Impaired activation of Notch-1 signaling hinders repair processes of bronchial epithelial cells exposed to cigarette smoke.

Notch-1 intervenes in the reparative processes of mucosa by controlling cell proliferation, differentiation and stem cell maintenance. Cigarette smoke alters airway epithelial homeostasis. The present study explored whether: Smokers showed altered Notch-1 expression; and whether in bronchial epithelial cells (16HBE): a) cigarette smoke extracts (CSE) altered the expression of Notch-1, of its ligand Jagged-1 (Jag-1) and the nuclear translocation of Notch-1; b) Notch-1 signaling activation as well as CSE modified Ki67, PCNA, p21, IL-33 expression, cell proliferation and repair processes. Notch-1 expression was assessed in the epithelium from large airway surgical samples from non-smoker and smoker subjects by immunohistochemistry.16HBE were cultured with/without CSE and Jag-1. A Notch-1 inhibitor (DAPT) was used as control. The expression of Notch-1, Jag-1, Ki67, PCNA, p21, IL-33 and cell proliferation (by CFSE) were all assessed by flow cytometry. Notch-1 nuclear expression was evaluated by immunofluorescence and western blot analysis. Repair processes were assessed by wound assay. Smokers had cytoplasmic but not nuclear Notch-1 expression. Although CSE increased Notch-1 expression, it counteracted Notch-1 signaling activation since it reduced Jag-1 expression and Notch-1 nuclear translocation. Notch-1 signaling activation by Jag-1 increased Ki67, PCNA and repair processes but reduced intracellular IL-33 and p21 expression without affecting cell proliferation. DAPT counteracted the effects of Notch-1 activation on PCNA and IL-33. CSE increased Ki67, PCNA, p21 and IL-33 expression but reduced cell proliferation and repair processes. In conclusion, cigarette smoke exposure, limiting Notch-1 signaling activation and hindering repair processes, amplifies injury processes in bronchial epithelial cells.

Tibia chronic osteomyelitis complicated by fracture in children: relevance of pedicle flaps in low resources setting.

The authors report three pediatric cases presenting with tibial osteomyelitis complicated by fracture for which flap coverage was performed in a low-resource setting. Pedicled flap transfers are rarely used for the treatment of chronic osteomyelitis in developing countries. However, these procedures are accessible to any orthopedic surgeon and enable satisfactory treatment of bone infection, reduce the duration of care, and enhance the reliability of bone grafts.

Surgical Management of Mycetoma in Chad: Experience from the French Forward Surgical Team Deployed in N'Djamena.

Mycetoma is a disease that occurs in the mycetoma belt, between latitudes 15̊ south and 30̊ north. It affects disadvantaged regions with limited access to medical and health facilities. Its general principles of care have changed little and are poorly known. We analyzed the management of mycetoma in Chad by French military surgeons deployed within the Epervier and Barkhane operations. This retrospective descriptive study was conducted among the cohort of Chadian patients managed by the N'Djamena forward surgical team from 2007 to 2018 as part of the medical support to the population. It includes 132 patients who had surgery for mycetoma. Surgical parameters of primary treatment and revisions procedures were analyzed. Postoperative follow-up was at least six months. Amputation was performed in 87/132 (66%) patients. Overall 11 (8.3%) required revision surgery, including 7 (5%) with eumycetoma recurrence. All recurrences occurred in the lower limb. The recurrence rate after excision was 10.2% (5/49) versus 2.3% after amputation (2/87). In the absence of effective and accessible medical treatment, surgery remains the basic treatment for mycetoma. Salvage surgery with local excision should always be considered. However, amputation is the only reliable treatment in cases with late presentation. It should not be proposed too early as limb function is preserved for a long time.

Type III open tibia fractures in low-resources setting. Part 3: achievement of bone union and treatment of segmental bone defects.

After presentations of the principles of limb salvage and soft-tissue coverage for Gustilo III open tibia fractures, this third part is dedicated to management of tibial non-unions in low-resource settings. Inter-tibiofibular grafting and the induced membrane technique are preferred because they make it possible to deal with almost all situations. Key technical points of these methods are presented, followed by treatment guidelines based on Catagni's classification and bone defect size.

