Active Lesions Research Articles

Childhood-Onset Sacroiliitis: Causes and Correlation Between Clinical Findings and Magnetic Resonance Imaging.

The aims of this study were to describe disease associations of magnetic resonance imaging (MRI)-confirmed and clinically symptomatic sacroiliitis in pediatric patients with rheumatic diseases and to examine the relationship between patient characteristics and MRI findings of the sacroiliac joint (SIJ). Demographic and clinical data were extracted from the electronic medical records of the patients with sacroiliitis followed in the last 5 years. Active inflammatory and structural damage lesions of the SIJ-MRI were examined by the modified Spondyloarthritis Research Consortium of Canada scoring system, and correlation analysis of these results with clinical characteristics was evaluated. A total of 46 symptomatic patients were found to have MRI-proven sacroiliitis of 3 different etiologies: juvenile idiopathic arthritis (JIA) (n = 17), familial Mediterranean fever (FMF) (n = 14), and chronic nonbacterial osteomyelitis (CNO) (n = 8). Seven patients, FMF and JIA (n = 6) and FMF and CNO (n = 1), had a co-diagnosis that might cause sacroiliitis. Although inflammation scores and structural damage lesions did not statistically differ between the groups, capsulitis and enthesitis on the MRI were more frequently detected in the CNO group. There was a negative correlation between symptom onset and inflammation scores of bone marrow edema. Disease composite scores and acute phase reactants were correlated with MRI inflammation scores. We demonstrated that JIA, FMF, and CNO were the major rheumatic causes of sacroiliitis in children originating from the Mediterranean region. Quantitative MRI scoring tools can be used to assess the inflammation and damage of the SIJ in rheumatic diseases, show discrepancies between them, and have an important correlation with various clinical and laboratory features.

Oral health of recreational ecstasy-users

In a cross-sectional study, dental records of 149 individuals visiting an Academic Dental Clinic in Amsterdam who reported recreational ecstasy use, defined as no more than twice a week, were systematically analyzed and compared to a group of age- and sex-matched non-drug-users. The parameters retrieved from the dental records were decayed, missing, and filled permanent teeth-index (DMFT-index), number of endodontically treated teeth, presence of active caries lesions, periodontitis, tooth wear, xerostomia, and self-reported use of oral hygiene devices. Periodontitis, active caries lesions, and xerostomia were statistically significantly more present in ecstasy-users. Ecstasy-users brush their teeth significantly less frequent per day than non-recreational-drug-users. There were no significant differences in DMFT-index and in the devices used for brushing and interdental cleaning, and frequency of use of these interdental devices between both groups. We conclude that periodontitis, active caries lesions, and xerostomia, are more frequently present in recreational ecstasy-users compared to age- and sex-matched non-users.

MRI in pediatric sacroiliitis, what radiologists should know.

MRI is used for early detection of inflammation of sacroiliac joints as it shows active lesions of sacroiliitis long before radiographs show damage to the sacroiliac joints. Early diagnosis of arthritis allows early treatment of inflammation and can help delay disease progression and prevent irreversible damage. Also, early identification of axial involvement in juvenile spondyloarthropathy is crucial, as treatment options are different than for peripheral juvenile spondyloarthropathy. In general, standard sequences used in adults are also applied to children. However, interpreting MR images of pediatric sacroiliac joints is more challenging than in adults, because of normal physiological changes during skeletal maturation, which can simulate disease on MR images. Furthermore, classical definitions of sacroiliitis used in adults, for both active inflammatory and structural lesions, can be difficult to extrapolate to children. The development of reliable pediatric-specific definitions for sacroiliitis is still in active study. Understanding both normal and pathological signal changes in children is important to distinguish physiologic findings from disease and to make a correct diagnosis. In this review, the main imaging characteristics of sacroiliitis on MRI in children and its frequent pitfalls will be illustrated, while also citing some discussion points regarding the scan protocol.

