Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study.

In contrast to the many reports of successful real-world cases of personalized bacteriophage therapy (BT), randomized controlled trials of non-personalized bacteriophage products have not produced the expected results. Here we present the outcomes of a retrospective observational analysis of the first 100 consecutive cases of personalized BT of difficult-to-treat infections facilitated by a Belgian consortium in 35 hospitals, 29 cities and 12 countries during the period from 1 January 2008 to 30 April 2022. We assessed how often personalized BT produced a positive clinical outcome (general efficacy) and performed a regression analysis to identify functional relationships. The most common indications were lower respiratory tract, skin and soft tissue, and bone infections, and involved combinations of 26 bacteriophages and 6 defined bacteriophage cocktails, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. In our dataset of 100 cases, eradication was 70% less probable when no concomitant antibiotics were used (odds ratio = 0.3; 95% confidence interval = 0.127-0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage-antibiotic synergy were documented in 43.8% (7/16 patients) and 90% (9/10) of evaluated patients, respectively. We observed a combination of antibiotic re-sensitization and reduced virulence in bacteriophage-resistant bacterial isolates that emerged during BT. Bacteriophage immune neutralization was observed in 38.5% (5/13) of screened patients. Fifteen adverse events were reported, including seven non-serious adverse drug reactions suspected to be linked to BT. While our analysis is limited by the uncontrolled nature of these data, it indicates that BT can be effective in combination with antibiotics and can inform the design of future controlled clinical trials. BT100 study, ClinicalTrials.gov registration: NCT05498363 .

Combining cross-sectional survey and register data improved the estimate of hepatitis C prevalence among patients attending a psychiatric emergency department in Denmark.

BACKGROUND: The prevalence of hepatitis C (HCV) among psychiatric patients is elevated compared to the background population in many studies, but the prevalence among Danish psychiatric patients is unknown. The aim of the study was to determine the HCV prevalence and the proportion of the psychiatric patient population that remains to be diagnosed and treated in a Danish setting. METHODS: During a 5-month period, patients attending the psychiatric emergency room in Vejle, Denmark, were offered point-of-care anti-HCV testing. Previous hepatitis C tests for all patients attending the Psychiatric Department in the study period were extracted from the national laboratory database (DANVIR). We combined the survey and register data in a capture-recapture estimate of undiagnosed patients with HCV. RESULTS: During the study 24.9% (589 of 2364) patients seen at the psychiatric department attended the emergency room. The prevalence of anti-HCV among those tested in the emergency room was 1.6%. The laboratory register identified 595/2364 patients previously tested for anti-HCV with a positive prevalence of 6.1%. The undiagnosed anti-HCV positives among the 1483 never tested was estimated to 1.1%. Thus the total estimated prevalence of anti-HCV was 2.3% (54/2364, 95% CI 1.7%-3.0%) in the population, of whom 70.4% had been diagnosed, and 72.2% of diagnosed patients had received treatment or cleared HCV. CONCLUSION: Combining survey and register data showed that the WHO target of 90% diagnosed and 80% treated was not met. To eliminate HCV in the psychiatric population, both undiagnosed and untreated patients must be targeted.

[Relapsing polychondritis]. / Relapsing Polychondritis.

Relapsing polychondritis (RP) is a rare multisystemic disease predominantly involving the extracellular matrix. Typical manifestations are chondritis of the ears, nose and trachea as well as an asymmetrical oligoarthritis or polyarthritis of small and also larger joints. Various other involvements have also been described. The treatment of RP is individually dependent on a variety of factors, e.g., organ manifestations. Glucocorticoids, immunosuppressants and targeted treatment are implemented. In the case of seronegative rheumatoid arthritis or vasculitis with an atypical course the symptoms of RP should be taken into consideration.

Effects of exercise training on muscle wasting, muscle strength and quality of life in adults with acute burn injury.

