Mitral annular plane systolic excursion for assessing left ventricular systolic dysfunction in patients with septic shock.

Background: Using easy-to-determine bedside measurements, we developed an echocardiographic algorithm for predicting left ventricular ejection fraction (LVEF) and longitudinal strain (LVLS) in patients with septic shock. Methods: We measured septal and lateral mitral annular plane systolic excursion (MAPSE), septal and lateral mitral S-wave velocity, and the left ventricular longitudinal wall fractional shortening in patients with septic shock. We used a conditional inference tree method to build a stratification algorithm. The left ventricular systolic dysfunction was defined as an LVEF <50%, an LVLS greater than -17%, or both. Results: We included 71 patients (males: 61%; mean [standard deviation] age: 61 [15] yr). Septal MAPSE (cut-off: 1.2 cm) was the best predictor of left ventricular systolic dysfunction. The level of agreement between the septal MAPSE and the left ventricular systolic dysfunction was 0.525 [0.299-0.751]. A septal MAPSE ≥1.2 cm predicted normal LVEF in 17/18 patients, or 94%. In contrast, a septal MAPSE <1.2 cm predicted left ventricular systolic dysfunction with impaired LVLS in 46/53 patients (87%), although 32/53 (60%) patients had a preserved LVEF. Conclusions: Septal MAPSE is easily measured at the bedside and might help clinicians to detect left ventricular systolic dysfunction early-especially when myocardial strain measurements are not feasible.

The PROMIZING trial enrollment algorithm for early identification of patients ready for unassisted breathing.

BACKGROUND: Liberating patients from mechanical ventilation (MV) requires a systematic approach. In the context of a clinical trial, we developed a simple algorithm to identify patients who tolerate assisted ventilation but still require ongoing MV to be randomized. We report on the use of this algorithm to screen potential trial participants for enrollment and subsequent randomization in the Proportional Assist Ventilation for Minimizing the Duration of MV (PROMIZING) study. METHODS: The algorithm included five steps: enrollment criteria, pressure support ventilation (PSV) tolerance trial, weaning criteria, continuous positive airway pressure (CPAP) tolerance trial (0 cmH2O during 2 min) and spontaneous breathing trial (SBT): on fraction of inspired oxygen (FiO2) 40% for 30-120 min. Patients who failed the weaning criteria, CPAP Zero trial, or SBT were randomized. We describe the characteristics of patients who were initially enrolled, but passed all steps in the algorithm and consequently were not randomized. RESULTS: Among the 374 enrolled patients, 93 (25%) patients passed all five steps. At time of enrollment, most patients were on PSV (87%) with a mean (± standard deviation) FiO2 of 34 (± 6) %, PSV of 8.7 (± 2.9) cmH2O, and positive end-expiratory pressure of 6.1 (± 1.6) cmH2O. Minute ventilation was 9.0 (± 3.1) L/min with a respiratory rate of 17.4 (± 4.4) breaths/min. Patients were liberated from MV with a median [interquartile range] delay between initial screening and extubation of 5 [1-49] hours. Only 7 (8%) patients required reintubation. CONCLUSION: The trial algorithm permitted identification of 93 (25%) patients who were ready to extubate, while their clinicians predicted a duration of ventilation higher than 24 h.

Pathology Assessments of Multiple Organs in Fatal COVID-19 in Intensive Care Unit vs. Non-intensive Care Unit Patients.

Purpose: The objective of the present study was to provide a detailed histopathological description of fatal coronavirus disease 2019 (COVID 19), and compare the lesions in Intensive Care Unit (ICU) and non-ICU patients. Methods: In this prospective study we included adult patients who died in hospital after presenting with confirmed COVID-19. Multiorgan biopsies were performed. Data generated with light microscopy, transmission electron microscopy (TEM) and RT-PCR assays were reviewed. Results: 20 patients were enrolled in the study and the main pulmonary finding was alveolar damage, which was focal in 11 patients and diffuse in 8 patients. Chronic fibrotic and inflammatory lesions were observed in 18 cases, with acute inflammatory lesions in 12 cases. Diffuse lesions, collapsed alveoli and dystrophic pneumocytes were more frequent in the ICU group (62.5%, vs. 25%; 63%, vs. 55%; 87.5%, vs. 54%). Acute lesions (82%, vs. 37.5%; p = 0.07) with neutrophilic alveolitis (63.6% vs. 0%, respectively; p = 0.01) were observed more frequently in the non-ICU group. Viral RNA was detected in 12 lung biopsies (60%) up to 56 days after disease upset. TEM detected viral particles in the lung and kidney biopsy samples up to 27 days after disease upset. Furthermore, abundant networks of double-membrane vesicles (DMVs, a hallmark of viral replication) were observed in proximal tubular epithelial cells. Conclusion: Lung injury was different in ICU and non-ICU patients. Extrapulmonary damage consisting in kidney and myocardial injury were more frequent in ICU patients. Our TEM experiments provided the first description of SARS-CoV-2-induced DMVs in kidney biopsy samples-a sign of intense viral replication in this organ.

