Active Lesions Research Articles

Urinary Biomarkers Associated With Pathogenic Pathways Reflecting Histologic Findings in Lupus Nephritis.

There is a pressing need to understand the pathogenesis of histologic findings and identify the biomarkers for predicting the histologic severity in lupus nephritis (LN). This study aimed to identify the pathogenic signal pathway and elucidate urinary biomarkers for predicting the presence or severity of histologic findings in LN. Urine samples from patients with biopsy-proven active LN were screened for 1,305 proteins using an aptamer-based proteomic assay. The diversity and expansion of individual renal histologic features in LN were quantified to identify the urinary proteins associated with the histologic findings found in each score. Candidate urinary proteins were validated in a validation cohort. Immunohistochemical staining of the renal tissues was performed to clarify the localization of the candidate proteins. Cluster analysis extracted five histologic subgroups according to their correlations with each histologic finding in LN. Protein groups that correlated with each histologic subgroup revealed a distinct pathogenesis in LN using pathway analyses. Enzyme-linked immunosorbent assay validation revealed that urinary calgranulin B (S100A9), monocyte chemotactic protein 1 (MCP-1), and insulin-like growth factor binding protein 5 (IGFBP-5) levels could specifically predict the presence and severity of active glomerular lesions, interstitial inflammation, and interstitial fibrosis, respectively. Immunohistochemical staining revealed the localization of these proteins in each lesion. Renal histologic findings may reflect the different pathogeneses involved in each lesion, and estimating the urinary calgranulin B, MCP-1, and IGFBP-5 levels may be useful in predicting the presence and severity of histologic findings in LN.

Shingles Virus-A Complete Review of Pathogenesis, Diagnosis, and Treatment

The varicella-zoster virus, or VZV, is a neurotropic human herpesvirus that is widespread throughout the world and belongs to the group Alphaherpesviridae. It is the root cause of varicella-induced chickenpox and shingles (Herpes Zoster [HZ]). The virus, which is spread by respiratory droplets or contact with active varicella lesions, is considered one of the most contagious illnesses. Herpetic neuralgia (HZ) can cause pain, ocular swelling, and possibly even irreversible or temporary blindness. Pain begins to subside in the second week following shingles, and it may persist long after the rash has healed. This can result in a difficult complication called postherpetic neurogynea (PHN). As one ages, the frequency and severity of PHN increase. Ninety percent of those who receive the two-dose immunization are able to avoid shingles and HZ.

Impact of paramagnetic rim lesions on disability and race in multiple sclerosis: mediation analysis.

Black American (BA) multiple sclerosis (MS) patients experience greater disability compared to White American (WA) patients. Here, we investigated the role of paramagnetic rim lesions (PRLs), a subset of chronic active lesions, on race-related disability in MS. We conducted a retrospective observational study comparing BA and WA MS patients. PRLs were identified through Quantitative Susceptibility Mapping (QSM) MRI. A causal mediation analysis explored the impact of PRLs on the relationship between race and disability, as measured by the Expanded Disability Status Scale (EDSS). The prevalence of PRLs in BA patients with MS was higher at 55% compared to WA patients at 39% (p = 0.022). A higher percentage of PRLs among all white matter lesions was observed with BA (8.01%) patients compared to WA (3.4%) patients (p = 0.003). In a regression analysis, controlling for significant patient-level covariates and income-level demographics, the percentage of PRLs was, on average, 4.61 points higher for BA patients than for WA patients (p = 0.003). In a separate regression analysis, accounting for covariates, BA patients exhibited significantly higher EDSS scores (p < 0.001). Further analysis demonstrated that the percentage of PRLs was a mediator in the association between BA patients and greater disability (p = 0.031). Higher proportion of PRLs in BA population accounted for 14% of the total effect of race on disability. BA patients exhibit greater disability, in part, due to their higher proportion of PRLs. This study underscores the substantial impact of chronic active lesions on disability outcomes in this specific minority MS patient population.

