The impact of vascular margin invasion on local recurrence after pancreatoduodenectomy in pancreatic adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PADC) still has nowadays a very impaired long-term survival. Most studies are focused on overall survival; however, local recurrence occurs about up to 50% of cases and seems to be highly related with margin resection status. We aim to analyze the impact of vascular resection margins on local recurrence (LR) and to assess its impact on overall and disease-free survival. METHODS: Eighty out of 191 patients who underwent pancreatoduodenectomy in a university hospital between 2006 and 2021 with PDAC diagnosis were analyzed and vascular margin status specifically addressed. Univariate and multivariate were performed. Time to LR was compared by using the Kaplan-Meier method and prognostic factors assessed using Cox regression hazards model. RESULTS: LR appeared in 10 (50%) of the overall R1 resections in the venous margin and 9 (60%) in the arterial one. Time to LR was significantly shorter when any margin was overall affected (23.2 vs 44.7 months, p = 0.01) and specifically in the arterial margin involvement (13.7 vs 32.1 months, p = 0.009). Overall R1 resections (HR 2.61, p = 0.013) and a positive arterial margin (HR 2.84, p = 0.012) were associated with local recurrence on univariate analysis, whereas arterial positive margin remained significant on multivariate analysis (HR 2.70, p = 0.031). CONCLUSIONS: Arterial margin invasion is correlated in our cohort with local recurrence. Given the limited ability to modify this margin intraoperatively, preoperative therapies should be considered to improve local margin clearance.

Synthesis, In Silico Study, and In Vitro Antifungal Activity of New 5-(1,3-Diphenyl-1H-Pyrazol-4-yl)-4-Tosyl-4,5-Dihydrooxazoles.

The increase in multi-drug resistant Candida strains has caused a sharp rise in life-threatening fungal infections in immunosuppressed patients, including those with SARS-CoV-2. Novel antifungal drugs are needed to combat multi-drug-resistant yeasts. This study aimed to synthesize a new series of 2-oxazolines and evaluate the ligands in vitro for the inhibition of six Candida species and in silico for affinity to the CYP51 enzymes (obtained with molecular modeling and protein homology) of the same species. The 5-(1,3-diphenyl-1H-pyrazol-4-yl)-4-tosyl-4,5-dihydrooxazoles 6a-j were synthesized using the Van Leusen reaction between 1,3-diphenyl-4-formylpyrazoles 4a-j and TosMIC 5 in the presence of K2CO3 or KOH without heating, resulting in short reaction times, high compound purity, and high yields. The docking studies revealed good affinity for the active site of the CYP51 enzymes of the Candida species in the following order: 6a-j > 4a-j > fluconazole (the reference drug). The in vitro testing of the compounds against the Candida species showed lower MIC values for 6a-j than 4a-j, and for 4a-j than fluconazole, thus correlating well with the in silico findings. According to growth rescue assays, 6a-j and 4a-j (like fluconazole) inhibit ergosterol synthesis. The in silico toxicity assessment evidenced the safety of compounds 6a-j, which merit further research as possible antifungal drugs.

Pars plana vitrectomy in patients aged 85 years and older: a single-centre, retrospective cohort study.

PURPOSE: To describe the epidemiology, indications and surgical results of pars plana vitrectomy (PPV) in patients over 85 years of age. METHODS: A retrospective cohort study was performed including all consecutive patients aged 85 years or older who underwent PPV between September 2018 and March 2022 in a single hospital in Madrid, Spain. Data on diagnosis, comorbidities, surgical indication, surgical details, surgical complications and surgical outcomes were collected from medical records. RESULTS: A total of 124 eyes of 119 patients (56 males, 47.1%) underwent PPV. Median age was 87 years (range 85-96). The most common surgical indications were complications of cataract surgery in 34 patients (28.6%), macular epiretinal membrane in 32 (26.9%), and rhegmatogenous retinal detachment (RRD) in 12 (10.1%). Mean preoperative best corrected visual acuity (BCVA) was 13.33 ± 42.34 ETDRS letters and improved to 40.05 ± 41.04 letters at 3 months (p < 0.001). BCVA had improved in 68.82% of patients at 3 months. Patients with chronic kidney disease (CKD; p < 0.001), RRD (p = 0.003), ocular trauma (p = 0.001) and age-related macular degeneration (AMD; p = 0.002) showed worse BCVA at 3 months from surgery. Patients with better preoperative BCVA (p < 0.001), and those who underwent 25G PPV (p = 0.041) showed better visual outcomes. CONCLUSIONS: PPV is an effective technique for improving visual acuity in patients aged 85 years and older with vitreoretinal diseases. Visual outcomes were better when patients had a better preoperative visual acuity and underwent 25G PPV. Patients with a previous diagnosis of AMD or CKD, and those undergoing surgery for ocular trauma or RRD had worse visual outcomes.

