Trends in Maternal Mortality From Obstetric Hemorrhage in France: 15 Years of Confidential Enquiry Into Maternal Deaths.

BACKGROUND: The aim of this study was to assess temporal trends in incidence and underlying causes of maternal deaths from obstetric hemorrhage in France and to describe clinical care before and after implementation of the first national guidelines published in 2004 and updated in 2014. METHODS: Data from all hemorrhage-related maternal deaths between 2001 and 2015 were extracted from the French Confidential Enquiry into Maternal Deaths. We compared the maternal mortality ratio (MMR), cause of obstetric hemorrhage, and death preventability by triennium. Critical care, transfusion, and obstetric management among women who died were described for 2001 to 2003 and 2013 to 2015. RESULTS: The MMR from obstetric hemorrhage significantly decreased over time from 2.3 of 100,000 livebirths (54 of 2,391,551) in 2001 to 2003 to 0.8 of 100,000 livebirths (19 of 2,412,720) in 2013 to 2015. In 2001 to 2003, uterine atony accounted for 50% (27 of 54) of maternal deaths vs 21% (4 of 19) in 2013 to 2015. As compared to 2001 to 2003, an increased proportion of women had hemodynamic continuous monitoring in 2013 to 2015 (30%, 9 of 30, vs 47%, 8 of 18) and received vasopressor infusion therapy (57%, 17 of 30, vs 72%, 13 of 18), and a smaller proportion was extubated during active hemorrhage (17%, 5 of 30, vs 0 of 18). Transfusion therapy was initiated more frequently and earlier in 2013 to 2015 (71 vs 58 minutes). In 2013 to 2015, 88% of maternal deaths due to hemorrhage remained preventable. The main identified improvable care factors were related to delays in diagnosis and surgical management, particularly after cesarean delivery. CONCLUSIONS: Maternal mortality by obstetric hemorrhage decreased dramatically in France between 2001 and 2015, particularly mortality due to uterine atony. Among women who died, we detected fewer instances of substandard transfusion management or critical care. Nevertheless, opportunities for improvement were observed in most of the recent cases.

Acute pain management after vaginal delivery with perineal tears or episiotomy.

BACKGROUND: A vaginal delivery may be associated with acute postpartum pain, particularly after perineal trauma. However, pain management in this setting remains poorly explored. OBJECTIVE: The aim of this systematic review was to evaluate the literature and to develop recommendations for pain management after a vaginal delivery with perineal trauma. EVIDENCE REVIEW: MEDLINE, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) and systematic reviews assessing pain after a vaginal delivery with perineal tears or episiotomy until March 2023. Cochrane Covidence quality assessment generic tool and the RoB Vis 2 tool were used to grade the quality of evidence. FINDINGS: Overall, 79 studies (69 RCTs and 10 systematic reviews and meta-analyses) of good quality of evidence were included. Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line treatment. Epidural morphine (≤2 mg) is recommended among women with labor epidural analgesia and severe perineal tears, with adequate respiratory monitoring. Local anesthetic infiltration, topical local anesthetic, ointment application, and pudendal nerve block are not recommended due to insufficient or lack of evidence. Ice or chemical cold packs are recommended for postpartum pain first-line treatment due to their simplicity of use. Transcutaneous nerve stimulation and acupuncture are recommended as adjuvants. When a perineal suture is indicated, a continuous suture compared with an interrupted suture for the repair of episiotomy or second-degree perineal tears is recommended for the outcome of pain. For women with first-degree or second-degree perineal tears, no suturing or glue compared with suturing is recommended for the outcome of pain. CONCLUSIONS: Postpartum pain management after a vaginal delivery with perineal trauma should include acetaminophen, NSAIDs, and ice or chemical cold packs. Epidural morphine should be reserved for severe perineal tears. A surgical repair technique should depend on perineal tear severity.

Dynamic assessment of prealbumin for nutrition support effectiveness in critically ill patients.

