Characterization of the Dorsal Ulnar Corner in Distal Radius Fractures in Postmenopausal Females: Implications for Surgical Decision Making.

PURPOSE: To characterize the dorsal ulnar corner fragment with regard to size and morphology using 3-dimensional software and computed tomography (CT) scans, as it presents in low-energy intra-articular distal radius fractures occurring in the female postmenopausal population. METHODS: A multicenter retrospective review was conducted to identify postmenopausal females with low-energy distal radius fractures treated surgically at level-1 trauma centers. Patients with low-energy injuries with preoperative CT scans were included. The Digital Imaging and Communications in Medicine (DICOM) data from CT scans were used to reconstruct intra-articular fracture patterns. The dorsal ulnar fragment was isolated in each CT scan and measured, then normalized based on lunate depth. RESULTS: Eighty patients met the inclusion criteria. The mean dimension measurements of the dorsal ulnar corner were dorsal surface height, 9.82 ± 5.02 mm (95% confidence interval [95% CI], 8.72-10.92); dorsal surface width, 9.06 ± 3.72 mm (95% CI, 8.25-9.88); articular surface width, 7.44 ± 3.92 mm (95% CI, 6.58-8.30); articular surface depth, 4.14 ± 2.39 mm (95% CI, 3.62-4.67). The mean lunate depth measurement (17.52 ± 1.48 mm) was used to normalize articular surface depth demonstrating that, on average, the dorsal ulnar corner comprises 23.6% of the articular surface ± 13.6% (95% CI, 20.7-26.6). CONCLUSIONS: The mean articular surface depth of the dorsal ulnar corner fragment in this study was less than 5 mm, accounting for approximately 24% of the volar-dorsal width of the distal radius at the lunate facet. CLINICAL RELEVANCE: These data expand current understanding of the morphology and size of the dorsal ulnar corner fracture fragment. If fixation of this fragment is a goal, surgeons may need to use longer screws that penetrate closer to the dorsal cortex than those required for extra-articular fractures or to consider alternative methods of fragment-specific fixation for adequate capture of this fragment.

Management of a Case of Mucor Colonization in Breast Tissue Expander Seroma Pocket.

Mucormycosis has a mortality rate reaching 90%, and is imperative that therapy be initiated rapidly once a diagnosis is made. Successful treatment consists of management of underlying risk factors, surgical debridement, and antifungal therapies. The dilemma whether or not to pursue extensive debridement presents when the wound is cultured positive but the patient is not systemically ill. We present the first reported case of successful medical treatment of a seroma pocket colonized with mucor in a patient undergoing bilateral reconstruction with tissue expander and acellular dermal matrix.

Surgical management of craniosynostosis in the setting of a ventricular shunt: a case series and treatment algorithm.

PURPOSE: Cerebrospinal fluid diversion via ventricular shunt is a common treatment for hydrocephalus. Change in cranial morphology associated with a sutural fusion has been termed shunt-related or induced craniosynostosis (SRC) or craniocerebral disproportion (CCD). We present a series of patients with SRC who underwent cranial vault remodeling (CVR) and our treatment algorithm. METHODS: Thirteen patients were retrospectively reviewed who had SRC and CVR; 92% of patients had a ventriculoperitoneal (VP) shunt placed for largely intraventricular hemorrhage of prematurity (69% of patients) at a mean age of 2.2 months. The shunt revision rate was 38.4%, and 54% of patients had a programmable shunt placed initially. RESULTS: The mean age at time of CVR was 3.6 years old. The most commonly affected sutures (CT confirmed) were the sagittal and coronal sutures, with three patients exhibiting pancraniosynostosis. The mean time from placement of the shunt to CT evidence of sutural fusion was 2.0 years. Abnormal head shape was noted in all 13 patients; 11 of these also had either chronic headaches, papilledema, seizures, or behavioral changes in the setting of functional shunt. Mean follow-up after the initial CVR was 3.3 years. No shunt infections were attributed to the CVR. The families of all patients were contacted and reported improvement in head shape with 60% of families reporting improvement in behavior, 75% reported improvement in headaches, and 40% reported decrease in seizure frequency or intensity. Shunt setting or type was not routinely changed after CVR. CONCLUSIONS: Our threshold for CVR in SRC is met when shunt malfunction has been ruled out and there are (1) radiographic evidence of craniosynostosis, (2) signs of increased ICP clinically or radiographically, and (3) cranial dysmorphism, i.e., dolichocephaly. The majority of cases of SRC result in improved cranial morphology in addition to some abatement of the symptoms of increased intracranial pressure. Early involvement of an experienced craniofacial/neurosurgical team could allow for early diagnosis and intervention which may prevent progression to more severe deformities. SRC is a complex entity, with multiple etiologies, and a future study is needed.