What do we know About the Usefulness of 18F-FDG PET-CT for the Management of Invasive Fungal Infection? An International Survey.

Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

Quantitative assessment of early caries lesion activity using novel dye-enhanced fluorescence imaging

ObjectivesThis study aimed to evaluate the validity of the dye-enhanced quantitative light-induced fluorescence (DEQLF) method for assessing early enamel caries activity. MethodsSeventy extracted human teeth with early enamel caries on smooth surfaces were included. Two dentists evaluated the caries activity using the Nyvad system followed by the DEQLF method. The teeth were hydrated with distilled water for 60 s, dehydrated with compressed air for 10 s, and stained with 100 μM fluorescein sodium solution for 10 s. White and fluorescent images were captured using a QLF-D 2+ Billuminator. The change in fluorescence (ΔΔG) was calculated using image analysis software. Independent-sample t-tests were performed to evaluate the difference in ΔΔG between active and inactive lesions for both DEQLF and conventional quantitative light-induced fluorescence (QLF) methods. Receiver operating characteristic (ROC) curve analysis was used to assess the validity of ΔΔG for distinguishing lesion activity using the area under the ROC curve (AUROC). ResultsAmong the 70 caries lesions, 33 were active and 37 were inactive. Using the DEQLF method, the ΔΔG for active lesions (3.8 ± 5.6) was significantly higher than that for inactive lesions (1.0 ± 2.5) (P < 0.05). With the conventional QLF method, there was no significant difference in ΔΔG between active (-1.1 ± 1.7) and inactive (-1.3 ± 1.7) lesions. DEQLF-derived ΔΔG demonstrated an AUROC of 0.72, a sensitivity of 0.67, and a specificity of 0.76. ConclusionsApplying the DEQLF method to human teeth enabled the quantitative assessment of lesion activity based on dye penetration. DEQLF-derived ΔΔG values showed significant differences based on lesion activity status and demonstrated high validity in distinguishing lesion activity. Clinical significanceClinicians can use the DEQLF method, which involves applying a fluorescent dye for 10 s prior to conventional QLF, to objectively quantify and distinguish the activity status of early enamel caries, potentially replacing the traditional reliance on subjective visual assessments.

Effectiveness of topical 25% silver nitrate solution followed by 5% fluoride varnish compared to 38% silver diamine fluoride in arresting and preventing dental caries among beta-thalassemia major patients: A randomized clinical trial

IntroductionThis is the first randomized non-inferiority clinical trial in the evidence literature to examine the effectiveness of topical 25% silver nitrate (SN) followed by 5% sodium fluoride (NaF) varnish is not much worse or acceptable to 38% silver diamine fluoride (SDF) in preventing and arresting dental caries among Beta-Thalassemia Major (BTM) patients. Method170 BTM participants aged 18 years and older with at least 1 or more active carious lesions were randomly allocated into 2 groups (1:1). 25% silver nitrate solution application followed by 5% NaF varnish was administered to Group I, and Group II received 38% SDF. The Nyvad criteria and DMFT index were used to assess caries arrest and prevention among both groups at 3- and 6-months interval. ResultsCaries arrest rate at 3 months was significantly higher in Group I (83.10%) when compared to Group II (76.16%) (p<0.05). While at 6 months, both the groups were comparable with arrest rate (76.16%) (p>0.05). The caries increment was comparable among both groups at 3 months, while at 6 months, caries increment was almost half in SN with NaF group compared to SDF group (p>0.05). Kaplan–Meir survival estimated the median survival time for caries increment was 17 and 39 weeks for Group I and 15 and 36 weeks for Group II at 3 and 6 months, respectively. ConclusionOne time application of 25% SN followed by 5% NaF is no worse than a 38% SDF in arresting and preventing dental caries among Thalassemia Major participants at 3 and 6 months. Clinical SignificanceThe study provides clinicians with a cost-effective, safer, readily available, non-invasive treatment option (25% SN followed by 5% NaF) for caries management.