OBJECTIVES: Exercise training during the acute phase of burns is difficult to implement but offers potential benefits. This multicenter trial explored the effects of an exercise program on muscular changes and quality of life during burn center stay. METHODS: Fifty-seven adults with burns ranging between 10% and 70% TBSA were allocated to receive either standard of care (n = 29), or additionally exercise (n = 28), consisting of resistance and aerobic training, commenced as early as possible according to safety criteria. Muscle wasting (primary outcome), quantified by ultrasound-derived quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA), muscle strength and quality of life (Burn Specific Health Scale-Brief (BSHS-B) and EQ-5D-5L) were assessed at baseline, four and eight weeks later, or hospital discharge. Mixed models were used to analyze between-group changes over time with covariates of interest added in stepwise forward modeling. RESULTS: The addition of exercise training to standard of care induced significant improvements in QMLT, RF-CSA, muscle strength and the BSHS-B subscale hand function (ß-coefficient. 0.055 cm/week of QMLT, p = 0.005). No added benefit was observed for other quality-of-life measures. CONCLUSIONS: Exercise training, administered during the acute phase of burns, reduced muscle wasting, and improved muscle strength throughout burn center stay.

A Deep Learning Image-to-Image Translation Approach for a More Accessible Estimator of the Healing Time of Burns.

OBJECTIVE: An accurate and timely diagnosis of burn severity is critical to ensure a positive outcome. Laser Doppler imaging (LDI) has become a very useful tool for this task. It measures the perfusion of the burn and estimates its potential healing time. LDIs generate a 6-color palette image, with each color representing a healing time. This technique has very high costs associated. In resource-limited areas, such as low- and middle-income countries or remote locations like space, where access to specialized burn care is inadequate, more affordable and portable tools are required. This study proposes a novel image-to-image translation approach to estimate burn healing times, using a digital image to approximate the LDI. METHODS: This approach consists of a U-net architecture with a VGG-based encoder and applies the concept of ordinal classification. Paired digital and LDI images of burns were collected. The performance was evaluated with 10-fold cross-validation, mean absolute error (MAE), and color distribution differences between the ground truth and the estimated LDI. RESULTS: Results showed a satisfactory performance in terms of low MAE ( 0.2370 ±0.0086). However, the unbalanced distribution of colors in the data affects this performance. SIGNIFICANCE: This novel and unique approach serves as a basis for developing more accessible support tools in the burn care environment in resource-limited areas.

Reliability and feasibility of skeletal muscle ultrasound in the acute burn setting.

OBJECTIVES: Despite the impact of muscle wasting after burn, tools to quantify muscle wasting are lacking. This multi-centre study examined the utility of ultrasound to measure muscle mass in acute burn patients comparing different methodologies. METHODS: B-mode ultrasound was used by two raters to determine feasibility and inter-rater reliability in twenty burned adults following admission. Quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA) were measured, comparing the use of i) a single versus average measurements, ii) a proximal versus distal location for QMLT, and iii) a maximum- versus no-compression technique for QMLT. RESULTS: Analysis of twenty burned adults (50 years [95%CI 42-57], 32%TBSA [95%CI 23-40]) yielded ICCs of> 0.97 for QMLT (for either location and compression technique) and> 0.95 for RF-CSA, using average measurements. Relative minimal detectable changes were smaller using no-compression than maximum-compression (6.5% vs. 15%). Using no-compression to measure QMLT was deemed feasible for both proximal and distal locations (94% and 96% of attempted measurements). In 9.5% of cases maximum-compression was not feasible. 95% of RF-CSA measurements were successfully completed. CONCLUSION: Ultrasound provides feasible and reliable values of quadriceps muscle architecture that can be adapted to clinical scenarios commonly encountered in acute burn settings.

Multifunctional Organocatalysts - Singly-Linked and Macrocyclic Bisphosphoric Acids for Asymmetric Phase-Transfer and Brønsted-Acid Catalysis.

The linking of phosphoric acids via covalent or mechanical bonds has proven to be a successful strategy for the design of novel organocatalysts. Here, we present the first systematic investigation of singly-linked and macrocyclic bisphosphoric acids, including their synthesis and their application in phase-transfer and Brønsted acid catalysis. We found that the novel bisphosphoric acids show dramatically increased enantioselectivities in comparison to their monophosphoric acid analogues. However, the nature, length and number of linkers has a profound influence on the enantioselectivities. In the asymmetric dearomative fluorination via phase-transfer catalysis, bisphosphoric acids with a single, rigid bisalkyne-linker give the best results with moderate to good enantiomeric excesses. In contrast, bisphosphoric acids with flexible linkers give excellent enantioselectivities in the transfer-hydrogenation of quinolines via cooperative Brønsted acid catalysis. In the latter case, sufficiently long linkers are needed for high stereoselectivities, as found experimentally and supported by DFT calculations.