Epidemiology and clinical characteristics of psoriatic arthritis-related uveitis in Madrid, Spain.

PURPOSE: To describe the epidemiology and clinical characteristics of psoriatic arthritis (PsA) related uveitis in Madrid, Spain. METHODS: A case series nested in a retrospective single-center cohort of 494 patients with PsA was performed. Patients older than 18 years old whit a clinical diagnosis PsA-related uveitis who attended the Ramon y Cajal University Hospital in Madrid, Spain, between 1st January 2017 and 31st December 2019 were included in the study. Epidemiological and clinical data were retrieved from the electronic medical records. RESULTS: Thirteen cases of psoriatic arthritis-related uveitis (6 men and 7 women) were included. PsA-related uveitis showed an incidence of 0.05 cases per 100,000 persons/year (CI95 0.00-0.35), and a prevalence of 2.19 cases per 100,000 persons (CI95 1.24-3.79). The prevalence of active uveitis in the cohort of PsA patients was 2.6%. The first episode of uveitis (mean age of 48.15 ± 15.41 years) was anterior and unilateral in 92.31% of the cases. Most of the patients had a recurrent course (69.2%) with 0.92 flare-ups per patient/year (CI95 0.85-0.96). The uveitis preceded the diagnosis of psoriatic arthritis in 62.5% of the patients. In patients with PsA-related uveitis, HLA-B27 was present in 23.1%, HLA-Cw6 in 7.7%. CONCLUSIONS: Uveitis is a PsA manifestation that affects roughly 1 in 37 PsA patients, and that may precede the articular symptoms. It generally presents as a unilateral acute anterior uveitis and has a recurrent course. The most frequent observed complications are elevated intraocular pressure and cataracts.

3D Printed Parahydrophobic Surfaces as Multireaction Platforms.

Parahydrophobic surfaces (PHSs) composed of arrays of cubic µ-pillars with a double scale of roughness and variable wettability were systematically obtained in one step and a widely accessible stereolithographic Formlabs 3D printer. The wettability control was achieved by combining the geometrical parameters (H = height and P = pitch) and the surface modification with fluoroalkyl silane compounds. Homogeneous distribution of F and Si atoms onto the pillars was observed by XPS and SEM-EDAX. A nano-roughness on the heads of the pillars was achieved without any post-treatment. The smallest P values lead to surfaces with static contact angles (CAs) >150° regardless of the H utilized. Interestingly, the relationship 0.6 ≤ H/P ≤ 2.6 obtained here was in good agreement with the H/P values reported for nano- and submicron pillars. Furthermore, experimental CAs, advancing and receding CAs, were consistent with the theoretical prediction from the Cassie-Baxter model. Structures covered with perfluorodecyltriethoxysilane with high H and short P lead to PHSs. Conversely, structures covered with perfluorodecyltrimethoxysilane exhibited a superhydrophobic behavior. Finally, several aqueous reactions, such as precipitation, coordination complex, and nanoparticle synthesis, were carried out by placing the reactive agents as microdroplets on the parahydrophobic pillars, demonstrating the potential application as chemical multi-reaction array platforms for a large variety of relevant fields in microdroplet manipulation, microfluidics systems, and health monitoring, among others.

A System-on-a-Chip Implementation of a Post-Quantum Cryptography Scheme for Smart Meter Data Communications.