Classification Criteria for Axial Disease in Youth with Juvenile Spondyloarthritis.

To develop and validate classification criteria for axial disease in youth with juvenile spondyloarthritis (SpA; AxJSpA). This international initiative consisted of four phases: 1) Item generation; 2) Item reduction; 3) Criteria development; and 4) Validation of the AxJSpA criteria by an independent team of experts in an internationally representative Validation cohort. These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free-listing exercise using input from international physicians and collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included: imaging: active inflammation, imaging: structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% CI: 91.4-99.7), sensitivity of 64.3% (95% CI: 54.9-73.1) and Area Under the Receiver Operating Characteristic (AUROC) curve of 0.81 (95% CI: 0.76-0.86). The new AxJSpA classification criteria require an entry criterion, physician diagnosis of juvenile SpA, and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies.

Astrocyte-derived clusterin disrupts glial physiology to obstruct remyelination in mouse models of demyelinating diseases

Multiple sclerosis (MS) is a debilitating demyelinating disease characterized by remyelination failure attributed to inadequate oligodendrocyte precursor cells (OPCs) differentiation and aberrant astrogliosis. A comprehensive cell atlas reanalysis of clinical specimens brings to light heightened clusterin (CLU) expression in a specific astrocyte subtype links to active lesions in MS patients. Our investigation reveals elevated astrocytic CLU levels in both active lesions of patient tissues and female murine MS models. CLU administration stimulates primary astrocyte proliferation while concurrently impeding astrocyte-mediated clearance of myelin debris. Intriguingly, CLU overload directly impedes OPC differentiation and induces OPCs and OLs apoptosis. Mechanistically, CLU suppresses PI3K-AKT signaling in primary OPCs via very low-density lipoprotein receptor. Pharmacological activation of AKT rescues the damage inflicted by excess CLU on OPCs and ameliorates demyelination in the corpus callosum. Furthermore, conditional knockout of CLU emerges as a promising intervention, showcasing improved remyelination processes and reduced severity in murine MS models.

Exploring expression levels of the cGAS-STING pathway genes in peripheral blood mononuclear cells of spinal tuberculosis patients

BackgroundThis study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker.MethodsPeripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon β (IFN-β) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package.ResultsThe results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P < 0.05), in patients with active lesions than in patients with stable lesions. The serum concentration of IFN-β was significantly higher in patients with active lesions (P = 0.028). Compared with healthy individuals, the expression level of the cGAS-STING pathway was elevated in PBMCs of TB patients (P < 0.05), and the difference in the expression level of IFN-β was not statistically significant (P > 0.05), and the serum IFN-β concentration was elevated (P < 0.05). The calculated AUC values for TBK1 and IRF3 in PBMCs, IFN-β in serum and erythrocyte sedimentation rate (ESR) to distinguish between patients with active and stable lesions were 0.732, 0.714, 0.839, and 0.714 respectively.ConclusionsThe expression level of TBK1 and IRF3 in PBMCs, and IFN-β in the serum of patients with spinal TB is positively correlated with disease activity. TBK1 has higher specificity and IFN-β in serum has higher sensitivity when used to differentiate between patients with active and stable lesions.

