Outcomes following limb salvage after combat hindfoot injury are inferior to delayed amputation at five years.

OBJECTIVES: The surgical challenge with severe hindfoot injuries is one of technical feasibility, and whether the limb can be salvaged. There is an additional question of whether these injuries should be managed with limb salvage, or whether patients would achieve a greater quality of life with a transtibial amputation. This study aims to measure functional outcomes in military patients sustaining hindfoot fractures, and identify injury features associated with poor function. METHODS: Follow-up was attempted in all United Kingdom military casualties sustaining hindfoot fractures. All respondents underwent short-form (SF)-12 scoring; those retaining their limb also completed the American Academy of Orthopaedic Surgeons Foot and Ankle (AAOS F&A) outcomes questionnaire. A multivariate regression analysis identified injury features associated with poor functional recovery. RESULTS: In 12 years of conflict, 114 patients sustained 134 fractures. Follow-up consisted of 90 fractures (90/134, 67%), at a median of five years (interquartile range (IQR) 52 to 80 months).The median Short-Form 12 physical component score (PCS) of 62 individuals retaining their limb was 45 (IQR 36 to 53), significantly lower than the median of 51 (IQR 46 to 54) in patients who underwent delayed amputation after attempted reconstruction (p = 0.0351).Regression analysis identified three variables associated with a poor F&A score: negative Bohler's angle on initial radiograph; coexisting talus and calcaneus fracture; and tibial plafond fracture in addition to a hindfoot fracture. The presence of two out of three variables was associated with a significantly lower PCS compared with amputees (medians 29, IQR 27 to 43 vs 51, IQR 46 to 54; p < 0.0001). CONCLUSIONS: At five years, patients with reconstructed hindfoot fractures have inferior outcomes to those who have delayed amputation. It is possible to identify injuries which will go on to have particularly poor outcomes.Cite this article: P. M. Bennett, T. Stevenson, I. D. Sargeant, A. Mountain, J. G. Penn-Barwell. Outcomes following limb salvage after combat hindfoot injury are inferior to delayed amputation at five years. Bone Joint Res 2018;7:131-138. DOI: 10.1302/2046-3758.72.BJR-2017-0217.R2.

Factors influencing infection in 10 years of battlefield open tibia fractures.

The aim of this study was to characterise severe open tibial shaft fractures sustained by the UK military personnel over 10 years of combat in Iraq and Afghanistan. The UK military Joint Theatre Trauma Registry was searched for all such injuries, and clinical records were reviewed for all patients. One hundred Gustilo-Anderson III tibia fractures in 89 patients were identified in the 10 year study period; the majority sustained injuries through explosive weapons (63, 68 %) with the remainder being injured from gunshot wounds. Three fractures were not followed up for 12 months and were therefore excluded. Twenty-two (23 %) of the remaining 97 tibial fractures were complicated by infection, with S. aureus being the causative agent in 13/22 infected fractures (59 %). Neither injury severity, mechanism, the use of an external fixator, the need for vascularised tissue transfer nor smoking status was associated with subsequent infection. Bone loss was significantly associated with subsequent infection (p < 0.0001, Fisher's exact test). This study presents 10 years of open tibial fractures sustained in Iraq and Afghanistan. Most infection in combat open tibia fractures is caused by familiar organisms, i.e. S. aureus. While the overall severity of a casualty's injuries was not associated with infection, the degree of bone loss from the fracture was.

The Ship's Doctor in the Royal Navy--100 years of tradition and progress.

The changing role of the Senior Service over the past century through numerous militarily heterogeneous environments and operations has necessitated an evolution in the role of the deployed Medical Officer. However: versatility, specialist knowledge, caring for a wide and varied patient population of friendly and enemy forces, and the dual role of being an officer as well as a doctor, have remained consistent. Identifiable changes in military medical officer training, the shape of the Defence Medical Services, and modern advances in treatment and communication have evolved the Ship's Doctor role from the pre-Second World War setting of a contracted Naval Medical Service, through growth, to a shrinking cadre again in a return to the contingency operations of today. Still, the role today remains attractive to a subset of doctors looking for something more from their medical practice; as the nature of conflict changes, so too will the role of the Ship's Doctor. The ongoing requirement for flexibility and versatility will remain. Medical Officers will continue to meet the need to provide high quality care to their patients and, as has always been the case, will continue to be drawn to the Service's principal appeal of an exciting world-wide role with the potential for unique experiences.

