Evaluation of C-Reactive Protein and Computer-Aided Analysis of Chest X-rays as Tuberculosis Triage Tests at Health Facilities in Lesotho and South Africa.

BACKGROUND: To improve tuberculosis case-finding, rapid, non-sputum triage tests need to be developed according to the World Health Organization target product profile (TPP) (>90% sensitivity, >70% specificity). We prospectively evaluated and compared artificial intelligence-based, computer-aided detection software, CAD4TBv7, and C-reactive protein assay (CRP) as triage tests at health facilities in Lesotho and South Africa. METHODS: Adults (≥18 years) presenting with ≥1 of the 4 cardinal tuberculosis symptoms were consecutively recruited between February 2021 and April 2022. After informed consent, each participant underwent a digital chest X-ray for CAD4TBv7 and a CRP test. Participants provided 1 sputum sample for Xpert MTB/RIF Ultra and Xpert MTB/RIF and 1 for liquid culture. Additionally, an expert radiologist read the chest X-rays via teleradiology. For primary analysis, a composite microbiological reference standard (ie, positive culture or Xpert Ultra) was used. RESULTS: We enrolled 1392 participants, 48% were people with HIV and 24% had previously tuberculosis. The receiver operating characteristic curve for CAD4TBv7 and CRP showed an area under the curve of .87 (95% CI: .84-.91) and .80 (95% CI: .76-.84), respectively. At thresholds corresponding to 90% sensitivity, specificity was 68.2% (95% CI: 65.4-71.0%) and 38.2% (95% CI: 35.3-41.1%) for CAD4TBv7 and CRP, respectively. CAD4TBv7 detected tuberculosis as well as an expert radiologist. CAD4TBv7 almost met the TPP criteria for tuberculosis triage. CONCLUSIONS: CAD4TBv7 is accurate as a triage test for patients with tuberculosis symptoms from areas with a high tuberculosis and HIV burden. The role of CRP in tuberculosis triage requires further research. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov identifier: NCT04666311.

Development of a clinical prediction score for Ebola virus disease screening at triage centers in the Democratic Republic of the Congo.

The 2018-2020 Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) was the largest since the disease's discovery in 1976. Rapid identification and isolation of EVD patients are crucial during triage. This study aimed to develop a clinical prediction score for EVD using clinical and epidemiological predictors. We conducted a retrospective cross-sectional study using surveillance data from EVD outbreak, collected during routine clinical care at the Ebola Transit Center (ETC) in Beni, DRC, from 2018 to 2020. The Spiegelhalter and Knill-Jones method was used for score development, including potential predictors with an adjusted likelihood ratio above 2 or below 0.50. Validation was performed using a dataset previously published in PLOSOne by Tshomba et al. Among 3725 patients screened, 3698 fulfilled the inclusion criteria, with 571 (15.4%) testing positive for EVD via RT-PCR Test. Seven predictive factors were identified: asthenia, sore throat, conjunctivitis, bleeding gums, hematemesis, contact with a sick person, and contact with a traditional healer. The prediction score achieved an Area under the receiver operating characteristic (AUROC) of 0.764, with 81.4% sensitivity and 53.6% specificity at a -1 cutoff. External validation demonstrated an AUROC of 0.766, with 80.8% sensitivity and 41.4% specificity at the -1 cutoff. Our study developed a screening tool to assess the risk of suspected patients developing EVD and being admitted to ETUs for RT-PCR testing and treatment. External validation results affirmed the model's reliability and generalizability in similar settings, suggesting its potential integration into clinical practice. Given the severity and urgency of EVD as well as the risk nosocomial EVD transmission, it is essential to continuously update these models with real-time data on symptoms, disease progression, patient outcomes and validated RDT during EVD outbreaks. This approach will enhance model accuracy, enabling more precise risk assessments and more effective outbreak management.

A prospective evaluation of the diagnostic accuracy of the point-of-care VISITECT CD4 Advanced Disease test in seven countries.