Video Color OCT Angiography for Myopic Choroidal Neovascularization

To investigate the myopic macular neovascularization (mMNV) features on dynamic video-color optical coherence tomography (OCT) angiography (OCTA) and the diagnostic rate versus the static, four-segmentations visualization mode. Retrospective cohort study PARTICIPANTS: Fifty-four patients with mMNV METHODS: Sixty-two eyes with high myopia complicated by mMNV were included. Clinical charts, fluorescein angiography and structural OCT were used as standard reference to assess lesion activity. Static and video-color OCTA were then analysed and compared by two independent reviewers. Morphology description of mMNV on video-color OCTA and differences in the proportion of diagnosis between video-colour and static OCTA. 62 eyes from 54 patients (mean age 63,22 years) were enrolled. Thirty-four (55%) mMNV were active and 28 (45%) inactive. Twenty-two (65%) active mMNV presented on video-color OCTA as an interlacing vascular network in the outer retina and the choriocapillaris. A tapered form was the prevalent size (72,7%). In 3 eyes (9%) an abnormal and irregular vascular network (AVN) was disclosed and in 5 (15%) only some blood flow alteration. All the lesions extended both in the outer retinal and the choriocapillaris. Eleven (39%) inactive mMNV presented on video-color OCTA as an interlacing vascular network too, in the outer retina and the choriocapillaris. Eight (29%) had some AVN and 6 (21%) only some blood flow alteration. The diagnostic rate of video-color vs static OCTA was 95% (IC 95% 86% to 99%) vs 77% (IC 95% 86% to 99%, p= 0.0009), and shows an advantage in favour of video-colour OCTA of 15% (CI 95%, 3%-27%) and 22% (CI 95%, 7%-38%) in active and inactive lesions, respectively (p<0.026). Lesion extension within both the outer retina and the choriocapillaris was present in 90% and 69% of cases on dynamic OCTA and static OCTA, respectively, with a proportion difference of 20% (CI 95%, 10%-31%, p= 0.0005). Concordance between the two examiners was high: 0.95 (95%, CI 0.88 to 1.00) and 0.96 (0.91 to 1.00) for active and inactive lesions, respectively. Video color-enhanced OCTA may help in diagnosing mMNV and should be considered by clinicians in addition to structural OCT and static OCTA.

Effects of fingolimod on focal and diffuse damage in patients with relapsing-remitting multiple sclerosis - The "EVOLUTION" study.

In multiple sclerosis (MS), MRI markers can measure the potential neuroprotective effects of fingolimod beyond its anti-inflammatory activity. In this study we aimed to comprehensively explore, in the real-word setting, whether fingolimod not only reduces clinical/MRI inflammatory activity, but also influences the progression of irreversible focal and whole brain damage in relapsing-remitting [RR] MS patients. The "EVOLUTION" study, a 24-month observational, prospective, single-arm, multicenter study, enrolled 261 RRMS patients who started fingolimod at 32 Italian MS centers and underwent biannual neurological assessments and annual MRI evaluations. Study outcomes included the proportions of evaluable RRMS patients achieving at 24months: (1) no new/enlarging T2-hyperintense white matter (WM) lesions and/or clinical relapses; (2) a modified classification of "No Evidence of Disease Activity 4" ("modified NEDA-4") defined as no new/enlarging T2-hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T2-FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs). At month 24, 76/160 (47.5%; 95% confidence interval [CI] = 39.8%;55.2%) RRMS patients had no clinical/MRI activity. Thirty-nine of 170 RRMS patients (22.9%; 95% CI = 16.6%;29.3%) achieved "modified NEDA-4" status. Forty-four of 72 RRMS patients (61.1%; 95% CI = 49.8%;72.4%) had less than 40% of active WM lesions evolving to PBHs. The study confirmed the established safety and tolerability profile of fingolimod. By comparing our results with those from the literature, the EVOLUTION study seems to indicate a neuroprotective effect of fingolimod, limiting inflammatory activity, brain atrophy and PBH development.

The level of dental fear and anxiety is higher in children with both severe Molar-Incisor Hypomineralisation and active dental caries lesions compared to children without these conditions

