An innovative educational program for adolescents on home parenteral nutrition for the "transition" to adulthood.

Facing with an increasing demand for transition to adult care management, our home parenteral nutrition (HPN) team designed an adolescent therapeutic educational program (ATEP) specifically intended for adolescents on long-term HPN. The aim of this study was to report on the first sessions of this program. Methods: The ATEP is designed in three sessions of five consecutive days, during school holidays over the year. It includes group sessions on catheter handling, disconnecting and connecting the PN and catheter dressing, dealing with unforeseen events (e.g., fever or catheter injury), but also sessions with psychologist, social worker, sports teacher, fashion specialist, meeting with adults who received HPN since childhood. Specific course for the accompanying parents were also provided. Six months after the last session, a 3-day trip to the attraction park "le Futuroscope," Poitiers, France, was organized without any parental presence. Results: After 3 ATEP courses, a total of 16 adolescents have been enrolled. They were aged between 13 and 17 years (median 14 IQR: 14-16.25). All were on long term HPN started during the neonatal period except for four who started PN at a median age of 10 years old (IQR: 1-10). At the time of the ATEP, their median PNDI was 105% (IQR: 95.5-120.8) while receiving a median of six infusions per week (IQR: 5-7). Thirteen received Taurolidine lock procedure. After the ATEP, 11 adolescents could be considered as fully autonomous, 4 as partially autonomous and one failed to gain any autonomy. Course evaluation by adolescents or parents was good to excellent. Conclusion: Through the holistic and multiprofessional approach of this training and the group cohesion, the adolescents were not only able to handle catheter care and PN connections but were able to understand and accept better their illness and project themselves into their own future.

PROPERTY: study protocol for a randomized, double-blind, multicenter placebo-controlled trial assessing neurotoxicity in patients with metastatic gastrointestinal cancer taking PHYCOCARE® during oxaliplatin-based chemotherapy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse effects of antineoplastic agents, ranging in prevalence from 19% to over 85%. Clinically, CIPN is a predominantly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. The high prevalence of CIPN among cancer patients makes it a major problem for both patients and survivors, as well as for their health care providers, especially because there is currently no single effective method of preventing CIPN; moreover, the options for treating this syndrome are very limited. Phycocyanin, a biliprotein pigment and an important constituent of the blue-green algae Spirulina platensis, has been reported to possess significant antioxidant and radical-scavenging properties, offering protection against oxidative stress, which is one of the hypothetic mechanisms, between others, of CIPN occurrence. METHODS: Our hypothesis is that phycocyanin may give protection against oxaliplatin-induced neuropathy in the treatment of gastrointestinal cancers. Our trial will be a randomized double-blind placebo-controlled study with 110 randomized patients suffering from metastatic gastrointestinal adenocarcinoma including esogastric, colorectal, and pancreatic cancers. Patients are being followed up in the gastroenterology or oncology departments of seven French hospitals. DISCUSSION: Due to the neuropathy, patients need to avoid injury by paying careful attention to home safety; patients' physicians often prescribe over-the-counter pain medications. If validated, our hypothesis should help to limit neurotoxicity without the need to discontinue chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT05025826. First published on August 27, 2021.

Long survival of patients with metastatic clear cell renal cell carcinoma. Results of real life study of 344 patients.

The treatment landscape in metastatic renal cell carcinoma has changed fundamentally over the last decade by the development of antiangiogenic agents, mammalian target of rapamycin inhibitors and immunotherapy. Outside of the context of a clinical trial, the treatments are used sequentially. We describe results under real-life conditions of a sequential treatment strategy, before the era of immunotherapy. All patients were treated according to their prognostic score (either Memorial Sloan Kettering Cancer Center or International Metastatic Renal Cell Carcinoma Database Consortium) for advanced renal cell carcinoma. A treatment strategy involving 1 to 4 lines was determined including a rechallenge criterion for the repeat use of a treatment class. Three hundred forty-four patients were included over 3 years. Overall survival was 57 months in patients with good or intermediate prognosis and 19 months in patients with poor prognosis. In the former group, the proportions of patients treated with 2 to 4 treatment lines were 70%, 38% and 16%, respectively. The best objective response rates for lines 1 to 4 were 46%, 36%, 16% and 17%, respectively. Grade III/IV toxicity did not appear to be cumulative. The recommended strategy was followed in 68% of patients. A large proportion of patients with good or intermediate prognosis who progress after two lines of treatment still have a performance status good enough to receive a systemic treatment, which justifies such a strategy. Overall survival of patients with good and intermediate prognosis was long, suggesting a benefit from the applied approach. These results might be used as selection criterion for the treatment of patients in the era of immune checkpoint inhibitors.

Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial.

BACKGROUND: There is no recommended therapy for malignant pleural mesothelioma that has progressed after first-line pemetrexed and platinum-based chemotherapy. Disease control has been less than 30% in all previous studies of second-line drugs. Preliminary results have suggested that anti-programmed cell death 1 (PD-1) monoclonal antibody could be efficacious in these patients. We thus aimed to prospectively assess the anti-PD-1 monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma. METHODS: This multicentre randomised, non-comparative, open-label, phase 2 trial was done at 21 hospitals in France. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, histologically proven malignant pleural mesothelioma progressing after first-line or second-line pemetrexed and platinum-based treatments, measurable disease by CT, and life expectancy greater than 12 weeks. Patients were randomly allocated (1:1) to receive intravenous nivolumab (3 mg/kg bodyweight) every 2 weeks, or intravenous nivolumab (3 mg/kg every 2 weeks) plus intravenous ipilimumab (1 mg/kg every 6 weeks), given until progression or unacceptable toxicity. Central randomisation was stratified by histology (epithelioid vs non-epithelioid), treatment line (second line vs third line), and chemosensitivity to previous treatment (progression ≥3 months vs <3 months after pemetrexed treatment) and used a minimisation method with a 0·8 random factor. The primary outcome was the proportion of patients who achieved 12-week disease control, assessed by masked independent central review; the primary endpoint would be met if disease control was achieved in at least 40% of patients. The primary endpoint was assessed in the first 108 eligible patients. Efficacy analyses were also done in the intention-to-treat population and safety analyses were done in all patients who received at least one dose of their assigned treatment. This trial is registered at ClinicalTrials.gov, number NCT02716272. FINDINGS: Between March 24 and August 25, 2016, 125 eligible patients were recruited and assigned to either nivolumab (n=63) or nivolumab plus ipilimumab (n=62). In the first 108 eligible patients, 12-week disease control was achieved by 24 (44%; 95% CI 31-58) of 54 patients in the nivolumab group and 27 (50%; 37-63) of 54 patients in the nivolumab plus ipilimumab group. In the intention-to-treat population, 12-week disease control was achieved by 25 (40%; 28-52) of 63 patients in the nivolumab group and 32 (52%; 39-64) of 62 patients in the combination group. Nine (14%) of 63 patients in the nivolumab group and 16 (26%) of 61 patients in the combination group had grade 3-4 toxicities. The most frequent grade 3 adverse events were asthenia (one [2%] in the nivolumab group vs three [5%] in the combination group), asymptomatic increase in aspartate aminotransferase or alanine aminotransferase (none vs four [7%] of each), and asymptomatic lipase increase (two [3%] vs one [2%]). No patients had toxicities leading to death in the nivolumab group, whereas three (5%) of 62 in the combination group did (one fulminant hepatitis, one encephalitis, and one acute kidney failure). INTERPRETATION: Anti-PD-1 nivolumab monotherapy or nivolumab plus anti-CTLA-4 ipilimumab combination therapy both showed promising activity in relapsed patients with malignant pleural mesothelioma, without unexpected toxicity. These regimens require confirmation in larger clinical trials. FUNDING: French Cooperative Thoracic Intergroup.