BACKGROUND & AIMS: Serum prealbumin is considered to be a sensitive predictor of clinical outcomes and a quality marker for nutrition support. However, its susceptibility to inflammation restricts its usage in critically ill patients according to current guidelines. We assessed the performance of the initial value of prealbumin and dynamic changes for predicting the ICU mortality and the effectiveness of nutrition support in critically ill patients. METHODS: This monocentric study included patients admitted to the ICU between 2009 and 2016, having at least one initial prealbumin value available. Prospectively recorded data were extracted from the electronic ICU charts. We used both univariable and multivariable logistic regressions to estimate the performance of prealbumin for the prediction of ICU mortality. Additionally, the association between prealbumin dynamic changes and nutrition support was assessed via a multivariable linear mixed-effects model and multivariable linear regression. Performing subgroup analysis assisted in identifying patients for whom prealbumin dynamic assessment holds specific relevance. RESULTS: We included 3136 patients with a total of 4942 prealbumin levels available. Both prealbumin measured at ICU admission (adjusted odds-ratio (aOR) 0.04, confidence interval (CI) 95% 0.01-0.23) and its change over the first week (aOR 0.02, CI 95 0.00-0.19) were negatively associated with ICU mortality. Throughout the entire ICU stay, prealbumin dynamic changes were associated with both cumulative energy (estimate: 33.2, standard error (SE) 0.001, p < 0.01) and protein intakes (1.39, SE 0.001, p < 0.01). During the first week of stay, prealbumin change was independently associated with mean energy (6.03e-04, SE 2.32e-04, p < 0.01) and protein intakes (1.97e-02, SE 5.91e-03, p < 0.01). Notably, the association between prealbumin and energy intake was strongest among older or malnourished patients, those suffering from increased inflammation and those with high disease severity. Finally, prealbumin changes were associated with a positive mean nitrogen balance at day 7 only in patients with SOFA <4 (p = 0.047). CONCLUSION: Prealbumin measured at ICU admission and its change during the first-week serve as an accurate predictor of ICU mortality. Prealbumin dynamic assessment may be a reliable tool to estimate the effectiveness of nutrition support in the ICU, especially among high-risk patients.

Risk factors for placenta accreta spectrum disorders in women with any prior cesarean and a placenta previa or low lying: a prospective population-based study.

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

Association of severe postpartum hemorrhage and development of psychological disorders: Results from the prospective and multicentre HELP MOM study.

OBJECTIVE: Post-partum hemorrhage (PPH) is the leading preventable cause of worldwide maternal morbidity and mortality. Risk factors for psychological disorders following PPH are currently unknown. HELP-MOM study aimed to determine the incidence and identify risk factors for psychological disorders following PPH. METHODS: HELP-MOM study was a prospective, observational, national, and multicentre study including patients who experienced severe PPH requiring sulprostone. The primary endpoint was the occurrence of psychological disorders (anxiety and/or post-traumatic disorder and/or depression) following PPH, assessed at 1, 3, and 6 months after delivery using HADS, IES-R, and EPDS scales. RESULTS: Between November 2014 and November 2016, 332 patients experienced a severe PPH and 236 (72%) answered self-questionnaires at 1, 3, and 6 months. A total of 161 (68%) patients declared a psychological disorder following severe PPH (146 (90.1%) were screened positive for anxiety, 96 (58.9%) were screened positive for post-traumatic stress disorder, and 94 (57.7%) were screened positive for post-partum depression). In multivariable analysis, the use of intra-uterine tamponnement balloon was associated with a lower risk to be screened positive for psychological disorder after severe PPH (OR = 0.33 [IC95% 0.15-0.69], p = 0.004, and after propensity score matching (OR=0.34 [IC95% 0.12-0.94], p = 0.04)). Low hemoglobin values during severe PPH management were associated with a higher risk of being screened positive for psychological disorders. Finally, we did not find differences in desire or pregnancy between patients without or with psychological disorders occurring in the year after severe PPH. DISCUSSION: Severe PPH was associated with significant psychosocial morbidity including anxiety, post-traumatic disorder, and depression. This should engage a psychological follow-up. Large cohorts are urgently needed to confirm our results. REGISTRATION: ClinicalTrials.gov under number NCT02118038.