Posterior Reversible Encephalopathy Syndrome After Self-Medication With an Oral Decongestant: A Case Report.

Introduction: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder caused by the dysregulation of cerebral perfusion. Case Presentation: We report on a 18-year-old female patient with a history of end-stage renal disease and thrice weekly hemodialysis. She was admitted to the emergency department with mental confusion, blurred vision, headaches, and vomiting, following self-medication with an oral decongestant containing pseudoephedrine. We observed hypointense lesions with T1-weighted MRI and hyperintense areas with T2-weighted and fluid-attenuated inversion recovery MRI sequences. The lack of diffusion restriction was consistent with a diagnosis of PRES. A concomitant Enterobacter cloacae hemodialysis catheter-bloodstream infection was also diagnosed. We hypothesize that both sepsis and inappropriate self-medication with oral pseudoephedrine contributed to hypertension, endothelial dysfunction, and vasogenic edema. The patient received intensive care and made a full recovery. Discussion: PRES is a life-threatening condition that requires intensive care. Identification of the etiology is the keystone of medical care. Inappropriate self-medication with an oral decongestant might trigger PRES - highlighting the importance of patient education.

Respiratory effects of lung recruitment maneuvers depend on the recruitment-to-inflation ratio in patients with COVID-19-related acute respiratory distress syndrome.

BACKGROUND: In the context of acute respiratory distress syndrome (ARDS), the response to lung recruitment maneuvers (LRMs) varies considerably from one patient to another and so is difficult to predict. The aim of the study was to determine whether or not the recruitment-to-inflation (R/I) ratio could differentiate between patients according to the change in lung mechanics during the LRM. METHODS: We evaluated the changes in gas exchange and respiratory mechanics induced by a stepwise LRM at a constant driving pressure of 15 cmH2O during pressure-controlled ventilation. We assessed lung recruitability by measuring the R/I ratio. Patients were dichotomized with regard to the median R/I ratio. RESULTS: We included 30 patients with moderate-to-severe ARDS and a median [interquartile range] R/I ratio of 0.62 [0.42-0.83]. After the LRM, patients with high recruitability (R/I ratio ≥ 0.62) presented an improvement in the PaO2/FiO2 ratio, due to significant increase in respiratory system compliance (33 [27-42] vs. 42 [35-60] mL/cmH2O; p < 0.001). In low recruitability patients (R/I < 0.62), the increase in PaO2/FiO2 ratio was associated with a significant decrease in pulse pressure as a surrogate of cardiac output (70 [55-85] vs. 50 [51-67] mmHg; p = 0.01) but not with a significant change in respiratory system compliance (33 [24-47] vs. 35 [25-47] mL/cmH2O; p = 0.74). CONCLUSION: After the LRM, patients with high recruitability presented a significant increase in respiratory system compliance (indicating a gain in ventilated area), while those with low recruitability presented a decrease in pulse pressure suggesting a drop in cardiac output and therefore in intrapulmonary shunt.

Temozolomide is a risk factor for invasive pulmonary aspergillosis: A case report and literature review.

BACKGROUND: Temozolomide is an oral alkylating agent incorporated in the treatment of glioblastoma multiforme (GBM) that can lead to lymphopenia. The standard treatment of GBM involves temozolomide chemotherapy with radiation, often with addition of corticosteroids for symptomatic management of cerebral edema. Some studies have reported an increased risk of opportunistic infections. CASE PRESENTATION: A 72-year-old man receiving Temozolomide for treatment of newly diagnosed GBM associated with radiotherapy and corticosteroids was admitted in an intensive care unit because a rapid deterioration of consciousness associated with acute respiratory failure. The diagnosis of invasive pulmonary aspergillosis (IPA) was made. The patient was successfully treated with voriconazole alone. CONCLUSIONS: This case shows that Temozolomide can be associated with severe invasive aspergillosis, which is in all likelihood associated with T lymphocyte immune dysfunction. Physicians should be aware of possible opportunistic infections when managing patients with glioblastoma, and patients exposed to this agent should be carefully monitored.