Strategies to Reduce Catheter-Related Bloodstream Infections in Pediatric Patients Receiving Home Parenteral Nutrition: The Efficacy of Taurolidine-Citrate Prophylactic-Locking.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) remain a major issue in patients who are receiving home parenteral nutrition (HPN). The aim of this interventional study was to assess the impact of a new strategy using taurolidine-citrate (T-C) prophylactic locks on the CRBSI rate in children with intestinal failure who are receiving HPN. METHODS: The rate of CRBSIs was monitored every calendar year in a prospective cohort of 195 children with intestinal failure. T-C locks were initiated from October 2011 in children with recurring CRBSIs (≥2 episodes per year). RESULTS: In the whole cohort, the median annual CRBSI rate per 1000 catheter days decreased significantly from 2.07 in 2008 to 2010 to 1.23 in 2012 to 2014 (P < .05). T-C locks were used in 40 patients. No adverse events were reported. In taurolidine-treated patients, the CRBSI rate per 1000 catheter days decreased from 4.16 to 0.25 (P < .0001). The cumulative percentage of patients free of CRBSI at 18 months was 92% (95% confidence interval [CI]: 71-98) on T-C lock vs 61% (95% CI: 49-72) in controls (P = .01). In multivariate analysis, factors associated with CRBSI were immune deficiency (adjusted hazard ratio 3.49; 95% CI: 1.01-12.17) and the young age of the parents (adjusted hazard ratio 4.79, 95% CI: 2.16-10.62), whereas T-C locks were protective (adjusted hazard ratio 0.22, 95% CI: 0.06-0.74). CONCLUSION: This study confirms the efficacy of T-C catheter locks in decreasing the incidence of CRBSIs in children with intestinal failure who are receiving HPN.

Outcome of home parenteral nutrition in 251 children over a 14-y period: report of a single center.

BACKGROUND: Parenteral nutrition (PN) is the main treatment for intestinal failure. OBJECTIVE: We aimed to review the indications for home parenteral nutrition (HPN) in children and describe the outcome over a 14-y period from a single center. DESIGN: We conducted a retrospective study that included all children who were referred to our institution and discharged while receiving HPN between 1 January 2000 and 31 December 2013. The indications for HPN were divided into primary digestive diseases (PDDs) and primary nondigestive diseases (PNDDs). We compared our results to a previous study that was performed in our unit from 1980 to 2000 and included 302 patients. RESULTS: A total of 251 patients were included: 217 (86%) had a PDD. The mean ± SD age at HPN onset was 0.7 ± 0.3 y, with a mean duration of 1.9 ± 0.4 y. The indications for HPN were short bowel syndrome (SBS) (59%), PNDD (14%), congenital enteropathies (10%), chronic intestinal pseudo-obstruction syndromes (9%), inflammatory bowel diseases (5%), and other digestive diseases (3%). By 31 December 2013, 52% of children were weaned off of HPN, 9% of the PDD subgroup had intestinal transplantation, and 10% died mostly because of immune deficiency. The major complications of HPN were catheter-related bloodstream infections (CRBSIs) (1.7/1000 d of PN) and intestinal failure-associated liver disease (IFALD) (51 children; 20% of cohort). An increased rate of CRBSIs was observed compared with our previous study, but we saw a decreasing trend since 2012. No noteworthy deceleration of growth was observed in SBS children 6 mo after weaning off HPN. CONCLUSIONS: SBS was the major indication for HPN in our cohort. IFALD and CRBSIs were potentially life-threatening problems. Nevertheless, complication rates were low, and deaths resulted mostly from the underlying disease.

Weaning Off Prognosis Factors of Home Parenteral Nutrition for Children With Primary Digestive Disease.

OBJECTIVES: The aim of the present study was to describe the indications for home parenteral nutrition (HPN) in children with primary digestive diseases and to identify factors associated with weaning off. METHODS: All the children initially discharged on HPN between January 1, 2000, and December 31, 2009, for chronic intestinal failure (IF) were included. The associations between clinical factors and weaning off of HPN were assessed using a multivariable Cox regression model. RESULTS: Among the 151 children (boys = 58%) included in this study, 98 (65%) presented with short bowel syndrome (SBS), 17 (11%) with digestive neuromuscular disorders, 14 (9%) with mucosal diseases, 13 (9%) with inflammatory bowel disease, and 9 (6%) with other primary digestive diseases. The probability of survival was ∼100%. At the end of the follow-up, the probability for weaning off of HPN was 0.73 (95% confidence interval 0.54-0.84) but varied according to the underlying cause of IF (for example, SBS and inflammatory bowel disease had a better prognosis). The median time until weaning off was 21 months (95% confidence interval 18-38 months). Unfavourable prognostic factors for weaning off of HPN included a bowel remnant of <40 cm, the presence of <50% of the colon, and daily lipid intakes >1.5 g · kg · day. Underlying disease was also associated with weaning off. CONCLUSIONS: HPN is a safe therapeutic option for children with chronic IF requiring long-term nutritional management. Prognostic factors for weaning off of HPN were identified, and they highlight the relevance of SBS anatomy and parenteral nutrition caloric intake. The outcome of children on HPN was primarily dependent on the underlying disease.

