Health-related quality of life and long-term sequelae in survivors of epidermal necrolysis: an observational study of 57 patients.

BACKGROUND: Few studies have investigated the global burden of sequelae and health-related quality of life (HRQoL) for survivors of epidermal necrolysis (EN). OBJECTIVES: To investigate the long-term HRQoL for survivors of EN using validated instruments. METHODS: We conducted a single-centre study that enrolled patients who were admitted for EN between 2010 and 2017. HRQoL was assessed via phone interview using the Short Form (SF)-36 questionnaire, Hospital Anxiety and Depression (HAD) scale, Impact of Event Scale-Revised, and general quality-of-life outcomes, including EN-specific sequelae. The primary outcome measure was the physical component summary (PCS) score of the SF-36. RESULTS: In total, 57 survivors of EN [19 (33%) with intensive care unit (ICU) admission] were interviewed via telephone at a median of 3·6 years (1·9-6·1) after hospital discharge. The median PCS score was 0·44 SDs below that of the age- and sex-matched reference population and was significantly lower for survivors of EN who were admitted to the ICU vs. those who were not [43·7 (28·7-49·3) vs. 51·2 (39·4-56·5), P = 0·042]. The proportion of patients with EN who had HAD-anxiety score ≥ 8 or HAD-depression score ≥ 5 was 54% and 21%, respectively. Physical and mental outcomes did not differ between patients with EN who were admitted to the ICU and survivors of septic shock. Reported EN-specific sequelae were cutaneous (77%), ocular (70%), psychological (60%), dental/oral (49%), genital (30%) and respiratory (18%), with median intensity on a visual analogue scale. CONCLUSIONS: Our study confirms the major burden and long-term impact of EN on quality of life for survivors and emphasizes the need for prolonged close follow-up after the acute phase. What's already known about this topic? Long-term sequelae have been reported in 90% of survivors of epidermal necrolysis (EN). Few studies have investigated the global burden of sequelae and health-related quality of life (HRQoL) in survivors of EN. What does this study add? Survivors of EN, particularly those admitted to the intensive care unit, had poorer physical HRQoL than the French reference population but had comparable HRQoL to survivors of septic shock. Survivors of EN exhibited symptoms of anxiety, depression and post-traumatic stress syndrome. The most frequent sequelae were cutaneous, ocular and psychological, with visual analogue scale scores of 5/10 and 6/10. These results confirm the burden of EN on quality of life.

The use of rituximab to prevent severe delayed haemolytic transfusion reaction in immunized patients with sickle cell disease.

BACKGROUND: Delayed haemolytic transfusion reaction (DHTR) is mainly caused by an immune response to transfused red blood cells (RBCs). Immunized patients have a high risk of producing antibodies in response to further transfusion. Controlling the immune response to RBCs is therefore a major goal in sickle cell disease (SCD). STUDY DESIGN: We report an observational study of eight alloimmunized SCD patients with history of severe DHTR who were treated with rituximab before a new transfusion to prevent further immunization and DHTR. RESULTS: Five patients showed a good clinical outcome following transfusion preceded by preemptive treatment with rituximab. The remaining patients presented mild DHTR. In all patients, the results of post-transfusion screening tests were identical to those of pretransfusion tests; no newly formed antibodies were detected. CONCLUSION: These cases suggest that rituximab prevents at least occurrence of newly formed antibodies in high responders and minimizes the risk of severe DHTR. This study confirms that DHTR is complex in SCD and does not rely only on the classical antigens/antibodies conflict. Considering potentially serious adverse effect of rituximab, this treatment should be considered cautiously, and only when transfusion is absolutely necessary in patients with history of severe DHTR linked to immunization.

Long-term follow-up of cardiac arrest survivors: Protocol of the DESAC (Devenir des survivants d'Arrets Cardiaques) study, a French multicentric prospective cohort.

