Factors associated with the persistence of medically unexplained symptoms in later life

Both the older patient and the health professionals involved, and most particularly the therapist, experience problems with the assessment of the nature and the treatment of the impact of physical symptoms for which no medical diagnosis has been found. As a result, many of these older patients remain deprived of an adequate diagnosis and fitting, evidence-based treatment.The results of the studies collected in this thesis have added to our knowledge on the various factors associated with the persistence of medically unexplained symptoms (MUS) in older patients, while offering tools to explore and quantify relevant factors (e.g. the Illness Cognition Questionnaire-plus, ICQ-plus). Besides the many similarities between older and younger patients struggling with MUS and those between patients presenting with either MUS or medically explained symptoms (MES) (or both), there are also meaningful differences. When, during the assessment and treatment of MUS in later life, attention is paid to specific age-related problems, there are no reasons to exclude older patients from treatment or research. To improve the clinical assessment and management of later-life MUS, therapist training and research need to be stepped up because the growing number of older adults with physical symptoms, be they explained or not, deserve our attention to help them improve their (daily) functioning and regain their quality of life

How to Approach Para-Aortic Lymph Node Metastases During Exploration for Suspected Periampullary Carcinoma:Resection or Bypass?

Background: Intraoperative para-aortic lymph node (PALN) sampling during surgical exploration in patients with suspected pancreatic head cancer remains controversial. Objective: The aim of this study was to assess the value of routine PALN sampling and the consequences of different treatment strategies on overall patient survival. Methods: A retrospective, multicenter cohort study was performed in patients who underwent surgical exploration for suspected pancreatic head cancer. In cohort A, the treatment strategy was to avoid pancreatoduodenectomy and to perform a double bypass procedure when PALN metastases were found during exploration. In cohort B, routinely harvested PALNs were not examined intraoperatively and pancreatoduodenectomy was performed regardless. PALNs were examined with the final resection specimen. Clinicopathological data, survival data and complication data were compared between study groups. Results: Median overall survival for patients with PALN metastases who underwent a double bypass procedure was 7.0 months (95% confidence interval [CI] 5.5–8.5), versus 11 months (95% CI 8.8–13) in the pancreatoduodenectomy group (p = 0.049). Patients with PALN metastases who underwent pancreatoduodenectomy had significantly increased postoperative morbidity compared with patients who underwent a double bypass procedure (p < 0.001). In multivariable analysis, severe comorbidity (ASA grade 2 or higher) was an independent predictor for decreased survival in patients with PALN involvement (hazard ratio 3.607, 95% CI 1.678–7.751; p = 0.001). Conclusion: In patients with PALN metastases, pancreatoduodenectomy was associated with significant survival benefit compared with a double bypass procedure, but with increased risk of complications. It is important to weigh the advantages of resection versus bypass against factors such as comorbidities and clinical performance when positive intraoperative PALNs are found

Role of the rdxA and frxA genes in oxygen-dependent metronidazole resistance of Helicobacter pylori

Almost 50 % of all Helicobacter pylori isolates are resistant to metronidazole, which reduces the efficacy of metronidazole-containing regimens, but does not make them completely ineffective. This discrepancy between in vitro metronidazole resistance and treatment outcome may partially be explained by changes in oxygen pressure in the gastric environment, as metronidazole-resistant (MtzR) H. pylori isolates become metronidazole-susceptible (MtzS) under low oxygen conditions in vitro. In H. pylori the rdxA and frxA genes encode reductases which are required for the activation of metronidazole, and inactivation of these genes results in metronidazole resistance. Here the role of inactivating mutations in these genes on the reversibility of metronidazole resistance under low oxygen conditions is established. Clinical H. pylori isolates containing mutations resulting in a truncated RdxA and/or FrxA protein were selected and incubated under anaerobic conditions, and the effect of these conditions on the MICs of metronidazole, amoxycillin, clarithromycin and tetracycline, and cell viability were determined. While anaerobiosis had no effect on amoxycillin, clarithromycin and tetracycline resistance, all isolates lost their metronidazole resistance when cultured under anaerobic conditions. This loss of metronidazole resistance also occurred in the presence of the protein synthesis inhibitor chloramphenicol. Thus, factor(s) that activate metronidazole under low oxygen tension are not specifically induced by low oxygen conditions, but are already present under microaerophilic conditions. As there were no significant differences in cell viability between the clinical isolates, it is likely that neither the rdxA nor the frxA gene participates in the reversibility of metronidazole resistance

