Potential impact of real-time processing and rapid susceptibility testing of blood samples in Gram-negative bloodstream infections in intensive care patients.

INTRODUCTION: Timely and appropriate therapy is critical in patients with Gram-negative bloodstream infections (GNBSI). Most bacteriology laboratories process blood specimen in the daytime, during laboratory operating hours, and use conventional culture for antimicrobial susceptibility testing (AST). We simulated the potential impact of real-time processing and rapid AST (7 hours) on early adaptation of the antibiotic regimen in intensive care unit (ICU) patients with GNBSI. METHODS: All GNBSI episodes occurring in the ICUs of 2 hospitals in Paris were included. Data were collected. For each episode of bacteremia, we simulated the impact of three strategies: (1) Real-time processing coupled with conventional techniques (Gram stain and standard AST); (2) Standard processing coupled with rapid AST; and (3) Real-time processing coupled with rapid AST. RESULTS: We included 109 episodes in 98 patients. Forty-two patients (48%) died during ICU stay. AST results led to a change of the antibiotic regimen in 66 (61%) episodes, mainly de-escalation (54/109, 55%). In standard care, median time from sample collection to definitive AST result was 65.9 hours (±26.7). The three strategies would have reduced time-to-result by 9.2 hours (±7.1), 30.8 hours (±19.7) and 40.0 hours (±20.6) respectively. Compared to standard care, strategies 1, 2 and 3 would have avoided 20, 69 and 90 patient-days of broad-spectrum antibiotics respectively. CONCLUSION: In addition to real-time processing of blood samples, rapid AST would be the most effective strategy to shorten time-to-result in critical patients with GNBSI.

Organ donation after out-of-hospital cardiac arrest: a population-based study of data from the Paris Sudden Death Expertise Center.

BACKGROUND: Organ shortage is a major public health issue, and patients who die after out-of-hospital cardiac arrest (OHCA) could be a valuable source of organs. Here, our objective was to identify factors associated with organ donation after brain death complicating OHCA, in unselected patients entered into a comprehensive real-life registry covering a well-defined geographic area. METHODS: We prospectively analyzed consecutive adults with OHCA who were successfully resuscitated, but died in intensive care units in the Paris region in 2011-2018. The primary outcome was organ donation after brain death. Independent risk factors were identified using logistic regression analysis. One-year graft survival was assessed using Cox and log-rank tests. RESULTS: Of the 3061 included patients, 136 (4.4%) became organ donors after brain death, i.e., 28% of the patients with brain death. An interaction between admission pH and post-resuscitation shock was identified. By multivariate analysis, in patients with post-resuscitation shock, factors associated with organ donation were neurological cause of OHCA (odds ratio [OR], 14.5 [7.6-27.4], P < 0.001), higher pH (OR/0.1 increase, 1.3 [1.1-1.6], P < 0.001); older age was negatively associated with donation (OR/10-year increase, 0.7 [0.6-0.8], P < 0.001). In patients without post-resuscitation shock, the factor associated with donation was neurological cause of OHCA (OR, 6.9 [3.0-15.9], P < 0.001); higher pH (OR/0.1 increase, 0.8 [0.7-1.0], P = 0.04) and OHCA at home (OR, 0.4 [0.2-0.7], P = 0.006) were negatively associated with organ donation. One-year graft survival did not differ according to Utstein characteristics of the donor. CONCLUSIONS: 4% of patients who died in ICU after OHCA led to organ donation. Patients with OHCA constitute a valuable source of donated organs, and special attention should be paid to young patients with OHCA of neurological cause.

A narrative review of family members' experience of organ donation request after brain death in the critical care setting.