Can we predict chemo-induced hematotoxicity in elderly patients treated with pegylated liposomal doxorubicin? Results of a population-based model derived from the DOGMES phase II trial of the GINECO.

INTRODUCTION: Use of anthracyclines is often limited in older patients due to cardiac and hematologic toxicities. Thanks to its reduced toxicity profile, Pegylated Liposomal Doxorubicin (PLD) allows an extended use of doxorubicin to this population. We aimed at modeling PLD-induced hematotoxicity in patients with metastatic breast cancer ≥70 years old and at finding predictive factors of neutrophil nadir value. METHODS: Sixty patients, enrolled in the DOGMES prospective multicentric phase II trial, were treated with PLD at 40mg/m(2) every 28days during six cycles. Trial design included geriatric covariates assessment at inclusion and monitoring of cells count every week for three cycles. A population model was developed to describe hematopoiesis and hematopoietic reserve in these patients. The effect of co-administered G-CSF (granulocyte colony-stimulating factor) was also examined. RESULTS: A pharmacodynamic model was built using data from 53 patients not receiving G-CSF. This model assumed an instantaneous effect of PLD on the system. Based on this model, exact neutrophil nadir value was computed and ranged between 0.069K/mm(3) and 2.63K/mm(3) confirming the weak hematotoxicity of PLD. The same model was then applied to the 7 patients receiving G-CSF and showed that basal neutrophil count was higher for these patients. No other difference was found between both cohorts. Among the covariates collected, three were predictive of neutrophil nadir value: diabetes, frailty syndrome and assistance at home. CONCLUSION: This developed model allowed the identification of predictive factors of nadir ANC and the identification of patients that are more likely to develop hematotoxicity that should be monitored with attention.

Pathology of inverted Takotsubo cardiomyopathy.

Myocardial dysfunction without coronary involvement may occur in acute cerebral diseases. The inverted Takotsubo pattern has been recently recognized as a novel heart neurologic stress-related syndrome. We report on the case of a 40-year-old woman presenting with massive subarachnoid hemorrhage and brain death. Echocardiography revealed an extensive left ventricular circumferential akinesis except at the apex. Histologic analysis of the heart confirmed the absence of myocardial infarction and revealed only sparse foci of myocyte necrosis with contraction bands in the akinetic areas.

Risk of post-traumatic stress symptoms in family members of intensive care unit patients.

RATIONALE: Intensive care unit (ICU) admission of a relative is a stressful event that may cause symptoms of post-traumatic stress disorder (PTSD). OBJECTIVES: Factors associated with these symptoms need to be identified. METHODS: For patients admitted to 21 ICUs between March and November 2003, we studied the family member with the main potential decision-making role. MEASUREMENTS: Ninety days after ICU discharge or death, family members completed the Impact of Event Scale (which evaluates the severity of post-traumatic stress reactions), Hospital Anxiety and Depression Scale, and 36-item Short-Form General Health Survey during a telephone interview. Linear regression was used to identify factors associated with the risk of post-traumatic stress symptoms. MAIN RESULTS: Interviews were obtained for family members of 284 (62%) of the 459 eligible patients. Post-traumatic stress symptoms consistent with a moderate to major risk of PTSD were found in 94 (33.1%) family members. Higher rates were noted among family members who felt information was incomplete in the ICU (48.4%), who shared in decision making (47.8%), whose relative died in the ICU (50%), whose relative died after end-of-life decisions (60%), and who shared in end-of-life decisions (81.8%). Severe post-traumatic stress reaction was associated with increased rates of anxiety and depression and decreased quality of life. CONCLUSION: Post-traumatic stress reaction consistent with a high risk of PTSD is common in family members of ICU patients and is the rule among those who share in end-of-life decisions. Research is needed to investigate PTSD rates and to devise preventive and early-detection strategies.

