Fatal mucormycosis and aspergillosis coinfection associated with haemophagocytic lymphohistiocytosis: A case report and literature review.

Invasive mould infections are life-threatening and mainly occur in immunocompromised patients. Whereas aspergillosis is described during haemophagocytic lymphohistiocytosis (HLH), only a few cases of concomitant mucormycosis with HLH have been reported. Here, we present an uncommon coinfection of mucormycosis and aspergillosis associated with HLH probably due to a varicella zoster virus (VZV) viraemia which was unresponsive to triple antifungal therapy (liposomal amphotericin B combined with isavuconazole and caspofungin). A review of the cases of mucormycosis with HLH showed that this uncommon association was always lethal and underscored the relevance of screening for mould infections in patients with HLH.

Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells.

Inflammation observed in SARS-CoV-2-infected patients suggests that inflammasomes, proinflammatory intracellular complexes, regulate various steps of infection. Lung epithelial cells express inflammasome-forming sensors and constitute the primary entry door of SARS-CoV-2. Here, we describe that the NLRP1 inflammasome detects SARS-CoV-2 infection in human lung epithelial cells. Specifically, human NLRP1 is cleaved at the Q333 site by multiple coronavirus 3CL proteases, which triggers inflammasome assembly and cell death and limits the production of infectious viral particles. Analysis of NLRP1-associated pathways unveils that 3CL proteases also inactivate the pyroptosis executioner Gasdermin D (GSDMD). Subsequently, caspase-3 and GSDME promote alternative cell pyroptosis. Finally, analysis of pyroptosis markers in plasma from COVID-19 patients with characterized severe pneumonia due to autoantibodies against, or inborn errors of, type I interferons (IFNs) highlights GSDME/caspase-3 as potential markers of disease severity. Overall, our findings identify NLRP1 as a sensor of SARS-CoV-2 infection in lung epithelia.

Accuracy of pulse pressure variations for fluid responsiveness prediction in mechanically ventilated patients with biphasic positive airway pressure mode.

The accuracy of pulse pressure variation (PPV) to predict fluid responsiveness using pressure-controlled (PC) instead of volume-controlled modes is under debate. To specifically address this issue, we designed a study to evaluate the accuracy of PPV to predict fluid responsiveness in severe septic patients who were mechanically ventilated with biphasic positive airway pressure (BIPAP) PC-ventilation mode. 45 patients with sepsis or septic shock and who were mechanically ventilated with BIPAP mode and a target tidal volume of 7-8 ml/kg were included. PPV was automatically assessed at baseline and after a standard fluid challenge (Ringer's lactate 500 ml). A 15% increase in stroke volume (SV) defined fluid responsiveness. The predictive value of PPV was evaluated through a receiver operating characteristic (ROC) curve analysis and "gray zone" statistical approach. 20 (44%) patients were considered fluid responders. We identified a significant relationship between PPV decrease after volume expansion and SV increase (spearman ρ = - 0.5, p < 0.001). The area under ROC curve for PPV was 0.71 (95%CI 0.56-0.87, p = 0.007). The best cut-off (based on Youden's index) was 8%, with a sensitivity of 80% and specificity of 60%. Using a gray zone approach, we identified that PPV values comprised between 5 and 15% do not allow a reliable fluid responsiveness prediction. In critically ill septic patients ventilated under BIPAP mode, PPV appears to be an accurate method for fluid responsiveness prediction. However, PPV values comprised between 5 and 15% constitute a gray zone that does not allow a reliable fluid responsiveness prediction.

BMI and pneumonia outcomes in critically ill covid-19 patients: An international multicenter study.

