Active Lesions Research Articles

Association of Root Biofilm Bacteriome with Root Caries Lesion Severity and Activity

Introduction: This research aimed to assess the association of root biofilm bacteriome with root caries lesion severity and activity in institutionalised Colombian elderlies and was conducted to gather data on the root caries bacteriome in this population. Methods: A bacteriome evaluation of biofilm samples from sound and carious root surfaces was performed. Root caries was categorised (ICDAS Root criteria) based on severity (sound surfaces, initial: non-cavitated, moderate/extensive combined: cavitated) and activity status (active and inactive). DNA was extracted and the V4 region of the 16S rRNA gene was sequenced; afterwards the classification of features was conducted employing amplicon sequence variants and taxonomic assignment via the Human Oral Microbiome Database (HOMD). Bacterial richness, diversity (Simpson’s and Shannon’s indices), and relative abundance estimation were assessed and compared based on root caries severity and activity status (including Sound surfaces). Results: A total of 130 biofilm samples were examined: sound (n = 45) and with root caries lesions (n = 85; by severity: initial: n = 41; moderate/extensive: n = 44; by activity: active: n = 60; inactive: n = 25). Species richness was significantly lower in biofilms from moderate/extensive and active groups compared to sound sites. There was a higher relative abundance of species like Lechtotricia wadei, Capnocytophaga granulosa, Cardiobacterium valvarum, Porphyromonas pasteri – in sound sites; Dialister invisus, Streptococcus mutans, Pseudoramibacter alactolyticus and Bacteroidetes (G-5) bacterium 511 – in moderate/extensive lesions, and Fusobacterium nucleatum subsp. animalis, Prevotella denticola, Lactobacillus fermentum, Saccharibacteria (TM7) (G-5)bacterium HMT 356 – in active lesions. Conclusion: Root caries bacteriome exhibited differences in species proportions between the compared groups. Specifically, cavitated caries lesions and active caries lesions showed higher relative abundance of acidogenic bacteria.

Scabies in a Preterm Infant Younger than 2 Months: What Do We Have?

Objective – To present a case of scabies in a preterm neonate treated with an off-label treatment (oral ivermectin) without any adverse effects.Case Report – A preterm female neonate (29+3 weeks of gestation) was diagnosed with scabies at 35 days of life (34+3 weeks of corrected gestational age), after her parents had been diagnosed, having been admitted at birth to the neonatal unit of a tertiary hospital. Treatment was initiated with topical off-label permethrin 5%, with the informed consent of the parents. Concomitantly with the patient, the parents received treatment with permethrin 5% and oral ivermectin on days 0, 7, 14 and 21 after diagnosis. No adverse effects resulting from the use of these treatments were reported. On physical examination, active lesions due to scabies were still observed two weeks after permethrin treatment, so it was decided to re-administer the treatment with topical 5% permethrin on days 0 and 14, associated with oral Ivermectin at 200μg/kg on days 0 and 7. The treatment was administered to the patient and her entire family. Fourteen days after completion of ivermectin treatment, the patient presented with complete resolution. Conclusion – After our experience with this case, and given the increasing prevalence of scabies in our environment, we propose that ivermectin is a useful alternative in the treatment of scabies in this age group; however, larger series of patients are needed to establish a recommendation in this regard, evaluating its risks and benefits.

An International Survey Investigating the Incidence and Management of Brown Fat Uptake on 18F-FDG PET/CT at Children's Hospitals and Interventions for Mitigation.