SIGLEC-1 in Systemic Sclerosis: A Useful Biomarker for Differential Diagnosis.

Systemic Sclerosis (SSc) is a clinically heterogeneous disease that includes an upregulation of type I interferons (IFNs). The aim of this observational study was to investigate the IFN-regulated protein Sialic Acid−Binding Ig-like Lectin 1 (SIGLEC-1) as a biomarker for disease phenotype, therapeutic response, and differential diagnosis in SSc. Levels of SIGLEC-1 expression on monocytes of 203 SSc patients were determined in a cross-sectional and longitudinal analysis using multicolor flow cytometry, then compared to 119 patients with other rheumatic diseases and 13 healthy controls. SSc patients higher SIGLEC-1 expression on monocytes (2097.94 ± 2134.39) than HCs (1167.45 ± 380.93; p = 0.49), but significantly lower levels than SLE (8761.66 ± 8325.74; p < 0.001) and MCTD (6414.50 ± 1846.55; p < 0.001) patients. A positive SIGELC-1 signature was associated with reduced forced expiratory volume (p = 0.007); however, we were unable to find an association with fibrotic or vascular disease manifestations. SIGLEC-1 remained stable over time and was independent of changes in immunosuppressive therapy. However, SIGLEC-1 is suitable for differentiating SSc from other connective tissue diseases. SIGLEC-1 expression on monocytes can be useful in the differential diagnosis of connective tissue disease but not as a biomarker for SSc disease manifestations or activity.

U-Net based Mapping from Digital Images to Laser Doppler Imaging for Burn Assessment.

The incidence of burn injuries is higher in low-and middle-income countries, and particularly in remote areas where the access to specialized burn assessment, care and recovery is limited. Given the high costs associated with one of the most used techniques to evaluate the severity of a burn, namely laser Doppler imaging (LDI), an alternative approach could be beneficial for remote locations. This study proposes a novel approach to estimate the LDI from digital images of a burn. The approach is a pixel-wise regression model based on convolutional neural networks. To minimize the dependency on the conditions in which the images are taken, the effect of two image normalization techniques is also studied. Results indicate that the model performs satisfactorily on average, presenting low mean absolute and squared errors and high structural similarity index. While no significant differences are found when changing the normalization of the images, the performance is affected by their quality. This suggests that changes in the intensity of the images do not alter the relevant information about the wound, whereas changes in brightness, contrast and sharpness do.

SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies.

OBJECTIVE: To evaluate sialic acid binding Ig-like lectin 1 (SIGLEC1) expression on monocytes by flow cytometry as a type I interferon biomarker in idiopathic inflammatory myopathies (IIM). METHODS: We performed a retrospective analysis of adult and paediatric patients with the diagnosis of IIM. SIGLEC1 expression was assessed by flow cytometry and was compared with Physician Global Assessment or Childhood Myositis Assessment Scale disease activity scores. Mann Whitney U test and receiver operating characteristic curves were used for cross-sectional data analysis (n=96), two-level mixed-effects linear regression model for longitudinal analyses (n=26, 110 visits). Response to treatment was analysed in 14 patients within 12 months, using Wilcoxon test. SIGLEC1 was compared with interferon-stimulated gene 15/MxA status by immunohistochemical staining of muscle biopsies (n=17). RESULTS: 96 patients with adult (a) and juvenile (j) dermatomyositis (DM, n=38), antisynthetase syndrome (AS, n=19), immune-mediated necrotising myopathy (IMNM, n=8), inclusion body myositis (IBM, n=9) and overlap myositis (n=22) were included. SIGLEC1 distinguished significantly between active and inactive disease with an area under the curve of 0.92 (95% CI 0.83 to 1) in DM and correlated with disease activity longitudinally (aDM: standardised beta=0.54, p<0.001; jDM: standardised beta=-0.70, p<0.001). Response to treatment in DM was associated with a decreasing SIGLEC1 (p<0.01, Wilcoxon test). SIGLEC1 was found upregulated in 8 of 19 patients with AS, 2 of 9 patients with IBM but not in IMNM. CONCLUSION: SIGLEC1 is a candidate biomarker to assess type I interferon activity in IIM and proved useful for monitoring disease activity and response to treatment in juvenile and adult DM.

DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain.

While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summary and critical evaluation of two epigenetic mechanisms, DNA methylation and non-coding RNA expression, on transcriptional modulation in nociceptive pathways during the development of tissue injury-associated pain. We assess the pre-clinical data and their translational implication and evaluate the potential of controlling DNA methylation and non-coding RNA expression as novel analgesic approaches and/or biomarkers of persistent pain.

Evaluation of SIGLEC1 in the diagnosis of suspected systemic lupus erythematosus.

OBJECTIVES: To evaluate and compare the diagnostic accuracy of SIGLEC1, a surrogate marker of type I IFN, with established biomarkers in an inception cohort of systemic lupus erythematosus (SLE). METHODS: SIGLEC1 was analysed by flow cytometry in 232 patients referred to our institution with suspected SLE between October 2015 and September 2020. RESULTS: SLE was confirmed in 76 of 232 patients (32.8 %) according to the 2019 EULAR/ACR classification criteria and their SIGLEC1 values were significantly higher compared with patients without SLE (P <0.0001). A sensitivity of 98.7 %, a specificity of 82.1 %, a negative predictive value (NPV) of 99.2 % and a positive predictive value (PPV) of 72.8 % were calculated for SIGLEC1. Adjusted to the highest reported prevalence of SLE, the NPV and PPV were >99.9 % and 0.1 %, respectively. Using receiver operating characteristic (ROC) analysis and DeLong testing, the area under the curve (AUC) for SIGLEC1 (AUC = 0.95) was significantly higher than for ANA (AUC = 0.88, P = 0.031), C3 (AUC = 0.83, P = 0.001) and C4 (AUC = 0.83, P = 0.002) but not for anti-dsDNA antibodies (AUC = 0.90, P = 0.163). CONCLUSION: IFN-I pathway activation is detectable in almost all newly diagnosed SLE patients. Thus, a negative test result for SIGLEC1 is powerful to exclude SLE in suspected cases.

A case of Flavonifractor plautii blood stream infection in a severe burn patient and a review of the literature.

BACKGROUND: Flavonifractor plautii is a strictly anaerobic rod shaped bacterium belonging to the family of Clostridiales. It is a commensal of the human intestinal microbiota which was seldom isolated from clinical samples, therefore clinical data are scarce. To date, only four cases of F. plautii infections were described, all occurring in immunosuppressed patients. CASE PRESENTATION: We report a case where F. plautii was isolated from the blood culture of a severe burn victim and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. DISCUSSION: To the best of our knowledge, this is the first case of F. plautii blood stream infection described in a burn patient.

Macrophage activation syndrome in a patient with adult-onset Still's disease following first COVID-19 vaccination with BNT162b2.

BACKGROUND: Adult-onset Still's disease (AOSD) is an autoinflammatory multi-systemic syndrome. Macrophage activation syndrome (MAS) is a potentially life-threatening complication of AOSD with a mortality rate of 10-20%. Especially viral infection is thought to be a common trigger for development of MAS. On the other hand, the occurrence of MAS following vaccinations is extremely rare and has been described in a few cases after measles or influenza vaccinations and more recently after ChAdOx1 nCoV-19 (COVID-19 viral vector vaccine, Oxford-AZ). CASE PRESENTATION: We report the case of a twenty-year-old female with adult-onset Still's disease (AOSD), who developed a MAS six days after receiving her first COVID-19 vaccine dose of BNT162b2 (mRNA vaccine, BioNTech/Pfizer) with ferritin levels of 136,680 µg/l (ref.: 13-150 µg/l). CONCLUSIONS: To the best of our knowledge, this is the first case report of development of MAS in a patient with preexisting AOSD after vaccination in general, and SARS-CoV-2 vaccination in particular. The new mRNA vaccines have generally shown a reassuring safety profile, but it has been shown that nucleic acids in general, including mRNA can act as pathogen-associated molecular patterns that activate toll-like receptors with extensive production of pro-inflammatory cytokines and further activation of immune cells. Proving an interferon 1 response in our patient directly after vaccination, we think that in this particular case the vaccination might have acted as trigger for the development of MAS. Even if it remains difficult to establish causality in the case of rare adverse events, especially in patients with autoimmune or autoinflammatory conditions, these complications are important to monitor and register, but do not at all diminish the overwhelming positive benefit-risk ratio of licensed COVID-19 vaccines.

