The 2021 WHO classification distinguishes adult-type diffuse gliomas as astrocytoma, oligodendroglioma, and glioblastoma. Recently, a new epigenetic subtype-high-grade glioma IDH-wildtype, subtype F (HGG-F)-has been described, characterized by gliomatosis-like infiltration, low proliferative index, and unexpectedly prolonged survival despite a grade 4 methylation profile. We report the first HGG-F evaluated with 18 F-DOPA PET. Despite extensive FLAIR-hyperintense lesions, tracer distribution was entirely normal. This "amino acid PET silence," contrasting with the typically intense uptake in high-grade gliomas, together with the gliomatosis-like MRI appearance, should raise suspicion for this emerging subtype.

Frame-based stereotactic biopsy has long been the gold standard for diagnostic brain biopsy, whereas robot-assisted stereotactic techniques have emerged as promising alternatives. However, rigorous methodological comparisons between these approaches remain scarce. To compare the diagnostic yield and complication rates of frame-and robot-assisted stereotactic brain biopsy using a rigorously matched cohort methodology. This retrospective, bicentric, comparative analysis included adult patients who underwent stereotactic brain biopsy between January 2011 and December 2019. Each patient who underwent robot-assisted biopsy (n = 230) was matched in a 2:1 ratio with patients who underwent frame-based biopsy (n = 460). Matching was performed based on clinically relevant criteria including lesion location, size, contrast enhancement, histopathology, and patient age. The primary outcomes were diagnostic yield and complication rates. The diagnostic yield was identical for both techniques 97.4

Background Epstein-Barr virus (EBV)-associated primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma closely linked to immunodeficiency. Imaging characteristics of EBV-associated are reported to differ from those of typical EBV-negative PCNSL. This study aims to describe the radiological and nuclear medicine imaging features in a large cohort of patients with EBV-associated PCNSL.Methods We conducted a multicenter retrospective descriptive study between 2008 and 2025 on patients with a diagnosis of EBV-associated PCNSL. MRI variables and FDG-PET/CT uptake were assessed.Results Fifty-eight cases of EBV-associated PCNSL were included. All but 1 patient were immunosuppressed. Multiple lesions were present in 71% of cases (41/58). Supratentorial involvement was observed in 90% of cases (52/58). Heterogeneous contrast enhancement was noted in 90% (52/58), with ring-like enhancement in 41% (24/58). Leptomeningeal enhancement occurred in 31% of cases (18/58), and within this group, 50% showed perivascular space enhancement. Lesions showed hypercellularity in 83% (48/58) and intralesional hemorrhage in 81% (47/58). An "eccentric target" sign was present in 26% of cases (15/58), while a "concentric target" sign in 14% (5/35). On FDG-PET, 25/30 patients had hypermetabolic lesions (25/30, 83%).Conclusion Diagnosing EBV-associated PCNSL is challenging due to its rarity and the broad differential diagnosis. Multiple necrotic and hemorrhagic lesions are the most suggestive MRI feature of EBV-associated PCNSL. "Eccentric" and "concentric" target signs, typically associated with CNS toxoplasmosis, can be observed. FDG-PET often reveals hypermetabolic lesions that support a neoplastic diagnosis. Histological confirmation remains essential for confidently treating this tumor entity.

Individual longitudinal changes in PET MTV and FLAIR volumes during treatment. For each patient, changes in PET-derived MTV (red line) and FLAIR lesion volume (blue line) are plotted over time, with treatment initiation marked as day 0. Numeric values indicate the change in volume at each time point, referenced either to baseline or to the lowest value observed (best response) in cases with multiple follow-ups. Each panel represents the data for a single patient.