Brown fat can present challenges in patients with cancer who undergo 18F-FDG PET scans. Uptake of 18F-FDG by brown fat can obscure or appear similar to active oncologic lesions, causing clinical challenges in PET interpretation. Small, retrospective studies have reported environmental and pharmacologic interventions for suppressing brown fat uptake on PET; however, there is no clear consensus on best practices. We sought to characterize practice patterns for strategies to mitigate brown fat uptake of 18F-FDG during PET scanning. Methods: A survey was developed and distributed via e-mail LISTSERV to members of the Children's Oncology Group diagnostic imaging committee, the Society for Nuclear Medicine and Molecular Imaging pediatric imaging council, and the Society of Chiefs of Radiology at Children's Hospitals between April 2022 and February 2023. Responses were stored anonymously in REDCap, aggregated, and summarized using descriptive statistics. Results: Fifty-five complete responses were submitted: 51 (93%) faculty and fellow-level physicians, 2 (4%) technologists, and 2 (4%) respondents not reporting their rank. There were 43 unique institutions represented, including 5 (12%) outside the United States. Thirty-eight of 41 (93%) institutions that responded on environmental interventions reported using warm blankets in the infusion and scanning rooms. Less than a third (n = 13, 30%) of institutions reported use of a pharmacologic intervention, with propranolol (n = 5, 38%) being most common, followed by fentanyl (n = 4, 31%), diazepam (n = 2, 15%), and diazepam plus propranolol (n = 2, 15%). Selection criteria for pharmacologic intervention varied, with the most common criterion being brown fat uptake on a prior scan (n = 6, 45%). Conclusion: Clinical practices to mitigate brown fat uptake on pediatric 18F-FDG PET vary widely. Simple environmental interventions including warm blankets or increasing the temperature of the injection and scanning rooms were not universally reported. Less than a third of institutions use pharmacologic agents for brown fat mitigation.

Penetration of SDF and AgF from the infected dentine towards the unaffected tooth structure.

The use of SEM-EDS line scan analysis to evaluate the movement of ions from dental materials towards the tooth structure and the concept of ion movement is well established. This analysis technique was used to determine the ion movement of two commercially available silver- and fluoride-containing products. This study aimed to compare the elemental analysis of primary molar teeth treated with silver diamine fluoride (SDF) and water-based silver fluoride (AgF) and to analyse the penetration of SDF and AgF from the infected dentine towards the healthy dentine. The teeth were cleaned from debris and contaminants off the roots and stored until use. A total of 15 primary molars with large active cavitated lesions, not extending into the pulp (specimens), were divided into three test groups: silver diamine fluoride (SDF) (n = 5), water-based silver fluoride (AgF) (n = 5), and deionised water (W) (n = 5) as the control group. The teeth were sectioned, embedded, and received SEM-EDS line scans. The line scan had a total length of 82.65 μm. The visible end of the infected dentine and the start of the more affected dentine were chosen as the starting point to ensure that the infected caries' line distribution towards the affected dentine's transition area was as standardized as possible. Therefore, the infected dentine length of the scan was 22.80 μm (8 scan points of 2.85 μm apart), and the affected dentine, including the healthy dentine, was 59.8 μm (21 scan points). The SEM-EDS line scan from each specimen determined the average fluoride, iodide, and silver weight percentage for that specimen. The 15 sample SEM-EDS line scans were used to determine the average ion movement in wt%. The Kruskall-Wallis test and Tukey's HSD test were completed at a p < 0.05. SDF and AgF presented no significant fluoride movement in terms of the weight percentage. There was, however, significantly more fluoride movement from infected caries to the healthy dentine with SDF and AgF (p = 0.0010053) compared to the control specimens treated with deionised water. There was no significant difference between SDF and AgF for the movement of the iodide (p = 0.5953) and silver (p = 0.3708) from infected caries to the healthy dentine. SDF and AgF easily penetrated through infected caries and affected tooth structure to the healthy dentine for the line scan of 82.65 μm. There was no significant difference between SDF and AgF for the movement of ions within the infected dentine nor in the affected/healthy dentine.

Investigating the feasibility of differentiating MS active lesions from inactive ones using texture analysis and machine learning methods in DWI images

BackgroundMagnetic resonance imaging (MRI) is commonly used in conjunction with a gadolinium-based contrast agent (GBCA) to distinguish active multiple sclerosis (MS) lesions. However, recent studies have raised concerns regarding the long-term effects of the accumulation of GBCA in the body. Thus, the purpose of this study is to investigate the possibility of using texture analysis in diffusion-weighted imaging (DWI) and machine learning algorithms to discriminate active from inactive MS lesions without the use of GBCA. MethodsTo achieve this purpose, we introduce an image processing pipeline. In the proposed pipeline, following registration and alignment of slices, MS lesions from DWI images are segmented and quantized. Next, different texture analysis methods are employed to extract texture features from the lesions. Then, a two-stage feature reduction method is applied, in which the first stage involves a statistical t-test and the second stage relies on principal component analysis (PCA), sequential forward selection (SFS), sequential backward selection (SBS), and ReliefF algorithms. Finally, we use five classifiers logistic regression (LR), support vector machine (SVM), decision tree (DT), K nearest neighbor (KNN), and linear discriminant analysis (LDA) in a 5-fold cross-validation procedure to determine active and inactive MS lesions. ResultsIn this study, we collected and prepared 255 active/inactive MS lesions from MRI scans of 34 patients diagnosed with MS, with a mean age of 35.56±10.89. Among 89 texture features extracted, 63 features showed statistically significant differences between the means of active and inactive lesions (P<0.05). The SVM classifier with the PCA feature reduction algorithm demonstrated the best performance with an average accuracy of 0.960 (±0.024), specificity and precision of 1.0, sensitivity of 0.913 (±0.053), and AUC of 0.957 (±0.027). ConclusionOur study indicates that DWI changes detected using texture analysis-based machine learning models can precisely differentiate active from inactive MS lesions. This finding provides valuable clinical information for the early diagnosis and effective monitoring of MS disease.

