Synthesis of Asymmetric Ionic Hybrid Detergents enables Micelles with Scalable Properties including Cell Compatibility.

Ionic detergents enable applications and cause harm in biospheres due to cell toxicity. The utility of covalent combinations between ionic and non-ionic detergent headgroups in modulating cell toxicity remains speculative due to the yet rarely explored synthesis. We close this gap and establish the modular synthesis of ionic/non-ionic hybrid detergents. We restructure a combinatorial methallyl dichloride one-pot coupling into a two-step coupling, which reduces by-products, improves product yields, and enables the gram-scale preparation of asymmetric, cationic/non-ionic and anionic/non-ionic hybrid detergents. Our modular synthesis delivers new modalities for the design of ionic detergents, including an unprecedented scaling of properties that determine applications, such as charge, critical micelle concentration (cmc), solubilizing properties, hard water tolerance, and cell compatibility. We uncover that shielding the charge in ionic headgroups can switch the detergent species that is toxic to cells from monomers to mixtures of monomers and micellar assemblies. Establishing the chemistry of ionic/non-ionic hybrid detergents provides a missing evolutionary link in the structural comparison of ionic and non-ionic detergents, enables an easy synthesis access to yet unexplored chemical spaces of asymmetric hybrid materials, and delivers new modalities for designing the toxicity of supramolecular nanomaterials.

Highly Sensitive, Easy-to-Use, One-Step Detection of Peroxide-, Nitrate- and Chlorate-Based Explosives with Electron-Rich Ni Porphyrins.

Homemade explosives, such as peroxides, nitrates, and chlorates, are increasingly abused by terrorists, criminals, and amateur chemists. The starting materials are easily accessible and instructions on how to make the explosives are described on the Internet. Safety considerations raise the need to detect these substances quickly and in low concentrations using simple methods. Conventional methods for the detection of these substances require sophisticated, electrically operated, analytical equipment. The simpler chemical detection methods are multistep and require several chemicals. We have developed a simple, one-step method that works similarly to a pH test strip in terms of handling. The analytical reaction is based on an acid-catalyzed oxidation of an electron-rich porphyrin to an unusually stable radical cation and dication. The detection limit for the peroxide-based explosive triacetone triperoxide (TATP), which is very frequently used by terrorists, is 40 ng and thus low enough to detect the substance without direct contact via the gas phase. It is sufficient to bring the stick close to the substance to observe a color change from red to green. Nitrates and chlorates, such as ammonium nitrate, urea nitrate, or potassium chlorate, are detected by direct contact with a sensitivity of 85-350 ng. A color change from red to dark brown is observed. The test thus detects all homemade explosives and distinguishes between the extremely impact-, shock-, and friction-sensitive peroxides and the less sensitive nitrates and chlorates by color change of a simple test strip.

Digital Therapeutic (Mika) Targeting Distress in Patients With Cancer: Results From a Nationwide Waitlist Randomized Controlled Trial.

BACKGROUND: Distress is highly prevalent among patients with cancer, but supportive care needs often go unmet. Digital therapeutics hold the potential to overcome barriers in cancer care and improve health outcomes. OBJECTIVE: This study conducted a randomized controlled trial to investigate the efficacy of Mika, an app-based digital therapeutic designed to reduce distress across the cancer trajectory. METHODS: This nationwide waitlist randomized controlled trial in Germany enrolled patients with cancer across all tumor entities diagnosed within the last 5 years. Participants were randomized into the intervention (Mika plus usual care) and control (usual care alone) groups. The participants completed web-based assessments at baseline and at 2, 6, and 12 weeks. The primary outcome was the change in distress from baseline to week 12, as measured by the National Comprehensive Cancer Network Distress Thermometer. Secondary outcomes included depression, anxiety (Hospital Anxiety and Depression Scale), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and quality of life (Clinical Global Impression-Improvement Scale). Intention-to-treat and per-protocol analyses were performed. Analyses of covariance were used to test for outcome changes over time between the groups, controlling for baseline. RESULTS: A total of 218 patients (intervention: n=99 and control: n=119) were included in the intention-to-treat analysis. Compared with the control group, the intervention group reported greater reductions in distress (P=.03; ηp²=0.02), depression (P<.001; ηp²=0.07), anxiety (P=.03; ηp²=0.02), and fatigue (P=.04; ηp²=0.02). Per-protocol analyses revealed more pronounced treatment effects, with the exception of fatigue. No group difference was found for quality of life. CONCLUSIONS: Mika effectively diminished distress in patients with cancer. As a digital therapeutic solution, Mika offers accessible, tailored psychosocial and self-management support to address the unmet needs in cancer care. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00026038; https://drks.de/search/en/trial/DRKS00026038.

