Clinical benefit of anti-PD-(L)1 immunotherapies in advanced cancer in France: a population-based estimate from 2014 to 2021.

BACKGROUND: In France, the potential benefit of new treatments is initially evaluated by the Haute Autorité de Santé to determine reimbursement and pricing, but rarely afterwards. Although immunotherapies (ITs) have considerably improved the survival of patients, few data are available on their long-term benefit at a population-treated level. The present retrospective study aimed to assess the clinical benefit of ITs compared to the previous standards of care (SoCs) in France from 2014 to 2021. MATERIALS AND METHODS: To do this, we analyzed all ITs from the anti-programmed cell death protein 1/programmed death-ligand 1 [anti-PD-(L)1] class used in monotherapy or in association with another treatment available in early access or reimbursed in France between 2014 and 2021, regardless of indication. The number of patients initiating an IT was retrieved by year, drug and indication. Using extrapolated Kaplan-Meier curves, utility scores and the population treated, the clinical benefit was expressed as the number of deaths prevented (DP), life-years (LYs) and quality-adjusted life years (QALYs) gained compared to previous SoC. RESULTS: Across the period, five ITs were marketed in 21 indications related to eight primary tumor sites. Between 2014 and 2021, 132 924 patients initiated an IT. By December 2021, 16 173 (13 804-17 141) deaths were delayed compared to previous SoC, mainly in lung cancer. Compared to their SoC, ITs provided a gain of 37 316 (33 581-41 048) additional LYs and 27 709 (23 784-30 450) additional QALYs. Lung cancer was the driver indication with 70.6% of LYs and 68.4% of QALYs gained followed by melanoma with 18.7% and 20.4% of the gain, respectively. CONCLUSIONS: Significant gains in DP, LYs and QALYs have been observed in France following the introduction of ITs.

The role of perinatal palliative care following prenatal diagnosis of major, incurable fetal anomalies: a multicentre prospective cohort study.

OBJECTIVE: To describe prenatal decision-making processes and birth plans in pregnancies amenable to planning perinatal palliative care. DESIGN: Multicentre prospective observational study. SETTING: Nine Multidisciplinary Centres for Prenatal Diagnosis of the Paris-Ile-de-France region. POPULATION: All cases of major and incurable fetal anomaly eligible for TOP where limitation of life-sustaining treatments for the neonate was discussed in the prenatal period between 2015 and 2016. METHODS: Cases of congenital defects amenable to perinatal palliative care were prospectively included in each centre. Prenatal diagnosis, decision-making process, type of birth plan, birth characteristics, pregnancy and neonatal outcome were collected prospectively and anonymously. MAIN OUTCOME MEASURE: Final decision reached following discussions in the antenatal period. RESULTS: We identified 736 continuing pregnancies with a diagnosis of a severe fetal condition eligible for TOP. Perinatal palliative care was considered in 102/736 (13.9%) pregnancies (106 infants); discussions were multidisciplinary in 99/106 (93.4%) cases. Prenatal birth plans involved life-sustaining treatment limitation and comfort care in 73/736 (9.9%) of the pregnancies. The main reason for planning palliative care at birth was short-term inevitable death in 39 cases (53.4%). In all, 76/106 (71.7%) infants were born alive, and 18/106 (17%) infants were alive at last follow-up, including four with a perinatal palliative care birth plan. CONCLUSIONS: Only a small proportion of severe and incurable fetal disorders were potentially amenable to limitation of life-sustaining interventions. Perinatal palliative care may not be considered a universal alternative to termination of pregnancy. TWEETABLE ABSTRACT: Perinatal palliative care is planned in 10% of continuing pregnancies with a major and incurable fetal condition eligible for TOP.

Time to next treatment or death as a candidate surrogate endpoint for overall survival in advanced melanoma patients treated with immune checkpoint inhibitors: an insight from the phase III CheckMate 067 trial.

