provide independent prognostic factors for 30-day mortality in the considered population. Considering a risk of death exceeding 80% (82.6% [95%CI: 61.2% - 95.0%]), patients aged over 80 years with at least 1 IADL impairment appear as poor candidates for ICU admission.

Prognosis of Old Intensive Care COVID-19 Patients at a Glance: The Senior COVID Study.

OBJECTIVE: Admission in the intensive care unit of the old patient with coronavirus disease 19 raises an ethical question concerning the scarce resources and their short-term mortality. METHODS: Patients aged over 60 from 7 different intensive care units admitted between March 1, 2020 and May 6, 2020, with a diagnosis of coronavirus disease 19 were included in the cohort. Twenty variables were collected during the admission, such as age, severity (Simplified Acute Physiology Score [SAPS] II), several data on physiological status before intensive care unit comorbidities, evaluation of autonomy, frailty, and biological variables. The objective was to model the 30-day mortality with relevant variables, compute their odds ratio associated with their 95% CI, and produce a nomogram to easily estimate and communicate the 30-day mortality. The performance of the model was estimated with the area under the receiving operating curve. RESULTS: We included 231 patients, among them 60 (26.0%) patients have died on the 30th day. The relevant variables selected to explain the 30-day mortality were Instrumental Activities of Daily Living (IADL) score (0.82 [0.71-0.94]), age 1.12 (1.07-1.18), SAPS II 1.05 (1.02-1.08), and dementia 6.22 (1.00-38.58). A nomogram was computed to visually represent the final model. Area under the receiving operating curve was at 0.833 (0.776-0.889). CONCLUSIONS: Age, autonomy, dementia, and severity at admission were important predictive variables for the 30-day mortality status, and the nomogram could help the physician in the decision-making process and the communication with the family.

Comparison between regional citrate anticoagulation and heparin for intermittent hemodialysis in ICU patients: a propensity score-matched cohort study.

BACKGROUND: Regional citrate anticoagulation (RCA) is the gold standard of anticoagulation for continuous renal replacement therapy but is rarely used for intermittent hemodialysis (IHD) in ICU. Few studies assessed the safety and efficacy of RCA during IHD in ICU; however, no data are available comparing RCA to heparin anticoagulation, which are commonly used for IHD. The aim of this study was to assess the efficacy and safety of RCA compared to heparin anticoagulation during IHD. METHODS: This retrospective single-center cohort study included consecutive ICU patients treated with either heparin anticoagulation (unfractionated or low-molecular-weight heparin) or RCA for IHD from July to September in 2015 and 2017. RCA was performed with citrate infusion according to blood flow and calcium infusion by diffusive influx from dialysate. Using a propensity score analysis, as the primary endpoint we assessed whether RCA improved efficacy, quantified with Kt/V from the ionic dialysance, compared to heparin anticoagulation. The secondary endpoint was safety. Exploratory analyses were performed on the changes in efficacy and safety between the implementation period (2015) and at long term (2017). RESULTS: In total, 208 IHD sessions were performed in 56 patients and were compared (124 RCA and 84 heparin coagulation). There was no difference in Kt/V between RCA and heparin (0.95 ± 0.38 vs. 0.89 ± 0.32; p = 0.98). A higher number of circuit clotting (12.9% vs. 2.4%; p = 0.02) and premature interruption resulting from acute high transmembrane pressure (21% vs. 7%; p = 0.02) occurred in the RCA sessions compared to the heparin sessions. In the propensity score-matching analysis, RCA was associated with an increased risk of circuit clotting (absolute differences = 0.10, 95% CI [0.03-0.18]; p = 0.008). There was no difference in efficacy and safety between the two time periods (2015 and 2017). CONCLUSION: RCA with calcium infusion by diffusive influx from dialysate for IHD was easy to implement with stable long-term efficacy and safety but did not improve efficacy and could be associated with an increased risk of circuit clotting compared to heparin anticoagulation in non-selected ICU patients. Randomized trials to determine the best anticoagulation for IHD in ICU patients should be conducted in a variety of settings.

Impact of early low-calorie low-protein versus standard-calorie standard-protein feeding on outcomes of ventilated adults with shock: design and conduct of a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

INTRODUCTION: International guidelines include early nutritional support (≤48 hour after admission), 20-25 kcal/kg/day, and 1.2-2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. METHODS AND ANALYSIS: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2-0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0-1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. ETHICS AND DISSEMINATION: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03573739.

