[Orthopedic surgery with limited resources after mass disasters and during armed conflicts : First international guidelines for the management of limb injuries and the experience of Doctors Without Borders]. / Unfallchirurgie mit eingeschränkten Ressourcen nach Katastrophen und während bewaffneter Konflikte : Erste internationale Leitlinien zur Versorgung von Extremitätenverletzungen und die Erfahrung von "Ärzte ohne Grenzen".

Disasters and armed conflicts are often the unfortunate basis for aid projects run by Doctors Without Borders/Médecins Sans Frontières (MSF). The nature of war and disasters means that surgery is an integral part of this medical emergency aid. In these situations, resources are usually limited. As a result, surgical work in these contexts differs significantly from the daily routine of a surgeon working in a highly resourced hospital. The principles of surgery do not change but surgeons must adapt their tactical approach to the changed context otherwise there is a high risk of failing to improve the health of patients and potentially jeopardizing their prospects for recovery. Every experienced war surgeon has learned new skills the hard way. The Field Guide to Manage Limb Injury in Disaster and Conflict has been written to help new surgeons who may face the challenges of disaster and war surgery and to avoid unnecessary suffering for patients ( https://icrc.aoeducation.org ). Under the guidance of the International Committee of the Red Cross (ICRC), with participation of the World Health Organization (WHO), financed by the AO Foundation, and featuring the experiences of experts from different organizations (amongst them MSF), the book details techniques and guidelines for surgery in low resource settings. The following article provides a short summary of some of the surgical challenges when working with limited resources and reflects on a few specific recommendations for so-called war surgery.

A Consensus Framework for the Humanitarian Surgical Response to Armed Conflict in 21st Century Warfare.

Importance: Armed conflict in the 21st century poses new challenges to a humanitarian surgical response, including changing security requirements, access to patients, and communities in need, limited deployable surgical assets, resource constraints, and the requirement to address both traumatic injuries as well as emergency surgical needs of the population. At the same time, recent improvements in trauma care and systems have reduced injury-related mortality. This combination of new challenges and medical capabilities warrants reconsideration of long-standing humanitarian surgery protocols. Objective: To describe a consensus framework for surgical care designed to respond to this emerging need. Design, Setting, and Participants: An international group of 35 representatives from humanitarian agencies, US military, and academic trauma programs was invited to the Stanford Humanitarian Surgical Response in Conflict Working Group to engage in a structured process to review extant trauma protocols and make recommendations for revision. Main Outcomes and Measures: The working group's method adapted core elements of a modified Delphi process combined with consensus development conference from August 3 to August 5, 2018. Results: Lessons from civilian and military trauma systems as well as recent battlefield experiences in humanitarian settings were integrated into a tiered continuum of response from point of injury through rehabilitation. The framework addresses the security and medical requirements as well as ethical and legal principles that guide humanitarian action. The consensus framework includes trained, lay first responders; far-forward resuscitation/stabilization centers; rapid damage control surgical access; and definitive care facilities. The system also includes nontrauma surgical care, injury prevention, quality improvement, data collection, and predeployment training requirements. Conclusions and Relevance: Evidence suggests that modern trauma systems save lives. However, the requirements of providing this standard of care in insecure conflict settings places new burdens on humanitarian systems that must provide both emergency and trauma surgical care. This consensus framework integrates advances in trauma care and surgical systems in response to a changing security environment. It is possible to reduce disparities and improve the standard of care in these settings.

Deletion of the G2A receptor fails to attenuate experimental autoimmune encephalomyelitis.