OBJECTIVE: Previous studies have unveiled a relationship between the severity of coronavirus disease 2019 (COVID-19) pneumonia and obesity. The aims of this multicenter retrospective cohort study were to disentangle the association of BMI and associated metabolic risk factors (diabetes, hypertension, hyperlipidemia, and current smoking status) in critically ill patients with COVID-19. METHODS: Patients admitted to intensive care units for COVID-19 in 21 centers (in Europe, Israel, and the United States) were enrolled in this study between February 19, 2020, and May 19, 2020. Primary and secondary outcomes were the need for invasive mechanical ventilation (IMV) and 28-day mortality, respectively. RESULTS: A total of 1,461 patients were enrolled; the median (interquartile range) age was 64 years (40.9-72.0); 73.2% of patients were male; the median BMI was 28.1 kg/m2 (25.4-32.3); a total of 1,080 patients (73.9%) required IMV; and the 28-day mortality estimate was 36.1% (95% CI: 33.0-39.5). An adjusted mixed logistic regression model showed a significant linear relationship between BMI and IMV: odds ratio = 1.27 (95% CI: 1.12-1.45) per 5 kg/m2 . An adjusted Cox proportional hazards regression model showed a significant association between BMI and mortality, which was increased only in obesity class III (≥40; hazard ratio = 1.68 [95% CI: 1.06-2.64]). CONCLUSIONS: In critically ill COVID-19 patients, a linear association between BMI and the need for IMV, independent of other metabolic risk factors, and a nonlinear association between BMI and mortality risk were observed.

Expression of Exhaustion Markers on CD8+ T-Cell Patterns Predict Outcomes in Septic Patients Admitted to the ICU.

RATIONALE: There is an unmet need to improve the description of the state of T-cell exhaustion in patients with sepsis, its reproducibility and correlation with the outcomes before including immunotherapy (like recombinant interleukin-7 or immune checkpoint inhibitors) in the therapeutic armamentarium against sepsis. DESIGN: Observational prospective study. SETTING: Two ICUs in a teaching hospital (France). PATIENTS: Eighty patients with sepsis admitted to the ICU. INTERVENTIONS: Quantification of CD4+ and CD8+ T-cell exhaustion at days 1 and 3. Quantification of the exhaustion markers (programmed death [PD]-1, 2B4, and cluster of differentiation [CD] 160) on T cells, the number of CD4+ regulatory T cells (CD3+ CD4+ CD25hi CD127Lo cells), and the phorbol myristate acetate/ionomycin/ionomycin-induced cytokines production (tumor necrosis factor-α, interleukin-2, and interferon-γ). MEASUREMENTS AND MAIN RESULTS: Using unsupervised clustering analysis, patients could be split in three clusters according to their dominant pattern expression of exhaustion markers on CD8+ T cells (i.e., 2B4lowPD-1lowCD160low, 2B4hiPD-1hiCD160low, and 2B4hiPD-1lowCD160hi) regardless of their underlying morbidities. Only 2B4hiPD-1hiCD160low CD8+ T cells had cytokine production defect, whereas 2B4hi PD-1lowCD160hi pattern correlated with cytokine overproduction. Patients with a predominant "highly activated" 2B4hiPD-1lowCD160hi pattern did not develop secondary bacterial infections. By multivariate analysis, Simplified Acute Physiology Score 2 gravity score at day 1 (p = 0.003) and patterns of exhaustion markers on CD8+ T cells (p = 0.03) were associated with the risk of death. Neither the level of CD4+ regulatory T cells nor the CD4+ exhaustion patterns were associated with the outcomes. CONCLUSIONS: Easy-to-use multicolor flow cytometry assessing 2B4, PD-1, and CD160 expression on CD8+ T cells at day 1 identifies septic patients with poor outcome and discriminates patient subsets in who immunomodulatory drugs should be tested.

Short- and long-term renal outcomes following severe rhabdomyolysis: a French multicenter retrospective study of 387 patients.