PURPOSE:Cystathionine (Cth) has emerged as a promising biomarker for identifying 1p/19q codeleted gliomas. However, little is known about the T2 relaxation time constant of Cth in gliomas. The aim of this study was to measure the T2 of Cth in vivo in glioma and compare it to the T2s of other metabolites at 3 T. METHODS:Ten participants with glioma were scanned at 3 T. Single-voxel proton PRESS spectra were acquired at four echo-times to determine the T2 relaxation time constants of Cth, N-acetylaspartate, scyllo-inositol, total creatine, and total choline. Processed spectra were analyzed using LCModel, and the results were fitted using a mono-exponential function to estimate the T2 relaxation time constants. T2 of Cth was also measured using high-resolution NMR. RESULTS:The T2 of Cth varied across participants (42-128 ms, with a mean and standard deviation of 75 ± 24 ms). Additionally, T2 relaxation time constants of Cth were shorter than those of singlets measured in glioma in the same participants. Distinct differences in T2 between the CH and CH2 proton groups in Cth were also observed both in vitro and in vivo. CONCLUSION:Knowledge of the T2 of Cth should improve its quantification and may help increase understanding of the intracellular environment in glioma cells, potentially providing insights into tumor metabolism in future studies.

Exploratory comparison of baseline 18F-DOPA-PET values in progressors (n=6) vs non-progressors (n=14) on IDH inhibitor treatment. Parameters include metabolic tumor volume (MTV), total lesion glycolysis (TLG), tumor-to-background maximum ratio (TBRmax), and mean ratio (TBRmean). P-values were calculated using the Mann-Whitney U test.

Contexte et objectif L’imagerie pondérée par transfert de proton amide APTw permet de visualiser la concentration en protéines des gliomes, contribuant ainsi la caractérisation et à l’évaluation pronostique des gliomes1. Cependant, des artefacts peuvent réduire la spécificité de cette technique, incluant la saturation directe de l’eau, le transfert de magnétisation semi-solide (ssMT) et la relaxation T12. Cette étude vise à évaluer si les corrections successives des métriques APTw (spillover, ssMT, T1) améliorent la detection de la mutation IDH et de la co-déléction 1p/19q, deux marqueurs moléculaires clés pour le diagnostic des gliomes. Méthodologie Quarante-six patients présentant un gliome diffus présumé éligible à la chirurgie ont été inclus prospectivement. Les acquisitions ont été réalisées à l’aide d’une séquence 3D snapshot-GRE CEST à 3 Tesla (B1 = 2 µT, T₁sat = 2 s), complétée par une cartographie B₀/B₁ (WASABI) et T₁ (Saturation Recovery, B₁ = 5 µT, 14 points de récupération). Les métriques analysées étaient :• MTRasym (standard, non corrigé)3,• MTRRex (corrigé pour la saturation directe de l’eau et le ssMT)4,• AREX (corrigé pour la saturation, le ssMT et T1)4.Les comparaisons statistiques ont utilisé des tests U de Mann-Whitney (correction de Benjamini-Hochberg) et des tests t de Welch sur les médianes, avec un seuil de significativité fixé à p corrigé < 0,05. Résultats Les métriques corrigées (MTRRex et AREX) séparaient significativement mieux les gliomes IDH-mutés (p ≤ 1,4×10⁻⁶) des gliomes IDH normal que la métrique standard MTRasym (p = 0,008) (Figure 1, A).Au sein des gliomes IDH-mutés, l’AREX distinguait les oligodendrogliomes (codélétés 1p/19q) des astrocytomes (non codélétés, p = 0,010), avec des valeurs plus élevées pour les oligodendrogliomes (Figure 1, B).La séquence de correction (MTRasym → MTRRex → AREX, Figure 2) améliorait la cohérence intra-groupe et la séparabilité des sous-types moléculaires. Conclusion La correction des artefacts liés au contenu liquide des lésions optimise la précision diagnostique de l’imagerie APT. Cette approche offre une méthode robuste, précise et biologiquement fondée pour la stratification moléculaire non invasive des gliomes.