Type III open tibia fractures in low-resources setting. Part 1: strategy and principles of limb salvage.

In developing countries, road traffic accidents result in many cases of open trauma, especially fractures, with the tibia area at particular risk in motorcycle crashes. Despite a high prevalence of severe leg trauma with multi-tissue injuries, few studies have focused on the challenge of their reconstruction in these limited-resource settings. The first part of this review presents the surgical strategy. Limitations and principles of initial limb salvage are detailed. Orthopedic procedures for early damage control, based on debridement and temporary bone stabilization, are often required. The priority is to shorten the time to initial surgical management to avoid infection, which jeopardizes reconstruction.

Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study.

BACKGROUND: In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. METHODS: 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. KEY RESULTS: Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). CONCLUSIONS & INFERENCES: The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity.

Myeloperoxidase-positive cell infiltration of normal colorectal mucosa is related to body fatness and is predictive of adenoma occurrence.

Body fatness is a risk factor for colorectal cancer, and promotes an inflammatory environment. Indeed, inflammation in normal colorectal mucosa may be a factor linking body fatness to colorectal carcinogenesis. In this study, we evaluated myeloperoxidase (MPO)-positive cells infiltration of normal colorectal mucosa as a marker of cancer-promoting inflammation in overweight and obese subjects. One hundred and three subjects with normal colonoscopy entered the study. Waist circumference (WC) and body mass index (BMI) were measured, and MPO-positive cells on histological sections of biopsies of normal colorectal mucosa were counted under a light microscope. The occurrence of adenomas was then evaluated on follow-up colonoscopies. Mean MPO-positive cell count (±s.e.m.) was higher in subject with a WC equal or above the obesity cutoff values according to gender (2.63±0.20 vs 2.06±0.18, P=0.03), and in subjects with BMI equal or above 25 kg m-2 (2.54±0.18 vs 1.97±0.20, P=0.03). A Cox proportional hazard model showed that mean MPO-positive cell count in normal colorectal mucosa was the only factor independently related to occurrence of adenomas in follow-up colonoscopies. Though preliminary, these results show that MPO-positive cell infiltration in normal colorectal mucosa is related with body fatness, as evaluated by WC and BMI, and it may be considered a useful and simple marker to estimate adenoma occurrence risk.

[Clubfoot treatment: Implementation of the Ponseti method in emerging countries]. / Traitement du pied bot varus équin idiopathique Mise en place de la méthode Ponseti dans un pays émergent.

Idiopathic clubfoot is one of the most frequent congenital deformities throughout the world. The Ponseti method is the gold standard for its treatment. This simple, low-cost method is very effective and very appropriate for countries with resource-limited or otherwise precarious health services. It is based on correction of the deformity by successive castings associated with a percutaneous Achilles tenotomy and then foot abduction bracing to maintain the correction. The Ponseti method is now well implemented in most emerging countries, largely due to internet development, but some barriers still limit its diffusion. This study aims to determine the principal barriers, to suggest some improvements, and to stress the essential points of its effective utilization by non-physicians.

The French Advanced Course for Deployment Surgery (ACDS) called Cours Avancé de Chirurgie en Mission Extérieure (CACHIRMEX): history of its development and future prospects.

INTRODUCTION: The composition of a French Forward Surgical Team (FST) has remained constant since its creation in the early 1950s: 12 personnel, including a general and an orthopaedic surgeon. The training of military surgeons, however, has had to evolve to adapt to the growing complexities of modern warfare injuries in the context of increasing subspecialisation within surgery. The Advanced Course for Deployment Surgery (ACDS)-called Cours Avancé de Chirurgie en Mission Extérieure (CACHIRMEX)-has been designed to extend, reinforce and adapt the surgical skill set of the FST that will be deployed. METHODS: Created in 2007 by the French Military Health Service Academy (Ecole du Val-de-Grâce), this annual course is composed of five modules. The surgical knowledge and skills necessary to manage complex military trauma and give medical support to populations during deployment are provided through a combination of didactic lectures, deployment experience reports and hands-on workshops. RESULTS: The course is now a compulsory component of initial surgical training for junior military surgeons and part of the Continuous Medical Education programme for senior military surgeons. From 2012, the standardised content of the ACDS paved the way for the development of two more team-training courses: the FST and the Special Operation Surgical Team training. The content of this French military original war surgery course is described, emphasising its practical implications and future prospects. CONCLUSION: The military surgical training needs to be regularly assessed to deliver the best quality of care in an context of evolving modern warfare casualties.