[Driving: What is the relevance and usability of the Reisberg scale in 2023?] / Conduite automobile : Quelle est la pertinence et l'utilité de l'échelle de Reisberg en 2023 ?

The publication of the decree on the care of people with neurocognitive disorders brought to the fore the Reisberg's Global Deterioration Scale, a scale that only few clinicians use in memory centers or in geriatric. This scale has a number of limitations, not least of which is that it is obsolete, since it does not take into account disease advances in scientific knowledge with biomarkers. Consequently, the stages evoked no longer correspond to current descriptions. Moreover, it only concerns Alzheimer's disease, whereas in our practice we encounter other neurodegenerative pathologies. Even if we decide to use another global assessment scale, such as the Clinical Dementia Rating or the Functional Assessment Staging, they cannot replace a personalized assessment. Indeed, it is important to stress that this decree does not take into account the relevance of personalized assessments using, for example, neuropsychological tests to estimate driving ability. A personalized assessment accompanied by a real-life driving test would be preferable than a score on a global scale. This article therefore presents the Global Deterioration Scale, highlighting its unsuitability for assessing whether or not to continue driving.

[Support and guidance in driving for patients with (or suspected of having) Alzheimer's disease or related diseases: position paper]. / Recommandations pour l'accompagnement et l'orientation pour la conduite des patients atteints (ou suspectés) d'une maladie d'Alzheimer ou de maladies apparentées : consensus des sociétés savantes françaises.

New ministerial decree restricts driving motorized vehicles for patients with Alzheimer's disease and related disorders. Reisberg stage 3, threshold used to contraindicate driving, appears to correspond to a mild stage of major neurocognitive impairment. A single scale gives an idea of the level of risk but does not provide a holistic assessment. The aim of this consensus is to put forward recommendations from several French learned societies for individualized cognitive assessments to minimize the risks associated with driving and its cessation. Fitness to drive should be raised at the earliest stages of the diagnostic process, and regularly throughout the follow-up. Consult a registered doctor is recommended to all patients wishing to continue driving. All documents must be given to the patient only. An alternative must always be offered to patients who are recommended a modal shift.

Impact of preoperative uni- or multimodal prehabilitation on postoperative morbidity: meta-analysis.

BACKGROUND: Postoperative complications occur in up to 43% of patients after surgery, resulting in increased morbidity and economic burden. Prehabilitation has the potential to increase patients' preoperative health status and thereby improve postoperative outcomes. However, reported results of prehabilitation are contradictory. The objective of this systematic review is to evaluate the effects of prehabilitation on postoperative outcomes (postoperative complications, hospital length of stay, pain at postoperative day 1) in patients undergoing elective surgery. METHODS: The authors performed a systematic review and meta-analysis of RCTs published between January 2006 and June 2023 comparing prehabilitation programmes lasting ≥14 days to 'standard of care' (SOC) and reporting postoperative complications according to the Clavien-Dindo classification. Database searches were conducted in PubMed, CINAHL, EMBASE, PsycINFO. The primary outcome examined was the effect of uni- or multimodal prehabilitation on 30-day complications. Secondary outcomes were length of ICU and hospital stay (LOS) and reported pain scores. RESULTS: Twenty-five studies (including 2090 patients randomized in a 1:1 ratio) met the inclusion criteria. Average methodological study quality was moderate. There was no difference between prehabilitation and SOC groups in regard to occurrence of postoperative complications (OR = 1.02, 95% c.i. 0.93 to 1.13; P = 0.10; I2 = 34%), total hospital LOS (-0.13 days; 95% c.i. -0.56 to 0.28; P = 0.53; I2 = 21%) or reported postoperative pain. The ICU LOS was significantly shorter in the prehabilitation group (-0.57 days; 95% c.i. -1.10 to -0.04; P = 0.03; I2 = 46%). Separate comparison of uni- and multimodal prehabilitation showed no difference for either intervention. CONCLUSION: Prehabilitation reduces ICU LOS compared with SOC in elective surgery patients but has no effect on overall complication rates or total LOS, regardless of modality. Prehabilitation programs need standardization and specific targeting of those patients most likely to benefit.