Clinicopathologic Spectrum of Renal Lesions Following Anti-TNF- α Inhibitor Therapy: A Single Center Experience.

Anti-tumor necrosis factor (TNF)-alpha inhibitors, as biological agents, are used in autoimmune inflammatory states, rheumatoid arthritis (RA), psoriatic arthritis (PA), and Crohn's disease. They can induce autoimmune serologic responses and clinical disorders including systemic vasculitis and lupus-like diseases, affecting the kidney. Retrospective analysis of clinicopathologic features of kidney disease following anti-TNF alpha therapy (treatment group) from our renal biopsy files from 2000-2018 is conducted and compared with 106 cases without therapy (control group). Forty-eight patients using anti-TNF-alpha agents had renal biopsies, RA in 30, PA in 6, Crohn's disease 6, RA and PA 1, RA and Crohn's disease 1, and others 4. 20 received etanercept, 15 adalimumab, 8 infliximab and 5 had 2 forms of agents manifesting new onset nephritic syndrome or CKD, 17 with acute kidney injury and 16 nephrotic syndrome, with recent ANCA and/or lupus serology. The renal lesions were crescentic glomerulonephritis in 8, 5 pauci-immune type and 5 ANCA+. Lupus or lupus-like nephritis seen in 6: ISN/RPS 2018 class II-2, class V-2, class III+V-1, class IV+V-1, 3 with concurrent fibrillary GN, scleroderma/TMA and amyloidosis. Renal lesions unrelated to anti-TNF-alpha therapy or underlying autoimmune disease in 23 (eg diabetic nephropathy, interstitial nephritis, acute tubular injury, infection-related GN), IgA nephropathy, renal sarcoidosis and AA amyloidosis were noted in 5 cases. Thrombotic microangiopathy was recognized in 5 cases, 1 associated with scleroderma and 1 antiphospholipid antibodies, and 2 nephrotic syndrome secondary to podocytopathy. The control group was similar with higher immune mediated GN, interstitial nephritis and amyloidosis. The renal lesions during anti-TNF-alpha therapy have an autoimmune basis such as ANCA, lupus or lupus-like disease, correlated with new onset serology, while others were similar to those observed in the control group. Renal biopsy findings integrated with clinical features and therapy can identify the underlying pathophysiologic process for appropriate management.

Selective emergence of antibody-secreting cells in the multiple sclerosis brain.

Although distinct brain-homing B cells have been identified in multiple sclerosis (MS), it is unknown how these further evolve to contribute to local pathology. We explored B-cell maturation in the central nervous system (CNS) of MS patients and determined their association with immunoglobulin (Ig) production, T-cell presence, and lesion formation. Exvivo flow cytometry was performed on post-mortem blood, cerebrospinal fluid (CSF), meninges and white matter from 28 MS and 10 control brain donors to characterize B cells and antibody-secreting cells (ASCs). MS brain tissue sections were analysed with immunostainings and microarrays. IgG index and CSF oligoclonal bands were measured with nephelometry, isoelectric focusing, and immunoblotting. Blood-derived B cells were cocultured under T follicular helper-like conditions to evaluate their ASC-differentiating capacity invitro. ASC versus B-cell ratios were increased in post-mortem CNS compartments of MS but not control donors. Local presence of ASCs associated with a mature CD45low phenotype, focal MS lesional activity, lesional Ig gene expression, and CSF IgG levels as well as clonality. Invitro B-cell maturation into ASCs did not differ between MS and control donors. Notably, lesional CD4+ memory T cells positively correlated with ASC presence, reflected by local interplay with T cells. These findings provide evidence that local B cells at least in late-stage MS preferentially mature into ASCs, which are largely responsible for intrathecal and local Ig production. This is especially seen in active MS white matter lesions and likely depends on the interaction with CD4+ memory T cells. Stichting MS Research (19-1057 MS; 20-490f MS), National MS Fonds (OZ2018-003).