Les lymphomes primitifs du système nerveux central (LPSNC) représentent une entité rare mais agressive des tumeurs cérébrales, dont la suspicion diagnostique repose largement sur l’imagerie. L’objectif du traitement est curatif, avec un taux de survie à long terme de 30 à 40 %. Ce poster passe en revue les caractéristiques typiques et atypiques des LPSNC en imagerie, en soulignant les pièges diagnostiques.Les LPSNC se présentent généralement sous forme de lésions unifocales ou multifocales, hyperdenses au scanner et hypointenses en IRM sur les séquences T2, reflétant leur hypercellularité. Le rehaussement, souvent homogène et intense, peut devenir hétérogène après administration de corticoïdes. Les localisations typiques incluent les ganglions de la base, le corps calleux, le cervelet et les régions périventriculaires. La restriction de la diffusion en IRM de diffusion est un marqueur classique, bien que les petites lésions (< 1 cm) puissent montrer une restriction moins marquée en raison de l’effet de volume partiel. L’œdème péritumoral et l’effet de masse sont variables et ne permettent pas, à eux seuls, de confirmer ou d’écarter le diagnostic.Des présentations atypiques sont de plus en plus reconnues, incluant des lésions nécrotico-hémorragiques, des lésions infiltrantes non rehaussées, ainsi que des localisations inhabituelles comme les méninges (dans les formes extra-axiales des MALT) ou la moelle épinière. Les composantes hémorragiques sont rares chez les patients immunocompétents, mais elles caractérisent souvent les lymphomes induits par le virus d’Epstein-Barr (EBV). Les formes sans prise de contraste sont également piégeuses, incluant des lésions focales ou des formes diffuses infiltratives, appelées « lymphomatosis cerebri ».L’imagerie avancée, telle que la perfusion T2, l’ASL et la spectroscopie par résonance magnétique (SRM), apporte des informations complémentaires. La SRM montre souvent une élévation marquée de la choline, une baisse du N-Acétyl Aspartate (NAA), et parfois des pics de lipides, atypiques pour une lésion non nécrotique. La perfusion T2 révèle généralement une faible néo-angiogenèse, avec une rupture de la barrière hémato-encéphalique. Cependant, une hyperperfusion, surtout en ASL, ne doit pas exclure le diagnostic.En conclusion, bien que rares, les formes atypiques de LPSNC nécessitent d’être connues pour éviter les erreurs diagnostiques et optimiser la prise en charge thérapeutique.

PURPOSE:Small-molecule inhibitors targeting isocitrate dehydrogenase (IDH) 1/2-mutant proteins have demonstrated benefit in IDH1/2-mutant gliomas. However, responses assessed by conventional MRI measurements are infrequent, delayed, and difficult to interpret, highlighting the need for early biomarkers of treatment benefit. In this study, we investigated 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine positron emission tomography (18F-DOPA-PET) and MRI responses in patients with IDH1/2-mutant glioma receiving IDH inhibitors (IDHi). EXPERIMENTAL DESIGN:Patients with IDH1/2-mutant glioma receiving IDHi as part of trials or expanded access programs with pre- and posttreatment MRI and 18F-DOPA-PET were included. Evaluations included 2D/3D measurements on T2-weighted fluid-attenuated inversion recovery images; T1-post-contrast, perfusion, and diffusion imaging for MRI; and metabolic tumor volume (MTV), total lesion glycolysis, and tumor-to-background ratios (TBR) for 18F-DOPA-PET. Disease response evaluation using volumetric assessments, RANO 2.0, and PET RANO 1.0 criteria were compared and correlated with outcomes. RESULTS:From 2021 to 2025, 20 patients with IDH1/2-mutant glioma (8 with astrocytoma and 12 with oligodendroglioma) receiving IDHi (4 receiving ivosidenib and 16 receiving vorasidenib) were analyzed. Significant reductions in 18F-DOPA-PET parameters including TBRmean, TBRmax, and MTV were observed in 10 of 20 patients, aligning with observed changes in perfusion and diffusion imaging. Nine partial responses and one complete response were identified using 18F-DOPA-PET, whereas both volumetric and standard 2D morphologic MRI assessments indicated stable disease as best response. PET response on MTV was correlated with prolonged tumor control. CONCLUSIONS:These results highlight the potential of 18F-DOPA-PET and advanced MRI sequences as valuable complements to standard RANO 2.0 MRI evaluations for assessing treatment response in patients with glioma undergoing IDHi therapy.