Transoesophageal Ultrasound Assessment of Lung Aeration in Patients With Acute Respiratory Distress Syndrome.

Introduction: The effect of positive end-expiratory pressure (PEEP) depends closely on the potential for lung recruitment. Bedside assessment of lung recruitability is crucial for personalized lung-protective mechanical ventilation in acute respiratory distress syndrome (ARDS) patients. Methods: We developed a transoesophageal lung ultrasound (TE-LUS) method in which a quantitative (computer-assisted) grayscale determination served as a guide to PEEP-induced lung recruitment. The method is based on the following hypothesis: when the PEEP increases, inflation of the recruited alveoli leads to significant changes in the air/water ratio. Normally ventilated areas are hypoechoic because the ultrasound waves are weakly reflected while poorly aerated areas or non-aerated areas are hyperechoic. We calculated the TE-LUS re-aeration score (RAS) as the ratio of the mean gray scale level at low PEEP to that value at high PEEP for the lower and upper lobes. A RAS > 1 indicated an increase in ventilated area. We used this new method to detect changes in ventilation in patients with a low (<0.5) vs. high (≥0.5) recruitment-to-inflation (R/I) ratio (i.e., the ratio between the recruited lung compliance and the respiratory system compliance at low PEEP). Results: We included 30 patients with moderate-to-severe ARDS. In patients with a high R/I ratio, the TE-LUS RAS was significantly higher in the lower lobes than in the upper lobes (1.20 [1.12-1.63] vs. 1.05 [0.89-1.38]; p = 0.05). Likewise, the TE-LUS RAS in the lower lobes was significantly higher in the high R/I group than in the low R/I group (1.20 [1.12-1.63] vs. 1.07 [1.00-1.20]; p = 0.04). Conclusion: The increase in PEEP induces a substantial gain in the ventilation detected by TE-LUS of poorly or non-aerated lower lobes (dependent lung regions), especially in patients with a high R/I ratio.

From Upper Respiratory Symptoms to Hemophagocytic Lymphohistiocytosis: Case Report of a Human Adenovirus Infection in Haploidentical Hematopoietic Stem Cell Transplant Recipient.

Human adenovirus infection is rare in adult population, except for in immunocompromised individuals. Recipients of allogenic haploidentical hematopoietic stem cell transplantation are reported at high risk for human adenovirus, which is often lethal when it evolves into the disseminated form. Despite existent guidelines, prevention, early diagnosis, and therapeutics remain challenging. Here, we report the case of a fatal evolution of human adenovirus respiratory infection and discuss the actual recommendations to prevent recurrence of this major issue.

Positive end-expiratory pressure in COVID-19-related ARDS: Do not forget the airway closure.

Airway closure is a physiological phenomenon in which the distal airways are obstructed when the airway pressure drops below the airway opening pressure. We assessed this phenomenon in 27 patients with coronavirus disease 2019-related acute respiratory distress syndrome. Twelve (44%) patients had an airway opening pressure above 5 cmH2O. The median airway opening pressure was 8 cmH2O (interquartile range, 7-10), with a maximum value of 17 cmH2O. Three patients had a baseline positive end-expiratory pressure lower than the airway opening pressure.

Estimation of Pulmonary Artery Occlusion Pressure Using Doppler Echocardiography in Mechanically Ventilated Patients.