Real-world experience with CLAIRYG® 50 mg/mL (intravenous immunoglobulin) in children under 12 years with primary immunodeficiency or immmune thrombocytopenia: a post-approval safety study.

Introduction: This study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg) liquid, in 59 children (aged < 12 years) with primary immunodeficiency diseases (PID) (n = 32) or immune thrombocytopenia (ITP) (n = 27) in France. Methods: The primary objective of the study was to assess the safety and tolerability of Clairyg®, recording all serious and non-serious adverse events (AEs), whether related (rAEs) or not related to the product. Secondary objectives aimed at evaluating the administration of Clairyg® under routine conditions and the available efficacy data to better document the benefit/risk ratio in this pediatric population. An exploratory objective was added to evaluate the potential factors associated with the occurrence of rAEs. Patients received Clairyg® according to the approved dosage under normal conditions of prescriptions over a median follow-up period of 11.8 months. Results: A total of 549 infusions (PID: n = 464 and ITP: n = 85), were administered, of which 58.8% were preceded by premedication. The most frequent rAEs were headache, vomiting, and pyrexia in both indications. Most of them were considered non-serious and mild or moderate in intensity. A severe single rAE was observed (aseptic meningitis) in a 4-year-old girl presenting with chronic ITP. The exploratory multivariate analysis of potential co-factors showed that the occurrence of rAEs is significantly linked to high IVIg doses and possibly to female gender. The annualized rate of serious bacterial infections was 0.11 for patients with PID. For patients with ITP, 74.1% experienced at least one bleeding episode during the follow-up, mostly a cutaneous one, and none had gastrointestinal, genitourinary, or central nervous system bleeding. Conclusion: Clairyg® was well tolerated and allowed for control of serious bacterial infection in PID and serious bleeding in ITP, which are the main complications in these respective pediatric disorders. No new safety signal was detected in children less than 12 years-old in real-life conditions of use.

Perioperative ketamine administration to prevent delirium and neurocognitive disorders after surgery: a systematic review and meta-analysis.

BACKGROUND: Surgery induces high rates of cognitive disorders, persisting for up to 12 months in elderly adults. This review aimed to assess the currently debated preventive effect of perioperative ketamine on postoperative delirium and postoperative neurocognitive disorders (POND). MATERIALS AND METHODS: Systematic review and meta-analysis including all randomized controlled trials investigating the effects of perioperative ketamine administration in adult patients compared to placebo or no intervention on postoperative delirium and/or POND between January 2007 and April 2022. Database searches were conducted in PubMed, Medline, Embase, Scopus, and Central. Random effects models were used to pool overall estimates. The GRADE approach was used to assess the quality of the evidence. RESULTS: From 1379 records screened, 14 randomized controlled trials with 1618 patients randomized met our inclusion criteria with a high level of consensus among reviewers, amongst whom 50% were at low-moderate risk of bias. There was no between-group difference in postoperative delirium [8 trials, 1265 patients, odds ratio (OR) 0.93, 95% CI (0.51-1.70), I2 =28%] and POND [5 trials, 494 patients, OR 0.52, 95% CI (0.15-1.80); I2 =78%]. There was no significant between-group difference in postoperative psychological adverse effects, level of pain, hospital length of stay, or mortality. Between-group subgroup analyses showed no difference in delirium or POND incidence according to surgical setting, ketamine dose, mode of administration, combination or not with other drug(s), and assessment timing or definition of cognitive disorders. CONCLUSION: Perioperative ketamine does not prevent postoperative delirium or POND. Significant study heterogeneity suggests that standardized measures for POND assessment and a specific focus on patients at high risk for POND should be used to improve the comparability of future studies.