Impact of Staphylococcus aureus regulatory mutations that modulate biofilm formation in the USA300 strain LAC on virulence in a murine bacteremia model.

Staphylococcus aureus causes acute and chronic forms of infection, the latter often associated with formation of a biofilm. It has previously been demonstrated that mutation of atl, codY, rot, sarA, and sigB limits biofilm formation in the USA300 strain LAC while mutation of agr, fur, and mgrA has the opposite effect. Here we used a murine sepsis model to assess the impact of these same loci in acute infection. Mutation of agr, atl, and fur had no impact on virulence, while mutation of mgrA and rot increased virulence. In contrast, mutation of codY, sarA, and sigB significantly attenuated virulence. Mutation of sigB resulted in reduced accumulation of AgrA and SarA, while mutation of sarA resulted in reduced accumulation of AgrA, but this cannot account for the reduced virulence of sarA or sigB mutants because the isogenic agr mutant was not attenuated. Indeed, as assessed by accumulation of alpha toxin and protein A, all of the mutants we examined exhibited unique phenotypes by comparison to an agr mutant and to each other. Attenuation of the sarA, sigB and codY mutants was correlated with increased production of extracellular proteases and global changes in extracellular protein profiles. These results suggest that the inability to repress the production of extracellular proteases plays a key role in attenuating the virulence of S. aureus in acute as well as chronic, biofilm-associated infections, thus opening up the possibility that strategies aimed at the de-repression of protease production could be used to broad therapeutic advantage. They also suggest that the impact of codY, sarA, and sigB on protease production occurs via an agr-independent mechanism.

XerC Contributes to Diverse Forms of Staphylococcus aureus Infection via agr-Dependent and agr-Independent Pathways.

We demonstrate that mutation of xerC, which reportedly encodes a homologue of an Escherichia coli recombinase, limits biofilm formation in the methicillin-resistant Staphylococcus aureus strain LAC and the methicillin-sensitive strain UAMS-1. This was not due to the decreased production of the polysaccharide intracellular adhesin (PIA) in either strain because the amount of PIA was increased in a UAMS-1xerC mutant and undetectable in both LAC and its isogenic xerC mutant. Mutation of xerC also resulted in the increased production of extracellular proteases and nucleases in both LAC and UAMS-1, and limiting the production of either class of enzymes increased biofilm formation in the isogenic xerC mutants. More importantly, the limited capacity to form a biofilm was correlated with increased antibiotic susceptibility in both strains in the context of an established biofilm in vivo. Mutation of xerC also attenuated virulence in a murine bacteremia model, as assessed on the basis of the bacterial loads in internal organs and overall lethality. It also resulted in the decreased accumulation of alpha toxin and the increased accumulation of protein A. These findings suggest that xerC may impact the functional status of agr. This was confirmed by demonstrating the reduced accumulation of RNAIII and AgrA in LAC and UAMS-1xerC mutants. However, this cannot account for the biofilm-deficient phenotype of xerC mutants because mutation of agr did not limit biofilm formation in either strain. These results demonstrate that xerC contributes to biofilm-associated infections and acute bacteremia and that this is likely due to agr-independent and -dependent pathways, respectively.

Regulatory Mutations Impacting Antibiotic Susceptibility in an Established Staphylococcus aureus Biofilm.

We previously determined the extent to which mutations of different Staphylococcus aureus regulatory loci impact biofilm formation as assessed under in vitro conditions. Here we extend these studies to determine the extent to which those regulatory loci that had the greatest effect on biofilm formation also impact antibiotic susceptibility. The experiments were done under in vitro and in vivo conditions using two clinical isolates of S. aureus (LAC and UAMS-1) and two functionally diverse antibiotics (daptomycin and ceftaroline). Mutation of the staphylococcal accessory regulator (sarA) or sigB was found to significantly increase susceptibilities to both antibiotics and in both strains in a manner that could not be explained by changes in the MICs. The impact of a mutation in sarA was comparable to that of a mutation in sigB and greater than the impact observed with any other mutant. These results suggest that therapeutic strategies targeting sarA and/or sigB have the greatest potential to facilitate the ability to overcome the intrinsic antibiotic resistance that defines S. aureus biofilm-associated infections.

Comparative impact of diverse regulatory loci on Staphylococcus aureus biofilm formation.

The relative impact of 23 mutations on biofilm formation was evaluated in the USA300, methicillin-resistant strain LAC. Mutation of sarA, atl, codY, rsbU, and sigB limited biofilm formation in comparison to the parent strain, but the limitation imposed by mutation of sarA was greater than that imposed by mutation of any of these other genes. The reduced biofilm formation of all mutants other than the atl mutant was correlated with increased levels of extracellular proteases. Mutation of fur- and mgrA-enhanced biofilm formation but in LAC had no impact on protease activity, nuclease activity, or accumulation of the polysaccharide intercellular adhesin (PIA). The increased capacity of these mutants to form a biofilm was reversed by mutation of sarA, and this was correlated with increased protease production. Mutation of sarA, mgrA, and sigB had the same phenotypic effect in the methicillin-sensitive strain UAMS-1, but mutation of codY increased rather than decreased biofilm formation. As with the UAMS-1 mgrA mutant, this was correlated with increased production of PIA. Examination of four additional clinical isolates suggests that the differential impact of codY on biofilm formation may be a conserved characteristic of methicillin-resistant versus methicillin-sensitive strains.