Microstructural alterations in different types of lesions and their perilesional white matter in relapsing-remitting multiple sclerosis based on diffusion kurtosis imaging.

In multiple sclerosis (MS), contrast enhancement lesions and chronic active lesions have been demonstrated to have different degrees of inflammation. Accordingly, they exist different degrees of tissue damage, one is short and acute, and another is slow and longstanding. This study aimed to explore whether diffusion parameters can differentiate different types of lesions, and investigate the microstructural damage between different types of MS lesions by using diffusion magnetic resonance imaging (dMRI) and its correlation with clinical biomarkers of disability and cognitive states. We retrospectively identified 77 contrast enhancement lesions (CELs), 384 iron rim lesions (IRLs), 393 non-iron rim lesions (NIRLs), their corresponding perilesional white matter (PLWM), and 68 normal-appearing white matter (NAWM) from 68 relapsing-remitting MS (RRMS). Additionally, 44 white matter in healthy controls (WM in HCs) were also enrolled in this study. The DTI and DKI parameters were measured in the above white matter, including kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD). All the patients were assessed with the Digital Span Test (DST), the Symbol Digit Modalities Test (SDMT), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Expanded Disability Status Scale (EDSS). The lowest KFA, FA, MK values and the highest MD values were found in CELs, followed by IRLs, NIRLs, NAWM, and WM in HCs. In KFA and FA values, there were significant differences between each type of lesion, as well as each type of PLWM (P < 0.05). The MK values of CELs and IRLs were significantly lower than NIRLs, but inversely for MD (P < 0.05). There were no differences between CELs and IRLs for MK (P=1) and MD (P=0.261). The results of MK and MD values in CELs-PLWM and IRLs-PLWM were similar to the CELs and IRLs. There were no significant differences between NAWM and WM in HCs in all the enrolled diffusion parameters (P >0.05) and the FA values between NIRLs-PLWM and NAWM or between NIRLs-PLWM and WM in HCs were no significant differences (P >0.05). The KFA and MD values in IRLs-PLWM (r =0.443, P =0.021; r =-0.518, P =0.006) were correlated with the DST scores and the KFA of CELs-PLWM (r =0.396, P =0.041) was correlated with SDMT scores. Our findings demonstrate that the KFA values have the potential to distinguish different types of MS white matter tissues. Furthermore, the diffusion parameters can reflect the microstructure abnormalities in different MS lesions and might help us better understand the pathological mechanism and lesion evolution.

Kidney Biopsy in Pregnant Women with Glomerular Diseases: Focus on Lupus Nephritis

Despite significant improvements of renal and obstetrical management, pregnancies in women with glomerular diseases and with lupus nephritis continue to be associated with increased complications both for the mother and the fetus as compared to those of pregnancies in healthy women. To reduce the risk of these complications, planning pregnancy in a phase of stable remission of the underlining disease is necessary. A kidney biopsy is an important event in any phase of pregnancy. A kidney biopsy can be of help during counselling before pregnancy in cases of incomplete remission of the renal manifestations. In these situations, histological data may differentiate active lesions that require the reinforcement of therapy from chronic irreversible lesions that may increase the risk of complications. In pregnant women, a kidney biopsy can identify new-onset systemic lupus erythematous (SLE) and necrotizing or primitive glomerular diseases and distinguish them from other, more common complications. Increasing proteinuria, hypertension, and the deterioration of kidney function during pregnancy may be either due to a reactivation of the underlying disease or to pre-eclampsia. The results of the kidney biopsy suggest the need to initiate an appropriate treatment, allowing the progression of the pregnancy and the fetal viability or the anticipation of delivery. Data from the literature suggest avoiding a kidney biopsy beyond 28 weeks of gestation to minimize the risks associated with the procedure vs. the risk of preterm delivery. In case of the persistence of renal manifestations after delivery in women with a diagnosis of pre-eclampsia, a renal kidney assessment allows the final diagnosis and guides the therapy.