BACKGROUND:The indications and timing of brain biopsy in adults with neurological diseases of unknown etiology remain controversial. We aimed to determine diagnostic yield, complications, outcomes, and survival after brain biopsy and evaluate whether early biopsy improves prognosis. METHODS:We analyzed adults who underwent brain biopsy (2008-2024) after non-diagnostic workup at our institution. Primary outcomes were diagnostic yield, 6-month functional status using modified Rankin Scale (mRS), and overall survival (OS). Early biopsy was defined as ≤1 month after symptom onset. Multivariable logistic regression identified predictors of favorable outcomes (mRS≤2), and Cox models assessed OS. RESULTS:Among 3014 biopsies, 294 met inclusion criteria (mean age 50.6 ± 15.3 years; 47% immunocompromised). Biopsy provided a contributory diagnosis in 69% of patients and changed management in 71%. Symptomatic complications occurred in 3.4% of patients. Functional independence (mRS≤2) increased from 44.6% at biopsy to 54.1% at 6 months (p = 0.003), with 22% mortality. Baseline independence (OR 7.15, 95%CI 3.94-12.97) and early biopsy (OR 2.03, 95%CI 1.05-3.93) predicted favorable outcomes, whereas solid organ tumor history (OR 0.32) and altered consciousness (OR 0.53) predicted worse recovery. Early biopsy yielded a higher diagnostic success rate (82% vs. 65%, p = 0.005). During 37.9-month follow- up, 31% died (mean OS 9.3 months). Longer OS was associated with baseline independence and autoimmune/inflammatory diagnosis, whereas solid-organ tumors, altered consciousness, and coma predicted shorter OS. CONCLUSIONS:Brain biopsy is safe and diagnostically useful for cryptogenic neurological diseases. Early biopsy independently predicts better functional outcomes and higher diagnostic yield, supporting earlier tissue sampling after inconclusive noninvasive evaluation.

Isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion are key molecular markers for glioma classification. Amide proton transfer weighted (APTw) and nuclear Overhauser effect-weighted (NOEw) markers showed promise for glioma characterization, by probing protein-related tissue properties. However, their interpretation is confounded by direct water saturation, macromolecules (semi-solid magnetization transfer-ssMT), and T1 relaxation. Here, we aimed to assess the performance of three APTw and NOEw metrics-uncorrected, spillover/ssMT-corrected (FMC), and fully spillover/ssMT- and T1-corrected (FMTC)-for glioma stratification. Fifty patients with suspected gliomas were prospectively enrolled (12 IDH-wild-type, 38 IDH-mutant, of which 21 with 1p/19q codeletion). Acquisitions were performed at 3 T using a 3D gradient echo readout with chemical exchange saturation transfer (B1 = 2 μT for APTw, 0.6 μT for NOEw; T1sat = 2 s), WASABI (WAter Shift And B1) for B0/B1 mapping, and saturation recovery for T1 mapping. Glioma subtypes were compared using metrics extracted from manually segmented masks, using two-tailed Mann-Whitney U tests, and the Benjamini-Hochberg false discovery rate (FDR) correction. Effect sizes were quantified using Cliff's δ with 95% bootstrap confidence intervals and classification performance was assessed by receiver operating characteristic analyses (area under the curve, AUC). IDH-mutant and wild-type gliomas differed significantly for the uncorrected APTw metric (p = 0.005, AUC = 0.79), with stronger discrimination following correction-APTw-FMC (p < 0.001, AUC = 0.94) and APTw-FMTC (p < 0.001, AUC = 0.96), both with large effect sizes. Only APTw-FMTC distinguished 1p/19q codeleted from non-codeleted gliomas before FDR correction (uncorrected p = 0.01, AUC = 0.74). The NOEw metrics did not differ between any molecular subgroups, likely due to limited sensitivity of this contrast at 3 T. These results suggest that correcting for fluid, ssMT, and T1 effects enhances the accuracy of APTw metrics, offering a more robust and biophysically grounded approach to noninvasive glioma diagnosis.

Abstract Background Clinical scores incompletely capture outcomes in primary central nervous system lymphoma (PCNSL). We quantified morphologic heterogeneity in pretreatment hematoxylin and eosin (H&E) whole slides. Patients and methods Three independent cohorts of immunocompetent, HIV- and EBV-negative patients treated recently were analyzed: LOC 2023 (122 slides), phase III BLOCAGE-01 (245 slides; NCT02313389 ), and external Barcelona (BCN; 41 slides). UNI embeddings, prototype learning, spatial metrics, and elastic-net Cox regression defined ITH-C. Results Models achieved bootstrap-corrected concordance of 0.797–0.834. Age-, sex-, and KPS-adjusted ITH-C HRs were 1.29 (95% CI 1.01–1.64), 1.27 (1.07–1.51), and 2.13 (1.35–3.37), respectively. Adding ITH-C increased MSKCC C-index from 0.671 to 0.717, 0.560 to 0.593, and 0.588 to 0.706. Spatial transcriptomics linked ITH-C to immune programs. Conclusions Routine H&E encodes prognostic spatial heterogeneity in PCNSL. ITH-C complements clinical scores, supporting prospective risk stratification.