A Case of Cutaneous Leishmaniasis Cured by a Combined Treatment of Topical Miltefosine and Injectable Amphotericin B

&lt;img src=” https://s3.amazonaws.com/production.scholastica/article/90983/large/prnano_1012023bg.jpg?1702069910”&gt; A male rural worker with cutaneous leishmaniasis (CL) was initially treated with repeated cycles of Meglumine Antimoniate (Glucantime®) and two cycles of Amphotericin B deoxycholate during a three-year period. However, the patient remained with two active lesions. An experimental topical treatment with liposomal Miltefosine was tested. The efficacy was determined from the MD’s in-spection of the patient and analysis of the lesions’ photographic images, lesions samples culture, and anti-Leishmania antibodies quantification. The parasites from the patient were isolated. The parasites were typified as Leishmania braziliensis, and their susceptibility to Miltefosine, Meglu-mine Antimoniate, and Amphotericin B was measured. The wound healing was initially good with the topical treatment, but the clinical cure was achieved only with a combination of the topical lipo-somal Miltefosine and intravenous Amphotericin B. Of note, the treatment efficacy was strongly correlated with the degree of stress suffered by the patient. To our knowledge, this is the first report on using a topical Miltefosine formulation on a CL patient.

Long-term effects of a community-based oral health intervention for young children in the Netherlands: A 5-year follow-up.

The aim of this study was to assess whether referral of parents of 6 months old children by a well-child care (WCC) clinic medical practitioner for an early first dental visit combined with the Non Operative Caries Treatment and Prevention (NOCTP) approach in dental practices was effective to maintain oral health in children. The study was conducted as a quasi-experimental comparative pre-post trial with a baseline measurement before the intervention. In total 1347 children were allocated at the age of 6 months and 306 children (intervention group: n = 166; care as usual (CAU) group: n = 140) underwent an oral examination at 5 years of age and their parents completed a questionnaire. Nonparametric tests and Hurdle models were used to determine differences in caries experience between the intervention and CAU groups. Children in the intervention group had significantly lower caries experience (d1,2,3mfs) than children in the CAU group (Median = 2 vs. 5, r = .15, p < .01). Children in the intervention group had significantly fewer inactive caries lesions compared with children in the CAU group (Median = 2 vs. 3, r = .18, p < .001). No differences were found for dentin caries experience and also no differences for active caries lesions. Referral of parents of newborns for a preventive first dental visit by a WCC medical practitioner combined with NOCTP in dental practices may offer a new opportunity to reduce enamel caries lesions in young children.

Expanding options of supportive care in IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, with a potentially serious prognosis. At present, management of IgAN is primarily based on therapeutic lifestyle changes, and excellent blood pressure control and maximized supportive treatment with the combination of inhibition of the renin-angiotensin-aldosterone system with either inhibitors of angiotensin-converting enzyme or angiotensin II receptor blockers and inhibitors of sodium-glucose cotransporter-2, and possibly in the future also with endothelin antagonists. Supportive care currently represents the cornerstone of treatment of IgAN. Targeted-release formulation of budesonide should replace systemic corticosteroids in patients with higher proteinuria and active histological lesions. New treatment options are aimed at immunopathogenesis of IgAN including depletion or modulation of Galactose-deficient-Immunoglobulin A1-producing B cells, plasma cells, and the alternate and/or lectin pathway of complement. The exact place of monoclonal antibodies and complement inhibitors will need to be determined. This article reviews potential supportive therapies currently available for patients with IgAN.