PurposeTo assess levels of dental fear and anxiety (DFA) in children with and without Molar-Incisor Hypomineralisation (MIH) and dental caries lesions.MethodsIn this cross-sectional observational study, 159 children between 8 and 12 years of age were included. For the evaluation of DFA, children responded to the validated version of the Children’s Fear Survey Schedule-Dental Subscale. MIH was assessed using the MIH Index. To evaluate the activity of dental caries lesions and dental caries experience, the Nyvad criterion and the dmft/DMFT index were used, respectively. Dental hypersensitivity was evaluated using air stimulation and a Visual Analogue Scale. The association between MIH and dental caries with DFA was assessed using the generalised linear model with Poisson family, identity link function and robust variance estimation. The significance level was set at 5%.ResultsThe mean DFA score was 28.3 (SD = 13.4) with scores ranging from 15 to 64. Amongst children presenting both MIH and dental caries, the perception of DFA was notably higher compared to those with either MIH or dental caries alone. The activity of caries lesion in patients with MIH also influenced DFA levels (diff: 18.6; 95% CI: 12.0–25.2; p < 0.001). Dental caries experience in the primary dentition also demonstrated statistical significance concerning DFA (95% CI: 0.8–13.3; p value = 0.027).ConclusionChildren with MIH exhibit higher levels of DFA than children without MIH. The experience of dental caries and the activity of caries lesions significantly influence the perception of DFA in children with MIH.

Utilization of Whole-Body Magnetic Resonance Imaging in Challenging Diagnoses in Pediatric Rheumatology.

The aim of this study was to investigate the use of whole-body magnetic resonance imaging (WBMRI) in cases where we suspected rheumatic disease in our pediatric rheumatology clinic. We conducted a retrospective analysis of demographic, clinical, laboratory, and imaging data pertaining to pediatric patients who presented at our clinic and underwent WBMRI over the last 5 years. Our investigation targeted children experiencing diffuse musculoskeletal pain, where precise localization was challenging and suspicion of rheumatological pathology persisted despite inconclusive results from conventional diagnostic modalities. A total of 87 patients (33 female) underwent WBMRI at our clinic, with a median age (minimum-maximum) of 11.3 (0.5-18) years. Whole-body magnetic resonance imaging was performed in 4 patients suspected with dermatomyositis (DM) where muscle biopsy was not feasible, revealing muscle involvement and myositis. Additionally, WBMRI was utilized in 4 patients diagnosed with chronic nonbacterial osteomyelitis (CNO) to assess recurrence, identifying new active lesions in 3 patients. Among the remaining 79 patients, 34 received a new diagnosis of CNO. Clinically, supported by additional findings in laboratory and WBMRI, 18 were diagnosed with juvenile idiopathic arthritis (JIA), 5 with protracted febrile myalgia syndrome (PFMS), 5 with acute osteomyelitis, and 1 with viral myositis. The results were normal for 17 patients. Most of the WBMRIs conducted at the clinic under study were primarily performed on patients suspected of having CNO. Additionally, WBMRI was found to be supportive and beneficial in cases of suspected DM, PFMS, and JIA during the diagnosis.

Comparative efficacy of subcutaneous versus intravenous natalizumab on annualized relapse rate: A post-hoc analysis of the REFINE study

BackgroundThe non-inferiority of the efficacy of subcutaneous (SC) vs intravenous (IV) administration of natalizumab (NTZ) once every 4 weeks in relapsing-remitting multiple sclerosis (RRMS) was recently demonstrated on the primary outcome of the REFINE study, i.e. MRI “combined unique active lesions number” (CUAL). To provide further evidence on the comparative efficacy of the two NTZ formulations, the effect of NTZ-SC vs NTZ-IV on annualized relapse rate (ARR) was investigated re-analysing the REFINE dataset. MethodsPost-hoc analysis of the REFINE study dataset aimed at exploring the non-inferiority of the efficacy of NTZ-SC vs NTZ-IV on ARR, i.e. the main secondary outcome of the REFINE study. Robustness of the non-inferiority analysis on CUAL with respect to the presence of cases from the SC arm who received a rescue treatment, including NTZ-IV, was also assessed by sensitivity analyses. Three non-inferiority margins were selected, corresponding to 25 %, 33 %, and 50 % fractions of the effect size of NTZ-IV vs placebo observed in the AFFIRM study on ARR (i.e. 0.125, 0.170, and 0.250). ResultsNinety-nine RRMS patients were included. The mean difference in the effect of NTZ-SC vs NTZ-IV on ARR was close to 0. The lower bound of the 95 % confidence interval (worst case scenario) was –0.119, corresponding to 25 % (p = 0.025) of the effect of NTZ-IV vs placebo on ARR. Sensitivity analyses confirmed the results of the primary non-inferiority analysis on the outcome CUAL. ConclusionsNTZ-SC resulted not inferior to NTZ-IV on ARR for all the non-inferiority margins. The non-inferiority analysis of the efficacy of NTZ-SC vs NTZ-IV on CUAL was demonstrated to be robust with respect to rescued patients.