Impact of individual extracellular proteases on Staphylococcus aureus biofilm formation in diverse clinical isolates and their isogenic sarA mutants.

We demonstrate that the purified Staphylococcus aureus extracellular proteases aureolysin, ScpA, SspA, and SspB limit biofilm formation, with aureolysin having the greatest impact. Using protease-deficient derivatives of LAC, we confirmed that this is due to the individual proteases themselves. Purified aureolysin, and to a lesser extent ScpA and SspB, also promoted dispersal of an established biofilm. Mutation of the genes encoding these proteases also only partially restored biofilm formation in an FPR3757 sarA mutant and had little impact on restoring virulence in a murine bacteremia model. In contrast, eliminating the production of all of these proteases fully restored both biofilm formation and virulence in a sarA mutant generated in the closely related USA300 strain LAC. These results confirm an important role for multiple extracellular proteases in S. aureus pathogenesis and the importance of sarA in repressing their production. Moreover, purified aureolysin limited biofilm formation in 14 of 15 methicillin-resistant isolates and 11 of 15 methicillin-susceptible isolates, while dispersin B had little impact in UAMS-1, LAC, or 29 of 30 contemporary isolates of S. aureus. This suggests that the role of sarA and its impact on protease production is important in diverse strains of S. aureus irrespective of their methicillin resistance status.

Impact of the functional status of saeRS on in vivo phenotypes of Staphylococcus aureus†sarA mutants.

We investigated the in vivo relevance of the impact of sarA and saeRS on protease production using derivatives of the USA300 strain LAC. The results confirmed that mutation of saeRS or sarA reduces virulence in a bacteremia model to a comparable degree. However, while eliminating protease production restored virulence in the sarA mutant, it had little impact in the saeRS mutant. Additionally, constitutive activation of saeRS (saeRS(C)) enhanced the virulence of LAC and largely restored virulence in the isogenic sarA mutant. Based on these results, together with our analysis of the representative virulence factors alpha toxin, protein A (Spa), and extracellular nucleases, we propose a model in which the attenuation of saeRS mutants is defined primarily by decreased production of such factors, while constitutive activation of saeRS increases virulence, and reverses the attenuation of sarA mutants, because it results in both increased production and decreased protease-mediated degradation of these same factors. This regulatory balance was also apparent in a murine model of catheter-associated infection, with the results suggesting that the impact of saeRS on nuclease production plays an important role during the early stages of these infections that is partially offset by increased protease production in sarA mutants.

saeRS and sarA act synergistically to repress protease production and promote biofilm formation in Staphylococcus aureus.

Mutation of the staphylococcal accessory regulator (sarA) limits biofilm formation in diverse strains of Staphylococcus aureus, but there are exceptions. One of these is the commonly studied strain Newman. This strain has two defects of potential relevance, the first being mutations that preclude anchoring of the fibronectin-binding proteins FnbA and FnbB to the cell wall, and the second being a point mutation in saeS that results in constitutive activation of the saePQRS regulatory system. We repaired these defects to determine whether either plays a role in biofilm formation and, if so, whether this could account for the reduced impact of sarA in Newman. Restoration of surface-anchored FnbA enhanced biofilm formation, but mutation of sarA in this fnbA-positive strain increased rather than decreased biofilm formation. Mutation of sarA in an saeS-repaired derivative of Newman (P18L) or a Newman saeRS mutant (ΔsaeRS) resulted in a biofilm-deficient phenotype like that observed in clinical isolates, even in the absence of surface-anchored FnbA. These phenotypes were correlated with increased production of extracellular proteases and decreased accumulation of FnbA and/or Spa in the P18L and ΔsaeRS sarA mutants by comparison to the Newman sarA mutant. The reduced accumulation of Spa was reversed by mutation of the gene encoding aureolysin, while the reduced accumulation of FnbA was reversed by mutation of the sspABC operon. These results demonstrate that saeRS and sarA act synergistically to repress the production of extracellular proteases that would otherwise limit accumulation of critical proteins that contribute to biofilm formation, with constitutive activation of saeRS limiting protease production, even in a sarA mutant, to a degree that can be correlated with increased enhanced capacity to form a biofilm. Although it remains unclear whether these effects are mediated directly or indirectly, studies done with an sspA::lux reporter suggest they are mediated at a transcriptional level.