Serum sulfatide level is associated with severe systemic vasculitis with kidney involvement.

Sulfatides are a type of sulfated glycosphingolipid that are secreted with lipoproteins into the serum. These molecules are involved in the inflammatory pathway of vessels in addition to coagulation and platelet aggregation. Previous studies have proposed that sulfatides play a pivotal role in regulating inflammation-related disorders. Systemic vasculitis (SV) diseases are generally caused by autoimmune diseases and often involve kidney vasculitis, which may lead to rapidly progressive kidney dysfunction and end-stage kidney disease. Our earlier pilot study revealed that the level of serum sulfatides (SSs) was significantly decreased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), a representative disease-causing SV with kidney involvement (SVKI), especially in patients exhibiting active crescentic findings on kidney biopsy. To further explore the clinical significance of an association between SS and SVKI, we analyzed and compared the SS level of patients with various SVKI diseases in this retrospective cohort study. Among patients admitted to our hospital between 2008 and 2021, we ultimately enrolled 26 patients with IgA vasculitis (IgAV), 62 patients with AAV, and 10 patients with anti-glomerular basement membrane disease (GBM) as examples of SVKI diseases, as well as 50 patients with IgA nephropathy (IgAN) and 23 donors for living kidney transplantation as controls. The mean ± standard deviation SS level in the donor, IgAN, IgAV, AAV, and GBM groups was 8.26 ± 1.72, 8.01 ± 2.21, 6.01 ± 1.73, 5.37 ± 1.97, and 2.73 ± 0.99 nmol/mL, respectively. Analysis of patients in the SVKI disease group showed that those with the crescentic class kidney biopsy finding exhibited a significantly lower SS level than did those with other class biopsy features. Additionally, the SS level had a higher detection ability for SVKI patients with crescentic class kidney biopsy findings (area under the receiver operating characteristic curve 0.90, 95% confidence interval 0.82-0.99) than did several other predictor candidates. Our results indicate that the SS level is decreased in more severe SVKI diseases and may be associated with active glomerular lesions in SVKI kidney biopsy samples.

Primary Small Cell Neuroendocrine Carcinoma of the Tonsil: A Rare Case Report and Review of Literature

Neuroendocrine tumors of the head and neck region are extremely infrequent. Small cell neuroendocrine carcinoma (NEC) of the tonsil is almost unheard of and carries a poor prognosis. There is no standard treatment protocol with regard to this tumor type. We present a 74-year-old male with complaints of odynophagia and swelling on the right side of the neck for one month. Physical examination showed a right neck level II lymph node with an ulceroproliferative mass involving the (R) tonsillar fossa, uvula, soft palate, and obstructing the oropharynx. MRI showed a right tonsillar mass measuring 3.4 × 3.3 × 1.4 cm with an ipsilateral level II lymph node measuring 2.7 × 1.9 cm. PET-CT scan showed a metabolically active right tonsillar lesion with a right level II lymph node. Histopathological examination revealed small cell NEC. On immunohistochemistry, tumor cells were strongly positive for PanCK, synaptophysin, chromogranin, CD56, and p16. Tumor cells were negative for CD45, CK7, CK20, and EBV-LMP. Ki-67 was 80%. The patient was treated with cisplatin and etoposide-based chemotherapy, and the tumor showed a very good response.

