The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties.

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.

[Caregiving in an exceptional environment: the military operating theater nurse in a tropical zone]. / Soignant en milieu d'exception : l'infirmier de bloc opératoire militaire en zone tropicale.

The profession of operating theater nurse in the French Armed Forces Medical Corps is often little-known. Called upon to serve in mainland France, but also deployed on overseas operations, they provide medical and surgical support to the French armed forces. Personal qualities - human, physical and technical - are essential to adapt to the environmental constraints of this isolated post.

[War wounds and ballistics]. / Plaies de guerre et balistique.

Ballistic wounds, which historically concerned military populations, now also affect civilian practice. Terrorist attacks, urban violence and certain accidents have brought them into the daily routine of some French hospitals. Their frequency fully justifies the need for every health-care professional to be aware of the major issues involved in their management. In this section, we will describe the various penetrating ballistic wounds and their specific features. We will also rectify certain preconceived ideas that should not be peddled by healthcare professionals, in order to maintain a high standard of care.

[War wounds in the operating theatre: Damage Control Surgery]. / Plaies de guerre au bloc opératoire : Damage ControlSurgery.

In the course of conflicts, the management of severe trauma patients in the operating room has led to the development of surgical and resuscitation techniques that ensure the survival of as many patients as possible. These techniques are based on the principles of Damage Control (DC) by a single, trained team. In this article, we look at the fundamentals of DC, followed by its application in each surgical field. The question of team training is at the heart of this approach.

Evaluation of follow-up and long-term outcomes of gunshot and stab wounds in a French civilian population.

PURPOSE: The data concerning long-term follow-up and outcomes of penetrating trauma are poorly detailed in the literature. The main objective of our study was to analyze the hospital and extra-hospital follow-up of penetrating trauma victims and to evaluate the late complications and long-term consequences of these traumas. METHODS: This work was a retrospective longitudinal monocentric observational study conducted at Laveran Military Hospital, from January 2007 to January 2017. All patients hospitalized for gunshot wound or stab wound management during this period were identified via a retrospective systematic query in the hospital information system using the ICD-10 codes. Epidemiological data, traumatism characteristics, hospital management, follow-up and traumatism consequences (i.e., persistent disability) were analyzed. To improve evaluation of traumatism long-term consequences, extra-hospital follow-up data from general physicians (GP) were collected by phone call. During this interview, 9 closed questions were asked to the GP. The survey evaluated: the date of the last consultation related to injury with the GP, the specific follow-up carried out by the GP, traumatism consequences, and recurrence of traumatism. Descriptive, univariate and multivariate with regression analysis were used for statistical analysis. RESULTS: A total number of 165 patients were included. Median (Q1, Q3) of hospital follow-up was 28 (4, 66) days. One hundred one patients (61.2%) went to their one-month consultation at hospital. GP follow-up was achieved for 76 patients (55.2%). Median (Q1, Q3) of GP follow-up was 47 (21, 75) months. Twenty-four patients (14.5%) have been totally lost to follow up. The overall follow-up identified 54 patients (32.7%) with long-term consequences, 20 being psychiatric disorders and 30 organic injuries. Organic consequences were mainly peripheral nerve damages (n = 20; 12.1%). Most of the psychiatric consequences were diagnosed during GP follow-up (n = 14; 70%). Seventeen cases (10.3%) of recurrence were found and late mortality occurred in 4 patients (2.4%). High injury severity score, older age and gunshot wound were significantly linked to long-term consequences. Data collection and analysis were carried out in accordance with MR004 reference methodology. CONCLUSION: This study showed a high rate of long-term consequences among patients managed for penetrating injury. If all organic lesions are diagnosed during hospital follow-up and jointly managed by hospital and extra-hospital physicians, most socio-psychiatric consequences were detected and followed by extra-hospital workers. However, for half of the patients, the extra-hospital follow-up could not be assessed. Thus, these consequences are very probably underestimated. It appears imperative to strengthen the compliance and adherence of these patients to the care network. Awareness and involvement of medical, paramedical teams and GP role seems essential to screen and manage these consequences.

Pulmonary Artery Bullet Embolism following Cardiac Gunshot Wound.

Penetrating chest trauma is common but few need surgical treatment (10-20%). The mortality of gunshot wounds of the heart is 45%, among the wounded arriving at the hospital. The suspicion of wound heart with an inlet in the heart area (limited by costal awnings down, clavicles top, and mid-clavicular line outside) and pericardial effusion remains a surgical indication. Gunshot wounds of the heart with migration of the projectile in the pulmonary artery are rare. Migration of projectile into the pulmonary artery is described most often with lesions of peripheral veins without concomitant cardiac involvement. The indication of projectile extraction is not clearly defined in the literature. Conservative management of selected cases of pulmonary artery bullet emboli may be warranted in light of the risks of extraction.

