Search

Background: 11 C-PBR28 positron emission tomography (PET), targeting the translocator protein, and paramagnetic rim lesions (PRL) have emerged as promising imaging markers of MS chronic inflammation. No consensus on which is the optimal marker exists., Objectives: To investigate the ability of 11 C-PBR28 PET and PRL assessment to identify chronic inflammation in white matter (WM) MS lesions and their relation to neurological impairment., Methods: Based on 11 C-PBR28 uptake, brain WM lesions from 30 MS patients were classified as PET active or inactive. The PRL presence was assessed on 7T phase reconstructions, T1/T2 ratio was calculated to measure WM microstructural integrity., Results: Less than half (44%) of non-PRL WM lesions were active on 11 C-PBR28 imaging either throughout the lesion (whole active) or at its periphery. PET peripherally active lesions and PRL did not differ in T1/T2 ratio and 11 C-PBR28 uptake. A positive correlation was observed between PRL and active PET lesion count. Whole active PET lesion volume was the strongest predictor (β = 0.97, p < 0.001) of increased Expanded Disability Status Scale scores., Conclusion: 11 C-PBR28 imaging reveals more active WM lesions than 7T PRL assessment. Although PRL and PET active lesion counts are related, neurological disability is better explained by PET whole active lesion volume., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.A.T. has received research support from Genentech; E.H. has received research support from the NMSS (FG-1507-05459, TA-1905-34039); J.A.S. has consulted for Novartis, Biogen, Celgene, and Genentech; T.G. is a recipient of the Grant for Multiple Sclerosis Innovation, funded by Merck; C.M. has received research support from Genentech. The remaining authors have nothing to disclose.

Blood oxygen saturation (SpO 2 ) is vital for patient monitoring, particularly in clinical settings. Traditional SpO 2 estimation methods have limitations, which can be addressed by analyzing photoplethysmography (PPG) signals with artificial intelligence (AI) techniques. This systematic review, following PRISMA guidelines, analyzed 183 unique references from WOS, PubMed, and Scopus, with 26 studies meeting the inclusion criteria. The review examined AI models, key features, oximeters used, datasets, tested saturation intervals, and performance metrics while also assessing bias through the QUADAS-2 criteria. Linear regression models and deep neural networks (DNNs) emerged as the leading AI methodologies, utilizing features such as statistical metrics, signal-to-noise ratios, and intricate waveform morphology to enhance accuracy. Gaussian Process models, in particular, exhibited superior performance, achieving Mean Absolute Error (MAE) values as low as 0.57% and Root Mean Square Error (RMSE) as low as 0.69%. The bias analysis highlighted the need for better patient selection, reliable reference standards, and comprehensive SpO 2 intervals to improve model generalizability. A persistent challenge is the reliance on non-invasive methods over the more accurate arterial blood gas analysis and the limited datasets representing diverse physiological conditions. Future research must focus on improving reference standards, test protocols, and addressing ethical considerations in clinical trials. Integrating AI with traditional physiological models can further enhance SpO 2 estimation accuracy and robustness, offering significant advancements in patient care.