INTRODUCTION: Family members of critically ill patients suffer from high levels of anxiety and depression in the ICU, and are at risk of developing post-ICU syndrome following ICU discharge. In the case of brain death, and potential organ donation, the family is at the center of the decision process: within a limited time frame, the family will be informed that the patient is brain-dead and will be approached about potential organ donation. MATERIALS AND METHODS: Family experience with organ donation has been the topic of several research papers allowing one to gain knowledge about family members' experience of organ donation, emphasizing specific needs, adequate support, and pointing out gaps in current delivery of family-centered care. In this narrative review, experts, clinicians, and researchers present the various legal systems regarding family implication in organ donation decisions; describe factors that influence the decision-making process; highlight family perspectives of care and respect for potential donors in the ICU environment; describe the impact of organ donation discussions and decisions on post-ICU syndrome; and suggest communication skills and support to be developed in the future. A research agenda for the next decade is also encouraged. CONCLUSION: Overall, challenges remain and concern all persons involved in the process, ICU doctors and nurses, the organ procurement organization, family members, and, in some cases, the patients themselves. Looking at the big picture will provide opportunities for further improvements.

Emotional prosodic change detection in autism Spectrum disorder: an electrophysiological investigation in children and adults.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by atypical behaviors in social environments and in reaction to changing events. While this dyad of symptoms is at the core of the pathology along with atypical sensory behaviors, most studies have investigated only one dimension. A focus on the sameness dimension has shown that intolerance to change is related to an atypical pre-attentional detection of irregularity. In the present study, we addressed the same process in response to emotional change in order to evaluate the interplay between alterations of change detection and socio-emotional processing in children and adults with autism. METHODS: Brain responses to neutral and emotional prosodic deviancies (mismatch negativity (MMN) and P3a, reflecting change detection and orientation of attention toward change, respectively) were recorded in children and adults with autism and in controls. Comparison of neutral and emotional conditions allowed distinguishing between general deviancy and emotional deviancy effects. Moreover, brain responses to the same neutral and emotional stimuli were recorded when they were not deviants to evaluate the sensory processing of these vocal stimuli. RESULTS: In controls, change detection was modulated by prosody: in children, this was characterized by a lateralization of emotional MMN to the right hemisphere, and in adults, by an earlier MMN for emotional deviancy than for neutral deviancy. In ASD, an overall atypical change detection was observed with an earlier MMN and a larger P3a compared to controls suggesting an unusual pre-attentional orientation toward any changes in the auditory environment. Moreover, in children with autism, deviancy detection depicted reduced MMN amplitude. In addition in children with autism, contrary to adults with autism, no modulation of the MMN by prosody was present and sensory processing of both neutral and emotional vocal stimuli appeared atypical. CONCLUSIONS: Overall, change detection remains altered in people with autism. However, differences between children and adults with ASD evidence a trend toward normalization of vocal processing and of the automatic detection of emotion deviancy with age.

Assessment of auditory discrimination in hearing-impaired patients.

Hearing loss can impair auditory discrimination, especially in noisy environments, requiring greater listening effort, which can impact socio-occupational life. To assess the impact of hearing loss in noisy environments, clinicians may use subjective or objective methods. Subjective methods, such as speech audiometry in noise, are used in clinical practice to assess reported discomfort. Objective methods, such as cortical auditory evoked potentials (CAEPs), are mainly used in research. Subjective methods mainly comprise speech audiometry in noise, in which the signal-to-noise ratio can be varied so as to determine the individual speech recognition threshold, with and without hearing rehabilitation, the aim being to highlight any improvement in auditory performance. Frequency discrimination analysis is also possible. Objective methods assess auditory discrimination without the patient's active participation. One technique used for patients with auditory rehabilitation is the study of auditory responses by CAEPs. This electrophysiological examination studies cortical auditory rehabilitation oddball paradigms, enabling wave recordings such as mismatch negativity, P300 or N400, and analysis of neurophysiological markers according to auditory performance. The present article reviews all these methods, in order to better understand and evaluate the impact of hearing loss in everyday life.

Hypoxic hepatitis after out-of-hospital cardiac arrest: Incidence, determinants and prognosis.