Synthetic co-culture in an interconnected two-compartment bioreactor system: violacein production with recombinant E. coli strains.

The concept of modular synthetic co-cultures holds considerable potential for biomanufacturing, primarily to reduce the metabolic burden of individual strains by sharing tasks among consortium members. However, current consortia often show unilateral relationships solely, without stabilizing feedback control mechanisms, and are grown in a shared cultivation setting. Such 'one pot' approaches hardly install optimum growth and production conditions for the individual partners. Hence, novel mutualistic, self-coordinating consortia are needed that are cultured under optimal growth and production conditions for each member. The heterologous production of the antibiotic violacein (VIO) in the mutually interacting E. coli-E. coli consortium serves as an example of this new principle. Interdependencies for growth control were implemented via auxotrophies for L-tryptophan and anthranilate (ANT) that were satisfied by the respective partner. Furthermore, VIO production was installed in the ANT auxotrophic strain. VIO production, however, requires low temperatures of 20-30 °C which conflicts with the optimum growth temperature of E. coli at 37 °C. Consequently, a two-compartment, two-temperature level setup was used, retaining the mutual interaction of the cells via the filter membrane-based exchange of medium. This configuration also provided the flexibility to perform individualized batch and fed-batch strategies for each co-culture member. We achieved maximum biomass-specific productivities of around 6 mg (g h)-1 at 25 °C which holds great promise for future applications.

Detergent Chemistry Modulates the Transgression of Planetary Boundaries including Antimicrobial Resistance and Drug Discovery.

Detergent chemistry enables applications in the world today while harming safe operating spaces that humanity needs for survival. Aim of this review is to support a holistic thought process in the design of detergent chemistry. We harness the planetary boundary concept as a framework for literature survey to identify progresses and knowledge gaps in context with detergent chemistry and five planetary boundaries that are currently transgressed, i.e., climate, freshwater, land system, novel entities, biosphere integrity. Our survey unveils the status of three critical challenges to be addressed in the years to come, including (i) the implementation of a holistically, climate-friendly detergent industry; (ii) the alignment of materialistic and social aspects in creating technical solutions by means of sustainable chemistry; (iii) the development of detergents that serve the purpose of applications but do not harm the biosphere in their role as novel entities. Specifically, medically relevant case reports revealed that even the most sophisticated detergent design cannot sufficiently accelerate drug discovery to outperform the antibiotic resistance development that detergents simultaneously promote as novel entities. Safe operating spaces that humanity needs for its survival may be secured by directing future efforts beyond sustainable chemistry, resource efficiency, and net zero emission targets.

Triplet sensitization enables bidirectional isomerization of diazocine with 130 nm redshift in excitation wavelengths.

Diazocines are bridged azobenzenes with phenyl rings connected by a CH2-CH2 group. Despite this rather small structural difference, diazocine exhibits improved properties over azobenzene as a photoswitch and most importantly, its Z configuration is more stable than the E isomer. Herein, we reveal yet another unique feature of this emerging class of photoswitches. In striking contrast to azobenzenes and other photochromes, diazocine can be selectively switched in E → Z direction and most intriguingly from its thermodynamically stable Z to metastable E isomer upon successive excitation of two different triplet sensitizers present in solution at the same time. This approach leads to extraordinary large redshift of excitation wavelengths to perform isomerization i.e. from 400 nm blue to 530 nm green light (Z → E) and from 530 nm green to 740 nm far-red one (E → Z), which falls in the near-infrared window in biological tissue. Therefore, this work opens up of potential avenues for utilizing diazocines for example in photopharmacology, smart materials, light energy harvesting/storage devices, and out-of-equilibrium systems.

Digital therapeutic to improve cancer-related well-being: a pilot randomized controlled trial.