Laparoscopic partial splenectomy: a technical tip.

BACKGROUND: Increased awareness of asplenia-related life-threatening complications has led to development of parenchyma sparing splenic resections. The aim of the study was to report a new technique of laparoscopic partial splenectomy, which helps minimize perioperative bleeding risks. METHODS: From November 2004 to October 2012, 12 patients underwent partial laparoscopic resection of the spleen. There were six men (50 %), and median age was 30 years (19-62). Transection of the splenic parenchyma was performed along a line situated 1 cm within the ischemic demarcation, which appeared after ligation of the sectorial vascular pedicles feeding the tumor. Antibiotic prophylaxis and preventive antibacterial immunization were prescribed systematically according to generally accepted guidelines. RESULTS: Mortality was nil, and operative complications occurred in 2 (17 %) patients. Conversion to open partial splenectomy and to laparoscopic total splenectomy was performed in one patient (8.3 %) each. Median operative time was 120 min (range 80-180 min). Median blood loss was 90 ml (range 10-450 ml), and transfusion was not required. Median tumor size was 7 cm (4-12 cm). The median in hospital stay was 5 days (4-7 days). Patients did not comply with long-term (>2 years) immunization and antibioprophylaxis rules. After a median follow-up of 5 years (18 months-9 years), no case of overwhelming post-splenectomy infections occurred. CONCLUSION: Laparoscopic partial splenectomy can be safely performed in patients with splenic tumors. Parenchyma transection 1 cm inside the ischemic demarcation line is a key technical point to minimize blood loss.

Obesity and Overweight: First Comprehensive Overview in the French Armed Forces.

INTRODUCTION: The global rise in obesity is well-established, with significant health implications. This study aims to comprehensively assess overweight and obesity prevalence within the French Armed Forces. MATERIALS AND METHODS: Using data from the Unique Medical-Military Software (UMMS) in 2018, a cross-sectional study was conducted on active French Military personnel aged 18 and above, who underwent periodic medical examinations (PME) in 2017. Body Mass Index (BMI) served as the main criterion for overweight and obesity classification. A representative sample was obtained through random sampling. RESULTS: The sample included 17,082 individuals, revealing an average age of 33.5 years, with 36.1% classified as overweight and 9.6% as obese. The mean BMI of women was significantly lower than that of men (23.9 vs 25.3 kg/m2-P < .001). Results indicated that 22.4% of women vs 38.5% of men were overweight (P < .001). For obesity, the difference was not significant (8.8% of women vs 9.8% of men-P = .138). BMI increased with age, and non-commissioned officers (NCOs) showed the highest prevalence of obesity. Gendarmes exhibited the highest BMI and overweight rates (50.1%) among military branches. CONCLUSION: While obesity is less prevalent in the French Armed Forces compared to the general population, the study emphasizes the equivalent prevalence of overweight. We confirm here that the global epidemic of obesity and overweight affects all armed forces. France seems less affected than other Western armies. Targeting specific groups, such as NCOs and the national gendarmerie, is crucial for prevention.

Training for a mass casualty incident: Conception, development, and implementation of a crew-resource management course for forward surgical teams.

BACKGROUND: Since 2021, the predeployment training of French FSTs has included a simulation-based curriculum consisting of organizational and human factors. The purpose of this article is to describe the development of a crew-resource management (CRM) training course dedicated for the forward surgical teams (FSTs) of the French Military Health Service. METHODS: The approach was based on three steps: (1) establishment of a conceptual framework of FSTs deployment; (2) development of an aircrew-like CRM training combining lectures, laboratory exercises, and situational training exercises to consider four fundamental "nontechnical" (cognitive and social) skills for effective and safe combat casualty care: (a) leadership, (b) decision-making, (c) coordination, and (d) situational awareness; (3) Implementation of teamwork evaluation tools. RESULTS: A multidisciplinary team designed a conceptual framework for FST preparedness, 24 French FSTs completed a high-quality training that takes into account both technical and nontechnical skills to maintain quality of combat care during mass-casualty incidents, FSTs' CRM skills were assessed using an audio/video recording of a simulated mass-casualty incident.

In situ repair of a primary Brucella-infected abdominal aortic aneurysm: long-term follow-up.