Caries lesions progression in adults: A prospective 2-year cohort study.

Dental caries is one of the most prevalent chronic non-communicable diseases worldwide. There is a lack of evidence, especially in adult populations, documenting caries disease progression considering lesion severity, activity and tooth surface-level characteristics. The study aimed to investigate the extent to which primary active caries lesions in adults affect caries lesions progression compared with inactive caries lesions over a 2-year follow-up period, considering their severity, surface and tooth type. A prospective study data set from a cohort of workers in a factory in Belarus were used. Participants aged 18-64 years with 20 or more natural teeth were included in the study. The participants were clinically examined twice within an interval of 2 years and completed a self-reported questionnaire. One calibrated examiner evaluated caries lesions using the International Caries Detection and Assessment System (ICDAS) and the Nyvad system. The primary outcome was caries lesions' progression. The lesion was classified as 'progressed' if it turned to a more advanced severity stage, was restored or missing/extracted due to caries. A multilevel Poisson regression was used to estimate the association between baseline caries lesions' characteristics and caries lesion progression. Out of 495 participants, 322 people completed clinical examinations at baseline and 2 years later, with an attrition rate of 35%. The prevalence of active DS1-6 and DS5-6 lesions at the baseline was 83.8% and 64.8%, respectively. In 2 years, 24% of active non-cavitated and 31% of active micro-cavitated/shadowed caries lesions progressed, while 15% of inactive caries lesions, non- or micro-cavitated/shadowed, progressed. The adjusted rate ratio (RR) for ICDAS3 + 4 caries lesions progression was 1.41 (CI 95% 1.16, 1.70) than ICDAS1 + 2 lesions. The RR for ICDAS1 + 2, active and ICDAS3 + 4, active lesions was 1.78 (CI 95%, 1.40, 2.27) and 1.97 (CI 95%, 1.53, 2.55), respectively than ICDAS1 + 2, inactive lesions. The RR for caries lesions progression on proximal surfaces and on pits and fissures was 1.57 (CI 95%, 1.30, 1.89) and 1.37 (CI 95%, 1.11, 1.67), respectively than smooth surface lesions. In caries active adults over 2 years, most non- and micro-cavitated/shadowed active and inactive caries lesions did not progress. Among caries lesions that showed progression, more severe lesions were more likely to progress than less severe lesions; active lesions were more likely to progress than inactive lesions. Pit and fissure caries lesions and proximal lesions were more likely to progress than smooth surface lesions.

Data-driven risk/benefit estimator for multiple sclerosis therapies.

Multiple sclerosis (MS) disease-modifying treatments (DMTs) are tested in patients pre-selected for favorable risk/benefits ratios but prescribed broadly in clinical practice. We aimed to establish data-driven computations of individualized risk/benefit ratios to optimize MS care. We derived determinants of DMTs efficacy on disability progression from re-analysis and integration of 61 randomized, blinded Phase 2b/3 clinical trials that studied 46,611 patients for 91,787 patient-years. From each arm we extracted 80 and computed 30 features to identify and adjust for biases, and to use in multiple regression models. DMTs mortality risks were estimated from age mortality tables modified by published hazard ratios. Baseline characteristics of the recruited patients determine disability progression rates and DMTs efficacies with high effect sizes. DMTs efficacies increase with MS lesional activity (LA) measured by relapses or contrast-enhancing lesions and decrease with increasing age, disease duration and disability. Unexpectedly, as placebo arms' relapse rate rapidly declines with trial duration, efficacy of MS DMTs likewise decreases quickly with treatment duration. Conversely, DMTs morbidity/mortality risks increase with age, advanced disability, and comorbidities. We integrated these results into an interactive personalized web based DMTs risk/benefit estimator. Results predict that prescribing DMTs to patients traditionally excluded from MS clinical trials causes more harm than benefit. Treatment with high efficacy drugs at MS onset followed by de-escalation to DMTs that do not increase infectious risks would optimize risk/benefit. DMTs targeting mechanisms of progression independent of LA are greatly needed as current DMTs inhibit disability caused by LA only.