The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) has held its 57th Congress in Valencia from 6 to 8 of June 2024. The SEPAR Congress is the leading meeting for the entire respiratory scientific community, which allows learning about the main scientific advances in this area and provides the ideal situation to create and strengthen ties. This year, under the title "Respiratory Health for everybody", the SEPAR Congress stressed the importance of raising awareness about the importance of caring for and protecting our respiratory system. In this review, we offer a summary of some notable issues addressed in six selected areas of interest: chronic obstructive pulmonary disease (COPD), asthma, interstitial lung diseases (ILDs), pulmonary vascular diseases, sleep and breathing disorders and respiratory physiotherapy., (© 2024 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry. Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60-90 min normalized standardized uptake value ratios sampled at mid-cortical depth and ∼3 mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors. Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (P = 0.007, by linear regression). Immunohistochemistry, validated using in situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator protein immunostaining was detected on meningeal MHC-class II+ macrophages and cortical-activated MHC-class II+ TMEM119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis. Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The in vivo relation between microglia activation and demyelination in multiple sclerosis is still unclear., Objective: We combined 11 C-PBR28 positron emission tomography and rapid estimation of myelin for diagnostic imaging (REMyDI) to characterize the relation between these pathological processes in a heterogeneous MS cohort., Methods: 11 C-PBR28 standardized uptake values normalized by a pseudo-reference region (SUVR) were used to measure activated microglia. A voxelwise analysis compared 11 C-PBR28 SUVR in the white matter of 38 MS patients and 16 matched healthy controls. The relative difference in SUVR served as a threshold to classify patients' lesioned, perilesional and normal-appearing white matter as active or inactive. REMyDI was acquired in 27 MS patients for assessing myelin content in active and inactive white matter and its relationship with SUVR. Finally, we investigated the contribution of radiological metrics to clinical outcomes., Results: 11 C-PBR28 SUVR were abnormally higher in several white matter areas in MS. Myelin content was lower in active compared to inactive corresponding white matter regions. An inverse correlation between SUVR and myelin content was found. Radiological metrics correlated with both neurological and cognitive impairment., Conclusion: our data suggest an inverse relation of microglia activation and myelination, particularly in perilesional white matter tissue., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: BTK inhibitors have been concurrently administered with anti-CD20 monoclonal antibodies (mAbs) in chronic lymphocytic leukemia (CLL). However, the optimal regimen for combining these two drugs remains pending., Methods: This multi-center phase 2 study aimed to analyze whether consolidation with ofatumumab improved the response in patients with CLL receiving front-line treatment with ibrutinib. Patients received 12 cycles of ibrutinib monotherapy. Those who achieved CR after this induction were maintained on ibrutinib. Conversely, those who did not attain CR continued with ibrutinib in addition to a consolidation, which involved 7 doses of ofatumumab. The primary objective was the complete response (CR) rate at cycle 20. This study is registered within the EU Clinical Trials Register (EudraCT 2016-004937-26)., Findings: Between September 8, 2017, and May 21, 2018, 84 patients (median age, 69 years) were included. After completion of 12 cycles of ibrutinib (n = 80), 4 patients (5%) were in CR, 67 (84%) in partial response (PR), and 6 patients (7%) had a PR with lymphocytosis (PRL). After consolidation with ofatumumab, 20 patients improved the response from PR to CR and 6 patients with PRL obtained a PR. Seventy-one patients (85%) completed 20 cycles of treatment, with a CR rate of 24/71 (34%). According to the intention-to-treat analysis at cycle 20, the ORR was 69/84 (82.2%), with a CRR of 24/84 (28.6%). Progression-free survival and overall survival at 48-months were 89.9% (CI: 82.4-95.5) and 92.2% (CI: 85.3-97.1), respectively., Interpretation: These findings underscore the potential for a consolidation strategy in CLL, wherein the addition of a mAb in patients with low tumor burden might enhance the quality of the response., Funding: The study was funded by Janssen that also supplied ibrutinib, whereas ofatumumab was supplied by Novartis., Competing Interests: P.A. Consulting/advisory: Roche, Genmab, Janssen, BMS, AbbVie, AstraZeneca, BeiGene; Honoraria: Roche, Genmab, Janssen, BMS, AbbVie, AstraZeneca, Gilead, Incyte. E.G-B. Consultancy: Janssen, Abbvie, Gilead, Kiowa, EUSAPharma, Incyte, Lilly, Beigene, Novartis; Speaker: Janssen, Abbvie, Takeda, Kiowa, Roche, EUSAPharma, Incyte, Astra-Zeneca; Travel: Janssen, Abbvie, EUSAPharma. C. F: Consulting/advisory: Janssen, AbbVie, AstraZeneca, Gilead; Honoraria: Roche, Janssen, AbbVie, AstraZeneca, Gilead, BeiGene. R.A. Consulting/advisory: Roche, Janssen, AbbVie, AstraZeneca, Takeda. JAH-R. Consultant: Janssen, Roche, Abbvie, Gilead, BMS/Celgene, Amgen, Takeda, Rovi, AstraZeneca, Beigene, Sandoz Novartis, Celltrion, EusaPharm, Sanofi, Lilly, Menarini Stemline; Speaker's Bureau: Janssen, Roche, Abbvie, Gilead, BMS/Celgene, Amgen, Takeda, AstraZeneca, Beigene, Lilly; Grant/Research Support: BMS/Celgene, Janssen, Sanofi. A.R. Honoraria: Janssen, BMS, Novartis, Roche, EUSA Pharma, Abbvie, Astra Zeneca, Sanofi, Takeda, Incyte, GSK Consulting/Advisory: Janssen, BMS, Pfizer, Roche, Abbvie, Gilead, Novartis, Takeda; Astra Zeneca, Beigene. L.F.C. Advisory, consultancy and research founding: Janssen, Roche, Abvvie, Beigene, Astra-Zeneca and Loxo. F.B. has received research funding and honoraria from Roche, Celgene, Takeda, AstraZeneca, Novartis, Abbvie and Janssen. The other authors have no conflicts of interest to declare., (© 2024 The Author(s).)