The security of Smart Meter (SM) systems will be a challenge in the era of quantum computing because a quantum computer might exploit characteristics of well-established cryptographic schemes to reach a successful security breach. From a practical perspective, this paper focuses on the feasibility of implementing a quantum-secure lattice-based key encapsulation mechanism in a SM, hardware-constrained equipment. In this regard, the post-quantum cryptography (PQC) scheme, FrodoKEM, an alternate candidate for the National Institute for Standards and Technology (NIST) post-quantum standardization process, is implemented using a System-on-a-Chip (SoC) device in which the Field Programmable Gate Array (FPGA) component is exploited to accelerate the most time-consuming routines in this scheme. Experimental results show that the execution time to run the FrodoKEM scheme in an SoC device reduces to one-third of that obtained by the benchmark implementation (i.e., the software implementation). Also, the attained execution time and hardware resource usage of this SoC-based implementation of the FrodoKEM scheme show that lattice-based cryptography may fit into SM equipment.

Neck adipose tissue accumulation is associated with higher overall and central adiposity, a higher cardiometabolic risk, and a pro-inflammatory profile in young adults.

OBJECTIVES: Neck adipose tissue (NAT) volume increases with general adiposity, with fat accumulating in different neck tissue compartments. In patients with certain malignant/benign tumours, the accumulation of NAT, and certain NAT distributions, have been associated with cardiometabolic risk (CMR). However, it is unknown whether the same relationships exist in healthy people, and whether NAT accumulation and distribution are related to the inflammatory status. METHODS: In this cross-sectional study, 139 young healthy adults (68% women) underwent a computed tomography scan to quantify the volume of compartmental (i.e., subcutaneous, intermuscular and perivertebral) and total NAT at the height of vertebra C5. Anthropometric indicators were measured, and body composition determined using dual energy X-ray absorptiometry. Information on CMR factors (i.e., blood glycaemic and lipid markers, blood pressure and physical fitness) was also gathered, and a CMR score calculated. Several plasma cytokines and serum components of the innate immune system were measured to determine the inflammatory status. RESULTS: Compartmental and total NAT volumes were directly related to body mass index (BMI), and lean, fat, and visceral adipose tissue (VAT) masses (all, P ≤ 0.05). Larger compartmental (especially intermuscular) and total NAT volumes were directly associated with the CMR score, several CMR factors (i.e., glycaemic and lipid markers and blood pressure), and the C3, C4 and leptin concentrations. They were, however, inversely correlated with the CMR factors high density lipoprotein-cholesterol (HDL-C) and physical fitness, and with the adiponectin concentration (all P ≤ 0.05). Several of these associations remained statistically significant (P ≤ 0.05) after adjustment for BMI, body fat percentage or VAT mass. Overall, results did not change after applying false discovery rate correction. CONCLUSIONS: NAT volume and its distribution among different tissue compartments is associated with the CMR and inflammatory profile of young healthy adults. Total NAT volume appears to be as valuable as VAT mass in terms of predicting CMR and inflammatory status.

Superhydrophobic µ-pillars via simple and scalable SLA 3D-printing: the stair-case effect and their wetting models.

In nature, superhydrophobic surfaces (SHSs) exhibit microstructures with several roughness scales. Scalable fabrication and build-up along the X-Y plane represent the promise of 3D printing technology. Herein we report 3D printed microstructures with a dual roughness scale that achieves SHS using a readily available Formlabs stereolithography (SLA) printer. Pillar-like structure (PLS) arrangements with a wide range of geometrical shapes were 3D printed at three resolutions and two printing orientations. We discovered that a tilted printing direction enables a stair-case pattern on the µ-PLS surfaces, conferring them a µ-roughness that reduces the solid-liquid contact area. The programmed resolution governs the number of polymerized layers that give rise to the stepped pattern on the µ-PLS surfaces. However, this is reduced as the printing resolution increases. Also, all samples' experimental contact angles were consistent with theoretical predictions from Cassie-Baxter, Wenzel, and Nagayama wettability models. The underlying mechanisms and governing parameters were also discussed. It is believed that this work will enable scalable and high throughput roughness design in augmenting future 3D printing object applications.

Survival analysis of time to SARS-CoV-2 PCR negativisation to optimise PCR prescription in health workers: the Henares COVID-19 healthcare workers cohort study.