Alemtuzumab-Related Lymphocyte Subset Dynamics and Disease Activity or Autoimmune Adverse Events: Real-World Evidence

alemtuzumab is a monoclonal anti-CD52 antibody acting on B and T cells in highly active multiple sclerosis (MS). We analyzed changes in lymphocyte subsets after alemtuzumab administration in relation to disease activity and autoimmune adverse events. lymphocyte subset counts were assessed longitudinally using linear mixed models. Subset counts at baseline and during follow-up were correlated with relapse rate, adverse events, or magnetic resonance (MRI) activity. we recruited 150 patients followed for a median of 2.7 years (IQR: 1.9-3.7). Total lymphocytes, CD4, CD8, and CD20 significantly decreased in all patients over 2 years (p < 0.001). Previous treatment with fingolimod increased the risk of disease activity and adverse events (p = 0.029). We found a higher probability of disease reactivation in males and in patients with over three active lesions at baseline. Higher EDSS scores at baseline and longer disease duration predicted the switch to other treatments after alemtuzumab. Our real-world study supports data from clinical trials in which lymphocyte subsets were not useful for predicting disease activity or autoimmune disease during treatment. The early use of an induction therapy such as alemtuzumab in patients with a lower EDSS score and short history of disease could mitigate the risk of treatment failure.

Asociación entre las características radiográficas y los tumores óseos de rodilla.

Bone neoplasms require an adequate clinical-radiographic evaluation for their diagnosis. Plain radiographs are the usual method to establish the diagnosis and evaluate differential diagnoses in the study of bone tumor pathology. To recognize the frequency of radiographic characteristics and associate them with bone tumor pathology. Radiographic data were collected from 132 patients with tumor pathology confirmed by biopsy from bone tumors service of the Traumatology and Orthopedics Hospital Unidades Médicas de Alta Especialidad Dr. Victorio de la Fuente Narváez, Instituto Mexicano del Seguro Social, Ciudad de México, during 2019. 132 patients were registered. The most frequent benign tumor was osteochondroma (27.3%), and malignant was osteosarcoma (9.8%). Active lytic lesions (odds ratio [OR]: 6.9; 95% confidence interval [95% CI]: 2.83-16.85) or aggressive (OR: 26.85; 95% CI: 3.21-224) were associated with giant cells tumors. Poorly differentiated intraosseous blast lesions of bone lineage (OR: 36.15; 95% CI: 4.4-295.5) were associated with osteosarcoma. The periosteal reaction (OR: 36.15; 95% CI: 4.4-295.5), the moth-eaten or permeative pattern (OR: 11.75; 95% CI: 1.26-109) and the central location of the lesion (OR: 3.03; 95% CI: 1.37-6.69) were associated with malignant tumor lesions. Poorly defined intraosseous blast lesions of bone lineage, periosteal reaction, and moth-eaten or permeative pattern of destruction are associated with malignant lesions.

89Zr-DFO-girentuximab for PET imaging of solid tumors likely to express high levels of carbonic anhydrase IX.