Large variations in eutrophication among estuaries reflect massive differences in composition and biomass of macroalgal drift.

The characteristics of detached macroalgae (drift) in nearby highly eutrophic and mesotrophic estuaries in south-western Australia are compared to elucidate the magnitude and types of changes that occur in macroalgal drift when estuaries receive excessive nutrient input. Drift characteristics in the large basins of the microtidal, eutrophic Peel-Harvey and mesotrophic Swan-Canning, which is not subjected to large nutrient inputs directly from agricultural land, differed markedly. Biomass (dry weight) in mesotrophic estuary was dominated by rhodophytes (92%), particularly Laurencia and Hypnea, and in eutrophic estuary by opportunistic chlorophytes (68%), especially Chaetomorpha and Ulva. Prevalence and biomass of drift were far greater in the eutrophic estuary, particularly during summer and autumn when macroalgal growth rose sharply. Macroalgal biomass in the eutrophic estuary was positively related to salinity. These results facilitate predictions of how climatic and other anthropogenic changes influence extent of macroalgal growth and thus change the estuarine environment.

Procalcitonin Exerts a Mediator Role in Septic Shock Through the Calcitonin Gene-Related Peptide Receptor.

OBJECTIVES: Clinically, procalcitonin represents the most widely used biomarker of sepsis worldwide with unclear pathophysiologic significance to date. Pharmacologically, procalcitonin was shown to signal through both calcitonin receptor and calcitonin gene-related peptide receptor in vitro, yet the identity of its biologically relevant receptor remains unknown. DESIGN: Prospective randomized animal investigations and in vitro human blood studies. SETTING: Research laboratory of a university hospital. SUBJECTS: C57BL/6J mice and patients with post-traumatic sepsis. INTERVENTIONS: Procalcitonin-deficient mice were used to decipher a potential mediator role in experimental septic shock and identify the relevant receptor for procalcitonin. Cecal ligation and puncture and endotoxemia models were employed to investigate septic shock. Disease progression was evaluated through survival analysis, histology, proteome profiling, gene expression, and flow cytometry. Mechanistic studies were performed with cultured macrophages, dendritic cells, and gamma delta T cells. Main findings were confirmed in serum samples of patients with post-traumatic sepsis. MEASUREMENTS AND MAIN RESULTS: Procalcitonin-deficient mice are protected from septic shock and show decreased pulmonary inflammation. Mechanistically, procalcitonin potentiates proinflammatory cytokine expression in innate immune cells, required for interleukin-17A expression in gamma delta T cells. In patients with post-traumatic sepsis, procalcitonin positively correlates with systemic interleukin-17A levels. In mice with endotoxemia, immunoneutralization of interleukin-17A inhibits the deleterious effect of procalcitonin on disease outcome. Although calcitonin receptor expression is irrelevant for disease progression, the nonpeptide calcitonin gene-related peptide receptor antagonist olcegepant, a prototype of currently introduced antimigraine drugs, inhibits procalcitonin signaling and increases survival time in septic shock. CONCLUSIONS: Our experimental data suggest that procalcitonin exerts a moderate but harmful effect on disease progression in experimental septic shock. In addition, the study points towards the calcitonin gene-related peptide receptor as relevant for procalcitonin signaling and suggests a potential therapeutic application for calcitonin gene-related peptide receptor inhibitors in sepsis, which warrants further clinical investigation.

Elevated STAT1 expression but not phosphorylation in lupus B cells correlates with disease activity and increased plasmablast susceptibility.