Background: While the short-term prognosis of cardiac arrest patients - nearly 250,000 new cases per year in Europe - has been extensively studied, less is known regarding the mid and long-term outcome of survivors. Objective: The aim of the DESAC study is to describe mid- and long-term survival rate and functional status of cardiac arrest survivors, and to assess the influence of pre and intra hospital therapeutic strategies on these two outcomes. Methods: Between Jul 2015 and Oct 2018, adult patients over 18 years who were discharged alive from any intensive care units (public and private hospitals) in the Ile-de-France area (Paris and suburbs, France) after a non-traumatic cardiac arrest were screened for participation in this multicentric study. Survivors were included after they signed (or the proxies) an informed consent before discharge during initial hospitalisation. We calculated that including 600 patients in total would allow an 80% power to demonstrate a 2 years survival rate difference of 10% between patients who did and those who did not receive therapeutic hypothermia after resuscitation. Pre- and in-hospital data related to the circumstances surrounding the event and to the therapeutic interventions (such as cardio-pulmonary resuscitation, defibrillation, emergent coronary revascularization, neuroprotective therapeutics) were collected. After discharge, patients were interviewed at 3 months, 6 months and every year thereafter for a minimum follow-up of 26 months and a maximum follow-up of 48 months. Information on vital status, occurrence of cardiovascular events, medications and a comprehensive assessment of the functional status (qualitive of life as assessed by the Short-Form General Health Survey (SF36) scale, activities of daily living (ADL) scale, neurological Cerebral Performance Categories (CPC) and Overall Performance Categories (OPC) scales, socio-professional activities) were collected at follow-up interviews. Discussion: The DESAC study should provide important information regarding several dimensions of the mid and long-term prognosis of cardiac arrest survivors and on the benefit (and potentially harm) of early therapeutic strategies.

[Acute chest syndrome in adult sickle cell patients]. / Syndrome thoracique aigu chez les patients drépanocytaires adultes.

Sickle cell disease is a frequent genetic condition, due to a mutation of the ß-globin gene, leading to the production of an abnormal S hemoglobin and characterized by multiple vaso-occlusive events. The acute chest syndrome is a severe complication associated with a significant disability and mortality. It is defined by the association of one or more clinical respiratory manifestations and a new infiltrate on lung imaging. Its pathophysiology is complex and implies vaso-occlusive phenomena (pulmonary vascular thrombosis, fat embolism), infection, and alveolar hypoventilation. S/S or S/ß0-thalassemia genotype, a history of vaso-occlusive crisis or acute chest syndrome, a low F hemoglobin level (<5%), a high steady-state hemoglobin level (> 10 g/dL), or a high steady-state leukocytosis (>10 G/L) are the main risk factors. Febrile chest pain, dyspnea, sometimes cough with expectorations are its main clinical manifestations, and bi-basal crackles are found at auscultation. Inferior alveolar opacities with or without pleural effusions are identified on chest X-ray or CT-scan. Management of the acute chest syndrome should be prompt and implies, besides the recognition of severity signs, a multimodal analgesia, oxygen supplementation, sometimes a parenteral antibiotic treatment and the frequent use of blood transfusions especially in the most severe cases. Prevention is important and includes a regular monitoring of hospitalized patients and the use of incentive spirometry.

Systematic review and literature appraisal on methodology of conducting and reporting critical-care echocardiography studies: a report from the European Society of Intensive Care Medicine PRICES expert panel.

BACKGROUND: The echocardiography working group of the European Society of Intensive Care Medicine recognized the need to provide structured guidance for future CCE research methodology and reporting based on a systematic appraisal of the current literature. Here is reported this systematic appraisal. METHODS: We conducted a systematic review, registered on the Prospero database. A total of 43 items of common interest to all echocardiography studies were initially listed by the experts, and other "topic-specific" items were separated into five main categories of interest (left ventricular systolic function, LVSF n = 15, right ventricular function, RVF n = 18, left ventricular diastolic function, LVDF n = 15, fluid management, FM n = 7, and advanced echocardiography techniques, AET n = 17). We evaluated the percentage of items reported per study and the fraction of studies reporting a single item. RESULTS: From January 2000 till December 2017 a total of 209 articles were included after systematic search and screening, 97 for LVSF, 48 for RVF, 51 for LVDF, 36 for FM and 24 for AET. Shock and ARDS were relatively common among LVSF articles (both around 15%) while ARDS comprised 25% of RVF articles. Transthoracic echocardiography was the main echocardiography mode, in 87% of the articles for AET topic, followed by 81% for FM, 78% for LVDF, 70% for LVSF and 63% for RVF. The percentage of items per study as well as the fraction of study reporting an item was low or very low, except for FM. As an illustration, the left ventricular size was only reported by 56% of studies in the LVSF topic, and half studies assessing RVF reported data on pulmonary artery systolic pressure. CONCLUSION: This analysis confirmed sub-optimal reporting of several items listed by an expert panel. The analysis will help the experts in the development of guidelines for CCE study design and reporting.