TPS738 Background: Carbonic anhydrase IX (CAIX) is a cell surface antigen that is widely expressed in many cancers including clear cell renal cell carcinoma, urothelial and triple negative breast cancers, and thus is a potential target for imaging and therapy. 89Zr-DFO-girentuximab (hereafter referred to as TLX250-CDx) is a diagnostic radiopharmaceutical for PET imaging that targets CAIX and has demonstrated clinical success in ccRCC imaging. Genitourinary (GU) cancer types that express CAIX lack robust diagnostic and management options. To improve the morbidity and mortality, diagnostic and therapeutic innovation is needed; theranostics with TLX250-CDx may play an integral role. Moreover, TLX250-CDx could assist with patient selection for immuno-oncology therapy as CAIX tumoral expression is associated with resistance to immunotherapy. Finally, TLX250-CDx imaging could provide a cost-effective method for monitoring response to various therapies. In this pilot study, patients with different tumor types likely to express CAIX that lack effective therapies will be evaluated for TLX250-CDx tumor uptake. Methods: This is an open-label, non-randomized study to evaluate feasibility of targeting CAIX for potential diagnostic and therapeutic applications. Data gathered from this pilot study will support a larger trial with patients with the tumor types expressing the greatest avidity forTLX250-CDx, as well as therapeutic studies targeting CAIX. The study's primary objective is to noninvasively evaluate TLX250-CDx PET/CT imaging of CAIX tumoral expression in different solid tumors. The secondary objective is to evaluate tolerability and safety of TLX250-CDx administration in patients with different tumor types. Patients with cancer types including cervical and ovarian (minimum 5 patients per type) will be enrolled. Patients must have at least one non-central nervous system measurable target lesion (as per RECIST 1.1) documented by conventional imaging performed within 30 days before dosing. Patients will receive a single administration of TLX250-CDx (37 MBq [1mCi] ± 10%, containing 10 mg of girentuximab), and will undergo PET/CT imaging 5 ± 2 days later. Tumor uptake of TLX250-CDx will be assessed per lesion, up to the 10 most active lesions. Qualitative visual analysis (presence or absence of localized uptake associated with tumor, as seen on contrast-enhanced CT, MRI and/or FDG PET/CT), will be used to evaluate concordance of tumor lesion detection between TLX250-CDx PET/CT and conventional imaging according to RECIST 1.1. Patient safety will be evaluated based on incidence and nature of adverse events and clinically significant changes in laboratory test values, vital signs, or physical exam. Statistics will be descriptive with no formal hypothesis. The study is ongoing. Acknowledgements: Stefanie D. Martina, MS (Telix Pharmaceuticals) provided writing/editorial support. Clinical trial information: NCT05563272 .

Serum Amyloid A: A Potential New Marker of Severity in Hidradenitis Suppurativa

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with systemic inflammation and high impact on quality of life. Treatment strategies are still inadequate with a lack of inflammation biomarkers. We conducted a prospective study to assess the correlation between serum amyloid A (SAA) levels and active lesion count; disease severity; Dermatology Life Quality Index (DLQI); smoking; BMI; and lesion sites. Methods: Forty-one patients (M/F: 22/19) were enrolled. Demographic, clinical, laboratory, and therapeutic data were assessed at baseline on patients not under treatment or in wash-out from systemic treatment for at least 2 weeks. Associations were investigated by univariate and multivariate analyses. Results: SAA levels were significantly associated with number of nodules (p = 0.005), abscesses (p < 0.001), fistulas (p = 0.016), and severe IHS4 (p = 0.088 and r = 0.514). Gluteal localization was correlated with high values of mSartorius and severe IHS4. Conclusions: We recommend assessment of SAA levels to monitor therapeutic response in patient with HS in order to prevent disease’s flare and potential complications.

Repeatability of metabolic tumor burden and lesion glycolysis between clinical readers.

The Metabolic Tumor Volume (MTV) and Tumor Lesion Glycolysis (TLG) has been shown to be independent prognostic predictors for clinical outcome in Diffuse Large B-cell Lymphoma (DLBCL). However, definitions of these measurements have not been standardized, leading to many sources of variation, operator evaluation continues to be one major source. In this study, we propose a reader reproducibility study to evaluate computation of TMV (& TLG) metrics based on differences in lesion delineation. In the first approach, reader manually corrected regional boundaries after automated detection performed across the lesions in a body scan (Reader M using a manual process, or manual). The other reader used a semi-automated method of lesion identification, without any boundary modification (Reader A using a semi- automated process, or auto). Parameters for active lesion were kept the same, derived from standard uptake values (SUVs) over a 41% threshold. We systematically contrasted MTV & TLG differences between expert readers (Reader M & A). We find that MTVs computed by Readers M and A were both concordant between them (concordant correlation coefficient of 0.96) and independently prognostic with a P-value of 0.0001 and 0.0002 respectively for overall survival after treatment. Additionally, we find TLG for these reader approaches showed concordance (CCC of 0.96) and was prognostic for over -all survival (p ≤ 0.0001 for both). In conclusion, the semi-automated approach (Reader A) provides acceptable quantification & prognosis of tumor burden (MTV) and TLG in comparison to expert reader assisted measurement (Reader M) on PET/CT scans.