Infected aortic aneurysms represent 0.85 to 1.3% of aortic aneurysms. Most often, the implicated bacteria species are Salmonella sp., Staphylococcus sp. and Streptococcus sp. Brucella-related infected aortic aneurysms are very rare. Most often, they result from endocarditis or from a local septic focus. Combined treatment by antibiotics and surgery is the standard for infectious aneurysms. In the absence of formal factual data, the surgical treatment is still discussed in the literature, especially since endovascular treatments have been in full expansion. We are reporting the case of a female patient presenting with a Brucella-related infra-renal abdominal aortic aneurysm, without primitive infectious source (area) or identified endocarditis. Surgical treatment with in situ prosthetic replacement and omentoplasty in association with adapted antibiotics allowed a favorable outcome with an excellent result after an 8-year follow up.

Toward A Serious Game to Help Future Military Doctors Face Mass Casualty Incidents.

INTRODUCTION: To prepare military doctors to face mass casualty incidents (MCIs), the French Army Health Service contributed to the development of TRAUMASIMS, a serious game (SG) for training medical responders to MCIs. METHODS: French military doctors participated in a three-phase training study. The initial war trauma training was a combination of didactic lectures (Phase 1), laboratory exercises (Phase 2), and situational training exercises (STX) (Phase 3). Phase 1 lectures reviewed French Forward Combat Casualty Care (FFCCC) practices based on the acronym MARCHE (Massive bleeding, Airway, Respiration, Circulation, Head, hypothermia, Evacuation) for the detection of care priorities and implementation of life-saving interventions, triage, and medical evacuation (MEDEVAC) requests. Phase 2 was a case-control study that consisted of a traditional text-based simulation of MCIs (control group) or SG training (study group). Phase 3 was clinical: military students had to simultaneously manage five combat casualties in a prehospital setting. MCI management was evaluated using a standard 20-item scale of FFCCC benchmarks, 9-line MEDEVAC request, and time to evacuate the casualty collection point (CCP). Emotional responses of study participants were secondarily analyzed. RESULTS: Among the 81 postgraduate military students included, 38 took SG training, and 35 trained with a text-based simulation in Phase 2. Regarding the error rates made during STX (Phase 3), SG improved FFCCC compliance (11.9% vs. 23.4%; p < .001). Additionally, triage was more accurate in the SG group (93.4% vs. 88.0%; p = .09). SG training mainly benefited priority and routine casualties, allowing faster clearance of the CCP (p = .001). Stress evaluations did not demonstrate any effect of immersive simulation. CONCLUSION: A brief SG-based curriculum (2 hours) improved FFCCC performance and categorization of casualties in MCI STX.

Overweight and Obesity in the French Army.

INTRODUCTION: Today, the prevalence of overweight and obesity is, respectively, 49% and 17% among French adults. This research investigates their existence in the French Armed Forces, in terms of the impact on military operative response and military readiness. As no previous studies have evaluated the weight status of the whole French Armed Forces, this work assesses the situation for the first time in France. MATERIAL AND METHODS: A prospective cross-sectional study was carried out between September 2016 and April 2017. A single anonymous questionnaire gathered the sociodemographic variables and usual care medical data. The source population was active duty members serving in units reporting to the South-Eastern French Regional Military Health Department. RESULTS: Among 1,589 respondents, prevalence of overweight and obesity was, respectively, 38.7% and 10%. Mean waist circumference was 78.2 ± 9.1 cm for women and 89.1 ± 10.5 cm for men. A third of female military and one-fifth of male military had a measure bigger than the standard International Diabetes Federation. Age, sex, weekly fitness activity, and rank were significant independent predictors of body weight excess. Less than 5% of the study population reported a diagnosis of comorbidity: diabetes 2%, high blood pressure 1%, and dyslipidemia 1.5%. CONCLUSIONS: As all armies, the French Armed Forces are affected by obesity. Nevertheless, the prevalence of obesity seems lower than in other Western armies. In the French army, as in the general population, obesity is correlated with socioeconomic status and level of education. However, compared to the general French population, there is less obesity and overweight in the French Armed Forces. Moreover, overweight and obese military members have a lower cardiovascular risk than their civilian counterparts. Enlistment standards, military occupational activity, and a mandatory high level of physical fitness could explain these different proportions of overweight and obesity. This raises the question of the protective effect of regular physical activity. Is this a serious way to fight against the growing prevalence of overweight and obesity in Western countries? Indeed, this is a significant public health issue, which also affects the military's quick response force capacity and strategic capabilities. Therefore, the identification of specific demographic characteristics should be considered in developing prevention programs.

Health workers' safety during tracheostomy in COVID-19 patients: Homemade protective screen.