OBJECTIVES: SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) - signal transducer and activator of transcription (STAT). JAK-STAT inhibition is an attractive therapeutic possibility for SLE. We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared with other autoimmune diseases and healthy controls (HD) and related it to disease activity. METHODS: Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T cells of 21 HD, 10 rheumatoid arthritis (RA), seven primary Sjögren's (pSS) and 22 SLE patients was analysed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs (peripheral blood mononuclear cells) of SLE patients and HD after IFNα and IFNγ incubation were further investigated. RESULTS: SLE patients showed substantially higher STAT1 but not pSTAT1 in B- and T-cell subsets. Increased STAT1 expression in B-cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker. STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ. CONCLUSION: Enhanced expression of STAT1 by B-cell candidates as a key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold a promise to block STAT1 expression and control plasmablast induction in SLE.

Deep Phenotyping of Urinary Leukocytes by Mass Cytometry Reveals a Leukocyte Signature for Early and Non-Invasive Prediction of Response to Treatment in Active Lupus Nephritis.

Non-invasive biomarkers are necessary for diagnosis and monitoring disease activity in lupus nephritis (LN) to circumvent risks and limitations of renal biopsies. To identify new non-invasive cellular biomarkers in the urine sediment of LN patients, which may reflect kidney inflammation and can be used to predict treatment outcome, we performed in-depth urinary immune cell profiling by mass cytometry. We established a mass cytometric workflow to comparatively analyze the cellular composition of urine and peripheral blood (PB) in 13 patients with systemic lupus erythematosus (SLE) with active, biopsy-proven proliferative LN. Clinical and laboratory data were collected at the time of sampling and 6 months after induction of therapy in order to evaluate the clinical response of each patient. Six patients with different acute inflammatory renal diseases were included as comparison group. Leukocyte phenotypes and composition differed significantly between urine and paired PB samples. In urine, neutrophils and monocytes/macrophages were identified as the most prominent cell populations comprising together about 30%-83% of nucleated cells, while T and B lymphocytes, eosinophils, and natural killer (NK) cells were detectable at frequencies of <10% each. The majority of urinary T cells showed phenotypical characteristics of activated effector memory T cells (EM) as indicated by the co-expression of CD38 and CD69 - a phenotype that was not detectable in PB. Kidney inflammation was also reflected by tissue-imprinted macrophages, which phenotypically differed from PB monocytes by an increased expression of HLA-DR and CD11c. The presence of activated urinary T cells and macrophages could be used for differential diagnosis of proliferative LN forms and other renal pathologies. Most interestingly, the amount of EM in the urine sediment could be used as a biomarker to stratify LN patients in terms of response to induction therapy. Deep immunophenotypic profiling of urinary cells in LN allowed us to identify a signature of activated T cells and macrophages, which appear to reflect leukocytic infiltrates in the kidney. This explorative study has not only confirmed but also extended the knowledge about urinary cells as a future non-invasive biomarker platform for diagnosis and precision medicine in inflammatory renal diseases.

Comparison of Spatiotemporal Gait Parameters Following Operative Treatment of Trimalleolar Ankle Fractures vs Healthy Controls.

BACKGROUND: Controversy continues regarding appropriate indications for posterior malleolus fracture fixation in unstable rotational trimalleolar ankle injuries, with limited data comparing gait in operatively treated trimalleolar ankle fractures vs control populations. The purpose of this study was to evaluate the effect of trimalleolar ankle fracture fixation on gait parameters in the early postoperative period as compared to a healthy control population. METHODS: Adult patients having undergone operative treatment of isolated trimalleolar ankle fractures were eligible for inclusion. A total of 10 patients met the inclusion criteria and participated in the analysis. Patients were evaluated using standard parameters of human gait 6 months after their index procedures, with gait values compared to a population of 17 non-age-matched healthy control subjects in addition to literature values of healthy populations of younger and older subjects. RESULTS: Significant differences were noted between the spatiotemporal gait parameters of healthy control subjects and patients who had undergone operative treatment of trimalleolar ankle fractures. However, within the fracture group itself, no differences were found between patients with or without posterior malleolar fixation for any of the tested gait parameters. When patients were compared to literature values of younger and older healthy control populations, they were found to have gait patterns more similar to older rather than younger individuals. CONCLUSION: Operative fixation of trimalleolar ankle fracture does not restore normal gait function in the early postoperative period. Fixation of the posterior malleolus in particular also does not appear to improve gait characteristics. Patients who undergo surgery for these injuries demonstrate gait patterns similar to those of healthy older adults. LEVEL OF EVIDENCE: Level II, Therapeutic (prospective cohort study).