Cone-Beam CT of the Extremities in Clinical Practice.

Cone-beam CT (CBCT) is a promising tool with increasing applications in musculoskeletal imaging due to its ability to provide thin-section CT images of the appendicular skeleton and introduce weight bearing, which accounts for loading forces that typically interact with and affect this anatomy. CBCT devices include an x-ray source directly opposite a digital silicon detector panel that performs a single rotation around an object of interest, obtaining thin-section images. Currently, the majority of research has been focused on the utility of CBCT with foot and ankle pathologic abnormalities, due to the complex architectural arrangement of the tarsal bones and weight-bearing nature of the lower extremities. Associated software can provide a variety of options for image reconstruction, including metal artifact reduction, three-dimensional biometric measurements, and digitally reconstructed radiographs. Advancements in this technology have allowed imaging of the knee, hip, hand, and elbow. As more data are published, it is becoming evident that CBCT provides many additional benefits, including fast imaging time, low radiation dose, lower cost, and small equipment footprint. These benefits allow placement of CBCT units outside of the traditional radiology department, including the orthopedic clinic setting. These technologic developments have motivated clinicians to define the scope of CBCT for diagnostics, surgical planning, and longitudinal imaging. As efforts are made to create standardized protocol and measurements, the current understanding and surgical approach for various orthopedic pathologic conditions will continue to shift, with the hope of improving outcomes. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Hematolymphoid neoplasms are common in bone marrow biopsies performed for non-specific, diffuse marrow signal alterations on magnetic resonance imaging.

AIMS: MRI is an imaging modality used for a wide range of clinical indications. Occasionally, non-specific, diffuse T1 marrow signal alterations are identified, which may prompt a bone marrow biopsy (BM). However, there is little data on the clinicopathologic significance of this signal alteration. This study evaluated the frequency and nature of pathologic findings in BM performed to evaluate diffuse MRI T1 marrow signal alterations. METHODS: Records from January 2003 to May 2015 were searched for BM performed to evaluate abnormal MRIs. 179 cases were identified. Patients with nodular/destructive bone lesions on MRI or other imaging studies, or a previous diagnosed metastatic tumor or hematologic malignancy were excluded, resulting in 45 cases. RESULTS: The patients included 22 males and 23 females with a median age of 56 years. The location of the MRI T1 marrow signal alterations included spine, pelvis, knee, skull, femur, and arm. 19/45 patients had neoplasms identified in the BM. The remaining 26 patients had benign BM findings. There was a significant difference in hemoglobin values in patients with neoplastic versus benign BM findings (p = 0.037, unpaired Student's t-test). CONCLUSIONS: Diffuse T1 marrow signal alterations on MRI should warrant a BM evaluation, as 42% of cases showed an underlying hematolymphoid neoplasm or metastatic tumor, even when patients with a known history of malignancy were excluded. When faced with a BM from a patient with a non-specific, diffuse MRI signal alteration, a pathologist should have a high index of suspicion for a malignant neoplasm, most often of hematopoietic/lymphoid type.

Weight-Bearing CT with Maximum Ankle Dorsiflexion to Identify Impingement and Tibial Plafond Stress Fracture: A Case Report.

CASE: A 25-year-old male pole vaulter presented with several months of right ankle pain. Radiographs showed an anterior tibial osteophyte with a small intra-articular body suggesting impingement. Weight-bearing computed tomography (CT) revealed an associated tibial plafond stress fracture. Subsequent arthroscopy with osteophyte resection and loose body removal significantly improved symptoms, and he gradually resumed training. CONCLUSION: Stress fractures should always be considered in athletes with ankle pain. A unique aspect of this case was the use of weight-bearing CT in diagnosis and surgical planning. To our knowledge, this is the first described case in which weight-bearing CT was used in this fashion.

Incorporation of secretory immunoglobulin A into biofilms can decrease their resistance to ciprofloxacin.

Extracellular matrices utilized by biofilms growing on inert surfaces are generally produced entirely by the bacteria growing within those biofilms, whereas symbiotic (mutualistic) biofilms growing in or on a wide range of plants and animals utilize host-derived macromolecules, such as mucoid substances, as components of their extracellular matrix. Incorporation of host-derived molecules may have a profound effect on the resistance to antibiotics of symbiotic biofilms, which may have important implications for medicine and biology. As an initial probe of the potential effects of host-derived molecules in the extracellular matrix on the sensitivity of biofilms to antibiotics, an in vitro model was used to evaluate the effects of ciprofloxacin on biofilms grown in the presence and absence of SIgA, a host-derived glycoprotein associated with biofilms in the mammalian gut. In five out of six strains of Escherichia coli tested, the incorporation of SIgA into the biofilms apparently reduced the resistance of the bacteria to ciprofloxacin. On the other hand, SIgA generally increased the resistance of planktonic bacteria to ciprofloxacin, perhaps due in part to the SIgA-mediated aggregation of the bacteria. These findings suggest that incorporation of host-derived molecules into the extracellular matrix of symbiotic biofilms might profoundly alter the properties of those biofilms, including the resistance of those biofilms to antibiotics.