Glucose metabolic rate from four-dimensional [18F]FDG PET/CT to differentiate sarcoid lesions from malignant lesions.

On 18F-Fludeoxyglucose (FDG) PET/CT, active sarcoid lesions are often difficult to differentiate from malignant lesions. We investigated the potential of the glucose metabolic rate (MRglc, mg/min/100 mL), a new quantification of glucose metabolic kinetics derived from direct reconstruction based on linear Patlak analysis, to distinguish between sarcoidosis and malignant lesions. A total of 100 patients with cardiac sarcoidosis (CS) and 67 patients with cancer who underwent four-dimensional FDG PET/CT were enrolled. The lesions with a standardized uptake value (SUV) ≥ 2.7 on the standard scan were included as active lesions in the analysis. SUV and MRglc were derived using data acquired between 30 min and 50 min on four-dimensional FDG PET/CT. The mean value in the volume of interest (size 1.5 cm3) was measured. The diagnostic performance of sarcoidosis using MRglc and SUV was evaluated using receiver-operating-characteristic (ROC) analysis. A total of 90 sarcoidosis lesions from 44 CS patients (18 males, 63.4 ± 12.2 years) and 87 malignant lesions from 57 cancer-bearing patients (32 males, 65 ± 14 years) were analyzed. SUV and MRglc for sarcoid lesions were significantly lower than those for malignant lesions (SUV, 4.98 ± 2.00 vs 6.21 ± 2.14; MRglc, 2.52 ± 1.39 vs 3.68 ± 1.61; p < 0.01). ROC analysis indicated that the ability to discriminate sarcoid patients from those with malignancy yielded areas under the curves of 0.703 and 0.754, with sensitivities of 64% and 77% and specificities of 75% and 72% for SUV 5.025 and MRglc 2.855, respectively. MRglc was significantly lower in sarcoid lesions than malignant lesions, and improved sarcoid lesions identification over SUV alone. MRglc improves sarcoid lymph node identification over SUV alone and is expected to shorten the examination time by eliminating delayed scans. Active sarcoid lesions are sometimes associated with FDG accumulation and should be differentiated from malignant lesions. SUV and metabolic rate of glucose (MRglc) strongly positively correlated, and MRglc could differentiate sarcoid and malignant lesions. MRglc allows for accurate evaluation and staging of malignant lesions.

Optical coherence tomography angiography in neovascular age-related macular degeneration: comprehensive review of advancements and future perspective.

Optical coherence tomography angiography (OCTA) holds promise in enhancing the care of various retinal vascular diseases, including neovascular age-related macular degeneration (nAMD). Given nAMD's vascular nature and the distinct vasculature of macular neovascularization (MNV), detailed analysis is expected to gain significance. Research in artificial intelligence (AI) indicates that en-face OCTA views may offer superior predictive capabilities than spectral domain optical coherence tomography (SD-OCT) images, highlighting the necessity to identify key vascular parameters. Analyzing vasculature could facilitate distinguishing MNV subtypes and refining diagnosis. Future studies correlating OCTA parameters with clinical data might prompt a revised classification system. However, the combined utilization of qualitative and quantitative OCTA biomarkers to enhance the accuracy of diagnosing disease activity remains underdeveloped. Discrepancies persist regarding the optimal biomarker for indicating an active lesion, warranting comprehensive prospective studies for validation. AI holds potential in extracting valuable insights from the vast datasets within OCTA, enabling researchers and clinicians to fully exploit its OCTA imaging capabilities. Nevertheless, challenges pertaining to data quantity and quality pose significant obstacles to AI advancement in this field. As OCTA gains traction in clinical practice and data volume increases, AI-driven analysis is expected to further augment diagnostic capabilities.