The management and outcome of open fractures of the femur sustained on the battlefield over a ten-year period.

This is a retrospective study of survivors of recent conflicts with an open fracture of the femur. We analysed the records of 48 patients (48 fractures) and assessed the outcome. The median follow up for 47 patients (98%) was 37 months (interquartile range 19 to 53); 31 (66%) achieved union; 16 (34%) had a revision procedure, two of which were transfemoral amputation (4%). The New Injury Severity Score, the method of fixation, infection and the requirement for soft-tissue cover were not associated with a poor outcome. The degree of bone loss was strongly associated with a poor outcome (p = 0.00204). A total of four patients developed an infection; two with S. aureus, one with E. coli and one with A. baumannii. This study shows that, compared with historical experience, outcomes after open fractures of the femur sustained on the battlefield are good, with no mortality and low rates of infection and late amputation. The degree of bone loss is closely associated with a poor outcome.

Medium-term outcomes following limb salvage for severe open tibia fracture are similar to trans-tibial amputation.

Extremity injuries define the surgical burden of recent conflicts. Current literature is inconclusive when assessing the merits of limb salvage over amputation. The aim of this study was to determine medium term functional outcomes in military casualties undergoing limb salvage for severe open tibia fractures, and compare them to equivalent outcomes for unilateral trans-tibial amputees. Cases of severe open diaphyseal tibia fractures sustained in combat between 2006 and 2010, as described in a previously published series, were contacted. Consenting individuals conducted a brief telephone interview and were asked to complete a SF-36 questionnaire. These results were compared to a similar cohort of 18 military patients who sustained a unilateral trans-tibial amputation between 2004 and 2010. Forty-nine patients with 57 severe open tibia fractures met the inclusion criteria. Telephone follow-up and SF-36 questionnaire data was available for 30 patients (61%). The median follow-up was 4 years (49 months, IQR 39-63). Ten of the 30 patients required revision surgery, three of which involved conversion from initial fixation to a circular frame for non- or mal-union. Twenty-two of the 30 patients (73%) recovered sufficiently to complete an age-standardised basic military fitness test. The median physical component score of SF-36 in the limb salvage group was 46 (IQR 35-54) which was similar to the trans-tibial amputation cohort (p=0.3057, Mann-Whitney). Similarly there was no difference in mental component scores between the limb salvage and amputation groups (p=0.1595, Mann-Whitney). There was no significant difference in the proportion of patients in either the amputation or limb salvage group reporting pain (p=0.1157, Fisher's exact test) or with respect to SF-36 physical pain scores (p=0.5258, Mann-Whitney). This study demonstrates that medium term outcomes for military patients are similar following trans-tibial amputation or limb salvage following combat trauma.

Mortality, survival and residual injury burden of Royal Navy and Royal Marine combat casualties sustained in 11-years of operations in Iraq and Afghanistan.

We present eleven years of prospectively-gathered data defining the full spectrum of the United Kingdom's (UK) Naval Service (Royal Navy and Royal Marines) casualties, and characterise the injury patterns, recovery and residual functional burden from the conflicts of the last decade. The UK Military Trauma Registry was searched for all Naval Service personnel injured between March 2003 and April 2013. These records were then cross-referenced with the records of the Naval Service Medical Board of Survey (NSMBOS), which evaluates injured Naval Service personnel for medical discharge, continued service in a reduced capacity or Return to Full Duty (RTD). Population at risk data was calculated from service records. There were 277 casualties in the study period: 63 (23%) of these were fatalities. Of the 214 survivors, 63 or 29% (23% of total) were medically discharged; 24 or 11% (9% of total) were placed in a reduced fitness category with medical restrictions placed on their continued military service. A total of 127 individuals (46% of the total and 59% of survivors) RTD without any restriction. The greatest number of casualties was sustained in 2007. There was a 3% casualty risk per year of operational service for Naval Service personnel. The most common reason cited by Naval Service Medical Board of Survey (NSMBOS) for medical downgrading or discharge was injury to the lower limb, with upper limb trauma the next most frequent. This study characterises the spectrum of injuries sustained by the Naval Service during recent conflicts with a very high rate of follow-up. Extremity injuries pose the biggest challenge to reconstructive and rehabilitative services striving to maximise the functional outcomes of injured service personnel.