[Indications and surgical technique of subtotal hysterectomy for a general surgeon practicing in austere environment with limited resources]. / Indications et technique chirurgicale de l'hystérectomie subtotale pour un chirurgien généraliste en situation isolée avec des ressources limitées.

Uterine fibromyomata in Africa, which represents the most frequent benign uterine disease, is a real public health. This pathology is frequent and most of times discovered at a late stage where the volume of the uterus is responsible for invalidating symptoms that impairs patients' quality of life. Subtotal hysterectomy, which preserves the cervix, is faster than total hysterectomy and reduces intraoperative (duration of operation, blood loss) and postoperative morbidity (urinary infection, vaginal cicatrization). Subtotal hysterectomy is adapted to countries with limited resources. Its realization requires the preoperative assessment of normal cervix and a regular post-operative follow-up of the cervix left in place.

Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem-Resistant Gram-Negative Bacteria.

Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.

War-related extremity injuries in children: 89 cases managed in a combat support hospital in Afghanistan.

BACKGROUND: Meeting paediatric needs is among the priorities of western healthcare providers working in Afghanistan. HYPOTHESIS: Insufficient information is available on paediatric wartime injuries to the extremities. Our objective here was to describe these injuries and their management on the field. MATERIALS AND METHODS: We retrospectively reviewed consecutive cases of injuries to the extremities in children (< 16 years of age) due to weapons and managed at the Kabul International Airport (KaIA) Combat Support Hospital between June 2009 and April 2013. We identified 89 patients with a mean age of 10.2 ± 3.5 years and a total of 137 elemental lesions. RESULTS: Explosive devices accounted for most injuries (78.6%) and carried a significantly higher risk of multiple lesions. There were 54 bone lesions (traumatic amputations and fractures) and 83 soft-tissue lesions. The amputation rate was 18%. Presence of bone lesions was associated with a higher risk of injury to blood vessels and nerves. Of the 89 patients, four (4.5%) died and eight (9%) were transferred elsewhere. Of the 77 remaining patients, at last follow-up (median, one month; range, 0.1-16 months), 73 (95%) had achieved a full recovery (healed wound and/or fracture) or were recovering with no expectation that further surgery would be needed. DISCUSSION: Despite the absence of paediatric surgeons, the combat support hospital provided appropriate care at the limb salvage and reconstruction phases. The highly specialised treatments needed to manage sequelae were very rarely provided. These treatments probably deserve to be developed in combat support hospitals.

Management of neglected open extremity fractures in low-resource settings: Experience of the French Army Medical Service in Chad.

INTRODUCTION: The purpose of this study was to report the experience of the French Army Medical Service in the management of neglected open extremity fractures and related-complications in Chad. HYPOTHESIS: Delayed treatment of open extremity fractures is possible in a low-resource setting. METHODS: An observational prospective study was performed in a French Forward Surgical Team deployed in N'Djamena for six months. RESULTS: Twenty-seven patients, 24 men and three women, mean age 30 years old with an open fracture that was managed more than 24 hours after it occurred were included. The mean treatment delay was 83 days. Fractures were located in the tibia in 20 cases. There were 15 non-infected and twelve infected fractures. The number of cases of debridement, flap coverage, and the overall number of procedures were higher in the group with infection, but the difference was not significant. Treatment of infected fractures was complicated by six early recurrent infections, while there were no complications in the group without infection. The mean follow-up was 4.4 months. Infection was controlled in eleven cases, however evaluation of fracture healing was limited because of the short follow-up in the group with infection. Functional outcome of the lower extremities was often complicated by knee stiffness. DISCUSSION: Delayed management of open fractures depends on the available resources. In low-resource settings, the goals of surgery should be modest. Treatment of non-infected injuries and osteomyelitis is possible. On the other hand, treatment of infected fractures and septic nonunions should be undertaken with caution if all the necessary aspects of treatment, in particular extended antibiotic treatment and sequential procedures are not possible. LEVEL OF EVIDENCE: level IV.