BACKGROUND: Rhabdomyolysis is a life-threatening disease that can lead to severe hyperkalemia, acute kidney injury (AKI) and hypovolemic shock. The predictive factors of AKI and acute to chronic kidney disease (CKD) transition remain poorly described. METHODS: This multicenter retrospective study enrolled 387 patients with severe rhabdomyolysis (CPK > 5000 U/L). Primary end-point was the development of severe AKI, defined as stage 2 or 3 of KDIGO classification. Secondary end-points included the incidence of AKI to CKD transition. RESULTS: Among the 387 patients, 315 (81.4%) developed AKI, including 171 (44.1%) with stage 3 AKI and 103 (26.6%) requiring RRT. Stage 2-3 AKI was strongly correlated with serum phosphate, potassium and bicarbonate at admission, as well as myoglobin over 8000 U/L and the need for mechanical ventilation. 42 patients (10.8%) died before day 28. In the 80 patients with available eGFR values both before and 3 months after the rhabdomyolysis, the decrease in eGFR (greater than 20 mL/min/1.73 m2 in 23 patients; 28.8%) was correlated to the severity of the AKI and serum myoglobin levels > 8000 U/L at admission. CONCLUSIONS: Severe rhabdomyolysis leads to AKI in most patients admitted to an ICU. Mechanical ventilation and severity of the rhabdomyolysis, including myoglobin level, are associated with the risk of stage 2-3 AKI. The long-term renal decline is correlated to serum myoglobin at admission.

Predictors of desaturation during patient transport to the postoperative anesthesia care unit: an observational study.

BACKGROUND: The transport of postoperative patients to the postoperative anesthesia care unit (PACU) is a high-risk period for hypoxemia. The aim of this study was to determine risk factors for hypoxemia during transfers to the PACU. METHODS: An observational, prospective, monocentric, and noninterventional study was conducted in the University Hospital of Toulouse in 2015 during a 5-week period. All patients who were transferred to PACU were included. Twenty-eight variables related to patient, surgery, and anesthesia were recorded. Hypoxemia during transfer was defined as Spo2 <90%. RESULTS: Five hundred five patients were included. The incidence of hypoxemia during transfer was 13%. After logistic regression analysis, 3 risk factors for desaturation were identified: sedation score >2, Spo2 <96% before exiting the operating room (OR), and body mass index >30 kg/m2. The 72% of patients were transferred without oxygen. Most of the hypoxemia appears in these patients. CONCLUSION: The development of hypoxemia during transfer from the OR to the PACU was greater in patients who were obese, were more sedated, or had lower oxygen saturations upon leaving the OR. The rates of hypoxemia were greater among patients in whom supplemental oxygen was not administered. Supplemental oxygen should be considered in higher risk patients.

The Doppler renal resistive index for early detection of acute kidney injury after hip fracture.

BACKGROUND: Postoperative acute kidney injury (AKI) is linked to an increase in morbidity and mortality, particularly in elderly populations. This study's aim was to assess the accuracy of the Doppler renal resistive index (RI) in detecting AKI at an early stage after hip fracture surgery. METHODS: This prospective single-centre study included 48 patients suffering hip fractures requiring surgery and who presented risk factors for the development of AKI. The RI was calculated preoperatively and postoperatively in patients without pain and with haemodynamic and respiratory stability. The occurrence of AKI was determined by measurements of serum creatinine according to AKIN criteria. RESULTS: Twenty-nine patients (60%) developed AKI during the first five postoperative days, without need for dialysis. The RI was increased in patients who developed postoperative AKI 0.68 (0.67-0.71) vs. 0.72 (0.7-0.73); P=0.014 for the preoperative index; and 0.6 (0.58-0.68) vs. 0.74 (0.71-0.76); P<0.0001 for the postoperative index. A postoperative index superior or equal to 0.706 is a marker for the early detection of AKI with a high sensitivity and a high specificity (76% and 89%, respectively). CONCLUSION: The calculation of the RI during the perioperative periods of hip fracture surgery predicts early and effectively the postoperative occurrence of AKI, thus allowing treatment to be anticipated so as to improve patient prognosis.

Doppler renal resistive index for early detection of acute kidney injury after major orthopaedic surgery: a prospective observational study.