Adaptation in a mouse colony monoassociated with Escherichia coli K-12 for more than 1,000 days.

Although mice associated with a single bacterial species have been used to provide a simple model for analysis of host-bacteria relationships, bacteria have been shown to display adaptability when grown in a variety of novel environments. In this study, changes associated with the host-bacterium relationship in mice monoassociated with Escherichia coli K-12 over a period of 1,031 days were evaluated. After 80 days, phenotypic diversification of E. coli was observed, with the colonizing bacteria having a broader distribution of growth rates in the laboratory than the parent E. coli. After 1,031 days, which included three generations of mice and an estimated 20,000 generations of E. coli, the initially homogeneous bacteria colonizing the mice had evolved to have widely different growth rates on agar, a potential decrease in tendency for spontaneous lysis in vivo, and an increased tendency for spontaneous lysis in vitro. Importantly, mice at the end of the experiment were colonized at an average density of bacteria that was more than 3-fold greater than mice colonized on day 80. Evaluation of selected isolates on day 1,031 revealed unique restriction endonuclease patterns and differences between isolates in expression of more than 10% of the proteins identified by two-dimensional electrophoresis, suggesting complex changes underlying the evolution of diversity during the experiment. These results suggest that monoassociated mice might be used as a tool for characterizing niches occupied by the intestinal flora and potentially as a method of targeting the evolution of bacteria for applications in biotechnology.

Volumetric Analysis in Autologous Fat Grafting to the Foot.

BACKGROUND: Pedal fat grafting is a safe, minimally invasive approach to treat pedal fat pad atrophy. Prior randomized controlled trials demonstrate that the fat as measured directly under the metatarsal heads disappears between 2 and 6 months after fat grafting, despite patients having relief for 2 years. The authors aim to use magnetic resonance imaging to further assess three-dimensional volume of fat in the foot after autologous fat grafting to help explain the mechanism for improved pain. METHODS: A prospective study was performed using magnetic resonance imaging before and at 6 months after pedal fat grafting to assess changes in the three-dimensional morphology of the fat. RESULTS: Seventeen patients (six men and 11 women) underwent injections with a mean volume of 5.8 cc per foot. At 6 months, patients demonstrated increased tissue thickness (p = 0.008) and volume (p = 0.04). Improvements were seen in pain (p < 0.05) and activity (p < 0.05). Foot pressures and forces were significantly decreased and positively correlated with increased fat pad volume (p < 0.05). CONCLUSIONS: Pedal fat grafting significantly increases metatarsal fat pad volume. The distribution of the fat may contribute to lasting clinical relief in these patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Amputation-Site Soft-Tissue Restoration Using Adipose Stem Cell Therapy.

Soft-tissue deficits in amputation stumps can lead to significant pain and disability. An emerging treatment option is stem cell-enriched fat grafting. This is the first study assessing the potential for this treatment modality in lower extremity amputation sites. In this prospective cohort study, five injured military personnel suffering from pain and limited function at amputation sites were recruited. Fat grafting enriched with stromal vascular fraction was performed at amputation sites to provide additional subcutaneous tissue padding over bony structures. Outcomes measures included complications, demographic data, physical examination, cellular subpopulations, cell viability, graft volume retention, pain, Lower Extremity Functional Scale, Functional Mobility Assessment, 36-Item Short-Form Health Survey, and rates of depression. Follow-up was 2 years. There were no significant complications. Volume retention was 61.5 ± 24.0 percent. Overall cell viability of the stromal vascular fraction was significantly correlated with volume retention (p = 0.016). There was no significant correlation between percentage of adipose-derived stem cells or number of cells in the stromal vascular fraction and volume retention. There was a nonsignificant trend toward improvement in pain scores (3.0 ± 2.5 to 1.2 ± 1.6; p = 0.180 at 2 years). There were no significant changes in disability indexes. Results from this pilot study demonstrate that stromal vascular fraction-enriched fat grafting is a safe, novel modality for the treatment of symptomatic soft-tissue defects in traumatic lower extremity amputations. Volume retention can be anticipated at slightly over 60 percent. Further studies are needed to assess efficacy. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, IV.

An acellular biologic scaffold treatment for volumetric muscle loss: results of a 13-patient cohort study.