T-piece versus pressure-support ventilation for spontaneous breathing trials before extubation in patients at high risk of reintubation: protocol for a multicentre, randomised controlled trial (TIP-EX).

INTRODUCTION: In intensive care unit (ICU), the decision of extubation is a critical time because mortality is particularly high in case of reintubation. To reduce that risk, guidelines recommend to systematically perform a spontaneous breathing trial (SBT) before extubation in order to mimic the postextubation physiological conditions. SBT is usually performed with a T-piece disconnecting the patient from the ventilator or with low levels of pressure-support ventilation (PSV). However, work of breathing is lower during PSV than during T-piece. Consequently, while PSV trial may hasten extubation, it may also increase the risk of reintubation. We hypothesise that, compared with T-piece, SBT performed using PSV may hasten extubation without increasing the risk of reintubation. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre randomised controlled trial comparing T-piece vs PSV for SBTs in patients at high risk of reintubation in ICUs. Nine hundred patients will be randomised with a 1:1 ratio in two groups according to the type of SBT. The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without invasive mechanical ventilation between the initial SBT (day 1) and day 28. Secondary outcomes include the number of days between the initial SBT and the first extubation attempt, weaning difficulty, the number of patients extubated after the initial SBT and not reintubated within the following 72 hours, the number of patients extubated within the 7 days following the initial SBT, the number of patients reintubated within the 7 days following extubation, in-ICU length of stay and mortality in ICU, at day 28 and at day 90. ETHICS AND DISSEMINATION: The study has been approved by the central ethics committee 'Ile de France V' (2019-A02151-56) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04227639.

Epidural analgesia in ICU chest trauma patients with fractured ribs: retrospective study of pain control and intubation requirements.

BACKGROUND: Nonintubated chest trauma patients with fractured ribs admitted to the intensive care unit (ICU) are at risk for complications and may require invasive ventilation at some point. Effective pain control is essential. We assessed whether epidural analgesia (EA) in patients with fractured ribs who were not intubated at ICU admission decreased the need for invasive mechanical ventilation (IMV). We also looked for risk factors for IMV. STUDY DESIGN AND METHODS: This retrospective, observational, multicenter study conducted in 40 ICUs in France included consecutive patients with three or more fractured ribs who were not intubated at admission between July 2013 and July 2015. RESULTS: Of the 974 study patients, 788 were included in the analysis of intubation predictors. EA was used in 130 (16.5%) patients, and 65 (8.2%) patients required IMV. Factors independently associated with IMV were chronic respiratory disease (P = 0.008), worse SAPS II (P < 0.0001), flail chest (P = 0.02), worse Injury Severity Score (P = 0.0003), higher respiratory rate at admission (P = 0.02), alcohol withdrawal syndrome (P < 0.001), and noninvasive ventilation (P = 0.04). EA was not associated with decreases in IMV requirements, median numerical rating scale pain score, or intravenous morphine requirements from day 1 to day 7. CONCLUSIONS: EA was not associated with a lower risk of IMV in chest trauma patients with at least 3 fractured ribs, moderate pain, and no intubation on admission. Further studies are needed to clarify the optimal pain control strategy in chest trauma patients admitted to the ICU, notably those with severe pain or high opioid requirements.

Independent recruitment of mediator and SAGA by the activator Met4.

Mediator is a key RNA polymerase II (Pol II) cofactor in the regulation of eukaryotic gene expression. It is believed to function as a coactivator linking gene-specific activators to the basal Pol II initiation machinery. In support of this model, we provide evidence that Mediator serves in vivo as a coactivator for the yeast activator Met4, which controls the gene network responsible for the biosynthesis of sulfur-containing amino acids and S-adenosylmethionine. In addition, we show that SAGA (Spt-Ada-Gcn5-acetyltransferase) is also recruited to Met4 target promoters, where it participates in the recruitment of Pol II by a mechanism involving histone acetylation. Interestingly, we find that SAGA is not required for Mediator recruitment by Met4 and vice versa. Our results provide a novel example of functional interplay between Mediator and coactivators involved in histone modification.