OBJECTIVES: Reverse transcriptase PCR (RT-PCR) is considered the gold standard in diagnosing COVID-19. Infected healthcare workers do not go back to work until RT-PCR has demonstrated that the virus is no longer present in the upper respiratory tract. The aim of this study is to determine the most efficient time to perform RT-PCR prior to healthcare workers' reincorporation. MATERIALS AND METHODS: This is a cohort study of healthcare workers with RT-PCR-confirmed COVID-19. Data were collected using the medical charts of healthcare workers and completed with a telephone interview. Kaplan-Meier curves were used to determine the influence of several variables on the time to RT-PCR negativisation. The impact of the variables on survival was assessed using the Breslow test. A Cox regression model was developed including the associated variables. RESULTS: 159 subjects with a positive RT-PCR out of 374 workers with suspected COVID-19 were included. The median time to negativisation was 25 days from symptom onset (IQR 20-35 days). Presence of IgG, dyspnoea, cough and throat pain were associated with significant longer time to negativisation. Cox logistic regression was used to adjust for confounding variables. Only dyspnoea and cough remained in the model as significant determinants of prolonged negativisation time. Adjusted HRs were 0.68 (0.48-096) for dyspnoea and 0.61 (0.42-0.88) for dry cough. CONCLUSIONS: RT-PCR during the first 3 weeks leads to a high percentage of positive results. In the presence of respiratory symptoms, negativisation took nearly 1 week more. Those who developed antibodies needed longer time to negativisate.

Stereoselective synthesis of (26R)-26-hydroxydiosgenin and its effect on the regulation of rat ovarian function.

The stereoselective cyclization of a C-16 acetylated 22,26-dioxocholestene derivative to give the spirostane E and F rings, under alkaline conditions, yields exclusively the (26R)-26-hydroxydiosgenin. Both experimental and computational data support the formation of a single diastereoisomer. The effect of diosgenin and (26R)-26-hydroxydiosgenin on rat ovary is also investigated.

Selective synthesis of trisubstituted pyrroles through the reactions of alkynyl Fischer carbene complexes with oxazolones.

An efficient and simple synthesis of novel trisubstituted 1H-pyrroles 4a-qvia 1,3-dipolar cycloaddition of Δ3-trifluoromethyloxazolones 2a-d with both chromium and tungsten alkynyl Fischer carbene complexes (1a-h) is described. An unexpected and unreported -CF3 group elimination process was observed in the pyrrole structure. Our experimental and theoretical data suggested that the metal fragment may be responsible for this phenomenon. The dipolar cycloaddition proceeded efficiently to produce a single regioisomer, which was unambiguously established through NMR and single-crystal X-ray diffraction studies. Nevertheless, the reaction of alkynyl carbenes bearing an α,ß,γ,δ-unsaturated moiety with excess oxazolone 2a produced a polycyclic compound 6 speculatively formed through a cascade reaction involving 1,6-, 1,4- and 1,2-nucleophilic addition steps.

Advanced Robotic Surgery of the Parapharyngeal Space: Transoral Robotic Styloidectomy in Eagle Syndrome.

Eagle syndrome (ES) is characterized by symptomatic elongation of the styloid process or ossification of the stylohyoid ligament causing irritation and inflammation of the trigeminal, facial, glossopharyngeal, and vagus nerves. The use of robotic surgery has been accepted as a first-line treatment for some head and neck squamous cell carcinomas but not for styloidectomy. The aim of this article is to document our experience with a transoral robotic approach to treat ES and to present the outcomes of 6 patients.The author present the transoral robotic surgery as a successful alternative for the surgical management of ES. Our experience with this approach has been excellent, granting an optimal vision of the surgical field with the consequent safe manipulation of the instruments avoiding injuries to healthy tissue.

Enantiodivergent Cyclization by Inversion of the Reactivity in Ambiphilic Molecules.

Inverting the reactivity of the functional groups in ambiphilic molecules provides a new synthetic strategy to perform late-stage enantiodivergence. Both enantiomers of the final compound can be obtained from a common chiral precursor. As a proof of concept, the synthesis of substituted five- and six-membered oxacycles is described. The key step is the cyclization of an ambiphilic linear precursor bearing a propargylic alcohol and an epoxide linked through an alkyl chain. Through a slight modification of these linear precursors and employing different reaction conditions, these functional groups can inverse their chemical reactivity, producing one enantiomer or another of the final product. This enantiodivergent cyclization involves three stereogenic centers that can undergo fully controlled retention or inversion of their configuration depending on the cyclization pathway that is activated. The cyclization provides late-stage enantiodivergence, enabling the synthesis of either enantiomers of the oxacycles from a common chiral substrate with total transfer of the enantiomeric purity.

Adherence to and Persistence With Statin Therapy in a Veteran Population.