The role of systemic ımmune ınflammatory ındex in showing active lesion ın patients with multiple sclerosis

BackgroundMultiple sclerosis (MS) has two pathophysiological processes, one inflammatory and the other degenerative. We investigated the relationship between active lesions on magnetic resonance imaging showing the inflammatory phase in MS patients and serum parameters that can be used as inflammatory biomarkers. Thus, we aim to detect the inflammatory period in clinical and radiological follow-up and to reveal the period in which disease-modifying treatments are effective with serum parameters.MethodsOne hundred eighty-six MS patients presented to our hospital between January 2016 and November 2021 and 94 age- and sex-matched healthy volunteers were recruited for our study. While 99 patients had active lesions on magnetic resonance imaging, 87 patients did not have any active lesions. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) were determined. The SII (systemic immune inflammatory index) value was calculated according to the platelet X neutrophil/lymphocyte ratio formula.ResultsNLR, MLR, PLR and SII values were found to be statistically significantly higher in MS patients than in the control group. The NLR, MLR, PLR and SII were higher in the active group with gadolonium than in the group without active lesions. In addition, the cutoff values that we can use to determine the presence of active lesions were 1.53, 0.18, 117.15, and 434.45 for NLR, MLR PLR and SII, respectively.ConclusionsWe found that all parameters correlated with radiological activity. In addition, we showed that we can detect the inflammatory period with high sensitivity and specificity with the cutoff value used for SII and PLR. Among these easily accessible and inexpensive evaluations, we concluded that SII, including the values in the PLR formula, can come to the fore.

C-Reactive Protein Levels Are Associated with Complement C4 Deposits and Interstitial Arteritis in ANCA-Associated Renal Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a potentially life-threatening systemic small-vessel vasculitis that is characterized by pauci-immune glomerulonephritis in case of kidney involvement, representing a major denominator of AAV mortality. Innate immunity with complement system activation is increasingly recognized in the pathogenesis of AAV and as an attractive therapeutic target. Although C-reactive protein (CRP) was thought to be a passive, nonspecific marker of inflammation, recent studies indicate that CRP plays a key role in the innate immune system by recognizing pathogens and altered self-determinants. Elevated baseline CRP at disease onset of AAV has already been described as a determinant of poor long-term outcomes. However, its clinical implications at disease onset of AAV, with respect to vasculitis manifestations and complement system activation that might also affect long-term outcomes, remain elusive. CRP levels were retrospectively analyzed in 53 kidney-biopsy-confirmed cases of ANCA-associated renal vasculitis; a total of 138 disease controls were also evaluated. Univariate and multivariate regression analysis was performed on clinicopathological parameters associated with CRP levels in ANCA-associated renal vasculitis. Results: Compared to disease controls, CRP elevation was common in ANCA-associated renal vasculitis and associated with de novo disease (p = 0.0169), critical illness (p = 0.0346), and severe deterioration of kidney function (p = 0.0167), independent of extrarenal disease manifestations. As confirmed by multiple regression analysis, CRP levels were correlated with active lesions predominated by interstitial arteritis in renal vasculitis, specifically with MPO-ANCA seropositivity (p = 0.0017). Based on analysis of systemic complement system activation and intrarenal complement deposits, CRP elevation was correlated specifically with complement C4 deposits in interstitial arteries in the subgroup with myeloperoxidase (MPO)-ANCA seropositivity (p = 0.039). Finally, this association was independent of systemic complement system activation, as reflected by the consumption of respective complement components. Here, we expand our current understanding of CRP in ANCA-associated renal vasculitis not only as an inflammatory marker, but potentially also as being involved in the pathogenesis of kidney injury by interaction with the complement system.