BACKGROUND: CD4 measurement is pivotal in the management of advanced HIV disease. VISITECT® CD4 Advanced Disease (AccuBio Limited, Alva, UK; VISITECT) is an instrument-free, point-of-care, semi-quantitative test allowing visual identification of a CD4 ≤200 cells/µl, or >200 cells/µl from finger-prick or venous blood. METHODS: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM (clinicaltrials.gov: NCT04089423), people living with HIV of ≥18 years old were prospectively recruited in seven countries from outpatient departments if a tuberculosis symptom was present, and from inpatient departments. Participants provided venous blood for CD4 measurement using flow cytometry (reference standard) and finger-prick blood for VISITECT (index text), performed at point-of-care. Sensitivity, specificity, and positive and negative predictive values of VISITECT to determine a CD4 ≤200 cells/µl were evaluated. RESULTS: Among 1604 participants, the median flow cytometry CD4 was 367 (IQR 128-626) cells/µl and 521 (32.5%) had a CD4 ≤200 cells/µl. VISITECT sensitivity was 92.7% (483/521, 95% CI 90.1-94.7%) and specificity was 61.4% (665/1083, 95% CI 58.4-64.3%). For participants with a CD4 between 0-100, 101-200, 201-300, 301-500, and >500 cells/µl, VISITECT misclassified 4.5% (95% CI 2.5-7.2%), 12.5 (95% CI 8.0-18.2%), 74.1% (95% CI 67.0-80.5%), 48.0% (95% CI 42.5-53.6%), and 22.6% (95% CI 19.3-26.3%), respectively. CONCLUSIONS: VISITECT's sensitivity, but not specificity, met the World Health Organization's minimal sensitivity and specificity threshold of 80% for point-of-care CD4 tests. VISITECT's quality needs to be assessed and its accuracy optimized. VISITECT´s utility as CD4 triage test should be investigated.

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.

Importance: Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION). Objective: To investigate whether there is an association between semaglutide and risk of NAION. Design, Setting, and Participants: In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023. Exposures: Prescriptions for semaglutide vs non-GLP-1 RA medications to manage either T2D or weight. Main Outcomes and Measures: Cumulative incidence and hazard ratio of NAION. Results: Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non-GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non-GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non-GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non-GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non-GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non-GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001). Conclusions and Relevance: This study's findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.

Optic Disc Cupping in Neuromyelitis Optica Spectrum Disorder, Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease, and Multiple Sclerosis and Its Relationship With Optical Coherence Tomography Parameters: A Multicenter Study.

BACKGROUND: Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning. METHODS: This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC. RESULTS: Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD (P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group (P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant (P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = -0.60 and R = -0.64, respectively), inversely moderate in patients with MOGAD (R = -0.34 and R = -0.40, respectively), and weak in patients with NMOSD (R = -0.03 and R = -0.17, respectively). CONCLUSIONS: Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD.

Symmetric leukoencephalopathy associated with systemic lupus erythematosus: A systematic review of a distinctive neurorheumatologic syndrome.

BACKGROUND: A symmetric leukoencephalopathy can occur in the context of systemic lupus erythematosus (SLE), often as a first manifestation of underlying rheumatologic disease. Recognition of this distinctive syndrome can prompt investigation for SLE when undiagnosed, or prompt treatment initiation when the diagnosis is already known. Earlier recognition of this syndrome could lead to more effective treatment of the disease. METHODS: Clinical, laboratory, and radiographic features of three patients were described from an academic medical center in the United States with treatment dates between 2015 and 2022. A systematic review of literature from 1991 to 2023 yielded data for an additional 23 patients. RESULTS: Twenty-six total patients with symmetric leukoencephalopathy were included in this study. The median age of the patients was 37 years (range 10-69), 22 patients (85 %) were female, and 4 (15 %) were male. Fourteen of 26 patients (54 %) had this as the first clinical manifestation of SLE. Contrast enhancement was present on MRI brain in 3/26 (88 %) patients. Twenty patients (77 %) were treated with pulse-dose steroids, and all but one patient received some immunomodulatory therapy. Seven patients (27 %) progressed to death. No meaningful predictive differences were found between patients who survived and those who did not. CONCLUSIONS: In this case series and literature review patients developed symmetric leukoencephalopathy in systemic lupus erythematosus most often as the first clinical manifestation of SLE. Clinicians should consider this syndrome in any patient with acute onset of symmetric leukoencephalopathy on brain magnetic resonance imaging.