Wartime upper extremity injuries: experience from the Kabul International Airport combat support hospital.

Few epidemiologic studies have been published about the surgical management of wartime upper extremity injuries (UEIs). The purpose of the present report was to analyze upper extremity combat-related injuries (CRIs) and non-combat related injuries (NCRIs) treated in the Kabul International Airport Combat Support Hospital. A retrospective study was conducted using the French surgical database OpEX (French military health service) from June 2009 to January 2013. During this period, 491 patients with a mean age of 28.7 ± 13 years were operated on because of an UEI. Among them, 244 (49.7%) sustained CRIs and 247 (50.3%) sustained NCRIs. A total number of 558 UEIs were analyzed. Multiple UEIs and associated injuries were significantly more common in the CRIs group. Debridement was the most common procedure in both groups. External fixator application, delayed primary closure and flap coverage were predominant in the CRIs group, as well as internal fracture fixation and tendon repair in the NCRIs group. The overall number of surgical episodes was significantly higher in the CRIs group. Due to the high frequency of UEIs in the theatres of operations, deployed orthopedic surgeons should be trained in basic hand surgery. Although the principles of CRIs treatment are well established, management of hand NCRIs remains controversial in this setting.

Surgical management of combat-related upper extremity injuries.

This review presents the current surgical management of combat-related upper extremity injuries during the acute phase. The strategy consists of saving the life, saving the limb and retaining function. Surgical tactics are based on damage control orthopaedics techniques of haemorrhage control, wound debridement, and temporary bone stabilization prior to evacuation out of the combat zone. Features of the definitive management of local casualties in battlefield medical facilities are also discussed. In this situation, reconstructive procedures have to take into account the limited resources and operational constraints.

Management of the complications of traditional bone setting for upper extremity fractures: the experiences of a French Forward Surgical Team in Chad.

The practice of traditional bone setting (TBS) in sub-Saharan Africa often leads to severe complications after upper extremity fracture. The purpose of this study was to evaluate the management of these complications by a French Forward Surgical Team deployed in Chad. An observational, prospective study was conducted over a six-month period between 2010 and 2011. During this period 28 patients were included. There were 20 males and 8 females with a mean age of 30.6 years (range 5-65 years). Thirteen patients (47%) had mal-union of their fracture, nine had non-union (32%), three children (10.5%) presented gangrene and three patients (10.5%) suffered from other complications. Fifteen (54%) patients did not undergo a corrective procedure either because it was not indicated or because they declined. Only 13 (46%) patients were operated on. Twelve of these patients were reviewed with a mean follow-up of 2.4 months. All of them were satisfied with conventional treatment. The infection seemed to be under control in every septic patient. Bone union could not be evaluated in most patients because of the short follow-up. Management of TBS complications is always challenging, even in a deployed Western medical treatment facility. Surgical expectations should be low because of the severity of the sequelae and the uncertainty of patient follow-up. Prevention remains the best treatment.

[Management of bilateral hand amputations in low-resources setting: the Krukenberg procedure is still indicated]. / Prise en charge des amputations bilatérales des mains en situation précaire : l'intervention de Krukenberg reste d'actualité.

Double hand amputation leads to complete loss of prehensive function and touch sense. Patients become totally dependent on others for survival. In developing countries, where sophisticated myoelectric prosthesis are not available, the Krukenberg procedure gives to these patients elementary self-sufficiency for daily-life. This procedure can be performed in low-resources setting and requires minimal rehabilitation. However, patient selection and preparation are critical because of an unattractive aesthetic aspect which limits this operation use in occidental countries.

[Comorbid puffy hand syndrome and factitious disorders: an unusual association with poor prognosis]. / Syndrome des grosses mains et troubles factices: une association exceptionnelle de mauvais pronostic.

The authors report an original clinical presentation of factitious disorders of the upper extremity in an ex-drug-addict patient with puffy hand syndrome. Chronic self-inflicted ulcerations appeared with sequential manner. The patient confessed deliberate self-harm and transfer of anxiety on his hands, the aspect of which had become intolerable. Association of puffy hand syndrome with comorbid psychosis and major depression explained immediate recurrence of ulcerations despite fitted medication and long-term psychotherapy.