OBJECTIVE: This randomized waitlist controlled pilot study aimed to evaluate the feasibility and preliminary efficacy of Mika, an app-based digital therapeutic intervention hypothesized to improve management and the support of cancer patients. METHODS: Patients with gynecological malignancies undergoing post-operative or routine outpatient chemotherapy were randomized (5:2) into intervention (Mika plus treatment-as-usual) and control (treatment-as-usual alone). Feasibility outcomes including dropout rate, reasons for dropout, and intervention adherence, as well as efficacy outcomes including depression, fatigue, and health literacy were assessed at baseline, 4, 8, and 12 weeks. Changes in efficacy outcomes from baseline to week 12 were evaluated in the intervention group only by means of Wilcoxon signed-rank tests. RESULTS: Seventy participants (intervention group, n=50; control group, n=20) with gynecological cancer (ovarian, cervical, and endometrial) were randomized. The dropout rate increased from 15.7% (11/70) between baseline and week 4 to 37.1% (26/70) between weeks 8 and 12. Primary reasons for dropout were death (n=10) and health status deterioration (n=11). The initial high intervention adherence observed between baseline and week 4 (86% usage rate, average usage time: 120 min, average number of logins: 16.7) declined in weeks 8 to 12 (46% usage rate, average usage time: 41 min, average number of logins: 9). Participants in the intervention group showed significant intra-individual reductions in depressive symptoms by 42% (d=0.85) and fatigue symptoms by 23.1% (d=0.5) from baseline to 12 weeks. CONCLUSIONS: This pilot study provides initial evidence of the feasibility and efficacy of Mika in improving the well-being of cancer patients. The high initial intervention adherence and significant reductions in depressive and fatigue symptoms suggest that Mika has the potential to improve the management and support of cancer patients. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) ID: DRKS00023791; retrospectively registered on February 24, 2022.

Emergence of mass spectrometry detergents for membrane proteomics.

Detergents enable the investigation of membrane proteins by mass spectrometry. Detergent designers aim to improve underlying methodologies and are confronted with the challenge to design detergents with optimal solution and gas-phase properties. Herein, we review literature related to the optimization of detergent chemistry and handling and identify an emerging research direction: the optimization of mass spectrometry detergents for individual applications in mass spectrometry-based membrane proteomics. We provide an overview about qualitative design aspects including their relevance for the optimization of detergents in bottom-up proteomics, top-down proteomics, native mass spectrometry, and Nativeomics. In addition to established design aspects, such as charge, concentration, degradability, detergent removal, and detergent exchange, it becomes apparent that detergent heterogeneity is a promising key driver for innovation. We anticipate that rationalizing the role of detergent structures in membrane proteomics will serve as an enabling step for the analysis of challenging biological systems.

An effective and optimized patient-specific QA workload reduction for VMAT plans after MLC-modelling optimization.

INTRODUCTION: Many complexity metrics characterize modulated plans. First, this study aimed at identify the optimal complexity metrics to reduce workload associated to patient-specific quality assurance (PSQA) for our equipment and processes. Second, it intended to optimize our MLC modelling to improve measurement and calculation agreement with expectation of further reducing PSQA workload. METHODS: Correlation and sensitivity at specificity equals to 1 were evaluated for PSQA results and different complexity metrics. Thresholds to stop PSQA were determined. After validation of the optimal complexity metric and threshold for our equipment and process, the MLC modelling was reviewed with a recently published methodology. This method is based on measurements with a Farmer-type ionization chamber of synchronous and asynchronous sweeping gap plans. Effect on the PSQA results and the identified threshold was investigated. RESULTS: In our center, the most appropriate complexity metric for reducing our PSQA workload was the Modulation Complexity Score for VMAT (MCSv). The optimization of the MLC modelling significantly reduced the number of controlled plans, specifically for one of our two Varian Clinac. Any plan with a MCSv >= 0.34 is treated without PSQA. CONCLUSION: This study rationalized and reduced our PSQA workload by approximately 30%. It is a continuing work with new TPS, machine or PSQA equipment. It encourages centers to re-evaluate their MLC modelling as well as assess the benefit of complexity metrics to streamline their PSQA workflow. An easier access, at least for reporting, at best for optimizing plans, into the TPS would be beneficial for the community.

Light-Controlled Destruction and Assembly: Switching between Two Differently Composed Cage-Type Complexes.