Malignant Melanoma with Atypical Phenotype and RAC1 Mutation

Abstract Introduction/Objective Melanoma, a highly invasive form of skin cancer associated with high mortality rates, poses significant challenges in diagnosis and treatment. RAC1, a member of the RHO family of GTPases, plays a crucial role as a molecular switch in cellular processes. A specific mutation in RAC1, caused by C &amp;gt; T transition induced by UV radiation, leads to P29S alteration, activating the SRF/MRTF pathway and triggering a phenotypic switch towards a mesenchymal phenotype. Methods/Case Report We present a case of a 74-year-old male patient who presented with a six-week history of right neck swelling. Ultrasonography revealed an enlarged lymph node in the right posterior triangle of the neck. PET scan showed a well- defined, moderately metabolically active lesion measuring 1.4x1.7cm. Initial biopsy indicated a diagnosis of malignant metastatic sarcomatous neoplasm. To establish a definitive diagnosis and determine the appropriate treatment plan, excision of the lymph node was performed. Histological examination revealed lymph node involvement by large, highly atypical cells exhibiting prominent nucleoli and frequent mitotic figures. Immunohistochemical analysis demonstrated positive staining for SOX10 and S100, while Melan-A and HMB45 were negative. Epithelial markers were also negative, although focal keratin positivity was observed. Further investigations were conducted to identify a primary or extranodal site. Routine dermatology visits had previously shown no evidence of primary cutaneous melanoma. Results (if a Case Study enter NA) Genomic profiling through next-generation sequencing (NGS) identified multiple alterations, including BRAF (G469R- exon 11, missense alteration), TP53 (R248W, missense alteration in TP53), RAC1 (P29S, missense alteration), TERT (Promoter Site Variant; chr5:g.1295228G&amp;gt;A c.-124C&amp;gt;T), and NF1 (Q1815, nonsense alteration). The tumor exhibited a high tumor mutational burden (TMB) and an ultraviolet (UV) signature characterized by C &amp;gt; T transitions. Conclusion Diagnosing melanoma with RAC1 mutation poses significant challenges due to its potential to induce phenotypic switching. Understanding the role of RAC1 mutations in driving melanoma progression can help improve diagnostic accuracy and guide targeted therapeutic strategies.

Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores

Routine immunofluorescence microscopy of glomerular immunodeposits in IgA nephropathy shows IgA, C3, and lambda light chains, and sometimes IgG, IgM, and kappa light chains. However, a previous study using high-resolution confocal microscopy showed IgG in all IgA nephropathy cases, likely representing autoantibodies specific for galactose-deficient IgA1. Here, we used high-resolution confocal microscopy to examine the composition of glomerular immunodeposits and colocalization of kappa and lambda light chains with IgA or IgG heavy chains in kidney-biopsy samples from twenty patients with IgA nephropathy, seventeen without IgG, and nine with no or trace kappa light chains by routine immunofluorescence microscopy. IgG was detected in all biopsies by high-resolution confocal microscopy. Single-optical-plane images showed similar colocalization of IgG heavy chains with kappa and lambda light chains. Colocalization of IgA heavy chains was greater with lambda light chains than with kappa light chains. Colocalization of IgG heavy chain with kappa light chains was higher than with lambda light chains in biopsies with endocapillary hypercellularity and crescents, i.e., biopsies with active lesions. We confirmed the utility of high-resolution confocal microscopy to detect components of glomerular immunodeposits not apparent on routine immunofluorescence microscopy and for colocalization of different components, potentially clarifying the pathogenesis of IgA nephropathy.

Incidence of Human and Free-Ranging Wild Rodent Infections with Leishmania (Viannia) braziliensis, Aetiological Agent of Cutaneous Leishmaniasis.

Human and wild rodent infection rates with Leishmania (Viannia) braziliensis are needed to differentiate transmission pathways in anthropogenically altered habitats. Human participants in northeast Brazil were tested by the leishmanin skin test (LST) and inspected for lesions/scars characteristic of American clinical leishmaniasis (ACL). Molecular (PCR/qPCR) test records of free-ranging rodents were available from a concurrent capture-mark-recapture study. Force of Infection (λ) and recovery (ρ) rates were estimated from cross-sectional and longitudinal datasets. Cumulative prevalences of human LST+ves and ACL scar+ves were 0.343-0.563 (n = 503 participants) and 0.122-0.475 (n = 503), respectively. Active ACL lesions were not detected. Annual rates of LST conversions were λ = 0.03-0.15 and ρ = 0.02-0.07. The probability of infection was independent of sex and associated with increasing age in addition to the period of exposure. Rodents (n = 596 individuals of 6 species) showed high rates of exclusively asymptomatic infection (λ = 0.222/month) and potential infectiousness to the sand fly vector. Spatially concurrent rodent and household human infection prevalences were correlated. Human exposure to L. (V.) braziliensis continues to be high despite the substantial drop in reported ACL cases in recent years. Spill-over transmission risk to humans from rodents in peridomestic habitats is likely supported by a rodent infection/transmission corridor linking houses, plantations, and the Atlantic Forest.