Simultaneous alleviation of verification and reference standard biases in a community-based tuberculosis screening study using Bayesian latent class analysis.

BACKGROUND: Estimation of prevalence and diagnostic test accuracy in tuberculosis (TB) prevalence surveys suffer from reference standard and verification biases. The former is attributed to the imperfect reference test used to bacteriologically confirm TB disease. The latter occurs when only the participants screening positive for any TB-compatible symptom or chest X-ray abnormality are selected for bacteriological testing (verification). Bayesian latent class analysis (LCA) alleviates the reference standard bias but suffers verification bias in TB prevalence surveys. This work aims to identify best-practice approaches to simultaneously alleviate the reference standard and verification biases in the estimates of pulmonary TB prevalence and diagnostic test performance in TB prevalence surveys. METHODS: We performed a secondary analysis of 9869 participants aged ≥15 years from a community-based multimorbidity screening study in a rural district of KwaZulu-Natal, South Africa (Vukuzazi study). Participants were eligible for bacteriological testing using Xpert Ultra and culture if they reported any cardinal TB symptom or had an abnormal chest X-ray finding. We conducted Bayesian LCA in five ways to handle the unverified individuals: (i) complete-case analysis, (ii) analysis assuming the unverified individuals would be negative if bacteriologically tested, (iii) analysis of multiply-imputed datasets with imputation of the missing bacteriological test results for the unverified individuals using multivariate imputation via chained equations (MICE), and simultaneous imputation of the missing bacteriological test results in the analysis model assuming the missing bacteriological test results were (iv) missing at random (MAR), and (v) missing not at random (MNAR). We compared the results of (i)-(iii) to the analysis based on a composite reference standard (CRS) of Xpert Ultra and culture. Through simulation with an overall true prevalence of 2.0%, we evaluated the ability of the models to alleviate both biases simultaneously. RESULTS: Based on simulation, Bayesian LCA with simultaneous imputation of the missing bacteriological test results under the assumption that the missing data are MAR and MNAR alleviate the reference standard and verification biases. CRS-based analysis and Bayesian LCA assuming the unverified are negative for TB alleviate the biases only when the true overall prevalence is <3.0%. Complete-case analysis produced biased estimates. In the Vukuzazi study, Bayesian LCA with simultaneous imputation of the missing bacteriological test results under the MAR and MNAR assumptions produced overall PTB prevalence of 0.9% (95% Credible Interval (CrI): 0.6-1.9) and 0.7% (95% CrI: 0.5-1.1) respectively alongside realistic estimates of overall diagnostic test sensitivity and specificity with substantially overlapping 95% CrI. The CRS-based analysis and Bayesian LCA assuming the unverified were negative for TB produced 0.7% (95% CrI: 0.5-0.9) and 0.7% (95% CrI: 0.5-1.2) overall PTB prevalence respectively with realistic estimates of overall diagnostic test sensitivity and specificity. Unlike CRS-based analysis, Bayesian LCA of multiply-imputed data using MICE mitigates both biases. CONCLUSION: The findings demonstrate the efficacy of these advanced techniques in alleviating the reference standard and verification biases, enhancing the robustness of community-based screening programs. Imputing missing values as negative for bacteriological tests is plausible under realistic assumptions.

Cranial nerve involvement, visual complications and headache syndromes in Lyme disease.

PURPOSE OF REVIEW: To provide a summary of the visual manifestations and cranial neuropathies seen in Lyme disease. RECENT FINDINGS: Lyme facial palsy remains the most common manifestation of Lyme neuroborreliosis. Recent investigations show likely evidence of vagal involvement in Lyme disease. SUMMARY: The literature on Lyme neuroborreliosis continues to evolve. Lyme disease can affect nearly any cranial nerve in addition to causing various headache syndromes. The most common manifestation is Lyme disease facial palsy, occurring in up to 5-10% of patients with documented Lyme disease. Headache syndromes are common in the context of facial palsy but can occur in isolation, and more specific headache syndromes including trigeminal and geniculate neuralgias can occur rarely. Signs and symptoms indicative of vestibulocochlear nerve involvement are relatively common, although it could be that these represent other vestibular involvement rather than a specific cranial neuropathy. Optic neuritis is a controversial entity within Lyme disease and is likely overdiagnosed, but convincing cases do exist. Physicians who see any cranial neuropathy, including optic neuritis, in an endemic area can consider Lyme disease as a possible cause.

