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The treatment of sepsis and septic shock remains a major public health issue due to the associated morbidity and mortality. Despite an improvement in the understanding of the physiological and pathological mechanisms underlying its genesis and a growing number of studies exploring an even higher range of targeted therapies, no significant clinical progress has emerged in the past decade. In this context, mesenchymal stem cells (MSCs) appear more and more as an attractive approach for cell therapy both in experimental and clinical models. Pre-clinical data suggest a cornerstone role of these cells and their secretome in the control of the host immune response. Host-derived factors released from infected cells (i.e., alarmins, HMGB1, ATP, DNA) as well as pathogen-associated molecular patterns (e.g., LPS, peptidoglycans) can activate MSCs located in the parenchyma and around vessels to upregulate the expression of cytokines/chemokines and growth factors that influence, respectively, immune cell recruitment and stem cell mobilization. However, the way in which MSCs exert their beneficial effects in terms of survival and control of inflammation in septic states remains unclear. This review presents the interactions identified between MSCs and mediators of immunity and tissue repair in sepsis. We also propose paradigms related to the plausible roles of MSCs in the process of sepsis and septic shock. Finally, we offer a presentation of experimental and clinical studies and open the way to innovative avenues of research involving MSCs from a prognostic, diagnostic, and therapeutic point of view in sepsis.

Ultrasound (US) measurements of diaphragmatic excursion (DE) are widely used to provide a non-invasive assessment of the diaphragmatic function at the bedside, especially in intensive care. However, this measurement has never been validated against a less operator-dependent technique such as MRI. Dynamic MRI is the only imaging modality that creates a four-dimensional reconstruction of the diaphragm. The primary objective of this study was to assess the agreement between DE obtained using dynamic MRI with those obtained using ultrasound. The secondary objectives were to define DE thresholds for the diagnosis of DD using MRI and to compare the performance of US and MRI to diagnose DD. Prospective single-center study in which consecutive outpatients referred for a dynamic thoracic MRI were included. This study was conducted at a university hospital in Paris, where there was daily access to ultrasound (US) and extensive expertise in diaphragmatic MRI The DE of each hemi-diaphragm was measured sequentially using ultrasound and MRI in random order, during spontaneous breathing (SB) and forced inspiration (FI) by independent observers blinded to each other. We analyzed the agreement between DE obtained using US and MRI for each hemi-diaphragm. We enrolled forty-five patients, aged 58 ± 36 years, of which twenty-eight (68%) had a confirmed DD. During SB, the mean bias for DE measurement was -3.8 mm, 95% CI [-7.1; -0.6] for the left hemi-diaphragm, and 1.0 mm, 95% CI [-3.5; 5.5] for the right hemi-diaphragm. Limits of agreement (millimeters) were [-25; 17] on the left side, and [-28; 30] on the right side. MRI threshold values for DE defining dysfunction were 11 mm for quiet SB, and 38 mm for FI. These thresholds had a sensitivity of 77.7% and a specificity of 77.4% during SB, with an AUC of 0.86. US and MRI provide different values for DE, probably because the measurements were not obtained exactly at the same localization. Nevertheless, diagnostic performances of MRI and US to recognize DD appeared comparable.

Mesenchymal stem cells (MSCs) play a critical role in response to stress such as infection. They initiate the removal of cell debris, exert major immunoregulatory activities, control pathogens, and lead to a remodeling/scarring phase. Thus, host-derived ‘danger’ factors released from damaged/infected cells (called alarmins, e.g., HMGB1, ATP, DNA) as well as pathogen-associated molecular patterns (LPS, single strand RNA) can activate MSCs located in the parenchyma and around vessels to upregulate the expression of growth factors and chemoattractant molecules that influence immune cell recruitment and stem cell mobilization. MSC, in an ultimate contribution to tissue repair, may also directly trans- or de-differentiate into specific cellular phenotypes such as osteoblasts, chondrocytes, lipofibroblasts, myofibroblasts, Schwann cells, and they may somehow recapitulate their neural crest embryonic origin. Failure to terminate such repair processes induces pathological scarring, termed fibrosis, or vascular calcification. Interestingly, many viruses and particularly those associated to chronic infection and inflammation may hijack and polarize MSC’s immune regulatory activities. Several reports argue that MSC may constitute immune privileged sanctuaries for viruses and contributing to long-lasting effects posing infectious challenges, such as viruses rebounding in immunocompromised patients or following regenerative medicine therapies using MSC. We will herein review the capacity of several viruses not only to infect but also to polarize directly or indirectly the functions of MSC (immunoregulation, differentiation potential, and tissue repair) in clinical settings.