AIM: Hypoxic hepatitis (HH) may complicate the course of resuscitated out-of-hospital cardiac arrest (OHCA) patients admitted in intensive care unit (ICU). Aims of this study were to assess the prevalence of HH, and to describe the factors associated with HH occurrence and outcome. METHODS: We conducted an observational study over a 6-year period (2009-2014) in a cardiac arrest center. All non-traumatic OHCA patients admitted in the ICU after return of spontaneous circulation (ROSC) and who survived more than 24h were included. HH was defined as an elevation of alanine aminotransferase over 20 times the upper limit of normal during the first 72h after OHCA. Factors associated with HH and ICU mortality were picked up by multivariate logistic regression. RESULTS: Among the 632 OHCA patients included in the study, HH was observed in 72 patients (11.4% (95% CI: 9.0%, 14.1%)). In multivariate analysis, time from collapse to ROSC [OR 1.02 per additional minute; 95% CI (1.00, 1.04); p=0.01], male gender [OR 0.53; 95% CI (0.29, 0.95); p=0.03] and initial shockable rhythm [OR 0.35; 95% CI (0.19, 0.65); p<0.01] were associated with HH occurrence. After adjustment for confounding factors, HH was associated with ICU mortality [OR 4.39; 95% CI (1.71, 11.26); p<0.01] and this association persisted even if occurrence of a post-CA shock was considered in the statistical model [OR 3.63; 95% CI (1.39, 9.48); p=0.01]. CONCLUSIONS: HH is not a rare complication after OHCA. This complication is mainly triggered by the duration of resuscitation and is associated with increased ICU mortality.

Ilio-psoas hematoma in the intensive care unit: a multicentric study.

BACKGROUND: Clinical features and outcomes of patients with spontaneous ilio-psoas hematoma (IPH) in intensive care units (ICUs) are poorly documented. The objectives of this study were to determine epidemiological, clinical, biological and management characteristics of ICU patients with IPH. METHODS: We conducted a retrospective multicentric study in three French ICUs from January 2006 to December 2014. We included IPH diagnosed both at admission and during ICU stay. Surgery and embolization were available 24 h a day for each center, and therapeutic decisions were undertaken after pluridisciplinary discussion. All IPHs were diagnosed using CT scan. RESULTS: During this period, we identified 3.01 cases/1000 admissions. The mortality rate of the 77 included patients was 30 %. In multivariate analysis, we observed that mortality was independently associated with SAPS II (OR 1.1, 95 % CI [1.013-1.195], p = 0.02) and with the presence of hemorrhagic shock (OR 67.1, 95 % CI [2.6-1691], p = 0.01). We found IPH was related to anticoagulation therapy in 56 cases (72 %), with guideline-concordant reversal performed in 33 % of patients. We did not found any association between anticoagulant therapy type and outcome. CONCLUSION: We found IPH is an infrequent disease, with a high mortality rate of 30 %, mostly related to anticoagulation therapy and usually affecting the elderly. Management of anticoagulation-related IPH includes a high rate of no reversal of 38 %.

Multifocal community-acquired necrotizing fasciitis caused by a Panton-Valentine leukocidin-producing methicillin-sensitive Staphylococcus aureus.

We describe a rare case of multifocal necrotizing fasciitis (NF) complicating a single vaccine injection. Injection of hepatitis B vaccine of a 16-year-old immunocompetent woman developed into rapidly spreading multifocal NF of the right arm and the thighs, with septic shock. Treatment with antimicrobial therapy and surgical debridements allowed amputation to be avoided with a favourable outcome. The etiological agent was a methicillin-sensitive Staphylococcus aureus (MSSA) isolate harboring the Panton-Valentine leukocidin (PVL) and five enterotoxins. PVL has recently been reported in large series of methicillin-resistant SA cases and has been associated with necrotizing infections. Some strains of MSSA could harbor PVL and enterotoxins. PCR investigation is not frequent but could improve the understanding of the mechanisms of lesions. This case is in keeping with the increasing incidence of MSSA harboring PVL and enterotoxins with multifocal dissemination NF and emphasizes the necessary precautions for skin decontamination before vaccine injection.

Microleakage after thermocycling of 4 etch and rinse and 3 self-etch adhesives with and without a flowable composite lining.