Functional Imaging As a Key Diagnostic Tool in the Follow-up of RRMM Patients after CAR-T-Cell Therapy

Introduction: Anti BCMA CAR T-cell therapy (CART) is establishing itself as a new standard of care for relapsed and refractory multiple myeloma (RRMM). However, the optimal follow-up strategy post CART has yet to be determined. Prior studies of our own and others have emphasized the role of functional imaging in monitoring RRMM patients post traditional chemotherapy, revealing residual disease in up to 50 % of otherwise minimal residual disease (MRD) negative patients (Rasche et al. Leukemia 2019). Whether a similar patchy disease pattern is relevant post CART remains unknown. To address this, we implemented a standardized follow-up program post CART, which includes 18F-FDG PET-CT, diffusion-weighted MRI, and bone marrow aspiration with MRD measurements at our center. Methods: We conducted monthly ambulatory visits and serological testing to monitor patients post CART infusion. Additionally, an extended follow-up visit at three months post CART infusion was performed, encompassing whole body PET-CT, whole body diffusion-weighted MRI, and bone marrow aspiration with MRD testing. Response assessments were based on IMWG criteria. MRI classified focal lesions as vital if they exhibited 1) significant diffusion-restriction, 2) a fat fraction less than 20 %, and 3) homogenous hypointensity on T2-weighted images. MRD measurements were performed with flow cytometry with a sensitivity of at least 10 -5 following the Euroflow recommendations. Results: From December 2021 to July 2023 we treated 37 heavily pretreated patients with idecabtagene vicleucel at our center. These patients had a median of 5 prior lines of therapy. High-risk cytogenetics, extra-medullary disease (EMD), and non-secretory disease were seen in 17, 14 and 6 patients, respectively. At data cut off, the ORR, VGPR and CR rates were 78 %, 27 % and 27 %, respectively. We observed primary refractory disease in 14 % of the patients. Among the 22 patients who underwent extended follow-up examinations at three months, the majority achieved MRD negativity, with only 7/22 (32 %) remaining MRD positive after CART. However, functional imaging revealed a higher number of patients with residual disease, with positive results on PET-CT and DW-MRI in 9/22 (41 %) and 10/22 (45 %) of patients, respectively. Notably, 6 of 22 (27 %) patients displayed active lesions on imaging despite MRD negativity at the iliac crest at this time point. Next, we focused on patients who experienced relapse from CART and sought to determine the necessary technology to detect relapse in this setting. Thirteen patients experienced relapse during the study period, and in 8 (61%) of them, functional imaging was the sole method to detect progressive disease. Only 1 patient transitioned from MRD negative to positive during the follow-up period, while the remaining 4 patients showed a significant M protein increase as defined by the IMWG criteria. Conclusion: In our heavily pretreated RRMM population, functional imaging emerged as a crucial diagnostic tool, detecting relapse alone in more than half of the patients. Our data supports inclusion of cross-sectional imaging in a comprehensive follow-plan after CART.

Long-term outcomes of lupus nephritis with low-level proteinuria: a multicentre, retrospective study.

Reportedly, patients with LN and low-level proteinuria have favourable short-term renal outcomes. We aimed to clarify the long-term renal outcomes and overall survival of these patients, and the significance of renal biopsy in the early phase with low-level proteinuria. We included 144 Japanese patients with biopsy-proven LN from 10 hospitals. Low-level proteinuria was defined by a urine protein:creatinine ratio (UPCR) of ≤1 g/gCr based on previous reports. The outcomes were end-stage renal disease (ESRD) and death. Compared with patients with high-level proteinuria (UPCR >1 g/gCr), those with low-level proteinuria [n = 67 (46.5%)] had significantly improved renal function at the time of renal biopsy, and low activity index and chronicity index while the frequency of class III/IV was similar (79.1% vs 84.4%, P = 0.409). In patients with low-level proteinuria, CYC usage was less, and the incidences of ESRD (3.0% vs 13.0%, P = 0.036) and death (3.0% vs 16.9%, P = 0.006) during the total observation period (median, 72 months) were low. Kaplan-Meier analysis showed significant differences in the incidence of ESRD and death between the groups. Multivariate Cox regression analysis revealed that the significant risk factors for ESRD were high chronicity index and hypertension, whereas those for death were increased age and high-level proteinuria. Patients with LN and low-level proteinuria had favourable long-term renal and life outcomes. As these patients have substantial active pathological lesions, renal biopsy in the early phase with low-level proteinuria could enable early diagnosis and treatment and thus improve prognosis.