Comparison of quantitative and calculated postpartum blood loss after vaginal delivery.

BACKGROUND: Because there is no consensus on the method of assessing postpartum blood loss, the comparability and relevance of the postpartum hemorrhage-related literature are questionable. Quantitative blood loss assessment using a volumetric technique with a graduated collector bag has been proposed to overcome limitations of intervention-based outcomes but remains partly subjective and potentially biased by amniotic fluid or missed out-of-bag losses. Calculated blood loss based on laboratory parameters has been studied and used as an objective method expected to reflect total blood loss. However, few studies have compared quantitative with calculated blood loss. OBJECTIVE: This study aimed to compare the distribution of postpartum blood loss after vaginal delivery assessed by 2 methods-quantitative and calculated blood loss-and the incidence of abnormal blood loss with each method. STUDY DESIGN: Data were obtained from the merged database of 3 multicenter, randomized controlled trials, all testing different interventions to prevent postpartum blood loss in individuals with a singleton live fetus at ≥35 weeks of gestation, born vaginally. All 3 trials measured blood loss volume by using a graduated collector bag. Hematocrit was measured in the eighth or ninth month of gestation and on day 2 postpartum. The 2 primary outcomes were: quantitative blood loss, defined by the total volume of blood loss measured in a graduated collector bag, and calculated blood loss, mathematically defined from the peripartum hematocrit change (estimated blood volume × [(antepartum hematocrit-postpartum hematocrit)/antepartum hematocrit], where estimated blood volume [mL]=booking weight [kg] × 85). We modeled the association between positive quantitative blood loss and positive calculated blood loss with polynomial regression and calculated the Spearman correlation coefficient. RESULTS: Among the 8341 individuals included in this analysis, the median quantitative blood loss (100 mL; interquartile range, 50-275) was significantly lower than the median calculated blood loss (260 mL; interquartile range, 0-630) (P<.05). The incidence of abnormal blood loss was lower with quantitative blood loss than calculated blood loss for all 3 thresholds: for ≥500 mL, it was 9.6% (799/8341) and 32.3% (2691/8341), respectively; for ≥1000 mL, 2.1% (176/8341) and 11.5% (959/8341); and for ≥2000 mL, 0.1% (10/8341) and 1.4% (117/8341) (P<.05). Quantitative blood loss and calculated blood loss were significantly but moderately correlated (Spearman coefficient=0.44; P<.05). The association between them was not linear, and their difference tended to increase with blood loss. Negative calculated blood loss values occurred in 23% (1958/8341) of individuals; among them, >99% (1939/1958) had quantitative blood loss ≤500 mL. CONCLUSION: Quantitative and calculated blood loss were significantly but moderately correlated after vaginal delivery. However, clinicians should be aware that quantitative blood loss is lower than calculated blood loss, with a difference that tended to rise as blood loss increased.

Timing and Preventability of Cardiovascular-Related Maternal Death.