We report on two regioisomeric, diazocine ligands 1 and 2 that can both be photoswitched between the E- and Z-configurations with violet and green light. The self-assembly of the four species (1-Z, 1-E, 2-Z, 2-E) with CoII ions was investigated upon changing the coordination vectors as a function of the ligand configuration (E vs Z) and regioisomer (1 vs 2). With 1-Z, Co2 (1-Z)3 was self-assembled, while a mixture of ill-defined species (oligomers) was observed with 2-Z. Upon photoswitching with 385 nm to the E configurations, the opposite was observed with 1-E forming oligomers and 2-E forming Co2 (2-E)3 . Light-controlled dis/assembly was demonstrated in a ligand competition experiment with sub-stoichiometric amounts of CoII ions; alternating irradiation with violet and green light resulted in the reversible transformation between Co2 (1-Z)3 and Co2 (2-E)3 over multiple cycles without significant fatigue by photoswitching.

Effect of an axial ligand on the self-assembly of molecular platforms.

Sub-monolayer amounts of trioxatriangulenium (TOTA) molecules functionalized with biphenyl on Ag(111) were investigated with scanning tunnelling microscopy. The molecule is comprised of a rod-shaped axial ligand and a triangular platform that tends to form hydrogen bonds in arrays. Two superstructures are observed, a hexagonal tiling and a phase of molecular double rows. While the former structure matches previous observations from other functionalized TOTA molecules the latter one was unexpected. Aided by density functional theory results, we analyse the observed intramolecular contrast and present a model of the new phase. We discuss possible interaction mechanisms underlying the molecular pattern.

Photoswitchable Diazocine-Based Estrogen Receptor Agonists: Stabilization of the Active Form inside the Receptor.

Photopharmacology is an emerging approach in drug design and pharmacological therapy. Light is used to switch a pharmacophore between a biologically inactive and an active isomer with high spatiotemporal resolution at the site of illness, thus potentially avoiding side effects in neighboring healthy tissue. The most frequently used strategy to design a photoswitchable drug is to replace a suitable functional group in a known bioactive molecule with azobenzene. Our strategy is different in that the photoswitch moiety is closer to the drug's scaffold. Docking studies reveal a very high structural similarity of natural 17ß-estradiol and the E isomers of dihydroxy diazocines, but not their Z isomers, respectively. Seven dihydroxy diazocines were synthesized and subjected to a biological estrogen reporter gene assay. Four derivatives exhibit distinct estrogenic activity after irradiation with violet light, which can be shut off with green light. Most remarkably, the photogenerated, active E form of one of the active compounds isomerizes back to the inactive Z form with a half-life of merely several milliseconds in water, but nevertheless is active for more than 3 h in the presence of the estrogen receptor. The results suggest a significant local impact of the ligand-receptor complex toward back-isomerization. Thus, drugs that are active when bound but lose their activity immediately after leaving the receptor could be of great pharmacological value because they strongly increase target specificity. Moreover, the drugs are released into the environment in their inactive form. The latter argument is particularly important for drugs that act as endocrine disruptors.

Hospitalization and Death in the First 30 days After Outpatient Lower Extremity Arterial Stenting.

PURPOSE: To compare the safety of outpatient versus inpatient endovascular treatment of lower extremity arterial disease (LEAD) using real-life data. MATERIALS AND METHODS: This retrospective observational study used real-life data from the French national health data information system on adult patients who underwent stenting for LEAD between 2013 and 2016. The outcomes of interest were all-cause mortality, all-cause hospitalization, planned hospitalization, and unplanned hospitalization at day 3 and day 30 after the index endovascular intervention for LEAD revascularization. A propensity score was used to control for indication bias. Outcome rates in outpatient and inpatient settings were compared with the Poisson regression model. Sensitivity analyses were performed by varying the definition of the outcomes of interest. RESULTS: During the study period, 26,715 interventions were performed among which 2819 (10.6%) were in outpatient settings. Outpatients were slightly younger than inpatients (64.73 ± 10.68 vs. 68.10 ± 11.50, respectively). The percentage of women patients was similar: 19.8% in the outpatient group and 27.2% in the inpatient group. Within 30 days after discharge, 73 patients (.31%) and 2 (.07%) patients (p = .02) died in the inpatient group and outpatient group, respectively. The death and rehospitalization rate were similar: 3.8 and 3.5 per 1000 person-months for inpatients and outpatients, respectively. No difference was observed after adjusting for patients' case-mix in the regression model (RR = .99; 95% CI [.82-1.19]). CONCLUSIONS: Outpatient stenting for LEAD did not present any additional risk of early postoperative rehospitalization or death compared with inpatient stenting.