BACKGROUND: Time to next treatment or death (TNT-D) may be a patient-relevant endpoint in patients treated with immune checkpoint inhibitors. This study investigated TNT-D as a surrogate endpoint (SE) for overall survival (OS) in previously untreated advanced melanoma patients. METHODS: Patient-level data from the 60-month results of the CheckMate 067 randomised, controlled trial were used. Analyses were carried out for nivolumab monotherapy or nivolumab with ipilimumab versus ipilimumab monotherapy. The SE 1-step validation method based on a joint frailty-copula model was used where the country of enrolment was applied to define clusters. Kendall's τ and the coefficient of determination (R2trial) were estimated for respective measurements of association at the individual and cluster levels. The surrogate threshold effect, the maximum threshold hazard ratio for TNT-D that would translate into OS benefit, was estimated. A leave-one-out cross-validation analysis was carried out to evaluate model robustness. RESULTS: Fifteen clusters of data were generated from 945 patients. For both nivolumab-containing arms, the association between TNT-D and OS was deemed acceptable at the individual level (Kendall's τ > 0.60) and strong at the cluster level, with R2trial fairly close to 1, with narrow confidence intervals. The estimated surrogate threshold effects were 0.61 for nivolumab versus ipilimumab and 0.49 for nivolimub + ipilimumab versus ipilimumab. Cross-validation results showed minimum variation of the correlation measures and satisfactory predictive accuracy for the model. CONCLUSION: Results suggest that TNT-D may be a valuable SE in previously untreated advanced melanoma patients treated with immune checkpoint inhibitors. Surrogacy analyses considering multiple randomised controlled trials are warranted for confirming these findings.

Management of lung cancer patients' quality of life in clinical practice: a Delphi study.

BACKGROUND: The assessment of health-related quality of life (HRQoL) has seen exponential growth in oncology clinical trials. However, the measurement of HRQoL has yet to be optimised in routine clinical practice. This study aimed at exploring the operationalisation of HRQoL in clinical practice with the goal of reaching a consensus from a panel of physicians. MATERIALS AND METHODS: Physicians involved in the management of lung cancer patients in France were recruited to participate in a Delphi study. The study involved three rounds of iterated queries to gain consensus on management aspects of HRQoL, including timing of discussion on HRQoL, which specific domains of HRQoL should be discussed, and what was the most appropriate method of assessment. The threshold adopted for consensus was at least 70% agreement among physicians. A scientific committee reviewed results following each round of the Delphi study. RESULTS: A representative panel of 60 physicians participated in this study. Consensus was obtained for HRQoL management at all time points in the patient care pathway. Panellists agreed that HRQoL discussions should occur during routine visits and hospitalisation. The involvement of patients' relatives was also recognised as important, except when discussing side-effects and involvement of a multidisciplinary team. There was a lack of consensus on a systematic assessment for all patients at each visit and no consensus on how HRQoL should be measured in clinical practice. CONCLUSIONS: HRQoL discussions are considered an integral part in the management of lung cancer patients, and are deemed key to success in patient-physician interaction. Further research is required to harmonise how best to implement HRQoL assessment.

Crop diversity management: Sereer smallholders' response to climatic variability in Senegal.

Beyond the observation of climatic variations and their impact on livelihoods, farmers' knowledge about climate change? can help understand how rural populations respond to environmental changes and what factors should policies consider when planning rural adaptation. This study documents Sereer farmers' observations of local environmental changes in the Fatick region of Senegal and explores how the farmers use crop diversity to adapt to those changes. Their observations of environmental changes were documented through focus group discussions and semi-structured interviews. Variations in crop diversity as well as farmers' explanations for these variations were assessed through surveys in two villages (n=126 households). Sereer farmers identify four distinct periods of similar climate trends and reported how they managed crop diversity in response to the climate variations between periods. Three management responses stand out: abandonment of long-cycle varieties during drought periods, adoption of short-cycle varieties during periods with shorter rainy seasons, and reinstating of long-cycle varieties with the return of rains. Sereer farmers consider that climate variations are important reasons to modify their crop varieties, although variety selection is also affected by other socio-economic and cultural reasons. This study illustrates the contributions that local knowledge can bring to understanding the local impact of climate change on smallholder farmers. Understanding how they use crop diversity to adapt to climate variations can be the bases of climate change adaptation policies that address local needs and constraints.