This study evaluated the microleakage of composite fillings prepared with 4 etch and rinse and 3 self-etch adhesive systems after thermocycling. Also evaluated was the potential improvement of cavity sealing when utilizing a low charged resin lining for cavity preparations. Seventy recently extracted teeth were randomly allocated to 7 experimental adhesive systems: two 3-step etch and rinse adhesive systems, Scotchbond Multipurpose (SBMP) and Optibond Solo Plus (OS); two 2-step etch and rinse adhesive systems, referred to as "one-bottle," Scotchbond 1 (SB1) and Gluma Comfort Bond + Desensitizer (G); and 3 self-etch "all-in-one" adhesives, Adper Prompt-L-Pop (PLP), Xeno III (X-III) and iBond (iB). On each tooth, 2 rectangular cavities were prepared at the cemento-enamel junction: 1 cavity was prepared with adhesive and the hybrid composite and the second was filled with the same adhesive and a thin layer of flowable composite (Filtek Flow) under the resin composite (Z100). All teeth were thermocycled for 800 cycles (5 degrees C-55 degrees C, 30 seconds dwell time). Leakage was evaluated on a 6-point (0-5) severity scale for enamel and dentin on 4 interfaces for each restoration. The results are expressed as means +/- standard deviation (SD). Microleakage scores were analyzed by means of generalized linear mixed models (GLMM), assuming an ordinal logistic link function. Covariates in the model were: (1) adhesives, (2) fluid composite and (3) interface. The model also accounts for repeated measurements on the various teeth. The authors found that the mean score of microleakage per tooth was significantly higher at the enamel rather than at the dentin interfaces (1.21 +/- 0.51 and 0.87 +/- 0.48; p<0.0001). In this study, there was no significant difference among the 4 etch and rinse adhesive systems. On the other hand, these adhesives yielded smaller mean scores of microleakage than the 3 self-etch systems (respectively, 0.85 +/- 0.2 and 1.3 +/- 0.5; p<0.0001). Among the self-etch adhesives, microleakage was significantly greater for PLP (1.74 +/- 0.46) than for the other self-etch products (p<0.0001), while X-III, an intermediary strong self-etch, was found to be as good as the etch and rinse systems, with a mean score of 0.97 +/- 0.27. In addition, results have also shown that an under layer of flowable composite significantly improved the water tightness of the PLP adhesive restorations (p=0.042). This in vitro study concluded that the self-etch adhesives remain less effective than etch and rinse. Nevertheless, X-III, a self-etch adhesive, showed acceptable performance in accordance with this study's 6-point severity scale of microleakage, but this needs to be confirmed in further clinical studies. On the other hand, this study failed to reveal that the addition of a thin layer of fluid composite improved the water tightness of the restoration, except for PLP.

Embryonic velar structure and function of two sibling species of Crepidula with different modes of development.

The structure and function of the embryonic velum of two closely related species of Crepidula with different modes of development are examined. The velum of C. dilatata, a direct developer whose embryos feed on nurse eggs, does not differ substantially from the velum of C. fecunda, a species with planktotrophic larvae. Although velar ciliation develops earlier in embryos of C. dilatata, embryos of both species were able to feed on small particles, using the opposed-band ciliary mechanism. However, the embryos of C. dilatata lose this ability as they grow. The embryos of C. dilatata were not able to swim, whereas those of C. fecunda swam consistently in vials of seawater. This difference in swimming ability is probably due to differences in velum-body size allometry between the two species.

[Prognostic value of the assessment of ischemic status at admission to the coronary care unit after pre-hospital thrombolysis]. / Intérêt pronostique de l'évaluation du statut ischémique à l'arrivée en USIC après une thrombolyse préhospitalière.