Acute bilateral leg amputation following combat injury in UK servicemen.

BACKGROUND: This study aims to characterise the injuries and surgical management of British servicemen sustaining bilateral lower limb amputations. METHODS: The UK Military Trauma Registry was searched for all cases of primary bilateral lower limb amputation sustained between March 2004 and March 2010. Amputations were excluded if they occurred more than 7 days after injury or if they were at the ankle or more distal. RESULTS: There were 1694 UK military patients injured or killed during this six-year study period. Forty-three of these (2.8%) were casualties with bilateral lower limb amputations. All casualties were men with a mean age of 25.1 years (SD 4.3): all were injured in Afghanistan by Improvised Explosive Devices (IEDs). Six casualties were in vehicles when they were injured with the remaining 37 (80%) patrolling on foot. The mean New Injury Severity Score (NISS) was 48.2 (SD 13.2): four patients had a maximum score of 75. The mean TRISS probability of survival was 60% (SD 39.4), with 18 having a survival probability of less than 50% i.e. unexpected survivors. The most common amputation pattern was bilateral trans-femoral (TF) amputations, which was seen in 25 patients (58%). Nine patients also lost an upper limb (triple amputation): no patients survived loss of all four limbs. In retained upper limbs extensive injuries to the hands and forearms were common, including loss of digits. Six patients (14%) sustained an open pelvic fracture. Perineal/genital injury was a feature in 19 (44%) patients, ranging from unilateral orchidectomy to loss of genitalia and permanent requirement for colostomy and urostomy. The mean requirement for blood products was 66 units (SD 41.7). The maximum transfusion was 12 units of platelets, 94 packed red cells, 8 cryoprecipitate, 76 units of fresh frozen plasma and 3 units of fresh whole blood, a total of 193 units of blood products. CONCLUSIONS: Our findings detail the severe nature of these injuries together with the massive surgical and resuscitative efforts required to firstly keep patients alive and secondly reconstruct and prepare them for rehabilitation.

Unilateral lower limb loss following combat injury: medium-term outcomes in British military amputees.

This is a case series of prospectively gathered data characterising the injuries, surgical treatment and outcomes of consecutive British service personnel who underwent a unilateral lower limb amputation following combat injury. Patients with primary, unilateral loss of the lower limb sustained between March 2004 and March 2010 were identified from the United Kingdom Military Trauma Registry. Patients were asked to complete a Short-Form (SF)-36 questionnaire. A total of 48 patients were identified: 21 had a trans-tibial amputation, nine had a knee disarticulation and 18 had an amputation at the trans-femoral level. The median New Injury Severity Score was 24 (mean 27.4 (9 to 75)) and the median number of procedures per residual limb was 4 (mean 5 (2 to 11)). Minimum two-year SF-36 scores were completed by 39 patients (81%) at a mean follow-up of 40 months (25 to 75). The physical component of the SF-36 varied significantly between different levels of amputation (p = 0.01). Mental component scores did not vary between amputation levels (p = 0.114). Pain (p = 0.332), use of prosthesis (p = 0.503), rate of re-admission (p = 0.228) and mobility (p = 0.087) did not vary between amputation levels. These findings illustrate the significant impact of these injuries and the considerable surgical burden associated with their treatment. Quality of life is improved with a longer residual limb, and these results support surgical attempts to maximise residual limb length.

Severe open tibial fractures in combat trauma: management and preliminary outcomes.