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients., Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients., Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients., Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL., Clinical Trial Registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hontecillas-Prieto, García-Domínguez, Palazón-Carrión, Martín García-Sancho, Nogales-Fernández, Jiménez-Cortegana, Sánchez-León, Silva-Romeiro, Flores-Campos, Carnicero-González, Ríos-Herranz, de la Cruz-Vicente, Rodríguez-García, Fernández-Álvarez, Martínez-Banaclocha, Gumà-Padrò, Gómez-Codina, Salar-Silvestre, Rodríguez-Abreu, Gálvez-Carvajal, Labrador, Guirado-Risueño, Provencio-Pulla, Sánchez-Beato, Marylene, Álvaro-Naranjo, Casanova-Espinosa, Rueda-Domínguez, Sánchez-Margalet and de la Cruz-Merino.)

Background: Paramagnetic rim white matter (WM) lesions (PRL) are thought to be a main driver of non-relapsing multiple sclerosis (MS) progression. It is unknown whether cerebrospinal fluid (CSF)-soluble factors diffusing from the ventricles contribute to PRL formation., Objective: To investigate the distribution of PRL and non-rim brain WM lesions as a function of distance from ventricular CSF, their relationship with cortical lesions, the contribution of lesion phenotype, and localization to neurological disability., Methods: Lesion count and volume of PRL, non-rim WM, leukocortical lesion (LCL), and subpial/intracortical lesions were obtained at 7-T. The brain WM was divided into 1-mm-thick concentric rings radiating from the ventricles to extract PRL and non-rim WM lesion volume from each ring., Results: In total, 61 MS patients with ⩾1 PRL were included in the study. Both PRL and non-rim WM lesion volumes were the highest in the periventricular WM and declined with increasing distance from ventricles. A CSF distance-independent association was found between non-rim WM lesions, PRL, and LCL, but not subpial/intracortical lesions. Periventricular non-rim WM lesion volume was the strongest predictor of neurological disability., Conclusions: Non-rim and PRL share a gradient of distribution from the ventricles toward the cortex, suggesting that CSF proximity equally impacts the prevalence of both lesion phenotypes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.A.T. has received research support from Genentech/Roche; E.H. has received research support by the NMSS fellowship FG-1507-05459; J.A.S. has consulted for Novartis, Biogen, Cellgene, and Genentech and received research support from Genentech/Roche; C.M. has received research support from Genentech/Roche. The remaining authors have nothing to disclose.