OBJECTIVE: To describe the clinical profile, management, and potential preventability of maternal cardiovascular deaths. METHODS: We conducted a retrospective, descriptive study of all maternal deaths resulting from a cardiovascular disease during pregnancy or up to 1 year after the end of pregnancy in France from 2007 to 2015. Deaths were identified through the nationwide permanent enhanced maternal mortality surveillance system (ENCMM [Enquête Nationale Confidentielle sur les Morts Maternelles]). Women were classified into four groups based on the assessment of the national experts committee: those who died of a cardiac condition and those who died of a vascular condition and, within these two groups, whether the condition was known before the acute event. Maternal characteristics, clinical features and components of suboptimal care, and preventability factors, which were assessed with a standard evaluation form, were described among those four groups. RESULTS: During the 9-year period, 103 women died of cardiac or vascular disease, which corresponds to a maternal mortality ratio from these conditions of 1.4 per 100,000 live births (95% CI 1.1-1.7). Analyses were conducted on 93 maternal deaths resulting from cardiac (n=70) and vascular (n=23) disease with available data from confidential inquiry. More than two thirds of these deaths occurred in women with no known pre-existing cardiac or vascular condition. Among the 70 deaths resulting from a cardiac condition, 60.7% were preventable, and the main preventability factor was a lack of multidisciplinary prepregnancy and prenatal care for women with a known cardiac disease. For those with no known pre-existing cardiac condition, preventability factors were related mostly to inadequate prehospital care of the acute event, in particular an underestimation of the severity and inadequate investigation of the dyspnea. Among the 23 women who died of a vascular disease, three had previously known conditions. For women with no previously known vascular condition, 47.4% of deaths were preventable, and preventability factors were related mostly to wrong or delayed diagnosis and management of acute intense chest or abdominal pain in a pregnant woman. CONCLUSION: Most maternal deaths attributable to cardiac or vascular diseases were potentially preventable. The preventability factors varied according to the cardiac or vascular site and whether the condition was known before pregnancy. A more granular understanding of the cause and related risk factors for maternal mortality is crucial to identify relevant opportunities for improving care and training health care professionals.

Host-to-graft Propagation of α-synuclein in a Mouse Model of Parkinson's Disease: Intranigral Versus Intrastriatal Transplantation.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies. Ectopic transplantation of human fetal ventral mesencephalic DA neurons into the striatum of PD patients have provided proof-of-principle for the cell replacement strategy in this disorder. However, 10 to 22 y after transplantation, 1% to 27% of grafted neurons contained α-syn aggregates similar to those observed in the host brain. We hypothesized that intrastriatal grafts are more vulnerable to α-syn propagation because the striatum is not the ontogenic site of nigral DA neurons and represents an unfavorable environment for transplanted neurons. Here, we compared the long-term host-to-graft propagation of α-syn in 2 transplantation sites: the SNpc and the striatum. METHODS: Two mouse models of PD were developed by injecting adeno-associated-virus2/9-human α-syn A53T into either the SNpc or the striatum of C57BL/6 mice. Mouse fetal ventral mesencephalic DA progenitors were grafted into the SNpc or into the striatum of SNpc or striatum of α-syn injected mice, respectively. RESULTS: First, we have shown a degeneration of the nigrostriatal pathway associated with motor deficits after nigral but not striatal adeno-associated-virus-hαsyn A53T injection. Second, human α-syn preferentially accumulates in striatal grafts compared to nigral grafts. However, no differences were observed for phosphorylated α-syn, a marker of pathological α-syn aggregates. CONCLUSIONS: Taken together, our results suggest that the ectopic site of the transplantation impacts the host-to-graft transmission of α-syn.

Association between early nutrition support and 28-day mortality in critically ill patients: the FRANS prospective nutrition cohort study.

BACKGROUND: Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort. METHODS: The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses. RESULTS: During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11). CONCLUSIONS: In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015.

Fibrinogen concentrate and maternal outcomes in severe postpartum hemorrhage: A population-based cohort study with a propensity score-matched analysis.