The object of this study was to assess and analyse TIMI (Thrombolysis in Myocardial Infarction) grade and secondary major cardiac events of patients with acute myocardial infarction benefiting from pre-hospital thrombolysis according to their predefined clinical and electrical "ischaemic status" (Active, Inactive, Intermediate) on admission to the coronary care unit and at the end of thrombolysis (90th minute). This single centre study was undertaken from March 1994 to August 1999 on 161 patients treated by thrombolysis by the emergency ambulance service for acute myocardial infarction (< or = 6 hours). The mean age was 56.2 +/- 11.3 years with 8.7% of women. On admission to the coronary care unit. 30.8% were classified as Inactive and 51.6% as Active. At the end of thrombolysis, 62.3% were classified as Inactive and 27.7% as Active. Nearly 93% of TIMI 3 flow was observed in Inactive patients at the 90th minute and 76.7% of TIMI < or = 2 flow in Active patients (p < 0.0001). Global hospital mortality was 2.48% but it was zero in the Inactive group at the end of thrombolysis. With an average follow-up of 26.9 +/- 15.8 months, the incidence of major cardiac events was 34.1%, including 16.1% of revascularisation of the target lesion. In multivariate analysis, predictive factors for TIMI < or = 2 at the end of thrombolysis included persistent pain, the number of leads with ST elevation and the absence of regression of ST elevation on admission to the coronary care unit. The only predictive factor for secondary major cardiac events was persistent ST elevation at the 90th minute of thrombolysis.

ERMANCIA: Epidemiology of Stroke in Martinique, French West Indies: Part I: methodology, incidence, and 30-day case fatality rate.

BACKGROUND AND PURPOSE: The ERMANCIA (Etude Réalisée en Martinique et Centrée sur l'Incidence de Accidents vasculaires cérébraux) study was designed to provide the first comparable epidemiological data on stroke in a black Caribbean population. METHODS: ERMANCIA was a prospective community-based study performed in Martinique (French West Indies) from June 1, 1998, to May 31, 1999. The black at-risk population was approximately 360 000. Multiple sources were used to identify hospitalized and nonhospitalized patients with first-ever stroke. RESULTS: Five hundred eighty patients (285 men and 295 women; mean+/-SD age, 71.2+/-14 years) suffered from a first-ever in a lifetime stroke, yielding a crude annual incidence of 164/100 000 per year (95% CI, 151 to 177). The rates adjusted by age and sex to the French population (1999 census) and to the European population were 202 (95% CI, 185 to 218) and 151 (95% CI, 139 to 164), respectively. Thirty-eight patients (6.5%) were not hospitalized during the acute phase of the stroke; 92.8% had CT scan. Pathological types of strokes were infarction (79.8%, including 23% of lacunar strokes), intracerebral hemorrhage (14.3%), subarachnoid hemorrhage (3.4%), and undetermined (2.4%). The main risk factors for stroke were hypertension (69.1%) and diabetes (29.5%). The 30-day case fatality rate was 19.3% (15.8% for cerebral infarction and 37.3% for intracerebral hemorrhage). CONCLUSIONS: In Martinique, the ERMANCIA population-based study showed a high stroke incidence and a high prevalence of hypertension and diabetes in the stroke population compared with those observed in continental France. Epidemiological data on stroke in African Caribbeans from Martinique are comparable to those reported in blacks from the United States and United Kingdom.

Ductal carcinoma in situ of the breast results of conservative and radical treatments in 716 patients.

Until now, less than 5% of the patients with breast ductal carcinoma in situ (DCIS) have been enrolled in clinical trials. Consequently, we have analysed the results of "current practice" among 716 women treated in eight French Cancer Centres from 1985 to 1992: 441 cases (61.6%) corresponded to impalpable lesions, 92 had a clinical size of less than or equal to 2 cm and 70 from 2 to 5 cm; in 113 cases, the size was unspecified. Median age was 53.2 years (range: 21-87 years). 145 patients underwent mastectomy (RS) and 571 conservative surgery (CS) without (136) or with (435) radiotherapy (CS+RT). The mean histological tumour sizes in these three groups were 25.6, 8.2, 14.8 mm, respectively (P<0.0001). After a 91-month median follow-up, local recurrence (LR) rates were 2.1, 30.1 and 13.8% in the RS, CS and CS +RT groups, respectively (P=0.001); LR were invasive in 59 and 60% in the CS and CS+RT groups, respectively. In these groups, the 8-year LR rates were 31.3 and 13.9%, respectively (P=0.0001). Nodal recurrence occurred in 3.7 and 1.8% in the CS and CS+RT groups. Metastases rates were 1.4, 4.4 and 1.4% in the RS, CS and CS+RT groups. Among the 60 cases of invasive LR, in CS and CS+RT groups 19% developed metastases. After multivariate analysis, we did not identify any significant LR risk factor in the CS group, whereas young age (<40 years) and incomplete excision were significant in the CS+RT group (P=0.012 and P=0.02, respectively).