In rheumatoid arthritis (RA), activated synovial tissue-derived mesenchymal stem cells (MSC) acquire a pathogenic phenotype and produce pro-inflammatory cytokines, chemokines, metalloproteinases, pro-osteoclastic and pro-angiogenic factors. The acquisition of this aggressive phenotype might be due to modified expression of micro-RNAs. We aimed to clarify the role of specific micro-RNAs (miR-146a-5p, miR-221-3p, miR-34a-3p, miR-150, miR-203a-3p and miR-155-3p) in an in vitro model of RA. Methods: Micro-RNA expression was determined in RA patient plasma and in commercial human synovial tissue-derived MSC-like cells stimulated with a panel of pro-inflammatory mediators (poly I:C, TNF-α, IL-1β, IFN-γ) to mimic the rheumatoid arthritis pathogenic setting. Next, unstimulated cells or TNF-α stimulated cells were transfected with miR-146a-5p mimic or miR-221-3p mimic. Protein and/or mRNA expressions of chemokines, cytokines, VEGF, MMPs and RANKL were determined by ELISA or qRT-PCR. MiR-34a-3p, miR-146a-5p, miR-150, miR-221-3p and miR-203a-5p were upregulated in RA patient plasma versus healthy controls. Moreover, synovial tissue-derived MSC-like cells expressed miR-146a-5p and miR-221-3p in response to pro-inflammatory mediators. Overexpression of miR-146a-5p increased CCL2 and CXCL8 expression and miR-221-3p increased IL-1β and IL-6 expression in synovial tissue-derived MSC-like cells stimulated with TNF-α. Conclusion: Overexpression of miR-146a-5p and miR-221-3p might favour inflammation and participate in rheumatoid arthritis pathogenesis.

Old world alphaviruses (e.g., chikungunya) are known to cause severe acute and chronic debilitating arthralgia/arthritis. However, atypical neurological manifestations and, in particular, unexpected cases of acute inflammatory Guillain–Barre syndrome (GBS) have been associated with the arthritogenic alphaviruses. The pathogenesis of alphavirus-associated GBS remains unclear. We herein addressed for the first time the role of Schwann cells (SC) in peripheral neuropathy post-alphaviral infection using the prototypical ONNV alphavirus model. We demonstrated that human SC expressed the recently identified alphavirus receptor MxRA8 and granting viral entry and robust replication. A canonical innate immune response was engaged by ONNV-infected SC with elevated gene expression for RIG-I, MDA5, IFN-β, and ISG15 and inflammatory chemokine CCL5. Transcription levels of prostaglandin E2-metabolizing enzymes including cPLA2α, COX-2, and mPGES-1 were also upregulated in ONNV-infected SC. Counterintuitively, we found that ONNV failed to affect SC regenerative properties as indicated by elevated expression of the pro-myelinating genes MPZ and MBP1 as well as the major pro-myelin transcription factor Egr2. While ONNV infection led to decreased expression of CD55 and CD59, essential to control complement bystander cytotoxicity, it increased TRAIL expression, a major pro-apoptotic T cell signal. Anti-apoptotic Bcl2 transcription levels were also increased in infected SC. Hence, our study provides new insights regarding the remarkable immunomodulatory role of SC of potential importance in the pathogenesis of GBS following alphavirus infection.

Chikungunya virus is widespread throughout the tropics, where it causes recurrent outbreaks of chikungunya fever. In recent years, outbreaks have afflicted populations in East and Central Africa, South America and Southeast Asia. The virus is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Chikungunya fever is characterized by severe arthralgia and myalgia that can persist for years and have considerable detrimental effects on health, quality of life and economic productivity. The effects of climate change as well as increased globalization of commerce and travel have led to growth of the habitat of Aedes mosquitoes. As a result, increasing numbers of people will be at risk of chikungunya fever in the coming years. In the absence of specific antiviral treatments and with vaccines still in development, surveillance and vector control are essential to suppress re-emergence and epidemics.Chikungunya fever is an acute febrile illness caused by chikungunya virus, a mosquito-borne alphavirus. This Primer by Bartholomeeusen and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of chikungunya fever, and discusses patient quality of life and open research questions for this condition.