Update on Neuro-ophthalmic Manifestations of Immune Checkpoint Inhibitors.

PURPOSE OF REVIEW: Immune checkpoint inhibitor (ICI) use has been on the rise for treatment of many different malignancies. Subsequently, more has been learned about immune-related adverse events (irAEs) that occur up to 12 months after treatment. This review summarizes the latest findings and management of neuro-ophthalmic associated irAEs. RECENT FINDINGS: irAEs can affect the afferent and efferent neuro-ophthalmic pathways, thereby targeting central and peripheral nervous systems. As more cases are being reported, it is becoming apparent that neuro-ophthalmic irAEs often present with atypical features when compared to their spontaneous autoimmune counterparts. These neuro-ophthalmic presentations can also be signs of a more extensive inflammatory process that spans other organ systems, such as myopathies, endocrinopathies, and paraneoplastic syndromes. Awareness of neuro-ophthalmic irAEs and their atypical presentations can lead to early detection, termination of ICI treatment, and immunosuppressant therapy initiation.

Correction: Viraemic-time predicts mortality among people living with HIV on second-line antiretroviral treatment in Myanmar: A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0271910.].

Computer-aided detection thresholds for digital chest radiography interpretation in tuberculosis diagnostic algorithms.

Objectives: Use of computer-aided detection (CAD) software is recommended to improve tuberculosis screening and triage, but threshold determination is challenging if reference testing has not been performed in all individuals. We aimed to determine such thresholds through secondary analysis of the 2019 Lesotho national tuberculosis prevalence survey. Methods: Symptom screening and chest radiographs were performed in participants aged ≥15 years; those symptomatic or with abnormal chest radiographs provided samples for Xpert MTB/RIF and culture testing. Chest radiographs were processed using CAD4TB version 7. We used six methodological approaches to deal with participants who did not have bacteriological test results to estimate pulmonary tuberculosis prevalence and assess diagnostic accuracy. Results: Among 17 070 participants, 5214 (31%) had their tuberculosis status determined; 142 had tuberculosis. Prevalence estimates varied between methodological approaches (0.83-2.72%). Using multiple imputation to estimate tuberculosis status for those eligible but not tested, and assuming those not eligible for testing were negative, a CAD4TBv7 threshold of 13 had a sensitivity of 89.7% (95% CI 84.6-94.8) and a specificity of 74.2% (73.6-74.9), close to World Health Organization (WHO) target product profile criteria. Assuming all those not tested were negative produced similar results. Conclusions: This is the first study to evaluate CAD4TB in a community screening context employing a range of approaches to account for unknown tuberculosis status. The assumption that those not tested are negative - regardless of testing eligibility status - was robust. As threshold determination must be context specific, our analytically straightforward approach should be adopted to leverage prevalence surveys for CAD threshold determination in other settings with a comparable proportion of eligible but not tested participants.

SARS-CoV-2 Parainfectious Optic Neuropathy: 3 Case Reports and a Review of the Literature.

