To describe donors after brain death with ongoing extracorporeal membrane oxygenation and to analyze the outcome of organs transplanted from these donors.
Retrospective analysis of the national ...information system run by the French Biomedicine Agency (CRISTAL database).
National registry data of all donors after brain death in France and their organ recipients between 2007 and 2013.
Donors after brain death and their organ recipients.
None.
During the study period, there were 22,270 brain-dead patients diagnosed in France, of whom 161 with extracorporeal membrane oxygenation. Among these patients, 64 donors on extracorporeal membrane oxygenation and 10,805 donors without extracorporeal membrane oxygenation had at least one organ retrieved. Donors on extracorporeal membrane oxygenation were significantly younger and had more severe intensive care medical conditions (hemodynamic, biological, renal, and liver insults) than donors without extracorporeal membrane oxygenation. One hundred nine kidneys, 37 livers, seven hearts, and one lung were successfully transplanted from donors on extracorporeal membrane oxygenation. We found no significant difference in 1-year kidney graft survival (p = 0.24) and function between recipients from donors on extracorporeal membrane oxygenation (92.7% 85.9-96.3%) and matching recipients from donors without extracorporeal membrane oxygenation (95.4% 93.0-97.0%). We also found no significant difference in 1-year liver recipient survival (p = 0.91): 86.5% (70.5-94.1) from donors on extracorporeal membrane oxygenation versus 80.7% (79.8-81.6) from donors without extracorporeal membrane oxygenation.
Brain-dead patients with ongoing extracorporeal membrane oxygenation have more severe medical conditions than those without extracorporeal membrane oxygenation. However, kidney graft survival and function were no different than usual. Brain-dead patients with ongoing extracorporeal membrane oxygenation are suitable for organ procurement.
Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain.
Among ...consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens.
Among 174 patients (132 men 76 %, age 63 53-75 years, SAPSII 38 27;55, median PSI score 106 78;130), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16-11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings.
Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.
Background
Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe ...the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching.
Results
76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years,
p
= 0.002) and had less lower limb (44.7% vs 70.9%,
p
< 0.001) and more abdomino-perineal NSTIs (43.4% vs 18.8%,
p
< 0.001). Enterobacterales and non-fermenting gram-negative bacteria were the most frequently isolated microorganisms in neutropenic patients. In-hospital mortality was significantly higher in neutropenic than in non-neutropenic patients (57.9% vs 28.5%,
p
< 0.001). Granulocyte colony-stimulating factor (G-CSF) administration was associated with a lower risk of in-hospital mortality in univariable Cox (hazard ratio (HR) = 0.43 95% confidence interval (CI) 0.23–0.82,
p
= 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI 0.22–0.94,
p
= 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI 0.09; 0.68,
p
= 0.006).
Conclusions
Critically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival.
BackgroundIn December 2019 a novel coronavirus designated SARS-CoV-2 was identified, and the disease COVID-19 has caused many deaths. SARS-CoV-2 infection has been associated with the development of ...cytokine storm (including interleukin 6 (IL-6)), which can cause lung damage and lack of oxygen. Tocilizumab (TCZ) inhibits ligand binding to the IL-6 receptor and may be a potential treatment for the hyperinflammation symptoms of COVID-19. However, data regarding the efficacy of TCZ in COVID-19 are lacking. The rapid spread of the pandemic in France, especially in the Paris region, constrained us to the off-label use of TCZ in patients with severe clinical conditions.MethodsA single-centre observational cohort study of 44 patients infected with COVID-19 was carried out between 6 April and 21 April 2020 in Groupe Hospitalier Intercommunal Le Raincy-Montfermeil (GHILRM). Twenty-two patients diagnosed with COVID-19 were treated with TCZ and were compared with 22 patients not treated with TCZ matched for age, gender and length of hospital stay for COVID-19. Respiratory rate and oxygen supplementation as well as laboratory parameters (such as C-reactive protein (CRP), aspartate aminotransferase and alanine aminotransferase) were collected at baseline and during 14 days of follow-up. Our primary objective was to assess the efficacy of TCZ on respiratory clinical conditions.FindingsThe average respiratory rate was lower in the TCZ group than in the control group (21.5 vs 25.5 breaths/min at day 14, 95% CI −7.5 to −0.4; p=0.03). Treated patients tended to be intubated less during the course of the disease (2/22 vs 6/22, 95% CI −0.4 to 0.1; p=0.12). In each group, 10 patients no longer required oxygen therapy. We found a significant decrease in CRP in treated patients on day 7 (p=0.04). TCZ caused cytolysis in more than half (14/22) of the patients but without clinical impact.InterpretationThere was a significant difference in the respiratory rate on day 14 of follow-up, with a greater decrease observed in the treated group. Fewer patients required mechanical ventilation in the TCZ group, especially among patients with more extensive CT lung damage, than in the control group. The same number of patients were weaned off oxygen on day 14 in the two groups, while the patients in the TCZ group had more severe impairment at inclusion. We consider that TCZ showed significant control of the biological inflammatory syndrome, suggesting that it may limit the effect of the cytokine storm. Our study seems to indicate the efficacy of TCZ, particularly in patients with severe initial pulmonary impairment. Selecting the best candidates and the best timing for TCZ therapy needs to be determined in randomised clinical trials.