High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure. METHODS: We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods. RESULTS: We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67-1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74-0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51-0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use. CONCLUSION: In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.

A 2-year multicenter, observational, prospective, cohort study on extracorporeal CO2 removal in a large metropolis area.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis. METHODS: To assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period. RESULTS: Seventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median V T was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3-8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related. CONCLUSIONS: Based on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079.

Deficiency of the 5-hydroxytryptamine transporter gene leads to cardiac fibrosis and valvulopathy in mice.

BACKGROUND: Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation is one proposed mechanism of the valvulopathy observed in individuals treated with the appetite suppressants fenfluramine and phentermine. One key protein limiting systemic availability of 5-HT is the 5-HT transporter (5-HTT) expressed by platelets and pulmonary vascular cells; 5-HTT is responsible for 5-HT uptake and subsequent inactivation of the amine passing through the lung. Here we investigated whether 5-HTT-deficient (5-HTT-KO) mice developed structural and/or functional cardiac abnormalities and valvulopathy. METHODS AND RESULTS: Cardiac endothelial cells expressed large amounts of 5-HTT in wild-type mice. 5-HTT deficiency appeared to be associated with marked interstitial, perivascular, and valvular fibrosis as evidenced by staining of cardiac collagen in 5-HTT-KO mice. Histological analysis provided evidence for valvulopathy characterized by valvular hyperplasia and prominent fibrosis at the attachment site and base of the leaflets. Echocardiography revealed an increase in left ventricular lumen diameter and a decrease in left ventricular diameter fractional shortening. Although 5-HT1B receptors mediated the 5-HT-induced collagen secretion by human cardiac myofibroblasts, the contribution of this receptor type to valvulopathy was ruled out because double-KO mice deficient in both 5-HTT and 5-HT1B receptors showed the same cardiac alterations as 5-HTT-KO mice. CONCLUSIONS: The present results establish a link between 5-HTT and the development of cardiac fibrosis and valvulopathy in vivo. 5-HTT-KO mice represent an especially relevant model for studying the mechanisms by which 5-HT induces valvulopathy.

Inhaled nitric oxide for acute chest syndrome in adult sickle cell patients: a randomized controlled study.

PURPOSE: Previous clinical trials suggested that inhaled nitric oxide (iNO) could have beneficial effects in sickle cell disease (SCD) patients with acute chest syndrome (ACS). METHODS: To determine whether iNO reduces treatment failure rate in adult patients with ACS, we conducted a prospective, double-blind, randomized, placebo-controlled clinical trial. iNO (80 ppm, N = 50) gas or inhaled nitrogen placebo (N = 50) was delivered for 3 days. The primary end point was the number of patients with treatment failure at day 3, defined as any one of the following: (1) death from any cause, (2) need for endotracheal intubation, (3) decrease of PaO2/FiO2 ≥ 15 mmHg between days 1 and 3, (4) augmented therapy defined as new transfusion or phlebotomy. RESULTS: The two groups did not differ in age, gender, genotype, or baseline characteristics and biological parameters. iNO was well tolerated, although a transient decrease in nitric oxide concentration was mandated in one patient. There was no significant difference in the primary end point between the iNO and placebo groups [23 (46 %) and 29 (58 %); odds ratio (OR), 0.8; 95 % CI, 0.54-1.16; p = 0.23]. A post hoc analysis of the 45 patients with hypoxemia showed that those in the iNO group were less likely to experience treatment failure at day 3 [7 (33.3 %) vs 18 (72 %); OR = 0.19; 95 % CI, 0.06-0.68; p = 0.009]. CONCLUSIONS: iNO did not reduce the rate of treatment failure in adult SCD patients with mild to moderate ACS. Future trials should target more severely ill ACS patients with hypoxemia. CLINICAL TRIAL REGISTRATION: NCT00748423.