As an aerosol and droplets generating procedure, tracheostomy increases contamination risks for health workers in the coronavirus disease context. To preserve the health care system capacity and to limit virus cross-transmission, protecting caregivers against coronavirus infection is of critical importance. We report the use of external fixator equipment to set up a physical interface between the patient's neck and the caregiver performing a tracheostomy in COVID-19 patients. Once the metal frame set in place, it is wrapped with a single-use clear and sterile cover for surgical C-arm. This installation is simple, easy, and fast to achieve and can be carried out with inexpensive material available in every hospital. This physical interface is an additional safety measure that prevents the direct projection of secretions or droplets. It should, of course, only be considered as a complement to strict compliance with barrier precautions and personal protective equipment.

Intratumor heterogeneity of prognostic DNA-based molecular markers in adrenocortical carcinoma.

BACKGROUND: The prognosis of adrenocortical carcinoma (ACC) is heterogeneous. Genomic studies have identified ACC subgroups characterized by specific molecular alterations, including features measured at DNA level (somatic mutations, chromosome alterations, DNA methylation), which are closely associated with outcome. The aim of this study was to evaluate intratumor heterogeneity of prognostic molecular markers at the DNA level. METHODS: Two different tissue samples (primary tumor, local recurrence or metastasis) were analyzed in 26 patients who underwent surgery for primary or recurrent ACC. DNA-related biomarkers with prognostic role were investigated in frozen and paraffin-embedded samples. Somatic mutations of p53/Rb and Wnt/ß-catenin pathways were assessed using next-generation sequencing (n = 26), chromosome alteration profiles were determined using SNP arrays (n = 14) and methylation profiles were determined using four-gene bisulfite pyrosequencing (n = 12). RESULTS: Somatic mutations for ZNRF3, TP53, CTNN1B and CDKN2A were found in 7, 6, 6 and 4 patients, respectively, with intratumor heterogeneity in 8/26 patients (31%). Chromosome alteration profiles were 'Noisy' (numerous and anarchic alterations) in 8/14 and 'Chromosomal' (extended patterns of loss of heterozygosity) in 5/14 of the study samples. For these profiles, no intratumor heterogeneity was observed. Methylation profiles were hypermethylated in 5/12 and non-hypermethylated in 7/12 of the study samples. Intratumor heterogeneity of methylation profiles was observed in 2/12 patients (17%). CONCLUSIONS: Intratumor heterogeneity impacts DNA-related molecular markers. While somatic mutation can differ, prognostic DNA methylation and chromosome alteration profile seem rather stable and might be more robust for the prognostic assessment.

Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma.

IMPORTANCE: The risk stratification of adrenocortical carcinoma (ACC) based on tumor proliferation index and stage is limited. Adjuvant therapy after surgery is recommended for most patients. Pan-genomic studies have identified distinct molecular groups closely associated with outcome. OBJECTIVE: To compare the molecular classification for prognostic assessment of ACC with other known prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective biomarker analysis, ACC tumor samples from 368 patients who had undergone surgical tumor removal were collected from March 1, 2005, to September 30, 2015 (144 in the training cohort and 224 in the validation cohort) at 21 referral centers with a median follow-up of 35 months (interquartile range, 18-74 months). Data were analyzed from March 2016 to March 2018. EXPOSURES: Meta-analysis of pan-genomic studies (transcriptome, methylome, chromosome alteration, and mutational profiles) was performed on the training cohort. Targeted biomarker analysis, including targeted gene expression (BUB1B and PINK1), targeted methylation (PAX5, GSTP1, PYCARD, and PAX6), and targeted next-generation sequencing, was performed on the training and validation cohorts. MAIN OUTCOMES AND MEASURES: Disease-free survival. Cox proportional hazards regression and C indexes were used to assess the prognostic value of each model. RESULTS: Of the 368 patients (mean [SD] age, 49 [16] years), 144 were in the training cohort (100 [69.4%] female) and 224 were in the validation cohort (142 [63.4%] female). In the training cohort, pan-genomic measures classified ACC into 3 molecular groups (A1, A2, and A3-B), with 5-year survival of 9% for group A1, 45% for group A2, and 82% for group A3-B (log-rank P < .001). Molecular class was an independent prognostic factor of recurrence in stage I to III ACC after complete surgery (hazard ratio, 55.91; 95% CI, 8.55-365.40; P < .001). The combination of European Network for the Study of Adrenal Tumors (ENSAT) stage, tumor proliferation index, and molecular class provided the most discriminant prognostic model (C index, 0.88). In the validation cohort, the molecular classification, determined by targeted biomarker measures, was confirmed as an independent prognostic factor of recurrence (hazard ratio, 5.96 [95% CI, 1.81-19.58], P = .003 for the targeted classifier combining expression, methylation, and chromosome alterations; and 2.61 [95% CI, 1.31-5.19], P = .006 for the targeted classifier combining methylation, chromosome alterations, and mutational profile). The prognostic value of the molecular markers was limited for patients with stage IV ACC. CONCLUSIONS AND RELEVANCE: The findings suggest that in localized ACC, targeted classifiers may be used as independent markers of recurrence. The determination of molecular class may improve individual prognostic assessment and thus may spare unnecessary adjuvant treatment.