Dental pulp inflammatory/immune response to a chitosan-enriched fibrin hydrogel in the pulpotomised rat incisor.

Current pulpotomy is limited in its ability to induce regeneration of the dental-pulp (DP) complex. Hydrogels are reported to be well-suited for tissue engineering and are unlikely to induce an inflammatory response that might damage the remaining tissue. The present study investigated the molecular and cellular actors in the early inflammatory/immune response and deciphered M1/M2 macrophage polarisation to a chitosan-enriched fibrin hydrogel in pulpotomised rat incisors. Both fibrin and fibrin-chitosan hydrogels induced a strong increase in interleukin-6 (IL-6) transcript in the DP when compared to the DP of untreated teeth. Gene expression of other inflammatory mediators was not significantly modified after 3 h. In the viable DP cell population, the percentage of leukocytes assessed by flow cytometry was similar to fibrin and fibrin-chitosan hydrogels after 1 d. In this leukocyte population, the proportion of granulocytes increased beneath both hydrogels whereas the antigen-presenting cell, myeloid dendritic cells, T cells and B cells decreased. The natural killer (NK) cell population was significantly decreased only in DPs from teeth treated with fibrin-chitosan hydrogel. Immunolabeling analysis of the DP/hydrogel interface showed accumulation of neutrophil granulocytes in contact with both hydrogels 1 d after treatment. The DP close to this granulocyte area contained M2 but no M1 macrophages. These data collectively demonstrated that fibrin-chitosan hydrogels induced an inflammatory/immune response similar to that of the fibrin hydrogel. The results confirmed the potential clinical use of fibrin-chitosan hydrogel as a new scaffold for vital-pulp therapies.

Antibiotic prophylaxis of infective endocarditis in patients with predisposing cardiac conditions: French cardiologists' implementation of current guidelines.

BACKGROUND: To prevent infective endocarditis (IE), with the exception of the United Kingdom, antibiotic prophylaxis (AP) is recommended in patients with predisposing cardiac conditions (PCCs) worldwide. To conclude on the relevance of this strategy, how the current guidelines are applied is a crucial point to investigate. The first aim of this study was to assess cardiologists' implementation of the current guidelines. The secondary objective was to identify specific areas where the training and knowledge of French cardiologists could be improved. METHODS: A national online survey was carried out among the 2228 cardiologist members of the French Society of Cardiology. RESULTS: The high risk PCCs for which IE AP is recommended were correctly identified by the vast majority of the respondents so that IE AP is mostly prescribed correctly in such patients. But only 12% identified all the right indications for IE AP according to 13 predefined PCCs (3 at high-risk, 6 at moderate-risk and 4 at low-risk of IE) so that some IE AP misuses are recorded, overprescription in particular. Only 47% prescribed the proper amoxicillin schedule and only 15% prescribed the appropriate clindamycin schedule in cases with penicillin allergy. CONCLUSION: This study evidenced relevant areas where the training of cardiologists could be improved such as knowledge of the risk of IE for certain PCCs and some common invasive dental procedures. Cardiologists' knowledge should be improved before any conclusion can be drawn on the relevance of this AP strategy and its influence on IE incidence.

Lipoxin A4 Attenuates the Inflammatory Response in Stem Cells of the Apical Papilla via ALX/FPR2.