Background Head injuries are the leading cause of trauma in Emergency Departments (EDs). Recent studies have shown epidemiological changes in patients consulting ED for head injuries. The main objective of this study was to describe the profile of head injury patients consulting in the EDs in France and assess i) head injury severity across age groups; ii) the delay between the occurrence of head injury and ED arrival; iii) factors associated with traumatic intracranial hemorrhage (ICH). Methods This cross-sectional study collected patient data over a three-day period in March 2023. All adult patients (≥ 18 years old) admitted to the ED with a head injury (defined as a trauma to the head) were included. TBI severity was classified according to patients’ initial Glasgow Coma Scale score in the ED: severe (3–8); moderate (9 -12); mild (13–15); and simple head trauma in the absence of transient or persistent neurological symptoms. Results Among the 71 participating EDs, 26,008 patients visited EDs and a total of 1070 patients (4.1%, IC 95 3.9—4.4) presented a head injury were included in the study, with a median age of 68.5 [37–85] years old. Most of the patients (66.7%) were referred to ED after a call to the Emergency Medical Dispatcher (EMD). The median time from head injury to ED visit was 2 h [1.0 – 5.5]. Ground-level falls were the leading cause of head injury (60.3%). Most of patient presented a simple head trauma ( n  = 715, 66.8%) followed by mild TBI ( n  = 337, 31.5%). CT head scans were performed for 636 patients (59.6%), of which 58 were positive. Traumatic ICH prevalence was 5.4% (95% CI: 4.1–6.9) and three patients (0.3%) required an urgent neurosurgical intervention. Neither preinjury anticoagulant ( p  = 0.97) nor antiplatelet ( p  = 0.93) use was associated with an increased risk of traumatic ICH. Conclusions One head injury patient out of two presenting in the ED is aged over 65 years. Patients referred by EMD were more likely to visit ED promptly. The majority of older patients underwent a head CT scan and preinjury anticoagulant use was not associated with increased risk of traumatic ICH.

Estudámos os efeitos da demonstração na aprendizagem de uma habilidade motora tenística (batimento de direita) por crianças sem prática da mesma. Pretendemos averiguar de que modo o estatuto do modelo (professor vs aluno), com idêntico grau de proficiência e a forma de demonstração (ao vivo vs vídeo) influenciam a aprendizagem de uma habilidade motora.Neste trabalho, participaram 60 crianças (30 do género feminino e 30 do género masculino) com 10,40 ±0,62 anos de idade, divididas homogeneamente, com base nos resultados obtidos num pré-teste em quatro grupos experimentais: demonstração em vídeo pelo aluno (AVÍDEO), demonstração ao vivo pelo aluno (AVIVO), demonstração em vídeo pelo professor (PVÍDEO) e demonstração ao vivo pelo professor (PVIVO). Cada participante realizou 129 batimentos de direita: pré-teste (3), duas sessões de prática semanal durante três semanas (120), pós-teste (3) e retenção (3) realizada uma semana após o pós-teste e as sessões de prática.Em todos os ensaios, os participantes foram filmados e avaliados individualmente considerando a realização correta de cada uma das sete componentes críticas do batimento de direita (dados qualitativos) e registada a pontuação obtida no primeiro ressalto da bola (dados quantitativos) dos ensaios avaliados. A ANOVA one-way foi usada para análise estatística dos dados entre grupos, nas sessões e nos testes. A observação de cada um dos grupos para analisar individualmente e comparar o desempenho motor e a exatidão entre as 6 aulas, e entre o pré-teste, pós-teste e retenção foi efetuada através da ANOVA de medidas repetidas one-way.Não foram detetadas diferenças com significado estatístico entre os quatro grupos experimentais no nível do desempenho motor. Apesar de o PVIVO ter obtido melhor performance na retenção comparativamente aos outros três grupos, os valores dos restantes grupos são muito próximos.Foram detetadas, na exatidão, diferenças com significado estatístico entre o PVIVO e os outros três grupos experimentais, na retenção. A superioridade do PVIVO no pós-teste e retenção face aos outros grupos no que concerne à exatidão é evidente. Esta superioridade, do PVIVO, pode ser explicada pela ligeira, mas maior variabilidade da velocidade da demonstração do aluno (modelo) em comparação ao professor (modelo).