Half the family members of intensive care unit patients do not want to share in the decision-making process: a study in 78 French intensive care units.

OBJECTIVE: To evaluate the opinions of intensive care unit staff and family members about family participation in decisions about patients in intensive care units in France, a country where the approach of physicians to patients and families has been described as paternalistic. DESIGN: Prospective multiple-center survey of intensive care unit staff and family members. SETTING: Seventy-eight intensive care units in university-affiliated hospitals in France. PATIENTS: We studied 357 consecutive patients hospitalized in the 78 intensive care units and included in the study starting on May 1, 2001, with five patients included per intensive care unit. INTERVENTIONS: We recorded opinions and experience about family participation in medical decision making. Comprehension, satisfaction, and Hospital Anxiety and Depression Scale scores were determined in family members. MEASUREMENTS AND MAIN RESULTS: Poor comprehension was noted in 35% of family members. Satisfaction was good but anxiety was noted in 73% and depression in 35% of family members. Among intensive care unit staff members, 91% of physicians and 83% of nonphysicians believed that participation in decision making should be offered to families; however, only 39% had actually involved family members in decisions. A desire to share in decision making was expressed by only 47% of family members. Only 15% of family members actually shared in decision making. Effectiveness of information influenced this desire. CONCLUSION: Intensive care unit staff should seek to determine how much autonomy families want. Staff members must strive to identify practical and psychological obstacles that may limit their ability to promote autonomy. Finally, they must develop interventions and attitudes capable of empowering families.

Cytotoxic T cell responses against mesothelioma by apoptotic cell-pulsed dendritic cells.

Malignant pleural mesothelioma is an uncommon tumor largely confined to the thoracic cavity, which is resistant to conventional therapies, therefore prompting an intensive search for effective treatment alternatives. This study focuses on dendritic cell (DC) vaccination for malignant pleural mesothelioma and evaluates the in vitro efficacy of antigen-loaded DC-based vaccines for the induction of major histocompatibility complex Class I-restricted antimesothelioma cytotoxic T lymphocyte responses. The source of tumor-associated antigens for HLA-A2(+) DCs from healthy donors was apoptotic HLA-A2(-) mesothelioma cells either lacking or expressing heat shock protein 70 according to whether tumor cells were heat shocked or not before ultraviolet-mediated apoptosis. Our results show that both apoptotic preparations were equivalent regarding the responsiveness of DCs to combined treatment with tumor necrosis factor-alpha and poly(inosinic-cytidylic) acid, as determined by similar increased expression of costimulatory molecules and interleukin-12 production. However, only DCs loaded with apoptotic heat shock protein 70-expressing cells were found to be potent in vitro inducers of cytotoxic T lymphocyte activity against HLA-A2(+) mesothelioma cells. Such elicited cytotoxic T lymphocytes also exhibit cytotoxic activity against an HLA-A2(+) melanoma cell line, suggesting recognition of shared antigens. These findings therefore carry the potential of offering an alternative, promising approach for the therapy of patients with malignant pleural mesothelioma.

Impact of a family information leaflet on effectiveness of information provided to family members of intensive care unit patients: a multicenter, prospective, randomized, controlled trial.

Comprehension and satisfaction are relevant criteria for evaluating the effectiveness of information provided to family members of intensive care unit (ICU) patients. We performed a prospective randomized trial in 34 French ICUs to compare comprehension of diagnosis, prognosis, treatment, and satisfaction with information provided by ICU caregivers, in ICU patient family representatives who did (n = 87) or did not (n = 88) receive a family information leaflet (FIL) in addition to standard information. An FIL designed specifically for this study was delivered at the first visit of the family representative: it provided general information on the ICU and hospital, the name of the ICU physician caring for the patient, a diagram of a typical ICU room with the names of all the devices, and a glossary of 12 terms commonly used in ICUs. Characteristics of the ICUs, patients, and family representatives were similar in the two groups. The FIL reduced the proportion of family members with poor comprehension from 40.9% to 11.5% (p < 0.0001). In the representatives with good comprehension, the FIL was associated with significantly better satisfaction (21 [18 to 24, quartiles] versus 27 [24 to 29, quartiles], p = 0.01). These results indicate that ICU caregivers should consider using an FIL to improve the effectiveness of the information they impart to families.