Risk factors for post-cardiopulmonary bypass vasoplegia in patients with preserved left ventricular function.

BACKGROUND: Although vasodilatory shock (VS) is one of the main complications of cardiopulmonary bypass (CPB), its pathophysiologic basis remains unclear. The aim of this study was to identify predisposing factors for the development of VS after CPB independent of ventricular function. METHODS: Thirty-six patients undergoing coronary artery bypass grafting who developed VS were compared with 72 control patients without post-CPB cardiogenic or vasoplegic shock, in a 2:1 case control study. Patients and controls underwent the same anesthetic protocol and were matched by age, sex, operation date, and left ventricle ejection fraction. RESULTS: Preoperative and intraoperative patient characteristics were not significantly different between the two groups. Preoperative use of angiotensin-converting enzyme inhibitors and intravenous heparin were independent predictors for post-CPB VS by multivariate analysis (relative risk of 2.26 and 2.78, respectively). Intensive care unit stay and hospital stay were significantly longer in VS cases than controls, without any difference in early postoperative mortality. CONCLUSIONS: The only independent risk factors for postoperative VS identified were preoperative use of angiotensin-converting enzyme inhibitors and intravenous heparin. These risk factors were independent of age, gender, anesthetic protocol, and left ventricle ejection fraction.

Closed drainage using redon catheters for poststernotomy mediastinitis: results and risk factors for adverse outcome.

BACKGROUND: Several different surgical techniques have been described for the treatment of poststernotomy mediastinitis. The present study was undertaken to evaluate the midterm results of primary closed drainage using Redon catheters and to identify risk factors for adverse outcome. METHODS: Hospital records of 72 patients in whom poststernotomy mediastinitis developed and who underwent closed drainage with Redon catheters between April 1, 1996, and December 31, 1999, were reviewed. Follow-up was complete and averaged 11.8 +/- 11.5 months. RESULTS: Of the 25 deaths (34.7%) recorded, 15 were directly attributable to mediastinitis. Actuarial estimates for freedom from mediastinitis-related death were 80.1% at 1 month and 77.4% at 1 year, 2 years, and 3 years. Logistic regression identified older age (odds ratio, 1.1; 95% confidence interval, 1.02 to 1.18), incubation time of 14 days or less (6.5; 1.33 to 31.4), and methicillin-resistant Staphylococcus aureus (5.8; 1.2 to 27.2) as independent risk factors for mediastinitis-related death. Reintervention for recurrent mediastinitis was necessary in 9 patients (12.5%) and occurred at a mean interval of 18.7 +/- 13.5 days from the first debridement. Actuarial estimates for freedom from reintervention were 87.1% at 1 month and 85.2% at 1 year, 2 years, and 3 years. The combined end point of treatment failure (mediastinitis-related death or reintervention) was recorded in 9 patients (26.4%). Actuarial estimates for freedom from treatment failure were 74.3% at 1 month and 72.7% at 1 year, 2 years, and 3 years. Logistic regression identified older age (1.01; 1.02 to 1.18), preoperative renal insufficiency (6.8; 1.04 to 44.5), and methicillin-resistant S aureus infection (4.8; 1.04 to 22.33) as independent risk factors for treatment failure (includes mediastinitis-related death and reintervention [with or without death]). CONCLUSIONS: Primary closed drainage using Redon catheters is an effective and simple treatment for most patients in whom poststernotomy mediastinitis develops. However, patients with methicillin-resistant S aureus infection or recurrent mediastinitis may benefit from a more aggressive approach.