Disease state associated with chronic toe lesions in hellbenders may alter anti-chytrid skin defenses

Hellbenders (Cryptobranchus alleganiensis) are large, aquatic salamanders from the eastern United States. Both subspecies, eastern and Ozark hellbenders, have experienced declines resulting in federal listing of Ozark hellbenders. The globally distributed chytrid fungus, Batrachochytrium dendrobatidis (Bd) has been detected in both subspecies, and Batrachochytrium salamandrivorans (Bsal) poses a new threat if introduced into North America. Ozark hellbenders also suffer a high prevalence of toe lesions of unknown etiology, with changes in host immunocompetence hypothesized to contribute. Antimicrobial peptides (AMPs) secreted from dermal granular glands may play a role in hellbender health. We collected skin secretions from free-ranging hellbenders and enriched them for small cationic peptides used for growth inhibition assays against Bd and Bsal. Generalized linear mixed models revealed the presence of active toe lesions as the strongest and only significant predictor of decreased Bd inhibition by skin peptides. We also found skin secretions were more inhibitory of Bsal than Bd. MALDI-TOF mass spectrometry revealed candidate peptides responsible for anti-chytrid activity. Results support the hypothesis that hellbender skin secretions are important for innate immunity against chytrid pathogens, and decreased production or release of skin peptides may be linked to other sub-lethal effects of disease associated with toe lesions.

Alternative sampling specimens for the molecular detection of mpox (formerly monkeypox) virus.

Mpox (formerly monkeypox) is a viral disease caused by the mpox virus (MPXV), endemic in Central and West Africa and currently causing a global outbreak of international concern. Much remains unknown about sample types most suited for mpox laboratory diagnosis. While it is established that high viral loads can be found in active skin lesions (currently the recommended mpox laboratory confirmation specimen type), WHO mpox testing guidelines encourage the use of oropharyngeal swabs as an additional sample type for mpox diagnosis and suggest investigating the value of other specimens like blood samples. In this study, we verified the value of select alternative specimen types for mpox laboratory confirmation. We included 25 patients with MPXV-confirmed skin lesions to compare diagnostic sensitivity of MPXV PCR testing on EDTA plasma and two upper respiratory specimens: oropharyngeal swabs and saliva. In our patient cohort with MPXV-confirmed skin lesions, diagnostic sensitivity of MPXV PCR was 80% in EDTA plasma, 64% in oropharyngeal swabs, and 88% in saliva. MPXV viral loads were significantly higher in saliva compared to oropharyngeal swabs and EDTA plasma. The WHO recommendation to collect oropharyngeal swabs as an additional specimen for mpox diagnosis might need to be revised to include saliva wherever feasible. We suggest investigating saliva as a diagnostic specimen in the absence of active skin lesions or during the phase preceding skin manifestations. Moreover, the relatively high MPXV DNA content of saliva warrants elucidating its potential role in disease transmission.

Painful facial, oral, and genital ulcers

Painful facial, oral, and genital ulcers

A Preliminary Study to Compare Recombinase Polymerase Amplification-Lateral Flow and Quantitative PCR in the Detection of Cutaneous Leishmania in Communities from the Volta Region of Ghana.