The meV XUV-RIXS facility at UE112-PGM1 of BESSY II.

Resonant inelastic X-ray scattering in the XUV-regime has been implemented at BESSY II, pushing for a few-meV bandwidth in inelastic X-ray scattering at transition metal M-edges, rare earth N-edges and the K-edges of light elements up to carbon with full polarization control. The new dedicated low-energy beamline UE112-PGM1 has been designed to provide 1 µm vertical and 20 µm horizontal beam dimensions that serve together with sub-micrometre solid-state sample positioning as the source point for a high-resolution plane grating spectrometer and a high-transmission Rowland spectrometer for rapid overview spectra. The design and commissioning results of the beamline and high-resolution spectrometer are presented. Helium autoionization spectra demonstrate a resolving power of the beamline better than 10 000 at 64 eV with a 300 lines mm-1 grating while the measured resolving power of the spectrometer in the relevant energy range is 3000 to 6000.

Highly Crowded Twisted Thienylene-Phenylene Structures: Evidence for Through-Space Orbital Coupling in a [4]Catenated Topology.

Sterically highly crowded and twisted thienylene-phenylenes are synthesized and structurally characterized. Single-crystal X-ray structure analyses and theoretical studies give evidence of through-space delocalization of π-electrons of peripheral (hetero)aromatic rings in toroidal and catenated topology.

The diagnostic value of cytokines for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine.

Vertebral osteomyelitis (VO) is a primary infection of the endplates of the vertebral bodies with secondary infection of the adjacent intervertebral discs. Diagnosis is often delayed due to unspecific symptoms and a lack of specific infection markers. In this prospective study, we determined the suitability of 27 cytokines for the discrimination of VO and degenerative diseases of the spine and compared its diagnostic potential in relation to the C-reactive protein (CRP), which is widely used as a non-specific inflammation marker in clinical diagnostics. The patients included in this study underwent surgical stabilization of the lumbar and/or thoracic spine with removal of 1 or more affected intervertebral discs, as therapy for VO (n = 16) or for erosive osteochondrosis (EO, control group, n = 20). We evaluated the cytokine and CRP concentrations before (pre-OP = -20-0d where 0 means the day of surgery) and after surgery (post-OP) on days 3-5, 6-11, 40-56, and 63-142. Compared to the control patients pre-OP, a significantly higher elevation of the 4 cytokines IL-6, IL-8, IL-12 (p70), and VEGF as well as CRP were found in the VO patients, showing an area under the curve > 0.80 pre-OP. No significant differences were observed between VO patients with high and low virulent bacteria with respect to all 5 elevated biomarkers. This is the first prospective study in which a broad spectrum of 27 cytokines was analysed via multiplex assay using sera from patients with and without VO. Our results show that, in addition to CRP, 4 different cytokines were significantly altered in VO but not control patients. The results implicate that these candidate cytokines may be used in a multiplex assay for discrimination between VO and degenerative diseases of the spine.

Azimuthal Dipolar Rotor Arrays on Surfaces.

A set of dipolar molecular rotor compounds was designed, synthesized and adsorbed as self-assembled 2D arrays on Ag(111) surfaces. The title molecules are constructed from three building blocks: (a) 4,8,12-trioxatriangulene (TOTA) platforms that are known to physisorb on metal surfaces such as Au(111) and Ag(111), (b) phenyl groups attached to the central carbon atom that function as pivot joints to reduce the barrier to rotation, (c) pyridine and pyridazine units as small dipolar units on top. Theoretical calculations and scanning tunneling microscopy (STM) investigations hint at the fact that the dipoles of neighboring rotors interact through space through pairs of energetically favorable head-to-tail arrangements.

Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates.

The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine meta-carborane, a water-soluble monosaccharide and a linking unit, namely glycine or ethylenediamine, for facile coupling with various tumor-selective biomolecules bearing a free amino or carboxylic acid group. In this work, coupling experiments with two selected biomolecules, a coumarin derivative and folic acid, were included. The task of every component in this approach was carefully chosen: the carborane moiety supplies ten boron atoms, which is a tenfold increase in boron content compared to the l-boronophenylalanine (l-BPA) presently used in BNCT; the sugar moiety compensates for the hydrophobic character of the carborane; the linking unit, depending on the chosen biomolecule, acts as the connection between the tumor-selective component and the boron-rich moiety; and the respective tumor-selective biomolecule provides the necessary selectivity. This approach makes it possible to develop a modular and feasible strategy for the synthesis of readily obtainable boron-rich agents with optimized properties for potential applications in BNCT.