Multimodal imaging assessment. A) Comparison of FLAIR volumes obtained from PET MTV with diffusion (apparent diffusion coefficient [ADC], mm²/s) and perfusion (relative cerebral blood volume [rCBV]) maps, shown at baseline and follow-up for patients 2 and 8. B) Longitudinal evolution of T1-weighted gadolinium-enhanced (T1G) lesions during treatment for patients 2, 8, and 18 (images for patient 15 unavailable), displayed alongside their corresponding PET images.

The 2021 WHO classification distinguishes adult-type diffuse gliomas as astrocytoma, oligodendroglioma, and glioblastoma. Recently, a new epigenetic subtype—high-grade glioma IDH-wildtype, subtype F (HGG-F)—has been described, characterized by gliomatosis-like infiltration, low proliferative index, and unexpectedly prolonged survival despite a grade 4 methylation profile. We report the first HGG-F evaluated with 18 F-DOPA PET. Despite extensive FLAIR-hyperintense lesions, tracer distribution was entirely normal. This “amino acid PET silence,” contrasting with the typically intense uptake in high-grade gliomas, together with the gliomatosis-like MRI appearance, should raise suspicion for this emerging subtype.

Stereotactic brain biopsy is a standard neurosurgical procedure for diagnosing intracranial lesions. Lesion size is often considered a limiting factor; however, the safety and diagnostic yield of biopsies in lesions < 10 mm remain poorly defined. This study evaluated the outcomes of frame-based stereotactic biopsies for lesions < 10 mm in size compared with larger lesions. We retrospectively analyzed all consecutive adult patients who underwent frame-based stereotactic biopsy for targeted lesions < 10 mm in maximum diameter between April 2009 and April 2024 at our institution. Each case was matched (1:3) with patients with lesions ≥ 10 mm based on age, lesion location, and contrast enhancement. The primary endpoint was diagnostic yield, and the secondary endpoints included complications graded using a validated severity scale. Continuous variables were compared using Student’s t-test or Wilcoxon’s rank-sum test. Of the 2,347 patients who underwent frame-based stereotactic biopsy during the inclusion period, 74 patients (3.2

Waterfall Plot of Individual Tumor Responses by PET and MRI Criteria. Individual percentage changes from baseline for metabolic tumor volume (MTV, RANO-PET 1.0, red bars), sum of products of diameters (SPD, light blue bars), and volumetric FLAIR (dark blue bars). Dashed lines indicate the partial response thresholds for each respective criterion. Below the plot, information is provided for each patient regarding the presence of baseline contrast-enhancing T1G lesion, progression during IDH inhibitor therapy according to RANO criteria, PFS in months.

BACKGROUND:Primary central nervous system lymphoma (PCNSL) treatment relies on a high-dose methotrexate-based chemotherapy (HD-MTX-based CT) regimen; however, whether there is a specific microbiota composition association with treatment response and clinical outcomes remains incompletely understood. METHODS:We conducted a prospective study of PCNSL patients, included in the clinical trial NCT02313389 and the ancillary study NCT04253496 from 2020 to 2023, where patients were treated with first-line HD-MTX-based polychemotherapy without a consolidation treatment. Stool (n = 52), cerebrospinal fluid (CSF, n = 52), and plasma samples (n = 35) were collected before and/or after therapy initiation to perform metagenomic, flow cytometry, and metabolomic analyses. Plasma metabolomic data of 90 patients also included in the BLOCAGE clinical trial was subsequently used as a validation cohort. RESULTS:Unsupervised clustering of microbial data identified two distinct gut microbial communities, differing in Parabacteroides distasonis abundance, which correlated with progression-free survival and overall survival in both uni- and multivariate analyses. Higher P. distasonis levels were linked to increased plasma betaine-valine metabolites and enhanced CD8 T cell infiltration in the CSF, suggesting a connection between gut microbiota and immune regulation. Stratifying the validation cohort by betaine-valine content confirmed these clinical associations. CONCLUSIONS:Our findings suggest that gut microbiome communities modulate clinical outcomes in PCNSL patients undergoing standard treatment. Moreover, after future validation in external cohorts, the quantification of Parabacteroides distasonis could potentially provide a basis for patient stratification and guide personalized therapeutic strategies in the near future.

Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options and poor prognosis. Epidermal growth factor receptor (EGFR) alterations, including amplifications, mutations, and fusions, are prevalent in GBM and represent potential therapeutic targets. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI), has demonstrated efficacy in EGFR-mutated non-small cell lung cancer and central nervous system metastases. However, its efficacy in GBM remains uncertain. We present 2 cases of recurrent GBM harboring distinct EGFR alterations treated with osimertinib. Both patients, despite showing EGFR amplification or activating mutations (G719D), experienced rapid disease progression and clinical deterioration during treatment. These findings highlight the resistance of GBM to osimertinib, possibly due to tumor heterogeneity, subclonal variation, or intrinsic mechanisms linked to EGFR amplification and redundant oncogenic pathways. Our observations align with prior trials of EGFR-TKIs in GBM, which have shown limited benefit. These cases underscore the complexity of targeting EGFR in GBM and the need for advanced therapeutic approaches, including next-generation EGFR inhibitors and antibody-drug conjugates, to overcome resistance. Further studies are crucial to optimize EGFR-targeted therapies in GBM.

OBJECTIVE:There is a lack of data regarding the benefit-risk ratio and therapeutic value of brain biopsy in very elderly patients with brain tumors. This study aimed to evaluate the safety of stereotactic biopsy in patients aged ≥ 80 years and assess the impact of the procedure on subsequent therapeutic management and overall survival (OS). METHODS:The authors retrospectively analyzed the medical records of all patients aged ≥ 80 years who underwent stereotactic biopsy for a newly diagnosed intracerebral tumor during a 15-year period at a single institution. RESULTS:During the period, 2350 stereotactic brain biopsies were performed, with 209 biopsies (8.9%) in 208 patients aged ≥ 80 years. Histological diagnosis was obtained in 96.2% of cases. Biopsy results differed from the suspected diagnosis in 23 patients (11.1%). After biopsy, 1.9% of the patients experienced persistent neurological deficit. After histopathological diagnosis, 80.7% of the cases received adjuvant treatment. Only a Karnofsky Performance Status (KPS) score ≥ 70% was a significant predictor of receiving complete adjuvant treatment (OR 24.3, 95% CI 7.0-84.1; p < 0.001). The median OS from biopsy was 5.6 months (IQR 2.4-13.5 months). Grade 4 glioma, KPS score < 70%, and tumor contrast enhancement on MRI predicted a shorter OS. Receiving complete first-line adjuvant therapy predicted a longer OS. In patients with grade 4 glioma, those exhibiting a methylated O 6-methylguanine-DNA methyltransferase (MGMT) promoter demonstrated significantly prolonged survival compared with patients with an unmethylated MGMT promoter (p < 0.001). CONCLUSIONS:Stereotactic biopsy for very elderly patients with brain tumors has a high diagnostic yield and a favorable safety profile, ultimately impacting patients' therapeutic management and OS. Nonetheless, it is crucial to consider the patient's prebiopsy condition. Specifically, a KPS score ≥ 70% was identified as a key factor in the decision-making process for biopsy in this population.

Stereotactic brain biopsy is a critical procedure in neurosurgery, particularly for the diagnosis of brain tumors and cryptogenic neurological diseases. Despite its safety profile, biopsy procedures carry a risk of complications. This study aimed to identify predictors of symptomatic complications in a large cohort and develop a risk prediction score. This retrospective single-center study examined data from 2,338 stereotactic brain biopsies performed over 15 years. The primary outcomes included complication rates, severity, timing, and management. Factors such as patient demographics, medical history, lesion characteristics, and biopsy procedures were analyzed. Predictive models were created using least absolute shrinkage and selection operator (LASSO) regression to select key variables with cross-validation and a random forest algorithm for further refinement. Owing to insufficient predictive performance for clinical use, we used variables selected by LASSO regression to construct an analytical multivariate model. Symptomatic complications occurred in 3.9