The multi-dimensional challenges of controlling respiratory virus transmission in indoor spaces:Insights from the linkage of a microscopic pedestrian simulation and SARS-CoV-2 transmission model

SARS-CoV-2 transmission in indoor spaces, where most infection events occur, depends on the types and duration of human interactions, among others. Understanding how these human behaviours interface with virus characteristics to drive pathogen transmission and dictate the outcomes of non-pharmaceutical interventions is important for the informed and safe use of indoor spaces. To better understand these complex interactions, we developed the Pedestrian Dynamics—Virus Spread model (PeDViS): an individual-based model that combines pedestrian behaviour models with virus spread models that incorporate direct and indirect transmission routes. We explored the relationships between virus exposure and the duration, distance, respiratory behaviour, and environment in which interactions between infected and uninfected individuals took place and compared this to benchmark ‘at risk’ interactions (1.5 metres for 15 minutes). When considering aerosol transmission, individuals adhering to distancing measures may be at risk due to build-up of airborne virus in the environment when infected individuals spend prolonged time indoors. In our restaurant case, guests seated at tables near infected individuals were at limited risk of infection but could, particularly in poorly ventilated places, experience risks that surpass that of benchmark interactions. Combining interventions that target different transmission routes can aid in accumulating impact, for instance by combining ventilation with face masks. The impact of such combined interventions depends on the relative importance of transmission routes, which is hard to disentangle and highly context dependent.</p

The multi-dimensional challenges of controlling respiratory virus transmission in indoor spaces:Insights from the linkage of a microscopic pedestrian simulation and SARS-CoV-2 transmission model

SARS-CoV-2 transmission in indoor spaces, where most infection events occur, depends on the types and duration of human interactions, among others. Understanding how these human behaviours interface with virus characteristics to drive pathogen transmission and dictate the outcomes of non-pharmaceutical interventions is important for the informed and safe use of indoor spaces. To better understand these complex interactions, we developed the Pedestrian Dynamics—Virus Spread model (PeDViS): an individual-based model that combines pedestrian behaviour models with virus spread models that incorporate direct and indirect transmission routes. We explored the relationships between virus exposure and the duration, distance, respiratory behaviour, and environment in which interactions between infected and uninfected individuals took place and compared this to benchmark ‘at risk’ interactions (1.5 metres for 15 minutes). When considering aerosol transmission, individuals adhering to distancing measures may be at risk due to build-up of airborne virus in the environment when infected individuals spend prolonged time indoors. In our restaurant case, guests seated at tables near infected individuals were at limited risk of infection but could, particularly in poorly ventilated places, experience risks that surpass that of benchmark interactions. Combining interventions that target different transmission routes can aid in accumulating impact, for instance by combining ventilation with face masks. The impact of such combined interventions depends on the relative importance of transmission routes, which is hard to disentangle and highly context dependent.</p

Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death.

Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment

Caractérisation des voies de signalisation impliquées dans le cannibalisme cellulaire induit par les radiations ionisantes

Many types of anticancer therapies are available to kill tumor cells. The tumoral cell death modalities may be different upon the treatment, the cell type and inter-individual sensitivity. Besides the typical cell death processes apoptosis and necrosis, cellular cannibalism has also been reported in patients’ tumoral biopsies. This cellular process is defined as the engulfment of one live cell by another live cell followed by the degradation of the inner cell. The mechanisms beyond cellular cannibalism are still partially understoof but it appears to be of clinical relevance. Indeed, we have shown that these events could be modulated by anticancer treatments and there are evidences of their utility as a potent prognostic biomarker in some cancers. This thesis presents the in vitro experiments which led to the identification of the signaling pathways involved in cellular cannibalism induced by ionizing radiation.Les stratégies thérapeutiques anticancer sont nombreuses et variées. Elles visent à déclencher la mort des cellules tumorales mais les processus de mort cellulaire diffèrent en fonction du traitement, du type de cellule ciblé et des caractéristiques du patient. A côté des mécanismes classiques tels que l’apoptose et la nécrose, on retrouve également du cannibalisme cellulaire dans les biopsies de tumeurs des patients. Ce phénomène dont les mécanismes sont encore peu caractérisés, correspond à l’internalisation d’une cellule vivante par une cellule vivante. Il est fréquemment suivi par la dégradation de la cellule internalisée. Cette modalité de mort atypique est intéressante car nous avons montré qu’elle pouvait être modulée par des traitements anticancéreux et des études ont également démontré qu’elle pouvait servir de biomarqueur pronostique dans certains types de cancer. Ces travaux de thèse ont permis d'identifier des voies de signalisation cellulaire activées lors du déclenchement du cannibalisme cellulaire par les radiations ionisante