The aim of this study was to report the pattern of severe open diaphyseal tibial fractures sustained by military personnel, and their orthopaedic-plastic surgical management.The United Kingdom Military Trauma Registry was searched for all such fractures sustained between 2006 and 2010. Data were gathered on demographics, injury, management and preliminary outcome, with 49 patients with 57 severe open tibial fractures identified for in-depth study. The median total number of orthopaedic and plastic surgical procedures per limb was three (2 to 8). Follow-up for 12 months was complete in 52 tibiae (91%), and half the fractures (n = 26) either had united or in the opinion of the treating surgeon were progressing towards union. The relationship between healing without further intervention was examined for multiple variables. Neither the New Injury Severity Score, the method of internal fixation, the requirement for vascularised soft-tissue cover nor the degree of bone loss was associated with poor bony healing. Infection occurred in 12 of 52 tibiae (23%) and was associated with poor bony healing (p = 0.008). This series characterises the complex orthopaedic-plastic surgical management of severe open tibial fractures sustained in combat and defines the importance of aggressive prevention of infection.

Aggressive soft tissue infections and amputation in military trauma patients.

Due to the nature of IED injuries, during the conflicts in Iraq and Afghanistan The traditional, two-stage amputation for unsalvageable combat lower limb injuries has evolved into a strategy of serial debridement and greater use of plastic surgical techniques in order to preserve residual limb length. This study aimed to characterise the current treatment of lower limb loss with particular focus on the impact of specific wound infections. The UK military trauma registry and clinical notes were reviewed for details of all lower limb amputation identifying: 51 patients with 70 lower limb amputations. The mean number of debridements per stump prior to closure was 4.1 (95% CI 3.5-4.7). A final more proximal amputation level was required in 21 stumps (30%). Recovery of A. hydrophillia from wounds was significantly associated with a requirement for a more proximal amputation level (p=0.0038) and greater number of debridements (p=0.0474) when compared to residual limb wounds withoutA. hydrophillia.

Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria.

Bacteria have existed on Earth for three billion years or so and have become adept at protecting themselves against toxic chemicals. Antibiotics have been in clinical use for a little more than 6 decades. That antibiotic resistance is now a major clinical problem all over the world attests to the success and speed of bacterial adaptation. Mechanisms of antibiotic resistance in bacteria are varied and include target protection, target substitution, antibiotic detoxification and block of intracellular antibiotic accumulation. Acquisition of genes needed to elaborate the various mechanisms is greatly aided by a variety of promiscuous gene transfer systems, such as bacterial conjugative plasmids, transposable elements and integron systems, that move genes from one DNA system to another and from one bacterial cell to another, not necessarily one related to the gene donor. Bacterial plasmids serve as the scaffold on which are assembled arrays of antibiotic resistance genes, by transposition (transposable elements and ISCR mediated transposition) and site-specific recombination mechanisms (integron gene cassettes).The evidence suggests that antibiotic resistance genes in human bacterial pathogens originate from a multitude of bacterial sources, indicating that the genomes of all bacteria can be considered as a single global gene pool into which most, if not all, bacteria can dip for genes necessary for survival. In terms of antibiotic resistance, plasmids serve a central role, as the vehicles for resistance gene capture and their subsequent dissemination. These various aspects of bacterial resistance to antibiotics will be explored in this presentation.

Experimental transmission of a ranavirus disease of common toads (Bufo bufo) to common frogs (Rana temporaria).

During investigations of epidemic frog mortality in Britain, a novel fatal systemic haemorrhagic disease of common toads was discovered. This disease resembles a systemic haemorrhagic disease of common frogs in Britain, which is one of a range of fatal disease syndromes, characterized by systemic haemorrhages, skin ulceration or a combination of these lesions, caused by ranavirus infection. Ranavirus previously isolated from diseased toads was inoculated into common frogs to evaluate if this virus could infect and cause disease in common frogs. All virus-inoculated frogs died with systemic haemorrhages between 6 and 8 days post-inoculation, giving similar results to those produced by the inoculation of frogs with ranavirus cultured from naturally diseased frogs. These results indicate that the same, or similar, viruses are affecting both frogs and toads in the field and confirm that ranavirus has emerged as an important cause of amphibian mortality in Britain.

Emerging epidemic diseases of frogs in Britain are dependent on the source of ranavirus agent and the route of exposure.