Abstract Background Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to ...describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching. Results 76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p < 0.001) and more abdomino-perineal NSTIs (43.4% vs 18.8%, p < 0.001). Enterobacterales and non-fermenting gram-negative bacteria were the most frequently isolated microorganisms in neutropenic patients. In-hospital mortality was significantly higher in neutropenic than in non-neutropenic patients (57.9% vs 28.5%, p < 0.001). Granulocyte colony-stimulating factor (G-CSF) administration was associated with a lower risk of in-hospital mortality in univariable Cox (hazard ratio (HR) = 0.43 95% confidence interval (CI) 0.23–0.82, p = 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI 0.22–0.94, p = 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI 0.09; 0.68, p = 0.006). Conclusions Critically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival.
We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the ...tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4
T cells and CD8
T-cell activation. Bacterial ablation also enabled efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression. Mechanistically, the PDA microbiome generated a tolerogenic immune program by differentially activating select Toll-like receptors in monocytic cells. These data suggest that endogenous microbiota promote the crippling immune-suppression characteristic of PDA and that the microbiome has potential as a therapeutic target in the modulation of disease progression.
We found that a distinct and abundant microbiome drives suppressive monocytic cellular differentiation in pancreatic cancer via selective Toll-like receptor ligation leading to T-cell anergy. Targeting the microbiome protects against oncogenesis, reverses intratumoral immune tolerance, and enables efficacy for checkpoint-based immunotherapy. These data have implications for understanding immune suppression in pancreatic cancer and its reversal in the clinic.
.
Pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance and immunotherapeutic resistance. We discovered upregulation of receptor-interacting serine/threonine protein kinase 1 ...(RIP1) in tumor-associated macrophages (TAMs) in PDA. To study its role in oncogenic progression, we developed a selective small-molecule RIP1 inhibitor with high in vivo exposure. Targeting RIP1 reprogrammed TAMs toward an MHCIIhiTNFα+IFNγ+ immunogenic phenotype in a STAT1-dependent manner. RIP1 inhibition in TAMs resulted in cytotoxic T cell activation and T helper cell differentiation toward a mixed Th1/Th17 phenotype, leading to tumor immunity in mice and in organotypic models of human PDA. Targeting RIP1 synergized with PD1-and inducible co-stimulator-based immunotherapies. Tumor-promoting effects of RIP1 were independent of its co-association with RIP3. Collectively, our work describes RIP1 as a checkpoint kinase governing tumor immunity.
Display omitted
•RIP1 promotes tolerogenic macrophage differentiation via suppression of STAT1 in cancer•GSK′547 (RIP1i) is a mono-selective kinase inhibitor that robustly targets RIP1 in vivo•RIP1i is tumor-protective via macrophage-mediated Th1/Th17 and CTL activation•RIP1i synergizes with checkpoint- and co-stimulatory receptor-based immunotherapies
Wang et al. synthesize a selective RIP1 inhibitor that can be used in vivo. Inhibition of RIP1, which is highly expressed in tumor-associated macrophages in pancreatic ductal adenocarcinoma, reverses local immune suppression and enhances the efficacy of checkpoint- and co-stimulatory receptor-based immunotherapy.
Normal pressure hydrocephalus syndrome, characterized by ventriculomegaly and the classic triad of symmetric gait disturbance, cognitive decline, and urinary incontinence, is the most common cause of ...hydrocephalus in the adult population and a significant cause of reversible dementia among older adults. The only effective treatment for this syndrome, to date, is a cerebrospinal fluid shunting procedure, commonly a ventriculoperitoneal, ventriculoatrial, or lumboperitoneal shunt. The shunting success rate ranges between 73 and 96%. Hence, early identification, proper diagnosis, and treatment are paramount.
We designed a protocol-based program supported on the best available evidence for an integral approach of patients with normal pressure hydrocephalus syndrome. The protocol consists of a series of patient-centered tests and interventions performed on adults with clinical suspicion, leading to optimized and sustainable outcomes for patients living with this condition.
The program obtained the recognition of the Joint Commission International as an accredited center of excellence. The objectives of our center are increasing awareness and knowledge of normal pressure hydrocephalus syndrome within the community, delivering optimized interdisciplinary care, mitigating risks, improving quality of life to patients and their families, and ultimately saving from oblivion a significant number of patients who would be otherwise condemned.
Diseccion espontanea de la arteria vertebral Cardozo, Alejandro; Cohen Cajiao, Jorge Ivan; Ortiz Lopez, Alexander ...
C.E.S. medicina,
01/2016, Volume:
30, Issue:
1
Journal Article
Peer reviewed
Open access
La disección arterial como causa de ataque cerebrovascular es infrecuente, presentándose más comúnmente en población joven asociado a un trauma menor que involucra la hiperextensión del cuello. ...Presentamos el reporte de un paciente hombre, joven, con un accidente cerebrovascular de fosa posterior y cuya etiología fue una disección espontánea de la arteria vertebral derecha. Palabras clave: Disección de arteria vertebral, Accidente cerebrovascular, Accidente cerebrovascular. Arterial dissection as a cause of stroke is uncommon, most commonly presenting in young people sometimes associated with trauma involving hyperextension of the neck as the only history which would suggest the traumatic origin. We present the case report of a young man with posterior stroke whose etiology was a spontaneous dissection of the right vertebral artery. Keywords: Vertebral artery dissection, Stroke, Cerebrovascular trauma.
PDF