Sirtuins and Metabolism Biomarkers in Relapsing-Remitting and Secondary Progressive Multiple Sclerosis: a Correlation Study with Clinical Outcomes and Cognitive Impairments.

Multiple sclerosis (MS) is a primary inflammatory demyelinating disease with different clinical courses and subtypes. The present study aimed to determine whether mitochondrial dysfunction and sirtuins 1 and 3, as metabolism and epigenetic modifying factors, might contribute to MS disease progression measured by physical disability and cognitive impairment.The volunteers (n = 20 controls, n = 59 MS) were recruited and assessed for cognitive function and disability scores; then, patients were clinically classified as relapsing-remitting (RR) in remission phase, RR in relapse phase, and secondary progressive MS. We measured sirtuin (SIRT) 1 and 3 levels, mitochondrial complex I, IV, aconitase, and α-ketoglutarate dehydrogenase (α-KGD) activity in the peripheral blood mononuclear cells (PBMCs). Furthermore, SIRT1, pyruvate, lactate, and cytochrome c (Cyt c) were determined in plasma. Finally, we performed postmortem tissue immunohistochemistry to assess the level of SIRT1 and SIRT3 in the brain lesions of patients with MS.Increased disability and cognitive impairment in patients were correlated. Plasma level of lactate showed a correlation with the disability in MS patients; moreover, a trend toward increased Cyt c plasma level was observed. Investigation of PBMCs exhibited decreased SIRT1 during the relapse phase along with a reduced complex IV activity in all MS subgroups. α-KGD activity was significantly increased in the RR-remission, and SIRT3 was elevated in RR-relapse group. This elevation correlated with disability and cognitive impairment. Finally, immunohistochemistry demonstrated increased levels of SIRT1 and 3 in the brain active lesion of patients with MS.Our data suggest that mitochondrial dysfunction and alteration in some epigenetics and metabolism modifying factors in the CNS and peripheral blood cells may contribute or correlate with MS progression.

Accuracy of Noncontrast T2 SPACE in Active MS Cord Lesion Detection.

The diagnosis of active MS lesions is often based on postgadolinium T1-weighted MR imaging. Recent studies suggest a risk of IV gadolinium to patients, predominantly based on gadolinium deposition in tissue. Noncontrast sequences have shown promise in MS diagnosis, but none differentiate acute from chronic MS lesions. We hypothesized that 3D T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (SPACE) MR imaging can help detect and differentiate active-versus-chronic MS lesions without the need for IV contrast. In this single-center retrospective study, 340 spinal MR imaging cases of MS were collected in a 24-month period. Two senior neuroradiologists blindly and independently reviewed postcontrast T1-weighted sagittal and T2-SPACE sagittal images for the presence of MS lesions, associated cord expansion/atrophy on T2-SPACE, and enhancement on postcontrast T1WI. Discrepancies were resolved by consensus between the readers. Sensitivity, specificity, and accuracy of T2-SPACE compared with postcontrast T1WI were computed, and interobserver agreement was calculated. The sensitivity of lesion detection on T2-SPACE was 85.71%, 95% CI, 63.66%-96.95%; with a specificity of 93.52%, 95% CI, 90.06%-96.05%; and an accuracy of 92.99%, 95% CI, 89.58%-95.56. Additionally, 16/21 (84.2%) acute enhancing cord lesions showed cord expansion on T2-SPACE. The interobserver agreement was 92%. Our study shows that T2-SPACE facilitates noncontrast detection of acute MS lesions with high accuracy compared with postcontrast T1WI and with high interobserver agreement. The lack of gadolinium use provides an advantage, bypassing any potential adverse effects of repetitive contrast administration.