Background: Leishmaniasis is a parasitic disease that mostly affects populations in tropical and subtropical countries. In Ghana, cutaneous leishmaniasis (CL) is the most common form of the disease affecting communities of the Volta Region. Conventional parasitological method (microscopy) is the commonly used test for CL diagnosis in many endemic countries, but has low sensitivity in chronic cases. Therefore, there is a clear need for a sensitive and easy-to-use point-of-care diagnostic method like an isothermal recombinase polymerase amplification-lateral flow (RPA-LF) test, suitable for use in austere and low-resource settings for the identification of CL cases. This study compared the efficacy of RPA-LF test with quantitative PCR (qPCR) in detecting Leishmania in suspected CL cases from the Volta Region. Methods: Twenty-five participants between 5 and 14 years were enrolled in the study from whom a total of 26 samples were obtained. Lesion samples were collected using FTA® filter papers applied to ulcerated lesions for molecular diagnosis. DNA isolated from filter papers was used for both the RPA-LF test and qPCR. Results: Twenty-two participants (88%) presented with one or two ulcerated active lesions per individual, while the rest of them had plaques or dried lesions. Among the 26 samples, 19/26 (73%) had concordant results when comparing the two diagnostic methods. Conclusion: Data from this study suggest that the RPA-LF test can be used in addition to a conventional parasitological diagnostic test (microscopy) to detect CL cases in communities of the Volta Region.

Less confident, successful and happy: patients with post-acne hyperpigmentation are stigmatized.

Stigmatization is a major issue for individuals with acne. Using a simple but expressive study design and a large sample representative of the German general population, this study showed that individuals with residual post-inflammatory hyperpigmentation (PIH) are stigmatized by the general population even in the absence of active lesions, prolonging the mental burden of acne. Considering that PIH can take years to fade, the results of this study underline the importance of preventing and treating PIH to reduce the mental burden for the affected individuals.

Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis

Proposed biosimilar natalizumab (biosim-NTZ) PB006 is the first biosimilar monoclonal antibody therapy developed for multiple sclerosis (MS) treatment. To evaluate matching efficacy, safety, and immunogenicity between biosim-NTZ and reference natalizumab (ref-NTZ) in patients with relapsing-remitting MS (RRMS). The Antelope trial was a phase 3, parallel-group, randomized, active-controlled study, conducted between October 2019 and March 2021, with last patient follow-up visit on August 23, 2021. The study took place in 48 centers in 7 countries. Of 531 patients with RRMS aged 18 to 60 years screened, 266 were excluded before randomization in line with study criteria. Eligible participants had 1 or more documented relapse within the previous year and either 1 or more gadolinium-enhancing T1-weighted or 9 or more T2-weighted brain lesions, Kurtzke Expanded Disability Status Scale score of 0 to 5.0 (inclusive), and John Cunningham virus index of 1.5 or less at screening. One patient withdrew consent before dosing. Intravenous infusions every 4 weeks of biosim-NTZ, 300 mg, or ref-NTZ, 300 mg (1:1 randomization), from week 0 to week 44 (end-of-study visit: week 48). At week 24, the ref-NTZ group was rerandomized and 30 patients were switched to biosim-NTZ for the remainder of the study. The primary end point was the cumulative number of new active lesions on magnetic resonance imaging (new gadolinium-enhancing T1-weighted lesions and new/enlarging T2-weighted lesions without double counting) over 24 weeks. Additional end points included further magnetic resonance imaging parameters, annualized relapse rate, and Kurtzke Expanded Disability Status Scale score. Safety, tolerability, and immunogenicity assessments included adverse events, laboratory evaluations, and positivity for anti-John Cunningham virus antibodies and antinatalizumab antibodies. A total of 264 participants (mean [SD] age, 36.7 [9.38] years; 162 [61.4%] female) received treatment with biosim-NTZ (n = 131) or ref-NTZ (n = 133). At week 24, the model-based mean difference in cumulative number of new active lesions between biosim-NTZ and ref-NTZ treatment groups was 0.17 (least square means [SE]: biosim-NTZ, 0.34 [0.34]; ref-NTZ, 0.45 [0.28]; 95% CI, -0.61 to 0.94 within the prespecified margins of ±2.1). No significant differences between treatment groups were observed across secondary efficacy end points, safety, tolerability, or immunogenicity assessments. Biosim-NTZ matched ref-NTZ in efficacy, safety, and immunogenicity for patients with RRMS in the tested setting. This phase 3 trial supports proposed biosim-NTZ as a biosimilar alternative to ref-NTZ for treating RRMS. ClinicalTrials.gov Identifier: NCT04115488.