Apparent Diffusion Coefficient in the Diagnosis and Follow-up of Multiple Sclerosis: Role of Magnetic Resonance Imaging

Background: Chronic Multiple Sclerosis (MS) modifies the apparent diffusion coefficient (ADC) value due to severe pathological changes. After trauma, it is the second most common cause of brain injury in healthy young adults. MRI is considered the initial imaging modality for MS diagnosis and follow-up. Objective: To assess the significance of the ADC in the diagnosis and follow-up of MS plaques across various disease subtypes. Methods: Forty MS patients were included in a case-control study at Ibn-Sina Teaching Hospital, Mosul Province, between June 1, 2022 and February 28, 2023. The patients had diffusion-weighted and traditional MR imaging with ADC measurement in plaques, and the normal white matter value of controls was compared to the patients' results. Results: The ADC values were higher in cases that were acute or secondary-progressive than in relapsing-remitting cases or normal white matter. In both types of newly generated plaques, there was an initial non-significant increase in ADC values compared to existing plaques. Overall, the ADC sensitivity, specificity, and accuracy in diagnosing MS were 85.7%, 95.2%, and 90.5% in acute cases, and 85.7%, 83.3%, and 84.6% in chronic cases, respectively, with no significant difference between active and inactive lesions. Conclusions: The apparent diffusion coefficient value can be included in the imaging protocol for the diagnosis and follow-up of various subtypes of MS.

Application value of volumetric CT value in quantifying the activity of a pulmonary tuberculoma.

The purpose of this study was to explore the auxiliary diagnostic value of volumetric CT value in quantifying the activity of a pulmonary tuberculoma. Chest CT image data of 112 patients with pulmonary tuberculomas who were diagnosed clinically between October 16, 2013 and March 21, 2023 were selected. With the shortest diameter axis>5 mm on the mediastinal window serving as the inclusion criterion, 108 active tuberculomas and 64 non-active tuberculomas were selected. The focused image was manually segmented using ITK-SNAP software, the volumetric CT value of the focus was calculated, and the ROC curve was analyzed. Using the final clinical diagnosis as the reference standard, the auxiliary diagnostic efficacy and consistency of the conventional CT film reading method and volumetric CT value in determining the activity of a pulmonary tuberculoma were compared. The volumetric CT value of 108 active pulmonary tuberculoma lesions (33.39 [28.17,36.23] HU) was significantly less than 64 inactive pulmonary tuberculoma lesions (78.91 [57.81,120.31] HU); the difference was statistically significant (Z = -10.888. P < 0.001). ROC curve analysis showed that at a maximum Yoden index value of 0.963, the optimal volumetric CT threshold value was 45.32 HU, the sensitivity and specificity of the volumetric CT value in determining the activity of a pulmonary tuberculoma were 97.2% and 100.0%, respectively, and the maximum area under the ROC curve was 0.998. Taking the final clinical diagnosis as the reference standard, the sensitivity, specificity, consistency, and kappa value of the conventional CT film reading method for determining the activity of a pulmonary tuberculoma were 72.2% (78/108), 70.3% (45/64), 71.5% (123/172), and 0.413, respectively, while the corresponding volumetric CT values were 97.2% (105/108), 100.0% (64/64), 98.3% (168/172), and 0.951, respectively. Accurately quantifying the volumetric CT value of a pulmonary tuberculoma focus determines the activity of a pulmonary tuberculoma, which has very important auxiliary diagnostic value.