OBJECTIVES: Evaluation of left atrial pressure is frequently required for mechanically ventilated critically ill patients. The objective of the present study was to evaluate the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for assessment of the pulmonary artery occlusion pressure (a frequent surrogate of left atrial pressure) in this population. DESIGN: A pooled analysis of three prospective cohorts of patients simultaneously assessed with a pulmonary artery catheter and echocardiography. SETTINGS: Medical-surgical intensive care department of two university hospitals in France. PATIENTS: Mechanically ventilated critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 98 included patients (males: 67%; mean ± SD age: 59 ± 16; and mean Simplified Acute Physiology Score 2: 54 ± 20), 53 (54%) experienced septic shock. Using the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, the predicted pulmonary artery occlusion pressure was indeterminate in 48 of the 98 patients (49%). Of the 24 patients with an elevated predicted left atrial pressure (grade II/III diastolic dysfunction), only 17 (71%) had a pulmonary artery occlusion pressure greater than or equal to 18 mm Hg. Similarly, 20 of the 26 patients (77%) with a normal predicted left atrial pressure (grade I diastolic dysfunction) had a measured pulmonary artery occlusion pressure less than 18 mm Hg. The sensitivity and specificity of American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for predicting elevated pulmonary artery occlusion pressure were both 74%. The agreement between echocardiography and the pulmonary artery catheter was moderate (Cohen's Kappa, 0.48; 95% CI, 0.39-0.70). In a proposed alternative algorithm, the best echocardiographic predictors of a normal pulmonary artery occlusion pressure were a lateral e'-wave greater than 8 (for a left ventricular ejection fraction ≥ 45%) or an E/A ratio less than or equal to 1.5 (for a left ventricular ejection fraction < 45%). CONCLUSIONS: The American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines do not accurately assess pulmonary artery occlusion pressure in ventilated critically ill patients. Simple Doppler measurements gave a similar level of diagnostic performance with less uncertainly.

The urine biomarkers TIMP2 and IGFBP7 can identify patients who will experience severe acute kidney injury following a cardiac arrest: A prospective multicentre study.

AIM: To determine whether the urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can identify patients who will develop severe acute kidney injury (AKI) soon after cardiac arrest. METHODS: We performed a prospective, multicentre study in three French ICUs. The performance of [TIMP-2]*[IGFBP7] was assessed for urine samples collected a median [IQR] of 240 [169-315] minutes post-collapse. The primary end-point was severe AKI (KDIGO stage 3), within 48 h of admission. RESULTS: Of the 115 patients analyzed, 32 (28%) developed severe AKI. Eleven of these required renal replacement therapy. The median [IQR] baseline [TIMP-2]*[IGFBP7] level was higher in patients who developed severe AKI (1.57 [0.80-6.62] (ng/ml)2/1000) than in those who did not (0.17 [0.05-0.59] (ng/ml)2/1000; p < 0.001). The baseline [TIMP2]*[IGFBP7] predicted -severe AKI with an area under the curve [95% confidence interval (CI)] of 0.91 [0.84-0.95], an optimal cut-off value of 0.39 (ng/ml)2/1000, a sensitivity [95%CI] of 97% [84-100], and a specificity of 72% [61-82]. A cut-off of 2.0 (ng/ml)2/1000 yielded a specificity of 98% [92-100]. For predicting severe AKI, baseline [TIMP-2]*[IGFBP7] was significantly more discriminant than baseline SCr (AUC [95%CI]: 0.73 [0.63-0.84]; p = 0.005), and slightly but not significantly more discriminant than baseline UO (AUC [95%CI]: 0.86 [0.78‒0.94], p = 0.08) Combining the baseline [TIMP2]*[IGFBP7] with baseline SCr and UO significantly improved the latter markers' predictive performance. CONCLUSION: Urine [TIMP-2]*[IGFBP7] effectively identify patients with a risk of severe AKI. Below a cut-off of 0.39 (ng/ml)2/1000, the risk of severe AKI is low.

Does low risk of infections as a marker of effective immunity predict increased risk of subsequent giant cell arteritis or polymyalgia rheumatica? A Danish population-based case-control study.