Similar to the onset phase of inflammation, its resolution is a process that unfolds in a manner that is coordinated and regulated by a panel of mediators. Lipoxin A4 (LXA4) has been implicated as an anti-inflammatory, pro-resolving mediator. We hypothesized that LXA4 attenuates or prevents an inflammatory response via the immunosuppressive activity of Stem Cells of the Apical Papilla (SCAP). Here, we report for the first time in vitro that in a SCAP population, lipoxin receptor ALX/FPR2 was constitutively expressed and upregulated after stimulation with lipopolysaccharide and/or TNF-α. Moreover, LXA4 significantly enhanced proliferation, migration, and wound healing capacity of SCAP through the activation of its receptor, ALX/FPR2. Cytokine, chemokine and growth factor secretion by SCAP was inhibited in a dose dependent manner by LXA4. Finally, LXA4 enhanced immunomodulatory properties of SCAP towards Peripheral Blood Mononuclear Cells. These findings provide the first evidence that the LXA4-ALX/FPR2 axis in SCAP regulates inflammatory mediators and enhances immunomodulatory properties. Such features of SCAP may also support the role of these cells in the resolution phase of inflammation and suggest a novel molecular target for ALX/FPR2 receptor to enhance a stem cell-mediated pro-resolving pathway.

Evaluation of unenhanced post-mortem computed tomography to detect chest injuries in violent death.

PURPOSE: The aim of this study was to assess the performances of unenhanced post-mortem computed tomography (CT) to detect thoracic injuries in violent death. MATERIALS AND METHODS: Retrospectively, we conducted a review of unenhanced CT scans of 67 victims of violent deaths with thoracic injuries and compared CT findings with the results of clinical autopsy. Our gold standard was a comparison of CT scans with autopsy discussed in a monthly forensic radiology multidisciplinary team meeting (MDTM). The data were collected by organ system: heart, pericardium, aorta, lungs, pleura, bone, and diaphragm and performance indices (sensitivity, specificity, accuracy) were calculated. RESULTS: Pleural (59/67) and bone (55/67) injuries detected on CT were also found at autopsy and confirmed by the MDTM (sensitivity and specificity 100%). Seventeen out of 67 diaphragmatic lesions were visible on CT. Eighteen out of 67 were confirmed during MDTM after autopsy, yielding overall sensitivity of 94% and specificity of 98%. Forty out of 67 lung contusions were found on CT with two false positives and one false negative yielding 95% sensitivity for CT with a specificity of 96%, and accuracy of 95%. Fourteen out of 67 aortic injuries were found on CT compared to 19 confirmed during MDTM (sensitivity 74%, specificity 85%, accuracy 82%). In terms of pericardial lesions, 19/67 were found on CT and 20 on autopsy and confirmed during MDTM (sensitivity 80%, specificity 94%, accuracy 85%). Ten out of 10/67 cardiac lesions were visible on CT imaging and 15 found on autopsy and confirmed during MDTM (sensitivity 57%, specificity 94%, accuracy 81%). CONCLUSION: Unenhanced post-mortem CT performs well to detect pleural, pulmonary, bone and diaphragmatic injuries but less well to identify cardiac and aortic injuries, for which the use of indirect signs is essential.

Application of Nanomedicine to the CNS Diseases.

Drug delivery to the brain is a challenge because of the many mechanisms that protect the brain from the entry of foreign substances. Numerous molecules which could be active against brain disorders are not clinically useful due to the presence of the blood-brain barrier. Nanoparticles can be used to deliver these drugs to the brain. Encapsulation within colloidal systems can allow the passage of nontransportable drugs across this barrier by masking their physicochemical properties. It should be noted that the status of the blood-brain barrier is different depending on the brain disease. In fact, in some pathological situations such as tumors or inflammatory disorders, its permeability is increased allowing very easy translocation of carriers. This chapter gathers the promising results obtained by using nanoparticles as drug delivery systems with the aim to improve the therapy of some CNS diseases such as brain tumor, Alzheimer's disease, and stroke. The data show that several approaches can be investigated: (1) carrying drug through a permeabilized barrier, (2) crossing the barrier thanks to receptor-mediated transcytosis pathway in order to deliver drug into the brain parenchyma, and also (3) targeting and treating the endothelial cells themselves to preserve locally the brain tissue. The examples given in this chapter contribute to demonstrate that delivering drugs into the brain is one of the most promising applications of nanotechnology in clinical neuroscience.

Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.

Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-ß, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria.

Intraoperative cerebral hypoperfusion and electroencephalogram suppression resulting in neurological complications after cardiac surgery : the need for an in depth investigation.

Reports on the demographic profile of older populations estimate that, in 2050, 19 countries will have at least 10% of their population aged 80 years or more. Many high risk elderly patients undergo cardiac surgery. In addition, advanced age has been shown to be a strong predictor of adverse neurological outcome. Despite sig- nificant improvements achieved in the perioperative care of cardiac surgical patients, neurological complications remain a global health issue. Recent findings have pointed out that cerebral hypoperfusion and too deep levels of anesthesia are major sources of adverse neurological outcomes. Cerebral near-in-frared spectroscopy provides information about cerebral perfusion non-invasively, and is increasingly used. Depth of anesthesia is evaluated using monitors that are based on processed electroencephalogram. This non-systematic review focuses on the results of studies performed with each monitor separately, and the need for a combined evaluation of their utility and eventual impact on neurological outcomes. The use of a combined cerebral monitoring strategy based on the two aforementioned monitors is proposed in order to optimize cerebral outcomes.

Thermal ablation techniques: a curative treatment of bone metastases in selected patients?

INTRODUCTION: Thermal ablation techniques (radiofrequency-ablation/cryotherapy) can be indicated with a curative intent. The success rate and prognostic factors for complete treatment were analysed. MATERIAL/METHODS: The medical records of all patients who had undergone curatively intended thermal ablation of bone metastases between September 2001 and February 2012 were retrospectively analysed. The goal was to achieve complete treatment of all bone metastases in patients with oligometastatic disease (group 1) or only of bone metastases that could potentially lead to skeletal-related events in patients with a long life expectancy (group 2). We report the rate of complete treatment according to patient characteristics, primary tumour site, bone metastasis characteristics, radiofrequency ablation/cryotherapy and the treatment group (group 1/group 2). RESULTS: Eighty-nine consecutive patients had undergone curatively intended thermal ablation of 122 bone metastases. The median follow-up was 22.8 months [IQR = 12.2-44.4]. In the intent-to-treat analysis, the 1-year complete treatment rate was 67% (95%CI: 50%-76%). In the multivariate analysis the favourable prognostic factors for complete local treatment were oligometastatic status (p = 0.02), metachronous (p = 0.004) and small-sized (p = 0.001) bone metastases, without cortical bone erosion (p = 0.01) or neurological structures in the vicinity (p = 0.002). CONCLUSION: Thermal ablation should be included in the therapeutic arsenal for the cure of bone metastases. KEY POINTS: • Thermal ablation techniques are currently performed to palliate pain caused by bone metastases. • In selected patients, thermal ablation can also be indicated with a curative intent. • Oligometastatic and/or metachronous diseases are good prognostic factors for local success. • Small-size (<2 cm) bone metastases and no cortical erosion are good prognostic factors.

Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.

OBJECTIVES: To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective. METHODS: A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections. RESULTS: Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110 mg, dabigatran in sequential dosages, dabigatran 150 mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY. CONCLUSIONS: Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As formally requested by the CEESP, these results need to be verified in a French clinical setting using stroke reduction and bleeding safety observed in real-life patient cohorts using these anticoagulants.

[Impact of the decrease of nitrous oxide use on the consumption of halogenated agents]. / Impact de la diminution d'utilisation du protoxyde d'azote sur la consommation d'agents halogénés.