A series of transmission studies was conducted to investigate the aetiology, or aetiologies, of emerging fatal epidemic disease syndromes affecting the common frog (Rana temporaria) in Britain. The syndromes, characterized by skin ulceration or systemic haemorrhages, were induced upon exposure to lesion homogenates or cultured ranavirus. The re-isolation of ranavirus from experimentally affected frogs fulfilled Koch's postulates. Aeromonas hydrophila, previously associated with similar lesions, was not significant to disease development. Unexpectedly, disease outcomes were influenced by both the source of agent and the route of exposure, indicating that different ranaviruses with different tissue tropisms and pathogeneses (possibly similar to quasi-species in RNA virus populations) are circulating in the British common frog population. Our findings confirm that ranavirus disease has emerged as an important cause of amphibian mortality in Britain.

Assessment of the fitness impacts on Escherichia coli of acquisition of antibiotic resistance genes encoded by different types of genetic element.

OBJECTIVES: Little is known of the fitness cost that antibiotic resistance exerts on wild-type bacteria, especially in their natural environments. We therefore examined the fitness costs that several antibiotic resistance elements imposed on a wild-type Escherichia coli isolate, both in the laboratory and in a pig gut colonization model. METHODS: Plasmid R46, Tn1 and Tn7 and a K42R RpsL substitution were separately introduced into E. coli 345-2 RifC, a rifampicin-resistant derivative of a recent porcine isolate. The insertion site of Tn1 was determined by DNA sequencing. The fitness cost of each resistance element was assessed in vitro by pairwise growth competition and in vivo by regularly monitoring the recovery of strains from faeces for 21 days following oral inoculation of organic piglets. Each derivative of 345-2 RifC carrying a resistance element was grown in antibiotic-free broth for 200 generations and the experiments to assess fitness were repeated. RESULTS: RpsL K42R was found to impose a small fitness cost on E. coli 345-2 RifC in vitro but did not compromise survival in vivo. R46 imposed a cost both before and after laboratory passage in vitro, but only the pre-passage strain was at a disadvantage in vivo. The post-passage isolate had an advantage in pigs. Acquisition of Tn7 had no impact on the fitness of E. coli 345-2 RifC. Two derivatives containing Tn1 were isolated and, in both cases, the transposon inserted into the same cryptic chromosomal sequence. Acquisition of Tn1 improved fitness of E. coli 345-2 RifC in vitro and in vivo in the case of the first derivative, but in the case of a second, independent derivative, Tn1 had a neutral effect on fitness. CONCLUSIONS: The fitness impact imposed on E. coli 345-2 RifC by carriage of antibiotic resistance elements was generally low or non-existent, suggesting that once established, resistance may be difficult to eliminate through reduction in prescribing alone.

Smooth muscle actin and vimentin as markers of testis development in the harbour porpoise (Phocoena phocoena).

Testicular development in the harbour porpoise Phocoena phocoena was examined using animals (n = 192) stranded or by-caught off the coast of England, Wales and Scotland. Classification of animals according to their stage of sexual development was undertaken using gonadal morphology and the distribution of cytoskeletal proteins. Smooth muscle actin (SMA) and vimentin proved particularly useful in this respect; SMA was prominent in the myoid peritubular cells of the adult testis, and two stages of peritubular cell SMA expression could be recognized ('absent' or 'incomplete'). The initial appearance of SMA in peritubular cells was associated with significant increases in body length and body weight (P < 0.001), and occurred during the second year of life. Vimentin, which was prominent in prespermatogonia and spermatogonia, sometimes showed a polarized cytoplasmic distribution. This correlated with a developmental stage at which the seminiferous tubule epithelium becomes populated by germ cells (mean age 1.8 years). Several antibodies were tested for their utility as Sertoli cell markers, but none was found to be specific or useful. Nevertheless, immunohistochemical localization of desmin, GATA-4, Ki67 and androgen receptor was possible despite the poor quality of tissue preservation. This study showed that immunohistochemical classification of these individuals provides a robust basis for the recognition of key physiological stages of sexual development in the male harbour porpoise. This may provide an alternative to the estimation of age, body weight and body length in future analyses aimed at detecting possible adverse effects of environmental pollutants on the reproductive potential of wild marine mammals.

An assessment of the risks associated with the use of antibiotic resistance genes in genetically modified plants: report of the Working Party of the British Society for Antimicrobial Chemotherapy.