Influence of Age on Sleeve Gastrectomy Results.

INTRODUCTION: Sleeve gastrectomy (SG) has been a booming technique for 10 years. Bariatric surgery in patients over 50 years can be an effective solution on weight loss and comorbidities. The association with the nutritional and psychological care is essential to allow a true change of life mode. We are studying the mid-term (3-year) outcomes after SG in patients over 50 years of age. METHODS: This retrospective study analyzes patients treated between January 2011 and December 2013. The 129 patients were divided into three groups: under 35 years (n = 52), 35-50 years (n = 49), and over 50 years (n = 28). RESULTS: The excess weight loss at 3 years were 75% for the under 35 years, 82% for the 35-50 years, and 69% for the over 50 years. Follow-up compliance at 3 years was 66%, 68%, 75%, respectively. Comorbidities were improved in all three groups with no significant difference for each comorbidity. CONCLUSION: SG is an effective technique on weight and comorbidities. The results at 3 years are similar in patients over the age of 50 who seem more able to follow up and change lifestyle.

Calling Chromosome Alterations, DNA Methylation Statuses, and Mutations in Tumors by Simple Targeted Next-Generation Sequencing: A Solution for Transferring Integrated Pangenomic Studies into Routine Practice?

Pangenomic studies identified distinct molecular classes for many cancers, with major clinical applications. However, routine use requires cost-effective assays. We assessed whether targeted next-generation sequencing (NGS) could call chromosomal alterations and DNA methylation status. A training set of 77 tumors and a validation set of 449 (43 tumor types) were analyzed by targeted NGS and single-nucleotide polymorphism (SNP) arrays. Thirty-two tumors were analyzed by NGS after bisulfite conversion, and compared to methylation array or methylation-specific multiplex ligation-dependent probe amplification. Considering allelic ratios, correlation was strong between targeted NGS and SNP arrays (r = 0.88). In contrast, considering DNA copy number, for variations of one DNA copy, correlation was weaker between read counts and SNP array (r = 0.49). Thus, we generated TARGOMICs, optimized for detecting chromosome alterations by combining allelic ratios and read counts generated by targeted NGS. Sensitivity for calling normal, lost, and gained chromosomes was 89%, 72%, and 31%, respectively. Specificity was 81%, 93%, and 98%, respectively. These results were confirmed in the validation set. Finally, TARGOMICs could efficiently align and compute proportions of methylated cytosines from bisulfite-converted DNA from targeted NGS. In conclusion, beyond calling mutations, targeted NGS efficiently calls chromosome alterations and methylation status in tumors. A single run and minor design/protocol adaptations are sufficient. Optimizing targeted NGS should expand translation of genomics to clinical routine.

DNA Methylation Is an Independent Prognostic Marker of Survival in Adrenocortical Cancer.

CONTEXT: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. OBJECTIVE: The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort. DESIGN: Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). SETTING: MS-MLPA was performed in a training cohort of 50 patients with ACC to identify the best set of probes correlating with disease-free survival (DFS) and overall survival (OS). These outcomes were validated in an independent cohort from 21 ENSAT centers. PATIENTS: The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors). MAIN OUTCOME MEASURES: DFS and OS. RESULTS: In the training cohort, mean methylation of 4 genes (PAX5, GSTP1, PYCARD, PAX6) was the strongest methylation marker. In the validation cohort, methylation was a significant prognostic factor of DFS (P < 0.0001) and OS (P < 0.0001). Methylation, Ki67, and ENSAT stage were combined in multivariate models. For DFS, methylation (P = 0.0005) and stage (P < 0.0001) but not Ki67 (P = 0.19) remained highly significant. For OS, methylation (P = 0.0006), stage (P < 0.0001), and Ki67 (P = 0.024) were independent prognostic factors. CONCLUSIONS: Tumor DNA methylation emerges as an independent prognostic factor in ACC. MS-MLPA is readily compatible with clinical routine and should enhance our ability for prognostication and precision medicine.