Axonal degeneration is a central pathological feature of multiple sclerosis and is closely associated with irreversible clinical disability. Current noninvasive methods to detect axonal damage in vivo are limited in their specificity and clinical applicability, and by the lack of proper validation. We aimed to validate an MRI framework based on multicompartment modeling of the diffusion signal (AxCaliber) in rats in the presence of axonal pathology, achieved through injection of a neurotoxin damaging the neuronal terminal of axons. We then applied the same MRI protocol to map axonal integrity in the brain of multiple sclerosis relapsing-remitting patients and age-matched healthy controls. AxCaliber is sensitive to acute axonal damage in rats, as demonstrated by a significant increase in the mean axonal caliber along the targeted tract, which correlated with neurofilament staining. Electron microscopy confirmed that increased mean axonal diameter is associated with acute axonal pathology. In humans with multiple sclerosis, we uncovered a diffuse increase in mean axonal caliber in most areas of the normal-appearing white matter, preferentially affecting patients with short disease duration. Our results demonstrate that MRI-based axonal diameter mapping is a sensitive and specific imaging biomarker that links noninvasive imaging contrasts with the underlying biological substrate, uncovering generalized axonal damage in multiple sclerosis as an early event., Competing Interests: AC, NT, CT, VB, EH, AM, JG, CM, SD No competing interests declared, (© 2024, Cerdán Cerdá, Toschi et al.)

Introduction: Hypogammaglobulinemia after front-line immunochemotherapy for follicular lymphoma is a poorly studied adverse event that could be related to the appearance of severe and/or recurrent non-neutropenic infections which could affect the quality of life of the patients, even motivating a need of long-term replacement therapy with human immunoglobulins., Methods: Observational, retrospective study aiming to estimate the incidence of hypogammaglobulinemia, as well as its severity and clinical consequences, and to explore possible predictive factors for its development. Specific immunoglobulin deficiencies were also studied., Results: 76.5% of patients had hypogammaglobulinemia during or after front-line treatment, mostly grade 1-2; with 38.8% patients who developed clinically relevant infections and 20% patients requiring human immunoglobulins replacement therapy. A high-risk FLIPI score was identified as a risk factor for hypogammaglobulinemia (ods ratio: 4.51; 95% confidence interval: 1.29-15.68; p  < 0.001) and basal gamma globulin level as a protective factor (odds ratio: 0.92; 95% confidence interval: 0.988-0.996; p   =  0.018). Any type of immunochemotherapy regimen was associated with different risks of hypogammaglobulinemia in our study., Conclusions: Hypogammaglobulinemia appears in a high percentage of patients with follicular lymphoma in a real-world population, identifying a high-risk FLIPI score as a risk factor for its development and basal gamma globulins as a protective factor., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

GABRIELL was a phase II single-arm study to evaluate the efficacy and safety of obinutuzumab plus bendamustine for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Seventy-two patients with active disease received treatment for up to six 28-day cycles. Overall response rate was 78.6% with a median progression-free survival (PFS) of 26 months, and overall survival (OS) not reached at the end of follow-up (36 months). Undetectable measurable residual disease (≤0.01%; 36.4% in bone marrow and 53.4% in peripheral blood) correlated with a significantly longer PFS and OS (vs. >0.01). Common grade ≥3 adverse events (76.4%) were neutropenia (58.3%), thrombocytopenia (26.4%) and febrile neutropenia (11.1%). TP53 disruption was the only independent predictive factor for response (Hazard ratio; HR: 0.228). Unmutated immunoglobulin heavy chain variable region (HR: 16.061) was a negative prognostic factor for PFS. In conclusion, the combination of obinutuzumab plus bendamustine is an active and generally adequately-tolerated treatment for R/R CLL.

The 55th SEPAR Congress was held in Pamplona from 2 to 4 of June 2022. Once again, it was the referral scientific meeting for specialists in pulmonology, thoracic surgery, nursing, physiotherapy, paediatric respiratory diseases and other disciplines involved in respiratory care. The Spanish Society of Pulmonology and Thoracic Surgery showed its national and international leadership in the management of respiratory diseases, which was reflected in a program with an excellent content and a high scientific level. In this review, we offer a summary of some notable aspects covered in six selected areas of interest: pulmonary vascular diseases, non-invasive mechanical ventilation and sleep disorders, asthma, chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ILD), and interventional pulmonolgy and lung transplant., (© 2022 Sociedad Española de Neumología y Cirugía Torácica (SEPAR). Published by Elsevier España, S.L.U.)