Development of genetically modified (GM) plants is contentious, in part because bacterial antibiotic resistance (AR) genes are used in their construction and often become part of the plant genome. This arouses concern that cultivation of GM plants might provide a reservoir of AR genes that could power the evolution of new drug-resistant bacteria. We have considered bacterial DNA transfer systems (conjugation, transduction and transformation) and mechanisms of recombination (homologous recombination, transposition, site-specific recombination and DNA repair) that together might productively transfer AR genes from GM plants to bacterial cells, but are unable to identify a credible scenario whereby new drug-resistant bacteria would be created. However, we cannot entirely rule out the possibility of rare transfer events that involve novel mechanisms. Hence, we also considered if occasional transfers of AR genes (bla(TEM), aph(3'), aadA) from GM plants into bacteria would pose a threat to public health. These AR genes are common in many bacteria and each is found on mobile genetic elements that have moved extensively between DNA molecules and bacterial cells. This gene mobility has already severely compromised clinical use of antibiotics to which resistance is conferred. Accordingly, the argument that occasional transfer of these particular resistance genes from GM plants to bacteria would pose an unacceptable risk to human or animal health has little substance. We conclude that the risk of transfer of AR genes from GM plants to bacteria is remote, and that the hazard arising from any such gene transfer is, at worst, slight.

Rifampicin resistance and its fitness cost in Enterococcus faecium.

OBJECTIVES: The genetic basis of rifampicin resistance and the associated fitness cost in Enterococcus faecium were investigated. METHODS: Twelve spontaneous rifampicin-resistant E. faecium mutants were selected from four parent strains recently isolated from porcine faecal material. The DNA sequence of the complete rpoB gene from the parent strains and of nucleotides -189 to +1785 from the mutants was determined from PCR amplicons. The fitness of the mutants was assessed by determining growth rate, by direct growth competition and by the ability of some of the mutants to survive in the pig intestine. RESULTS: The rpoB genes of the parent strains diverged from each other by 1-10% and each encoded proteins that were 1208 amino acids in length. All mutants had a single amino acid substitution in the region implicated in rifampicin resistance in other organisms. Six mutants carried the substitution H489Y/Q, two mutants carried the substitution R492H, one mutant carried the substitution Q480H, two mutants carried the substitutions S494L and V224I, and one mutant carried the substitutions G485D and V224I. Per generation fitness costs of the mutants ranged from a gain of 2.5% to a cost of 10%. Mutants with the substitution H489Y/Q were the most fit, whereas the double mutants were the least fit. The mutant with the substitution H489Q was able to survive in the pig gut for 12 days. There was some correlation between the rifampicin MIC and fitness cost, with higher MICs being associated with higher fitness costs. CONCLUSIONS: Substitutions in RpoB are associated with rifampicin resistance in E. faecium. The fitness cost of resistance is variable and can sometimes be absent.

Cefuroxime resistance in non-beta-lactamase Haemophilus influenzae is linked to mutations in ftsI.

The penicillin binding protein (PBP) genes dacA, dacB and ftsI from 14 cefuroxime-resistant (CXM(R)) isolates and three clinical isolates with low CXM MIC for non-beta-lactamase-producing Haemophilus influenzae type b were molecularly characterized. One strain, 5788, was used to transform H. influenzae Rd to CXM(R) for direct comparison of the pbps in the same genetic background. No obvious mutations in the dacA and dacB gene products could be associated with CXM(R). One amino acid substitution in the ftsI gene product in particular, S357N, could give rise to CXM(R). Sequence analysis from the CXM(R) transformants also implicated FtsI; in this case, the substitutions were V511A and R517H. To verify S357N substitution, the protein sequence of H. influenzae FtsI was threaded through the S. pneumoniae PBP 2X structure giving an average root mean square deviation of the alpha-carbon chains of 0.5 A. The S357N substitution alters both the residue size and charge. One explanation for the contribution of S357N to CXM(R) is that the asparagine side-chain produces unfavourable steric hindrance with the side chain of Val-362 changing the torsion angles of the asparagine residue, which in turn may influence the position of the loop V362-P366 adjacent to the active site. Whilst other groups have examined the contribution of H. influenzae PBPs in ampicillin resistance, this is the first report analysing their role in CXM(R).