Intratumoral Immunotherapy: Is It Ready for Prime Time?

PURPOSE OF REVIEW: This review presents the rationale for intratumoral immunotherapy, technical considerations and safety. Clinical results from the latest trials are provided and discussed. RECENT FINDINGS: Intratumoral immunotherapy is feasible and safe in a wide range of cancer histologies and locations, including lung and liver. Studies mainly focused on multi-metastatic patients, with some positive trials such as T-VEC in melanoma, but evidence of clinical benefit is still lacking. Recent results showed improved outcomes in patients with a low tumor burden. Intratumoral immunotherapy can lower systemic toxicities and boost local and systemic immune responses. Several studies have proven the feasibility, repeatability, and safety of this approach, with some promising results in clinical trials. The clinical benefit might be improved in patients with a low tumor burden. Future clinical trials should focus on adequate timing of treatment delivery during the course of the disease, particularly in the neoadjuvant setting.

Inflammatory Bowel Diseases and School Absenteeism.

OBJECTIVES: Inflammatory bowel diseases (IBDs) are chronic diseases which negatively affect the schooling of children. The aim is to analyze school absenteeism and its causes in children followed for IBD. METHODS: A prospective multicenter study of IBD patients aged from 5 to 18 years old, from September 2016 to June 2017. Data on absenteeism and its causes were collected via a monthly questionnaire completed by patients or their family by mail. The results were compared with existing data supplied by the school authorities (497 students without IBD divided by class). RESULTS: A total of 106 patients (62 boys), median age of 14 (5-18), were included. The global response rate was 83.1%. The patients with IBD were absent an average of 4.8% ±â€Š5.5% of school days during the school year, against 3.2% ±â€Š1.6% for non IBD group (P = 0.034). Digestive disorders accounted for 34% of the causes of absenteeism. Approximately 27% of the absences were due to scheduled events (hospitalizations, endoscopy, or consultations). By excluding the absences for scheduled care, the rate of school absenteeism of patients with IBD is significantly lower than that of non-IBD group. CONCLUSION: Children with IBD are more frequently absent from school than non-IBD group. The main cause of school absenteeism appears to be associated with the disease itself. The share of scheduled absenteeism is quite large. The organization and scheduling of the patients' care path must be a priority to maximally limit the negative impact of their disease on the patients' schooling.

Functional abdominal pain disorders and patient- and parent-reported outcomes in children with inflammatory bowel disease in remission.

BACKGROUND: Chronic abdominal pain occurs frequently in pediatric patients with inflammatory bowel disease (IBD) in remission. AIMS: To assess the prevalence and factors associated with Functional Abdominal Pain Disorders among IBD children in remission (IBD-FAPD). METHODS: Patients with IBD for > 1 year, in clinical remission for ≥ 3 months were recruited from a National IBD network. IBD-FAPDs were assessed using the Rome III questionnaire criteria. Patient- or parent- reported outcomes were assessed. RESULTS: Among 102 included patients, 57 (56%) were boys, mean age (DS) was 15.0 (± 2.0) years and 75 (74%) had Crohn's disease. Twenty-two patients (22%) had at least one Functional Gastrointestinal Disorder among which 17 had at least one IBD-FAPD. Past severity of disease or treatments received and level of remission were not significantly associated with IBD-FAPD. Patients with IBD-FAPD reported more fatigue (peds-FACIT-F: 35.9 ± 9.8 vs. 43.0 ± 6.9, p = 0.01) and a lower HR-QoL (IMPACT III: 76.5 ± 9.6 vs. 81.6 ± 9.2, p = 0.04) than patients without FAPD, and their parents had higher levels of State and Trait anxiety than the other parents. CONCLUSIONS: Prevalence of IBD-FAPD was 17%. IBD-FAPD was not associated with past severity of disease, but with fatigue and lower HR-QoL.

Cognitive Deficits and Inflammatory Response Resulting from Mild-to-Moderate Traumatic Brain Injury in Rats Are Exacerbated by Repeated Pre-Exposure to an Innate Stress Stimulus.