[Role of host response during severe bacterial infection]. / Rôle de l'hôte au cours des infections bactériennes sévères.

Explosion of knowledge both in human genomics and in host inflammatory response explains the increasing interest in infectious disease genetics over the last 5 years. However, twin and adoptee studies have suggested more than 15 years ago, that host genetic factors are major determinants of susceptibility to infectious diseases in humans. Recently, candidate gene studies (association studies) and human genomewide analysis have been used to identify infectious diseases susceptibility and resistance genes. Rarely, a single gene defect has been directly related to devastating consequences such as interferon-gamma receptor mutations leading to fatal infections with ubiquitous mycobacteria. For clinical practice, gene polymorphisms of specific host immune defence elements appear to be of major importance. These genetic variants, which modify the regulation or function of the mediators, have been associated with susceptibility and/or outcome of severe sepsis and septic shock. All steps of the host response to bacteria may be affected by genetic factors. For example, Fc gamma receptor, Toll like receptor or mannose binding protein mutations have been shown to modify the detection of pathogens leading to pneumococcal severe infections, Gram-negative bacteria septic shock, and meningococcal disease, respectively. Polymorphisms of cytokine genes (TNF-alpha, TNF-beta, IL-1-ra) have been reported to influence the level of secreted mediators and to unbalance the inflammatory cascade. Coagulation response to sepsis may also be affected by gene variants such as the plaminogen activator inhibitor 1 (PAI-1) common functional polymorphism which increases the risk of death from meningococcal infection or severe trauma. The impact of these findings on the understanding of infectious disease pathogenesis and on the design of future preventive and therapeutic strategies should be considerable.

[African Quin: results of a pragmatic study on the diagnosis of uncomplicated malaria attacks and treatment using quinine in French-speaking Africa]. / African-Quin: résultats d'une étude pragmatique sur le diagnostic de l'accès palustre simple et son traitement par la quinine en Afrique francophone.

Management and treatment of disease do not always conform with official recommendations. African-quin is a pragmatic multicentric study carried out in 13 African countries to evaluate non-conformities in the management and treatment of uncomplicated malarial attacks using quinine. This study involved a total of 3,981 patients with documented uncomplicated malarial attacks diagnosed by 500 clinical physicians. Physicians were supplied with quinine tablets (125 mg et 500 mg Quinimax containing 125 mg and 500 mg of quinine base respectively) to allow treatment according to the dose recommendations of the WHO (24 mg/kg/day of quinine base). In 38% of the 3,981 patients, diagnosis was based on clinical findings without measurement of parasitemia. The median dose of Quinimax was 15.4 mg/kg/day in 3 intakes in 67% and 2 intakes in 33%. The dose was 23.2 mg/kg/day for patients under 12 years and 14.7 mg/kg/day for patients over 18 years (p < 0.001). Treatment lasted for at least 5 days in 62% of patients. Fever control was achieved within a mean delay of 3.9 +/- 1.5 days and was followed by a rapid decrease in clinical symptoms. Clinical control (normal temperature) was obtained in 96% of patients. The dose of Quinimax was the same regardless of whether treatment was a success or failure. The results of this study demonstrate the gap between official recommendations and everyday clinical practice and raise several important questions concerning the basis for decision-making, treatment goals, drug dosage, and treatment duration.