Use of the COPD Assessment Test (CAT) to screen for COPD in dairy farmers: AIRBAg study.

OBJECTIVES: People at risk of chronic obstructive pulmonary disease (COPD) can benefit from appropriate medical management before severe symptoms appear. This study assesses the value of the COPD Assessment Test (CAT) questionnaire for screening dairy farmers, who tend to be slow or reluctant to seek health care. METHODS: During the time period 2012-2017, 2089 randomly selected dairy farmers in Brittany (France) were invited to complete self-administered questionnaires (including the CAT) and to undergo an occupational health check-up using an electronic mini-spirometer and conventional spirometry. Those showing symptoms suggestive of COPD and/or a ratio FEV1 /FEV6 < 80% were sent to a pulmonologist for a further check-up, including spirometry with a reversibility test. Multivariate logistic models based on CAT scores and socio-demographic or work-related factors were developed to predict COPD. RESULTS: The 1231 farmers who underwent the occupational health check-up included 1203 who met the inclusion/exclusion criteria. Pulmonologist identified 16 (1.3%) cases of COPD. A multivariate logistic regression model (covariates: CAT sum score, on-farm time, BMI, smoking status, free-stall mulching) provided an area under the receiver-operating characteristic curve (AUC) of 0.87 (95% CI: 0.75-0.98). Using a cut-off of 0.007 gave a sensitivity of 93.8% and a specificity of 62.4%. Another model that included CAT breathlessness and the same covariates performed marginally better (AUC = 0.88, 95% CI: 0.77-0.98). CONCLUSION: Our predictive models can both benefit dairy farmers by providing early diagnosis and management of their COPD and avoid unnecessary, costly spirometry during the screening process.

The diagnostic value of soluble urokinase-type plasminogen activator receptor (suPAR) for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine.

BACKGROUND: There is still a challenge in discriminating between vertebral osteomyelitis and degenerative diseases of the spine. To this end, we determined the suitability of soluble urokinase-type plasminogen activator receptor (suPAR) and compared the diagnostic potential of suPAR to CRP. METHODS: Patients underwent surgical stabilization of the lumbar and/or thoracic spine with removal of one or more affected intervertebral discs, as therapy for vertebral osteomyelitis (n = 16) or for erosive osteochondrosis (control group, n = 20). In this prospective study, we evaluated the suPAR and CRP levels before (pre-OP) and after surgery (post-OP) on days 3-5, 6-11, 40-56, and 63-142. RESULTS: The suPAR levels in vertebral osteomyelitis patients were significantly higher than those from controls pre-OP, 3-5 days post-OP, and 6-11 days post-OP. Significantly higher CRP levels were observed in the vertebral osteomyelitis group than in the controls pre-OP and 6-11 days post-OP. Levels of suPAR and CRP correlated positively in all patients in the pre-OP period: r = 0.63 (95% CI: 0.37-0.79), p < 0.0001. The values for the area under the receiver operating characteristics curve (AUC) for pre-OP and the overall model post-OP were 0.88 (95% CI: 0.76-1.00) and 0.84 (95% CI: 0.71-0.97) for suPAR, 0.93 (95% CI: 0.85-1.00) and 0.77 (95% CI: 0.62-0.93) for CRP, and 0.98 (95% CI: 0.96-1.00) and 0.91 (95% CI: 0.82-1.00) for the combination of suPAR and CRP. The AUC for suPAR pre-OP revealed an optimum cut-off value, sensitivity, specificity, NPV, and PPV of 2.96 ng/mL, 0.69, 1.00, 0.80, and 1.00, respectively. For CRP, these values were 11.58 mg/L, 0.88, 0.90, 0.90, and 0.88, respectively. CONCLUSION: The present results show that CRP is more sensitive than suPAR whereas suPAR is more specific than CRP. Moreso, our study demonstrated that improvement in the diagnostic power for discrimination of vertebral osteomyelitis and degenerative diseases of the spine can be achieved by a combination of both suPAR and CRP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02554227, posted Sept. 18, 2015, and updated Aug. 13, 2019.