Traumatic brain injury (TBI) is common in both military and civilian populations, and often results in neurobehavioral sequelae that impair quality of life in both patients and their families. Although individuals who are chronically exposed to stress are more likely to experience TBI, it is still unknown whether pre-injury stress influences the outcome after TBI. The present study tested whether behavioral and cognitive long-term outcome after TBI in rats is affected by prior exposure to an innate stress stimulus. Young adult male Sprague-Dawley rats were exposed to the predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) or to water (WAT); exposure was repeated eight times at irregular intervals over a 2-week period. Rats were subsequently subjected to either mild-to-moderate bilateral brain injury (lateral fluid percussion [LFP]) or sham surgery (Sham). Four experimental groups were studied: Sham-WAT, Sham-TMT, LFP-WAT and LFP-TMT. Compared with Sham-WAT rats, LFP-WAT rats exhibited transient locomotor hyperactivity without signs of anxiety, minor spatial learning acquisition and hippocampal long-term potentiation deficits, and lower baseline activity of the hypothalamic-pituitary-adrenal axis with slightly stronger reactivity to restraint stress. Exposure to TMT had only negligible effects on Sham rats, whereas it exacerbated all deficits in LFP rats except for locomotor hyperactivity. Early brain inflammatory response (8 h post-trauma) was aggravated in rats pre-exposed to TMT, suggesting that increased brain inflammation may sustain functional deficits in these rats. Hence, these data suggest that pre-exposure to stressful conditions can aggravate long-term deficits induced by TBI, leading to severe stress response deficits, possibly due to dysregulated inflammatory response.

Vaccination coverage of children with inflammatory bowel disease after an awareness campaign on the risk of infection.

BACKGROUND: Children with inflammatory bowel disease are at risk of vaccine-preventable diseases mostly due to immunosuppressive drugs. AIM: To evaluate coverage after an awareness campaign informing patients, their parents and general practitioner about the vaccination schedule. METHODS: Vaccination coverage was firstly evaluated and followed by an awareness campaign on the risk of infection via postal mail. The trial is a case-control study on the same patients before and after the awareness campaign. Overall, 92 children were included. A questionnaire was then completed during a routine appointment to collect data including age at diagnosis, age at data collection, treatment history, and vaccination status. RESULTS: Vaccination rates significantly increased for vaccines against diphtheria-tetanus-poliomyelitis (92% vs. 100%), Haemophilus influenzae (88% vs. 98%), hepatitis B (52% vs. 71%), pneumococcus (36% vs. 57%), and meningococcus C (17% vs. 41%) (p<0.05). Children who were older at diagnosis were 1.26 times more likely to be up-to-date with a minimum vaccination schedule (diphtheria-tetanus-poliomyelitis, pertussis, H. influenzae, measles-mumps-rubella, tuberculosis) (p=0.002). CONCLUSION: Informing inflammatory bowel disease patients, their parents and general practitioner about the vaccination schedule via postal mail is easy, inexpensive, reproducible, and increases vaccination coverage. This method reinforces information on the risk of infection during routine visits.

Technical aspects of an impact acceleration traumatic brain injury rat model with potential suitability for both microdialysis and PtiO2 monitoring.

This report describes technical adaptations of a traumatic brain injury (TBI) model-largely inspired by Marmarou-in order to monitor microdialysis data and PtiO2 (brain tissue oxygen) before, during and after injury. We particularly focalize on our model requirements which allows us to re-create some drastic pathological characteristics experienced by severely head-injured patients: impact on a closed skull, no ventilation immediately after impact, presence of diffuse axonal injuries and secondary brain insults from systemic origin... We notably give priority to minimize anaesthesia duration in order to tend to banish any neuroprotection. Our new model will henceforth allow a better understanding of neurochemical and biochemical alterations resulting from traumatic brain injury, using microdialysis and PtiO2 techniques already monitored in our Intensive Care Unit. Studies on efficiency and therapeutic window of neuroprotective pharmacological molecules are now conceivable to ameliorate severe head-injury treatment.

Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg?

Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR) is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation) is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation) is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new "gold standard" and adapted medical education are required to optimize the management of patients with metabolic crisis.