BACKGROUND: Parainfectious optic neuritis is an inflammatory reaction that occurs shortly after an infection without direct invasion by a pathogen. The clinical profile depends on the infectious organism. Cases of SARS-CoV-2 parainfectious optic neuritis have been reported in the literature, but there are no reviews that have applied strict inclusion criteria to more definitively establish the clinical profile associated with SARS-CoV-2. METHODS: We present 3 new cases of SARS-CoV-2 parainfectious optic neuritis. We also review the literature for definite cases by selecting only those with unambiguous clinical features and MRI findings of optic neuritis, positive SARS-CoV-2 polymerase chain reaction or serology, and the absence of myelin oligodendrocyte-glycoprotein or aquaporin-4 antibodies or other diseases associated with optic neuritis. RESULTS: We report 2 cases of monophasic, unilateral SARS-CoV-2 parainfectious optic neuritis with optic disc edema and nadir visual acuities of finger counting. We report 1 case of mild SARS-CoV-2 parainfectious optic neuritis that featured cotton wool spots, peripapillary wrinkles and hemorrhages, and recurrence after an initial steroid taper. We identified 6 cases of unambiguous SARS-CoV-2 parainfectious optic neuritis from the literature. Combining our case series with the case reports in the literature, the average age was 42.8 years, 3/9 had bilateral disease, 6/8 had optic disc edema, 8/9 had nadir visual acuity of finger counting or worse, and all recovered visual acuity to 20/40 or better after therapy with steroids. CONCLUSIONS: SARS-CoV-2 parainfectious optic neuritis has a clinical profile that is atypical for idiopathic optic neuritis but fairly typical of parainfectious forms of optic neuritis with a severely reduced nadir visual acuity, high likelihood of bilaterality, high incidence of optic disc edema, and prompt and significant response to corticosteroids. Further study with long-term follow-up and epidemiologic investigation will be needed to further characterize this clinical entity.

Attrition one year after starting antiretroviral therapy before and after the programmatic implementation of HIV "Treat All" in Sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Evidence on the real-world effects of "Treat All" on attrition has not been systematically reviewed. We aimed to review existing literature to compare attrition 12 months after antiretroviral therapy (ART) initiation, before and after "Treat All" was implemented in Sub-Saharan Africa and describe predictors of attrition. METHODS: We searched Embase, Google Scholar, PubMed, and Web of Science in July 2020 and created alerts up to the end of June 2023. We also searched for preprints and conference abstracts. Two co-authors screened and selected the articles. Risk of bias was assessed using the modified Newcastle-Ottawa Scale. We extracted and tabulated data on study characteristics, attrition 12 months after ART initiation, and predictors of attrition. We calculated a pooled risk ratio for attrition using random-effects meta-analysis. RESULTS: Eight articles and one conference abstract (nine studies) out of 8179 screened records were included in the meta-analysis. The random-effects adjusted pooled risk ratio (RR) comparing attrition before and after "Treat All" 12 months after ART initiation was not significant [RR = 1.07 (95% Confidence interval (CI): 0.91-1.24)], with 92% heterogeneity (I2). Being a pregnant or breastfeeding woman, starting ART with advanced HIV, and starting ART within the same week were reported as risk factors for attrition both before and after "Treat All". CONCLUSIONS: We found no significant difference in attrition before and after "Treat All" one year after ART initiation. While "Treat All" is being implemented widely, differentiated approaches to enhance retention should be prioritised for those subgroups at risk of attrition. PROSPERO NUMBER: CRD42020191582 .

Piloting a new method to estimate action thresholds in medicine through intuitive weighing.

OBJECTIVES: In clinical decision-making, physicians take actions such as prescribing treatment only when the probability of disease is sufficiently high. The lowest probability at which the action will be considered, is the action threshold. Such thresholds play an important role whenever decisions have to be taken under uncertainty. However, while several methods to estimate action thresholds exist, few methods give satisfactory results or have been adopted in clinical practice. We piloted the adapted nominal group technique (aNGT), a new prescriptive method based on a formal consensus technique adapted for use in clinical decision-making. DESIGN, SETTING AND PARTICIPANTS: We applied this method in groups of postgraduate students using three scenarios: treat for rifampicin-resistant tuberculosis (RR-TB), switch to second-line HIV treatment and isolate for SARS-CoV-2 infection. INTERVENTIONS: The participants first summarise all harms of wrongly taking action when none is required and wrongly not taking action when it would have been useful. Then they rate the statements on these harms, discuss their importance in the decision-making process, and finally weigh the statements against each other. MAIN OUTCOME MEASURES: The resulting consensus threshold is estimated as the relative weights of the harms of the false positives divided by the total harm, and averaged out over participants. In some applications, the thresholds are compared with an existing method based on clinical vignettes. RESULTS: The resulting action thresholds were just over 50% for RR-TB treatment, between 20% and 50% for switching HIV treatment and 43% for COVID-19 isolation. These results were considered acceptable to all participants. Between sessions variation was low for RR-TB and moderate for HIV. Threshold estimates were moderately lower with the method based on clinical vignettes. CONCLUSIONS: The aNGT gives sensible results in our pilot and has the potential to estimate action thresholds, in an efficient manner, while involving all relevant stakeholders. Further research is needed to study the value of the method in clinical decision-making and its ability to generate acceptable thresholds that stakeholders can agree on.