Silver diamine fluoride with sodium fluoride varnish versus silver diamine fluoride in arresting early childhood caries: a 6-months follow up of a randomized field trial

BackgroundEarly childhood caries (ECC) is the most prevalent chronic health problem in young children, and it can be arrested using professionally applied fluoride such as Sodium fluoride (NaF) varnish and Silver Diamine Fluoride (SDF). This trial compared two interventions to arrest ECC lesions: 38% SDF combined with 5% NaF varnish versus 38% SDF and assessed whether the arrest rate was affected by baseline lesion severity measured by ICDAS.MethodsChildren aged ≤ 4 years from 4 nurseries in a rural area in Alexandria, Egypt joined the study in March 2022. They were included if they had at least one active carious lesion with ICDAS codes ≥ 3. They were randomized to receive either 38% SDF with 5% NaF varnish or 38% SDF alone. In both groups, the agents were applied at baseline and after 6 months on the caries lesions. NaF was additionally applied on all teeth in the oral cavity, and it was also applied after three months. The primary outcome was lesion arrest status after six months. Parents’ satisfaction with their children’s appearance was the secondary outcome. Pearson Chi-Square test was used for bivariate comparison and multi-level multiple logistic regression was used to assess the effect of the intervention on caries arrest controlling for confounders. The interaction between the intervention and baseline lesion severity (categorized into moderate and severe lesions) was assessed and the p value was calculated.ResultsThe study included 1606 lesions in 220 children, median (IQR) age = 48(9) months. The percentages of arrested lesions after the application of SDF + NaF and SDF only were 77.7% and 73.2% (p = 0.035). In multivariable analysis, SDF + NaF had significantly greater caries arrest effect than SDF alone (AOR = 2.12, p = 0.03) with significant difference (p = 0.03) between moderate (AOR = 4.10, p = 0.005) and advanced (AOR = 1.92, p = 0.08) lesions. Most parents were satisfied with their children’s appearance with no significant difference between groups (SDF + NaF = 84.5%, SDF = 78.18%, p = 0.23).ConclusionSDF + NaF had a higher arrest rate than SDF alone and this difference was significant in moderate but not advanced lesions. The findings have implications for the non-invasive management of ECC.Trial registrationThis trial was registered in the clinicaltrials.gov registry (#NCT05642494).

Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile.

The major phenotypes of inflammatory bowel disease(IBD) include ulcerative colitis (UC) and Crohn's disease (CD), which cause debilitating symptoms, including bloody diarrhea, abdominal discomfort, and fever. Patients require life-long immunosuppressive medications, which cause adverse side effects as additional morbidity factors. However, IBD is initiated and perpetuated by inflammatory cytokines, and given that in patients with IBDmyeloid lineage leukocytes are elevated with activation behaviorand release inflammatory cytokines, selective depletion of elevated granulocytes and monocytes by granulomonocytapheresis is a relevant therapeutic option for IBD patients. Therefore, a column filled with specially designed beads as granulomonocytapheresiscarriers for selective adsorption of myeloid lineage leukocytes (Adacolumn) has been applied to treat patients with active IBD. Patients receive up to 10 granulomonocytapheresis sessions at one or two sessions per week. During each session, the carriers adsorb up to 60% of the myeloid leukocytes from the blood that passes through the granulomonocytapheresis column. Efficacy rates in the UC setting have been as high as 85% in steroid-naïve patients, and 100% in drug-naïve, first-episode cases, but patients with a long duration of active IBD and extensive colonic lesions that have become refractory to pharmacological treatmenthave not responded well. However, granulomonocytapheresis has a favorable safety profile. Given that immunosuppressive medications used to treat IBDpotentially may increase the risk of severe viral infection, non-drug granulomonocytapheresisshould be a favorable treatment strategy. Further, by targeting granulomonocytapheresisto patients with background features and identifying a patient as a likely responder, futile use of medical resources is avoided.

Óriás congenitális nevusból, csecsemőkorban kialakult melanoma malignum, esetbemutatás és az irodalom áttekintése

Authors present a case of a 37- year-old young female patient, who presented to the emergency department with transient dizziness. The performed cranial MRI confirmed the presence of a solitary brain metastasis. PET CT revealed an FDG-avid active lesion in the lung, with slightly enlarged lymph nodes. The brain tumor was surgically removed and histologically it corresponded to malignant melanoma metastasis. According to tumor board decision combined immunotherapy was initiated. Dermatological examination revealed that the patient was being treated for a histologically neuro-mixoid-appearing melanoma that developed at 3 months of age from a giant congenital nevus at birth and later metastasized regionally. Multiple radical surgeries were performed and she received vincristine and platina based chemotherapy. She was symptom-, and complaint-free for decades under regular check-ups until the onset of vertigo. In connection with the case the authors discuss the specific features of childhood melanomas, in particular the early-onset forms arising from congenital giant.