OBJECTIVE: Nitrous oxide (N2O) toxicity and its impact on pollution lead to restrict its use. A decrease of N2O consumption should increase the hypnotic inhaled consumption. This monocentric study estimated consumptions and costs of halogenated agents (HA) and N2O over 5 years when the N2O consumption was reduced. STUDY DESIGN: Retrospective from a computerized database. PATIENTS: Between 2006 and 2010, 34,097 procedures were studied after two meetings exposing the risks of the N2O. METHODS: At the end of anesthesia, consumptions of hypnotic agents (millilitres transmitted by the injectors and the blender) were archived in the database. The annual consumption of agents was obtained by adding the individual consumptions, then divided by the annual number of cases. The costs were given by the hospital pharmacy from invoices. RESULTS: N2O consumption per anesthesia constantly decreased during the study, from 75.1L by act to 22.7L. The sum of the annual consumptions of N2O and air did not change suggesting that total fresh gas flow remained stable. Between 2006 and 2010, the sevoflurane consumption by act increased by 25%, from 16.5 to 20.6mL, and desflurane consumption by 37%, from 46.1 to 63.1mL by patient. The costs of the administration of hypnotic agents remained stable. CONCLUSION: N2O consumption decrease had an impact on the consumption of HA. The cost reduction of the N2O was counterbalanced by the increase of halogenated vapor cost. The profit of the ecological impact of the reduction in N2O use could be quantified.

Tomodensitometric survey of the distance between thoracic and abdominal vital organs and the wall according to BMI, abdominal diameter and gender: proposition of an indicative chart for the forensic activities.

INTRODUCTION: Forensic doctors are frequently asked by magistrates when dealing principally with knife wounds, about the depth of the blade which may have penetrated the victim's body. Without the use of imaging, it is often difficult to respond to this question, even in an approximate way. Knowledge of the various distances between organs and the skin wall would allow an assessment to be made of the minimum blade length required to obtain the injuries observed. The objective of this study is thus to determine average distances between the vital organs of the thorax and abdomen, and the skin wall, taking into account the person's body mass index (BMI). MATERIALS AND METHODS: This is a prospective single-center study, carried out over a 2-month period at University Hospital in Angers. A sample of 200 people was studied. The inclusion criteria were as follows: all patients coming to the radiology department and the emergency department for an abdominal, thoracic or thoraco-abdominal scan with injection. The exclusion criteria included patients presenting a large lymphoma, a large abdominal or retroperitoneal tumor, a tumor in one of the organs targeted by our study and patients presenting ascites. The organs focused on were: the pericardium, pleura, aorta, liver, spleen, kidneys, abdominal aorta and femoral arteries. The shortest distance between the organ and the skin wall was noted. Median distances were calculated according to gender, abdominal diameter and BMI. RESULTS: We associated these values to propose an indicative chart which may be used by doctors in connection with their forensic activities. DISCUSSION: The problem of the depth of a wound is frequently exposed to the expert. Without a reliable tool, it is difficult to value and a personal interpretation is often done. Even if, in current days, tomodensitometry is frequently done in vivo or after death, measurement can be difficult because of the local conditions. We classified values according to the different factors of fat repartition (BMI, abdominal diameter, gender). These tables, collectively used, permit evaluation of the distance between wall and thoracic or abdominal vital organs. CONCLUSION: We suggest an indicative chart designed for forensic doctors in their professional life to help determine the minimum penetration length for a knife, which may wound a vital organ.

Fatal falls from bicycles: a case report.

Though rare occurrences, fatal falls from bicycles are generally linked to the absence of a protective helmet and/or a collision with another vehicle. The case presented here is exceptional due to its circumstances and the consequences of the accident: a fall with no obstacle at a low speed that brought about multiple traumas and the death of a cyclist wearing a protective helmet. Comparing this against a review of cyclist accidentology literature, this case is unique. The increased use of autopsy in terms of forensic accidentology is to be encouraged so as not to misunderstand the possibility of such lesion-based consequences following a simple fall from a bicycle.