BACKGROUND: A relative cardiovascular risk reduction of 25% to 35% has been reported in patients starting a statin for elevated cholesterol; yet many patients fail to consistently take these medications as directed. OBJECTIVE: To evaluate factors affecting adherence and persistence with statin therapy. METHODS: This retrospective study analyzed data from a Veterans Affairs database of facilities west of the Rocky Mountains. Patient demographics, co-morbidities, and prescription information was collected for individuals newly prescribed a statin between July 1, 2007, and December 31, 2012. Adherence was determined using the medication possession ratio (MPR). Persistence was defined as the time from initiation of therapy until a refill gap of 135 days or greater occurred. RESULTS: Of 164 687 unique patients, overall adherence to statins a mean MPR of 0.843. Approximately 63% of patients were persistent with statin therapy 675 days after statin initiation. Patients prescribed pravastatin, atorvastatin, lovastatin, and rosuvastatin and those who took more than 1 different statin during the follow-up period had statistically significantly higher rates of adherence than those prescribed simvastatin. Older patients and those with a greater number of active prescriptions were found to be more adherent to statin medications. Patients with hypertension were more adherent to a statin, and those with diabetes mellitus and/or posttraumatic stress disorder (PTSD) were less adherent. Conclusion and Relevance: In veterans, overall statin adherence was excellent. Certain populations may benefit from interventions targeted at improving statin adherence, including younger veterans, those prescribed fewer medications, those taking simvastatin, and veterans with PTSD or diabetes mellitus.

Enantiopure 4-oxazolin-2-ones and 4-methylene-2-oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles.

Enantiopure 3-((R)- and 3-((S)-1-phenylethyl)-4-oxazoline-2-ones were evaluated as chiral building blocks for the divergent construction of heterocycles with stereogenic quaternary centers. The N-(R)- or N-(S)-1-phenylethyl group of these compounds proved to be an efficient chiral auxiliary for the asymmetric induction of the 4- and 5-positions of the 4-oxazolin-2-one ring through thermal and MW-promoted nucleophilic conjugated addition to Michael acceptors and alkyl halides. The resulting adducts were transformed via a cascade process into fused six-membered carbo- and heterocycles. The structure of the reaction products depended on the electrophiles and reaction conditions used. Alternative isomeric 4-methylene-2-oxazolidinones served as chiral precursors for a versatile and divergent approach to highly substituted cyclic carbamates. DFT quantum calculations showed that the formation of bicyclic pyranyl compounds was generated by a diastereoselective concerted hetero-Diels-Alder cycloaddition.

Isosteric Substitution of 4 H-1,2,4-Triazole by 1 H-1,2,3-Triazole in Isophthalic Derivative Enabled Hydrogel Formation for Controlled Drug Delivery.

In this work, we demonstrated that the simple substitution of the 1,2,4-triazole moiety in 5-( 4H-1,2,4-triazol-4-yl)isophthalic acid (5-TIA) by the 1 H-1,2,3-triazol-5-yl unit enables the preparation of a hydrogelator (click-TIA). In sharp contrast to 5-TIA, its isostere click-TIA undergoes self-assembly in water upon sonication, leading to the formation of stable supramolecular viscoelastic hydrogels with a critical gelation concentration of 6 g/L. Hydrogels made of click-TIA as well as hybrid hydrogels made of the mixture click-TIA + 5-TIA (molar ratio 1:0.2) were used to compare different properties of the materials (i.e., rheological properties, thermal properties, mechanical stability, morphology). In terms of toxicity, neither click-TIA nor 5-TIA showed cytotoxic effects on cellular viability of HeLa cells up to 2.3 × 10-3 g/L when compared to untreated cells incubated with DMSO. Furthermore, the hydrogels were used for the encapsulation and in vitro controlled release of oxytetracycline that followed first-order kinetics. For the hydrogel made of click-TIA, a maximum drug release of ∼60% was reached after ∼8 h within a pH range between 6.5 and 10. However, the release rate was reduced to approximately half of its value at pH values between 1.2 and 5.0, whereas the use of hybrid hydrogels made of click-TIA + 5-TIA allowed to reduce the original rate at pH ≤ 6.5.

Identification of putative second genetic hits in schizophrenia carriers of high-risk copy number variants and resequencing in additional samples.