Lysophosphatidylcholine (LPC) is a chemotactic lysolipid produced during inflammation by the hydrolytic action of phospholipase A(2) enzymes. LPC stimulates chemotaxis of T cells in vitro through activation of the G protein-coupled receptor, G2A. This has led to the proposition that G2A contributes to the recruitment of T cells to sites of inflammation and thus promotes chronic inflammatory autoimmune diseases associated with the generation and subsequent tissue infiltration of auto-antigen-specific effector T cells. However, one study suggests that G2A may negatively regulate T cell proliferative responses to antigen receptor engagement and thereby attenuates autoimmunity by reducing the generation of autoreactive T cells. To address the relative contribution of these G2A-mediated effects to the pathophysiology of T cell-mediated autoimmune disease, we examined the impact of G2A inactivation on the onset and severity of murine experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Wild type (G2A(+/+)) and G2A-deficient (G2A(-/-)) C57BL/6J mice exhibited a similar incidence and onset of disease following immunization with MOG(35-55) peptide. Disease severity was only moderately reduced in G2A(-/-) mice. Similar numbers of MOG(35-55) specific T cells were generated in secondary lymphoid organs of MOG(35-55)-immunized G2A(+/+) and G2A(-/-) mice. Comparable numbers of T cells were detected in spinal cords of G2A(+/+) and G2A(-/-) mice. We conclude that the proposed anti-proliferative and chemotactic functions of G2A are not manifested in vivo and therefore therapeutic targeting of G2A is unlikely to be beneficial in the treatment of MS.

Complement in BuB/BnJ mice revisited: serum C3 levels and complement opsonic activity are not elevated.

With the exception of a few strains such as BuB/BnJ, complement activity in most inbred strains of mice is remarkably similar. The BuB/BnJ strain reportedly has high levels of complement activity and elevated serum levels of C3 and other complement proteins. However, we observed that BuB/BnJ mice have serum C3 levels comparable to those seen in C57BL/6, Balb/c and several other strains of inbred mice. More importantly, using bacteria as a substrate for activation and deposition of complement as a direct biological assay to assess serum complement opsonic activity, we found that BuB/BnJ mice do not have elevated complement activity compared to other inbred mouse strains. In contrast hemolytic assays indicate BuB/BnJ sera to be most active. These results indicate that accepted views regarding mouse serum complement activity need to be re-examined.

PSGL-1 is not required for development of experimental autoimmune encephalomyelitis.

Adhesion molecules are essential mediators for lymphocyte trafficking through the blood-brain barrier into the CNS in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the role of the selectin molecules and their ligand, P-selectin glycoprotein-1 (PSGL-1) which mediates tethering and rolling of the leukocytes in demyelinating disease remains controversial. This study demonstrates that mice deficient in PSGL-1 are not significantly different in the development and progression of EAE compared to wild type controls. Our observations suggest that PSGL-1-selectin interactions are redundant and not required for the development of EAE. Our data also indicate that other adhesion molecules are necessary for the initial rolling events leading to leukocyte infiltration into the CNS during EAE.

Impaired CD14-dependent and independent response of polymorphonuclear leukocytes in preterm infants.

UNLABELLED: Preterm newborn infants are especially susceptible to Gram-negative sepsis that is associated with a lethality of up to 40%. AIMS: We tested whether polymorphonuclear leukocytes (PMN) from preterm infants exhibit an impaired antibacterial response upon stimulation with lipopolysaccharide (LPS) from Escherichia coli when compared to full term newborns or adults. METHODS: We studied the effect of LPS on the expression of the surface proteins CD11b and CD14 and the secretion of elastase by PMN from preterm infants, term infants and adults ex vivo. RESULTS: We found a significantly reduced antibacterial activity of PMN from preterm infants upon stimulation with LPS as indicated by low surface expression of the adhesion molecule CD11b and the reduced secretion of PMN elastase. LPS-induced CD11b expression was dependent on binding of LPS to the surface protein CD14 as CD14 antibodies inhibited LPS dependent CD11b upregulation. Furthermore CD14 expression was lower on PMN from preterm infants than from adults. In addition, CD14 independent upregulation of CD11b in response to tumor necrosis factor (TNF-alpha), N-formyl peptides (FMLP) and phorbol ester (PMA) was impaired. CONCLUSION: PMN from preterm infants are distinctly hyporesponsive to LPS, which may explain the predisposition of these children to invasive disease due to gramnegative bacteria.