Objective: This study aimed to investigate at 7.0-T MRI a) the role of multiple sclerosis (MS) cortical lesions in cortical tissue loss b) their relation to neurological disability., Methods: In 76 relapsing remitting and 26 secondary progressive MS patients (N = 102) and 56 healthy subjects 7.0-T T 2 * -weighted images were acquired for lesion segmentation; 3.0-T T 1 -weighted structural scans for cortical surface reconstruction/cortical thickness estimation. Patients were dichotomized based on the median cortical lesion volume in low and high cortical lesion load groups that differed by age, MS phenotype and degree of neurological disability. Group differences in cortical thickness were tested on reconstructed cortical surface. Patients were evaluated clinically by means of the Expanded Disability Status Scale (EDSS)., Results: Cortical lesions were detected in 96% of patients. White matter lesion load was greater in the high than in the low cortical lesion load MS group (p = 0.01). Both MS groups disclosed clusters (prevalently parietal) of cortical thinning relative to healthy subjects, though these regions did not show the highest cortical lesion density, which predominantly involved frontal regions. Cortical thickness decreased on average by 0.37 mm, (p = 0.002) in MS patients for each unit standard deviation change in white matter lesion volume. The odds of having a higher EDSS were associated with cortical lesion volume (1.78, p = 0.01) and disease duration (1.15, p < 0.001)., Conclusion: Cortical thinning in MS is not directly related to cortical lesion load but rather with white matter lesion volume. Neurological disability in MS is better explained by cortical lesion volume assessment.

Purpose: New therapeutic options are needed in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Lenalidomide-based schedules can reverse rituximab refractoriness in lymphoma., Patients and Methods: In the phase II R2-GDP trial, 78 patients unsuitable for autologous stem cell transplant received treatment with the following schedule: lenalidomide 10 mg Days (D)1-14, rituximab 375 mg/m2 D1, cisplatin 60 mg/m2 D1, gemcitabine 750 mg/m2 D1 and D8, and dexamethasone 20 mg D1-3, up to 6 cycles (induction phase), followed by lenalidomide 10 mg (or last lenalidomide dose received) D1-21 every 28 days (maintenance phase). Primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and monitorization of key circulating immune biomarkers (EU Clinical Trials Register number: EudraCT 2014-001620-29)., Results: After a median follow-up of 37 months, ORR was 60.2% [37.1% complete responses (CR) and 23.1% partial responses (PR)]. Median OS was 12 months (47 vs. 6 months in CR vs. no CR); median PFS was 9 months (34 vs. 5 months in CR vs. no CR). In the primary refractory population, ORR was 45.5% (21.2% CR and 24.3% PR). Most common grade 3-4 adverse events were thrombocytopenia (60.2%), neutropenia (60.2%), anemia (26.9%), infections (15.3%), and febrile neutropenia (14.1%). Complete responses were associated with a sharp decrease in circulating myeloid-derived suppressor cells and regulatory T cells., Conclusions: R2-GDP schedule is feasible and highly active in R/R DLBCL, including the primary refractory population. Immune biomarkers showed differences in responders versus progressors., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background and Purpose: Corpus callosum (CC) atrophy is a strong predictor of multiple sclerosis (MS) disability but the contributing pathological mechanisms remain uncertain. We aimed to apply advanced MRI to explore what drives the often nonuniform callosal atrophy., Methods: Prospective brain 7 Tesla and 3 Tesla Human Connectom Scanner MRI were performed in 92 MS patients. White matter, leukocortical, and intracortical lesions were manually segmented. FreeSurfer was used to segment the CC and topographically classify lesions per lobe or as deep white matter lesions. Regression models were calculated to predict focal CC atrophy., Results: The frontal and parietal lobes contained the majority (≥80%) of all lesion classifications in both relapsing-remitting and secondary progressive MS subtypes. The anterior subsection of the CC had the smallest proportional volume difference between subtypes (11%). Deep, temporal, and occipital white matter lesions, and occipital intracortical lesions were the strongest predictors of middle-posterior callosal atrophy (adjusted R 2  = .54-.39, P < .01)., Conclusions: Both white matter and cortical lesions contribute to regional corpus callosal atrophy. The lobe-specific lesion topology does not fully explain the inhomogeneous CC atrophy., (© 2022 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)