Current and Future Role of Medical Imaging in Guiding the Management of Patients With Relapsed and Refractory Non-Hodgkin Lymphoma Treated With CAR T-Cell Therapy

International audienceChimeric antigen receptor (CAR) T-cells are a novel immunotherapy available for patients with refractory/relapsed non-Hodgkin lymphoma. In this indication, clinical trials have demonstrated that CAR T-cells achieve high rates of response, complete response, and long-term response (up to 80%, 60%, and 40%, respectively). Nonetheless, the majority of patients ultimately relapsed. This review provides an overview about the current and future role of medical imaging in guiding the management of non-Hodgkin lymphoma patients treated with CAR T-cells. It discusses the value of predictive and prognostic biomarkers to better stratify the risk of relapse, and provide a patient-tailored therapeutic strategy. At baseline, high tumor volume (assessed on CT-scan or on [18F]-FDG PET/CT) is a prognostic factor associated with treatment failure. Response assessment has not been studied extensively yet. Available data suggests that current response assessment developed on CT-scan or on [18F]-FDG PET/CT for cytotoxic systemic therapies remains relevant to estimate lymphoma response to CAR T-cell therapy. Nonetheless, atypical patterns of response and progression have been observed and should be further analyzed. The potential advantages as well as limitations of artificial intelligence and radiomics as tools providing high throughput quantitative imaging features is described

Current treatment and outcomes of traumatic sternal fractures-a systematic review

PURPOSE: Traumatic sternal fractures are rare injuries. The most common mechanism of injury is direct blunt trauma to the anterior chest wall. Most (> 95%) sternal fractures are treated conservatively. Surgical fixation is indicated in case of fracture instability, displacement or non-union. However, limited research has been performed on treatment outcomes. This study aimed to provide an overview of the current treatment practices and outcomes of traumatic sternal fractures and dislocations. METHODS: A systematic review of literature published from 1990 to June 2017 was conducted. Original studies on traumatic sternal fractures, reporting sternal healing or sternal stability were included. Studies on non-traumatic sternal fractures or not reporting sternal healing outcomes, as well as case reports (n = 1), were excluded. RESULTS: Sixteen studies were included in this review, which reported treatment outcomes for 191 patients. Most included studies were case series of poor quality. All patients showed sternal healing and 98% reported pain relief. Treatment complications occurred in 2% of patients. CONCLUSIONS: Treatment of traumatic sternal fractures and dislocations is an underexposed topic. Although all patients in this review displayed sternal healing, results should be interpreted with caution since most included studies were of poor quality

Current treatment and outcomes of traumatic sternal fractures-a systematic review

PURPOSE: Traumatic sternal fractures are rare injuries. The most common mechanism of injury is direct blunt trauma to the anterior chest wall. Most (> 95%) sternal fractures are treated conservatively. Surgical fixation is indicated in case of fracture instability, displacement or non-union. However, limited research has been performed on treatment outcomes. This study aimed to provide an overview of the current treatment practices and outcomes of traumatic sternal fractures and dislocations. METHODS: A systematic review of literature published from 1990 to June 2017 was conducted. Original studies on traumatic sternal fractures, reporting sternal healing or sternal stability were included. Studies on non-traumatic sternal fractures or not reporting sternal healing outcomes, as well as case reports (n = 1), were excluded. RESULTS: Sixteen studies were included in this review, which reported treatment outcomes for 191 patients. Most included studies were case series of poor quality. All patients showed sternal healing and 98% reported pain relief. Treatment complications occurred in 2% of patients. CONCLUSIONS: Treatment of traumatic sternal fractures and dislocations is an underexposed topic. Although all patients in this review displayed sternal healing, results should be interpreted with caution since most included studies were of poor quality