Volumetric muscle loss (VML) is a severe and debilitating clinical problem. Current standard of care includes physical therapy or orthotics, which do not correct underlying strength deficits, and surgical tendon transfers or muscle transfers, which involve donor site morbidity and fall short of restoring function. The results of a 13-patient cohort study are described herein and involve a regenerative medicine approach for VML treatment. Acellular bioscaffolds composed of mammalian extracellular matrix (ECM) were implanted and combined with aggressive and early physical therapy following treatment. Immunolabeling of ultrasound-guided biopsies, and magnetic resonance imaging and computed tomography imaging were performed to analyse the presence of stem/progenitor cells and formation of new skeletal muscle. Force production, range-of-motion and functional task performance were analysed by physical therapists. Electrodiagnostic evaluation was used to analyse presence of innervated skeletal muscle. This study is registered with ClinicalTrials.gov, numbers NCT01292876. In vivo remodelling of ECM bioscaffolds was associated with mobilisation of perivascular stem cells; formation of new, vascularised, innervated islands of skeletal muscle within the implantation site; increased force production; and improved functional task performance when compared with pre-operative performance. Compared with pre-operative performance, by 6 months after ECM implantation, patients showed an average improvement of 37.3% (P<0.05) in strength and 27.1% improvement in range-of-motion tasks (P<0.05). Implantation of acellular bioscaffolds derived from ECM can improve strength and function, and promotes site-appropriate remodelling of VML defects. These findings provide early evidence of bioscaffolding as a viable treatment of VML.

An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss.

Biologic scaffolds composed of naturally occurring extracellular matrix (ECM) can provide a microenvironmental niche that alters the default healing response toward a constructive and functional outcome. The present study showed similarities in the remodeling characteristics of xenogeneic ECM scaffolds when used as a surgical treatment for volumetric muscle loss in both a preclinical rodent model and five male patients. Porcine urinary bladder ECM scaffold implantation was associated with perivascular stem cell mobilization and accumulation within the site of injury, and de novo formation of skeletal muscle cells. The ECM-mediated constructive remodeling was associated with stimulus-responsive skeletal muscle in rodents and functional improvement in three of the five human patients.

Altering and assessing persistence of genetically modified E. coli MG1655 in the large bowel.

One of the primary factors limiting the efficacy of probiotic therapies is short persistence time. Utilizing a novel method for assessment of persistence in the large bowel independent of survival of the organisms in the upper GI tract, we tested whether overexpression of the type 1 pilus, a colonization factor, or the presence of secretory immunoglobulin A (sIgA) might increase the persistence time of a laboratory strain of E. coli in the gut. For this purpose, cecal ostomies were created in mice and bacteria were placed in the ostomies, with or without sIgA. The persistence of the bacteria was assessed by evaluating the length of time after placement in which the bacteria were found in fecal samples. E. coli MG1655 expressing pili with the mannose-specific adhesin persisted in vivo significantly longer [mean (hours) +/- SEM: 91.50 +/- 15.98, n = 12] than bacteria expressing pili without adhesin [43.67 +/- 8.22, n = 12] (P = 0.01) and significantly longer than bacteria expressing neither pili nor adhesin [22.00 +/- 4.22, n = 12] (P = 0.0004). Although the persistence time of bacteria was not significantly affected by the presence of sIgA, the sIgA did cause a relative increase in retention of inert particles. These results, combined with an acute increase in stool production and stool water content in those animals not receiving sIgA following introduction of bacteria, suggest that sIgA might have anti-inflammatory properties in the gut when administered with enteric bacteria. Modifying expression of probiotic colonization factors may provide substantial benefit to patients with digestive tract diseases by virtue of increased persistence of the probiotic and, in the case of sIgA, an anti-inflammatory effect. This novel in vivo model may be useful in evaluating persistence time in a variety of current and future probiotic regimens.

Immunoglobulin-mediated agglutination of and biofilm formation by Escherichia coli K-12 require the type 1 pilus fiber.

The binding of human secretory immunoglobulin A (SIgA), the primary immunoglobulin in the gut, to Escherichia coli is thought to be dependent on type 1 pili. Type 1 pili are filamentous bacterial surface attachment organelles comprised principally of a single protein, the product of the fimA gene. A minor component of the pilus fiber (the product of the fimH gene, termed the adhesin) mediates attachment to a variety of host cell molecules in a mannose inhibitable interaction that has been extensively described. We found that the aggregation of E. coli K-12 by human secretory IgA (SIgA) was dependent on the presence of the pilus fiber, even in the absence of the mannose specific adhesin or in the presence of 25 mM alpha-CH(3)Man. The presence of pilus without adhesin also facilitated SIgA-mediated biofilm formation on polystyrene, although biofilm formation was stronger in the presence of the adhesin. IgM also mediated aggregation and biofilm formation in a manner dependent on pili with or without adhesin. These findings indicate that the pilus fiber, even in the absence of the adhesin, may play a role in biologically important processes. Under conditions in which E. coli was agglutinated by SIgA, the binding of SIgA to E. coli was not increased by the presence of the pili, with or without adhesin. This observation suggests that the pili, with or without adhesin, affect factors such as cell surface rigidity or electrostatic repulsion, which can affect agglutination but which do not necessarily determine the level of bound immunoglobulin.