BACKGROUND: Postoperative acute kidney injury (AKI) is a cause of morbidity and mortality. Its diagnosis requires better markers than variations in diuresis or postoperative serum creatinine. OBJECTIVES: The aim of this study was to evaluate the accuracy of Doppler renal resistive index for early detection of AKI after hip or knee arthroplasty. DESIGN: A prospective observational study. SETTING: A single-centre study in a university hospital. PATIENTS: Fifty men and women older than 65 years, requiring hip or knee replacement with at least two perioperative AKI risk factors, including diabetes, arteritis, chronic heart or renal dysfunction, and prescription of angiotensin-converting enzyme (ACE) inhibitors. Exclusion criteria were poor abdominal echogenicity, arrhythmia, respiratory failure or agitation. INTERVENTION: Renal resistive index was measured preoperatively and in the postanaesthesia care unit. RESULTS: Sixteen patients presented with AKI in the postoperative period. Resistive index was increased in this group in both the preoperative [0.72 (0.69 to 0.73) vs. 0.66 (0.58 to 0.71); P = 0.01] and postoperative periods [0.75 (0.71 to 0.75) vs. 0.67 (0.62 to 0.72); P = 0.0001]. Resistive index evaluated by ROC curves and AUC to detect AKI was 0.862 [95% confidence interval (95% CI) 0.735 to 0.943]. The most accurate cut-off value was a postoperative resistive index of 0.705 (sensitivity = 94%, specificity = 71%, LR+ = 3.19 and LR- = 0.09). The grey area between 0.705 and 0.73, corresponding to the inconclusive zone, included 26% (13/50) of all the patients. CONCLUSION: Postoperative resistive index appears to be effective for early detection of AKI after major orthopaedic surgery. Resistive index can be measured in the postoperative care unit in patients at risk of AKI. TRIAL REGISTRATION NUMBER: 29-0512.

The efficacy of skin temperature for block assessment after infraclavicular brachial plexus block.

BACKGROUND: Although it has been reported that an increase in skin temperature indicates block success with higher specificity and sensibility than skin sensitivity to pinprick and cold, the methodology previously used computer-assisted infrared thermography, a technique that is expensive and requires substantial personnel training. In this prospective observational study, we evaluated whether a simple infrared thermometer can reliably predict block effectiveness after infraclavicular brachial plexus blockade. METHODS: Thirty consecutive patients undergoing upper limb surgery under infraclavicular block were enrolled. From the end of the local anesthetic injection, skin temperature was measured in all four major nerve distribution areas, and the sensory block onset (using cold and pinprick with 0 = no sensation to 2 = normal) were evaluated every 5 min for 30 min. A successful block was defined as the absence of sensation to cold (swab soaked with alcohol) and pinprick (needle) with a score of "0" within 30 min after the injection in the 4 major nerve distribution areas (radial, ulnar, median and musculocutaneous). Skin temperature measurements were performed using a noncontact temperature probe. RESULTS: One-hundred-twenty nerves (30 patients, 4 nerves per patient) were anesthetized. Twenty-five patients had a successful block. Four patients required supplementation for block failure. General anesthesia was performed in one patient. Skin temperature variation was not different among different nerves. There was a statistically significant increase in cutaneous temperature after nerve block compared to the same skin area before the procedure (P < 0.0001 from T5 to T30). Average temperature variations in blocked versus unblocked nerves at the same time were significantly different (P < 0.05 at T5 then P < 0.0001 from T10 to T30). When temperature in a specific sensory territory increased 1 degree C or more, at 5 and 10 min, the specific nerve was blocked (the score was "0"). Thus, when temperature changes in all 4 nerves were noted at 5 and 10 min, the block was successful at 30 min. No change in temperature in the contralateral arm or in the core temperature was observed. CONCLUSION: Skin temperature assessment with an infrared thermometer is a reliable, simple and early indicator of a successful nerve block.