STUDY OBJECTIVE: Fibrinogen concentrate is used to treat severe postpartum hemorrhage despite limited evidence of its effectiveness in obstetric settings. We aimed to explore the association between its administration and maternal outcomes in women with severe postpartum hemorrhage. DESIGN, SETTING AND PATIENTS: This secondary analysis of the EPIMOMS prospective population-based study, exploring severe maternal morbidity, as defined by national expert consensus (2012-2013, 182,309 deliveries, France), included all women with severe postpartum hemorrhage and transfused with red blood cells during active bleeding. MEASUREMENTS: The primary endpoint was maternal near-miss or death, and the secondary endpoint the total number of red blood cells units transfused. INTERVENTIONS: We studied fibrinogen concentrate administration as a binary variable and then by the timing of its administration. We used multivariable analysis and propensity score matching to account for potential indication bias. MAIN RESULTS: Among the 730 women with severe postpartum hemorrhage and transfused, 313 (42.9%) received fibrinogen concentrate, and 142 (19.5%) met near-miss criteria or died. The risk of near-miss or death was not significantly lower among the women treated with fibrinogen concentrate than among those not treated, in either the multivariable analysis (adjusted RR = 1.03; 95% CI, 0.72-1.49; P = 0.855) or the propensity score analysis (RR = 0.85; 95% CI, 0.55-1.32; P = 0.477). Among women treated with fibrinogen concentrate, administration more than three hours after red blood cell transfusion started was associated with a higher risk of near-miss or death than administration before or within 30 min after the transfusion began (adjusted RR = 2.07; 95% CI, 1.10-3.89; P = 0.024). Results were similar for the secondary endpoint. CONCLUSIONS: The use of fibrinogen concentrate in severe postpartum hemorrhage needing red blood cell transfusion during active bleeding is not associated with improved maternal outcomes.

Long-Term Evaluation of Intranigral Transplantation of Human iPSC-Derived Dopamine Neurons in a Parkinson's Disease Mouse Model.

Parkinson's disease (PD) is a neurodegenerative disorder associated with loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). One strategy for treating PD is transplantation of DA neuroblasts. Significant advances have been made in generating midbrain DA neurons from human pluripotent stem cells. Before these cells can be routinely used in clinical trials, extensive preclinical safety studies are required. One of the main issues to be addressed is the long-term therapeutic effectiveness of these cells. In most transplantation studies using human cells, the maturation of DA neurons has been analyzed over a relatively short period not exceeding 6 months. In present study, we generated midbrain DA neurons from human induced pluripotent stem cells (hiPSCs) and grafted these neurons into the SNpc in an animal model of PD. Graft survival and maturation were analyzed from 1 to 12 months post-transplantation (mpt). We observed long-term survival and functionality of the grafted neurons. However, at 12 mpt, we observed a decrease in the proportion of SNpc DA neuron subtype compared with that at 6 mpt. In addition, at 12 mpt, grafts still contained immature neurons. Our results suggest that longer-term evaluation of the maturation of neurons derived from human stem cells is mandatory for the safe application of cell therapy for PD.

Heterogeneity of PD-MCI in Candidates to Subthalamic Deep Brain Stimulation: Associated Cortical and Subcortical Modifications.

BACKGROUND: Parkinson's disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. OBJECTIVE: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups. METHODS: Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels. RESULTS: 320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes. CONCLUSION: Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia.

Guidelines for the choice of intravenous fluids for vascular filling in critically ill patients, 2021.

PURPOSE: To provide recommendations for the appropriate choice of fluid therapy for resuscitation of critically ill patients. DESIGN: A consensus committee of 24 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Society of Emergency Medicine (Société française de médecine d'urgence, SFMU) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guideline elaboration process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Some recommendations were left ungraded. METHODS: Four fields were defined: patients with sepsis or septic shock, patients with haemorrhagic shock, patients with acute brain failure, and patients during the peripartum period. For each field, the panel focused on two questions: (1) Does the use of colloids, as compared to crystalloids, reduce morbidity and mortality, and (2) Does the use of some specific crystalloids effectively reduce morbidity and mortality. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. The analysis of the literature and the recommendations were then conducted according to the GRADE methodology. RESULTS: The SFAR/SFMU guideline panel provided nine statements on the appropriate choice of fluid therapy for resuscitation of critically ill patients. After two rounds of rating and various amendments, strong agreement was reached for 100% of the recommendations. Out of these recommendations, two have a high level of evidence (Grade 1 +/-), six have a moderate level of evidence (Grade 2 +/-), and one is based on expert opinion. Finally, no recommendation was formulated for two questions. CONCLUSIONS: Substantial agreement among experts has been obtained to provide a sizable number of recommendations aimed at optimising the choice of fluid therapy for resuscitation of critically ill patients.