Evaluation of hospital length of stay and revenues as a function of admission mode, clinical pathways including observation unit stay and hospitalization characteristics.

OBJECTIVES: Hospital length of stay (days) and revenues per day (euros) could be different depending on admission mode. To determine the impact of admission mode as a function of clinical pathway, we conducted the present study. Data sources: We included 159,206 admissions to three academic hospitals during a four-year period. Data were obtained from the electronic system of the hospital trust. STUDY DESIGN: A case (through-emergency department)-control (elective (EA)) study was conducted (77,052), matched by age, stay severity and type, disease-related group, and discharge mode. Principal findings: Through-emergency department were significantly elderly, more severe, had more intensive care stays, a higher mortality rate, longer length of stay (days) (9.5 ± 12 vs. 6.8 ± 9.5; p < 0.0001), and lower revenues per day (647 ± 451 vs. 721 ± 422; p = 0.01). In case-control study, mean differences between cases and controls were: longer length of stay -0.64 and revenues per day -75.6; for ≥75 years -1.2 and -102.1; medical -0.9 and -90.4; and discharge to facilities care centers -1.5 and -81.8. Among cases, 40% had a stay in observation unit before being admitted in hospital ward. Differences were strongly reduced for patients who did not go to observation unit before being admitted. Differences were reduced from 0.64 to 0.2 days for length of stay and from 79 to 41 euros for revenues per day when patients did not stay in observation unit before being admitted. CONCLUSIONS: We conclude that admission mode is associated with length of stay and revenues. However, as differences are weak, elective admissions should not be prioritized on economic arguments. Otherwise, our study indicates that among through-emergency department admissions, observation unit stay is associated with longer length of stay and lower revenues.

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.

Visualization of ribonucleotide reductase catalytic oxidation establishes thioredoxins as its major reductants in yeast.

Thioredoxins and/or glutaredoxins assist ribonucleotide reductase, and other such enzymes that require disulfide bond reduction during their catalytic cycle. In Saccharomyces cerevisiae, the presence of either pathway is essential but which of these pathways operates in ribonucleotide reductase reduction and how this function contributes to the pathways' essential nature have not been definitively established. We have identified two in vivo redox forms of the S. cerevisiae ribonucleotide reductase R1 subunit, which correspond to catalytically reduced or oxidized enzymes. Cells lacking thioredoxins, which exhibit an elongated S phase, accumulate R1 in its oxidized form and also contain significantly decreased deoxyribonucleotide levels during the S phase. Overexpressing R1 in these cells increases both the amount of the R1 reduced form and the concentrations of deoxyribonucleotides and accelerates DNA replication. These results establish thioredoxins as the major RNR reducing system in yeast and indicate that impaired RNR reduction accounts for the S phase defects of thioredoxin-deficient cells.

[Primary epiploic appendagitis: a nonsurgical and often misdiagnosed pathology]. / Appendagite épiploïque primitive: un diagnostic non chirurgical souvent méconnu.

INTRODUCTION: Primary epiploic appendagitis (PEA) is characterized by the association of localized abdominal pain with guarding. Depending on its localization, it may simulate acute appendicitis or diverticular sigmoiditis. Symptoms correspond to necrosis of the epiploic appendix due the torsion and vascular occlusion of the main epiploic pedicle. OBSERVATION: A 34-year-old man (BMI=29.38) was examined for persistent localized abdominal pain of the left lower quadrant three days after receiving systemic antibiotic therapy for what was diagnosed as mild diverticular sigmoiditis. Abdominal examination showed localized guarding in the left lower quadrant, with no fever, vomiting or diarrhea. Laboratory results showed no inflammatory response. Abdominal ultrasound showed no evidence of left hydronephrosis. Helical CT showed a localized zone of necrosis of the epiploic appendix of the sigmoid colon and thus confirmed the diagnosis without surgical exploration. Symptoms regressed after a week of analgesic treatment. DISCUSSION: PEA is a rare disease. It often occurs in mildly overweight adult men (around 35 years of age). The combination of acute abdomen with localized abdominal guarding and no evidence of fever or inflammation is the typical presentation. Surgical exploration (laparoscopy) can be avoided for diagnosis if helical CT shows a localized fatty zone situated outside the colon wall with a high attenuating dot point that corresponds to central necrosis of the epiploic appendix.