OBJECTIVE: It has been suggested that a hyper-effective immune system ("hyper-immunity") is central to the pathogenesis of giant cell arteritis and polymyalgia rheumatica (GCA/PMR). We examined if a low risk of infections, as a marker of hyper-immunity, can predict increased subsequent risk of GCA/PMR. PATIENTS AND METHODS: We conducted a population-based case-control study including all patients aged ≥50 years with incident GCA/PMR diagnosed between 1997 and 2012 in Northern Denmark. For each case, we selected 10 population controls matched on gender, age, place of residence, and time spent in the region. Complete history of hospital-treated infections and community-based anti-infective prescriptions was assessed in population-based registries. We used conditional logistic regression to compute OR of GCA/PMR associated with infections while adjusting for comorbidities, immunosuppressive treatment, and other potential confounders. RESULTS: We included 7,225 GCA/PMR cases and 72,250 controls. When excluding all infections occurring within the last year before GCA/PMR diagnosis, there was no decreased risk for GCA/PMR in people with a history of hospital-treated infection (adjusted OR=1.04, 95% CI: 0.98-1.10) or community anti-infective treatment (adjusted OR=1.07, 95% CI: 0.99-1.16). Within the last year preceding the GCA/PMR index date, patients with hospital-treated infections (adjusted OR=1.59, 95% CI: 1.44-1.75) or community anti-infective treatment (adjusted OR=1.63, 95% CI: 1.48-1.79) had a greatly increased risk of a GCA/PMR diagnosis. CONCLUSION: These results do not support the hypothesis of "hyper-immunity" leading to GCA/PMR. Instead, incident GCA/PMR is preceded by a slightly increased risk of infection, which may be related to protopathic bias or support theories that infections may be directly involved in the pathogenesis of GCA/PMR.

The Warburg Effect as a Type B Lactic Acidosis in a Patient With Acute Myeloid Leukemia: A Diagnostic Challenge for Clinicians.

INTRODUCTION: The Warburg effect (WE) is an uncommon cause of type B lactic acidosis (LA) due to a deregulation of carbohydrate metabolism in neoplastic cells where lactic fermentation predominates over oxidative phosphorylation regardless of the oxygen level. CASE PRESENTATION: We report the case of a 57-year-old man presenting with concomitant acute myeloid leukemia and type B LA with asymptomatic hypoglycemia. We did not find arguments for a septic state, liver dysfunction, or acute mesenteric ischemia. The WE was suspected, and chemotherapy was immediately undertaken. We observed a rapid and sustained decrease in lactate level and normalization of blood glucose. Unfortunately, we noted a relapse of acute leukemia associated with WE soon after treatment initiation and the patient died in the Intensive Care unit. DISCUSSION: Some patients may present complications directly related to an underlying hematological malignancy. The WE is one of these complications and should be suspected in patients with both hypoglycemia and LA. We propose a checklist in order to help clinicians manage this life-threatening complication. Before considering WE, clinicians should eliminate diagnoses such as septic shock or mesenteric ischemia, which require urgent and specific management. CONCLUSION: The diagnosis of WE can be challenging for clinicians in the Hematology department and the Intensive Care unit. Prompt diagnosis and rapid, adapted chemotherapy initiation may benefit patient survival.

Th17 and CD24hiCD27+ regulatory B lymphocytes are biomarkers of response to biologics in rheumatoid arthritis.

BACKGROUND: The aim was to describe the regulatory B and T cells (Breg and Treg) and T helper 17 (Th17) lymphocytes before and under treatment with biologic drugs, and to assess their potential predictive value as biomarkers of response in rheumatoid arthritis (RA). METHODS: This was a non-randomised, single-centre, prospective study. Patients with active RA (American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010) who required the initiation or switch to any biologic drug except rituximab were included. The main judgement criterion was the frequency and absolute number of CD24hiCD27+ Breg and CD24hiCD38hi T2/Breg cells, CD25hiCD127low Treg and CD45RA-CD161+CCR6+ Th17 cells measured at inclusion in both patients and controls, and after 1, 3 and 6 months of treatment (M1, M3 and M6) in patients with RA, and compared with the M6 response to treatment (EULAR response and Disease Activity Score in 28 joints (DAS28) remission). RESULTS: Thirty-one patients with RA and 17 controls were included. There was a reduction in T2/Breg frequency at M0 in patients (p < 0.001) and absolute numbers (p = 0.014) and in immunopositive vs. immunonegative RA (p = 0.016). DAS28 remission at M6 was associated with increased frequency of Treg (p = 0.01). A higher level of CD24hiCD27+ Breg at baseline was associated with DAS28 remission at M6 (p = 0.04) and a good EULAR response at M6 for abatacept-treated patients (p = 0.01). A lower M0 level of Th17 was associated with a good EULAR response at M6 (p = 0.007), notably under anti-cytokine drugs (p = 0.048). CONCLUSIONS: Altogether, these data, although preliminary, suggest that phenotyping of T and B cells has potential value for the stratification of biologic drugs, notably with respect to choosing between abatacept and anti-cytokine blockade.