Infectious disease surveillance and modelling across geographic frontiers and scientific specialties

Infectious disease surveillance for mass gatherings (MGs) can be directed locally and globally; however, epidemic intelligence from these two levels is not well integrated. Modelling activities related to MGs have historically focused on crowd behaviours around MG focal points and their relation to the safety of attendees. The integration of developments in internet-based global infectious disease surveillance, transportation modelling of populations travelling to and from MGs, mobile phone technology for surveillance during MGs, metapopulation epidemic modelling, and crowd behaviour modelling is important for progress in MG health. Integration of surveillance across geographic frontiers and modelling across scientific specialties could produce the first real-time risk monitoring and assessment platform that could strengthen awareness of global infectious disease threats before, during, and immediately after MGs. An integrated platform of this kind could help identify infectious disease threats of international concern at the earliest stages possible; provide insights into which diseases are most likely to spread into the MG; help with anticipatory surveillance at the MG; enable mathematical modelling to predict the spread of infectious diseases to and from MGs; simulate the effect of public health interventions aimed at different local and global levels; serve as a foundation for scientific research and innovation in MG health; and strengthen engagement between the scientific community and stakeholders at local, national, and global levels.     

Prediction of evolution toward brain death upon admission to ICU in comatose patients with spontaneous intracerebral hemorrhage using simple signs

The aim of the study was to identify the predictors of brain death (BD) upon admission to the intensive care unit (ICU) of comatose patients with spontaneous intracerebral hemorrhage (ICH). Patients admitted in our ICU from 2002 to 2010 for spontaneous ICH and placed under mechanical ventilation were retrospectively analyzed. Of the 72 patients, 49% evolved to BD, 39% died after withdrawal of life support, and 12% were discharged alive. The most discriminating characteristics to predict BD were included in two models; Model 1 contained ≥3 abolished brainstem responses [adjusted odds ratios (OR) = 8.4 (2.4, 29.1)] and the swirl sign on the baseline CT‐scan [adjusted OR = 5.0 (1.6, 15.9)] and Model 2 addressed the abolition of corneal reflexes [unilateral/bilateral: adjusted OR = 4.2 (0.9, 20.1)/8.8 (2.4, 32.3)] and the swirl sign on the baseline CT‐scan [adjusted OR = 6.2 (1.9, 20.0)]. Two scores predicting BD were created (sensitivity: 0.89 and 0.88, specificity: 0.68 and 0.65). Risk of evolution toward BD was classified as low (corneal reflexes present and no swirl sign), high (≥1 corneal reflexes abolished and swirl sign), and intermediate. Simple signs at ICU admission can predict BD in comatose patients with ICH and could increase the potential for organ donation.     

Involvement of antibody-dependent cell-mediated cytotoxicity in inflammatory demyelination in a mouse model of neuromyelitis optica

The progressive accumulation of extracellular amyloid plaques in the brain is a common hallmark of Alzheimer’s disease (AD). We recently identified a novel species of Aβ phosphorylated at serine residue 8 with increased propensity to form toxic aggregates as compared to non-phosphorylated species. The age-dependent analysis of Aβ depositions using novel monoclonal phosphorylation-state specific antibodies revealed that phosphorylated Aβ variants accumulate first inside of neurons in a mouse model of AD already at 2 month of age. At higher ages, phosphorylated Aβ is also abundantly detected in extracellular plaques. Besides a large overlap in the spatiotemporal deposition of phosphorylated and non-phosphorylated Aβ species, fractionized extraction of Aβ from brains revealed an increased accumulation of phosphorylated Aβ in oligomeric assemblies as compared to non-phosphorylated Aβ in vivo. Thus, phosphorylated Aβ could represent an important species in the formation and stabilization of neurotoxic aggregates, and might be targeted for AD therapy and diagnosis.     

Minimally invasive surgery versus percutaneous radio frequency ablation for the treatment of single small (≤3 cm) hepatocellular carcinoma: a case–control study

Background

Patients with single small hepatocellular carcinoma (HCC) can be managed by surgical resection or radio frequency ablation (RFA), with similar recurrence and survival rates. Recently, minimally invasive surgery (MIS) has been introduced in liver surgery, and the advantage/drawback balance between surgery and RFA needs reassessment.

Methods

Patients with Child-Pugh class A or B cirrhosis, and with single 1–3 cm HCC, undergoing MIS (laparoscopic or robot-assisted) or RFA from July 1998 to December 2012 were compared.

Results

Overall, 45 patients underwent MIS, and 60 underwent RFA. Groups were not statistically different regarding type of underlying liver disease, HCC size, and AFP. However, RFA patients showed worse liver synthetic function with lower albumin and higher bilirubin serum levels, and higher ASA scores. Patients with HCC in segments 2–6 were more often treated by MIS. The incidence of complications was similar between groups (RFA: 6/60, 10 % vs. MIS: 5/45, 11 %, p = 0.854), and there was no measurable difference in the rate of procedure-related blood transfusions (RFA: 1/60, 1.7 % vs. MIS: 3/45, 6.7 %, p = 0.185). Local recurrence was only detected after RFA (11.7 %, p = 0.056, log-rank). Overall survival was higher in the MIS group (p = 0.042), with median survivals of 100 ± 13.5 versus 68 ± 15.9 months.

Conclusion

The present data need further validation. Selected patients with single ≤3-cm HCCs can be safely treated by MIS, without increased risk of perioperative complication, and with a lower risk of local recurrence. MIS should be especially favoured in patients with peripheral HCCs in segments 2–6, and/or when a histological assessment is desirable.

     

Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism

Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C^high monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis.     

Evaluating Twitter as a complementary data source for pharmacovigilance

Background: Social media are currently considered as a potential complementary source of knowledge for drug safety surveillance. Our primary objective was to estimate the frequency of adverse drug reactions (ADRs) experienced by Twitter users. Our secondary objective was to determine whether tweets constitute a valuable and informative source of data for pharmacovigilance purposes, despite limitations on character number per tweet.

Research design and methods: We selected a list of 33 drugs subject to careful monitoring due to safety concern in France and Europe, and extracted tweets using the streaming API from 30 September 2014 to 5 April 2015. Two pharmacovigilance centers classified these tweets manually as potential ADR case reports.

Results: Among 10,534 tweets, 848 (8.05%) implied or mentioned an ADR without meeting the four FDA criteria required for reporting an ADR, and 289 (2.74%) tweets were classified as ‘case reports.’ Among them 20 (7.27%) tweets mentioned an unexpected ADR and 33 (11.42%) tweets mentioned a serious ADR.

Conclusions: With the use of dedicated tools, Twitter could become a complementary source of information for pharmacovigilance, despite a major limitation regarding causality assessment of ADRs in individual tweets, which may improve with the new limitation to 280 characters per tweet.