Neuro-ophthalmic complications of varicella-zoster virus.

PURPOSE OF REVIEW: This review broadly describes recent neuro-ophthalmic manifestations of varicella-zoster virus (VZV) reported in literature. RECENT FINDINGS: Despite varicella vaccination, the incidence of herpes zoster continues to rise, potentially leading to devastating consequences when ocular complications occur.A small but growing literature documents cases of retinal disease because of varicella reactivation after SARS-CoV-2 vaccination, ischemic optic neuropathy occurring during herpes zoster ophthalmicus, VZV-induced orbital apex syndrome, and immune-mediated ocular complications in patients with prior neuro-ophthalmic manifestations of VZV. SUMMARY: It is important for clinicians to keep abreast of the diverse neuro-ophthalmic manifestations of VZV as early diagnosis and treatment often lead to better visual outcomes.

A novel approach to hypophysitis: outcomes using non-glucocorticoid immunosuppressive therapy.

OBJECTIVE: To determine pituitary function before and after nonglucocorticoid immunosuppressive therapy (NGIT) in subjects with hypophysitis and evaluate their clinical and radiologic outcomes. DESIGN: Retrospective, longitudinal study. METHODS: We reviewed a large database, selected subjects with hypophysitis treated with NGIT, and collected information on the duration of therapy, and clinical, hormonal, and radiologic outcomes. RESULTS: Twelve subjects met the inclusion criteria. Five subjects had primary hypophysitis (PH), while seven had secondary hypophysitis (SH) due to an underlying systemic inflammatory disease. Mean age ± SD was 48.0 ± 15.7 years and 40.9 ± 13.0 years, for PH and SH, respectively. The majority were female (PH 60% and SH 86%). BMI ± SD at presentation was 25.2 ± 2.5 kg/m2 and 26.8 ± 6.7 kg/m2 for PH and SH, respectively. The most common symptom at presentation was fatigue (75%). All PH subjects (100%) and 2 (28.6%) SH subjects had polyuria/polydipsia. There was a significant decrease in mean pituitary stalk thickness after NGIT (P = .0051) (mean duration 16.5 ± 4.8 months). New hormone loss or recovery occurred rarely. Mycophenolate mofetil was the most used NGIT: adverse effects prompted discontinuation in 2 out of 7 subjects. CONCLUSIONS: Subjects with hypophysitis receiving NGIT had stable or improved brain/pituitary magnetic resonance imaging findings with a significant decrease in pituitary stalk thickness. NGITs did not improve anterior pituitary function. Our findings suggest that NGIT may be considered as an alternative therapy for patients with hypophysitis who require immunosuppression.

MRI Apparent Diffusion Coefficient (ADC) as a Biomarker of Tumour Response: Imaging-Pathology Correlation in Patients with Hepatic Metastases from Colorectal Cancer (EORTC 1423).

Background: Tumour apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (MRI) is a putative pharmacodynamic/response biomarker but the relationship between drug-induced effects on the ADC and on the underlying pathology has not been adequately defined. Hypothesis: Changes in ADC during early chemotherapy reflect underlying histological markers of tumour response as measured by tumour regression grade (TRG). Methods: Twenty-six patients were enrolled in the study. Baseline, 14 days, and pre-surgery MRI were performed per study protocol. Surgical resection was performed in 23 of the enrolled patients; imaging-pathological correlation was obtained from 39 lesions from 21 patients. Results: There was no evidence of correlation between TRG and ADC changes at day 14 (study primary endpoint), and no significant correlation with other ADC metrics. In scans acquired one week prior to surgery, there was no significant correlation between ADC metrics and percentage of viable tumour, percentage necrosis, percentage fibrosis, or Ki67 index. Conclusions: Our hypothesis was not supported by the data. The lack of meaningful correlation between change in ADC and TRG is a robust finding which is not explained by variability or small sample size. Change in ADC is not a proxy for TRG in metastatic colorectal cancer.