Copy number variants (CNVs) conferring risk of schizophrenia present incomplete penetrance, suggesting the existence of second genetic hits. Identification of second hits may help to find genes with rare variants of susceptibility to schizophrenia. The aim of this work was to search for second hits of moderate/high risk in schizophrenia carriers of risk CNVs and resequencing of the relevant genes in additional samples. To this end, ten patients with risk CNVs at cytobands 15q11.2, 15q11.2-13.1, 16p11.2, or 16p13.11, were subjected to whole-exome sequencing. Rare single nucleotide variants, defined as those absent from main public databases, were classified according to bioinformatic prediction of pathogenicity by CADD scores. The average number of rare predicted pathogenic variants per sample was 13.6 (SD 2.01). Two genes, BFAR and SYNJ1, presented rare predicted pathogenic variants in more than one sample. Follow-up resequencing of these genes in 432 additional cases and 432 controls identified a significant excess of rare predicted pathogenic variants in case samples at SYNJ1. Taking into account its function in clathrin-mediated synaptic vesicle endocytosis at presynaptic terminals, our results suggest an impairment of this process in schizophrenia.

PERIPHERAL RETINAL VASCULITIS: Analysis of 110 Consecutive Cases and a Contemporary Reappraisal of Tubercular Etiology.

PURPOSE: Describe the clinical features and outcomes of patients with peripheral retinal vasculitis (RV) and describe clinical characteristics of presumed tubercular RV in a nonendemic setting. METHODS: Retrospective cohort study of 110 consecutive patients with peripheral RV at a tertiary referral eye care center in the United Kingdom. Retinal vasculitis was defined as RV with vitritis associated with peripheral retinal ischemia. Patients who also had positive Quantiferon Gold in Tube test, positive tuberculin skin test, and/or other evidence of systemic tuberculosis such as biopsy were labeled with presumed tubercular RV. Treatment success was defined as resolution of inflammation, and successful tapering of oral corticosteroids to less than 10 mg/day or topical steroids to less than twice a day. RESULTS: Mean age of the study population was 42.69 ± 14.95 years. Patients were predominantly Asian (49.1%) and Male (67.0%). A total of 73.2% had bilateral involvement. Sixty-nine (62.72%) patients had presumed tubercular RV. A total of 52.8% patients received antitubercular therapy, 65.5% received oral corticosteroids, and 17.3% required steroid-sparing oral immunosuppressive agents. A total of 85.19% of patients with presumed tubercular RV achieved treatment success with concurrent antitubercular therapy as against 75.61% of patients with nontubercular RV. CONCLUSION: This is the largest study of the epidemiology, clinical features, and outcomes of both peripheral RV and presumed tubercular RV to date. Presumed tubercular RV commonly seems to affect young males of Asian descent and had vitreous hemorrhage as common clinical findings and also demonstrated a good treatment outcome with antitubercular therapy.

What does IGRA testing add to the diagnosis of ocular tuberculosis? A Bayesian latent class analysis.

BACKGROUND: To evaluate the contribution made to the diagnostic work-up for patients with suspected ocular tuberculosis (TB) by QuantiFERON-TB Gold In-Tube (QFT) tests using latent class analysis model. METHODS: A single centre retrospective cohort study. A Bayesian latent class model was constructed on the basis of demographics, phenotypes and test results from patients attending a tertiary referral center in the UK. This estimated the probability of ocular TB for each patient in two versions, first with and then without QFT. The estimated probability of ocular TB was compared with treatment failure. RESULTS: From a database of 365 patients with clinical signs suggestive of ocular TB, 267 patients who had QFT and complete data were evaluated. Mean age was 45.0 ± 15.4 years with 141 (52.9%) male and 148 (50.5%) of Asian ethnicity. QFT was positive in 208 (70.1%) patients and ATT was instituted in 145 (49.5%) patients with 100 (34.1%) patients also having concurrent systemic corticosteroid therapy. The best estimate of a QFT level separating TB-positive and TB-negative patients was extremely low. This weak discrimination between TB and non-TB groups was reflected in poor positive and negative predictive values for treatment failure. CONCLUSIONS: The latent class model did not successfully predict treatment failure, despite taking all variables into account. The threshold between TB and non-TB in QFT values was implausibly low and removing QFT from the model made prediction slightly worse. A larger prospective study is required to establish the role of all tests, demographics and phenotypes in diagnosis.