Dual-Energy CT for Detecting Painful Knee Prosthesis Loosening.

Background Dual-energy CT (DECT) is an alternative to radiography and single-energy CT (SECT) for detecting prosthesis-related complications. Purpose To compare the diagnostic performance of DECT, SECT, and radiography for knee prosthesis loosening, with use of surgery or imaging follow-up reference standards. Materials and Methods In this prospective single-center study from December 2018 to June 2021, participants with unilateral painful knee prostheses underwent radiographic, SECT, and DECT imaging. Five blinded readers, four radiologists, and one orthopedic surgeon evaluated the images. Prosthesis loosening was diagnosed by a periprosthetic lucent zone greater than 2 mm. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of each method were determined and compared with use of a multireader multicase analysis. Results There were 92 study participants (mean age ± SD, 70 years ± 9.4; 67 women) evaluated. Tibial and femoral loosening were diagnosed in 47 and 24 participants, respectively. For the tibia, mean sensitivity and specificity for arthroplasty loosening were 88% and 91%, respectively, for DECT, 73% and 78% for SECT, and 68% and 81% for radiography. For the tibia, DECT demonstrated similar diagnostic performance (AUC, 0.90) to SECT (AUC: 0.90 vs AUC: 0.87, respectively; P = .13) but was superior to radiography (AUC: 0.90 vs AUC: 0.82; P = .002). Overall diagnostic performance of DECT (AUC, 0.87) for the femur was superior to both SECT and radiography (P < .001). Conclusion Dual-energy CT had generally better diagnostic performance in detecting loosening of tibial and femoral components after total knee arthroplasty compared with single-energy CT or radiography. Clinical trial registration no. 2942 © RSNA, 2022.

Pediatric Recurrent Pericarditis: Appropriateness of the Standard of Care and Response to IL-1 Blockade.

OBJECTIVE: To analyze, in a cohort of pediatric patients with recurrent pericarditis undergoing anti-interleukin (IL)-1 treatment: the agent and dosing used as first-line treatment, the long-term efficacy of IL-1 blockers, the percentage of patients achieving a drug-free remission, and the presence of variables associated with drug-free remission. STUDY DESIGN: Data were collected from patients' charts. The annualized relapse rate (ARR) was used for evaluation of treatment efficacy, and bivariate logistic regression analysis was used for variables associated with drug-free remission. RESULTS: Fifty-eight patients, treated between 2008 and 2018, were included in the study (mean follow-up. 2.6 years). Of the 56 patients treated with first-line drugs, 14 not responsive patients were underdosed. Fifty-seven patients were treated with anakinra: the ARR before and during daily treatment was 3.05 and 0.28, respectively (P < .0001); an increase to 0.83 was observed after the reduction/withdrawal of treatment (P < .0001). The switch from anakinra to canakinumab (5 patients) was associated to an increase of the ARR (0.49 vs 1.46), but without statistical significance (P = .215). At last follow-up, only 9 of the 58 patients had withdrawn all treatments. With the limits of a retrospective study and the heterogeneity between the patients enrolled in the study, a shorter duration of treatment with anakinra was the only variable associated with drug-free remission. CONCLUSIONS: This study shows that most pediatric patients with recurrent pericarditis needing IL-1 blockade received an inadequate treatment with first-line agents. The effectiveness of anakinra is supported by this study, but few patients achieved drug-free remission. The different rate of response to anakinra and canakinumab may suggest a possible role of IL-1α in the pathogenesis of recurrent pericarditis.

The Role of Working Memory and Short-Term Memory in Sentence Comprehension: A Systematic Review and Meta-Analysis in Probable Alzheimer's Disease.

The role of either short-term memory (STM) or working memory (WM) in sentence comprehension is a matter of debate. Although it is commonly accepted that memory resources are necessary for sentence comprehension, there is no agreement regarding the nature of their role. The aim of this review is to investigate and synthesize assessment tools and correlation data between STM or WM and sentence comprehension in probable Alzheimer's disease (AD). To this aim, a systematic review and meta-analysis of the literature was conducted according to the PRISMA guidelines. PubMed, Web of Science, Scopus, PsycInfo, and LLBA databases were searched. Two independent authors selected peer-reviewed articles published in English and focused on the relationship between STM or WM and sentence comprehension in probable AD. A total of 11 case-control studies were included at the end of the selection process. Most studies adopted offline tasks to evaluate sentence comprehension, while a small number of authors applied online experimental tasks. The digit span forward and backward were the most employed standardized tests to evaluate phonological STM and WM, respectively. The meta-analysis results supported the association between performance on STM and WM and comprehension tasks. However, moderate heterogeneity was found, mainly due to the small number of included studies, especially for STM, and the substantial variability of the adopted tasks. Therefore, in order to clarify the specific source of language comprehension deficits, new and sophisticated experiments should be conducted using adequate material.

A case of acute bilateral iodine-induced submandibular sialadenitis: Ultrasound findings.

Acute sialadenitis is a rare adverse reaction to iodine-based contrast agents. Ultrasound (US) is usually the preferred imaging method to evaluate the salivary glands; along with clinical and anamnestic data, US allows the diagnosis of contrast-induced sialadenitis. We present a case of acute bilateral submandibular sialadenitis induced by intravenous administration of iodine-based contrast media for a contrast-enhanced computed tomography scan diagnosed by US.

New Inhibitors of the Human p300/CBP Acetyltransferase Are Selectively Active against the Arabidopsis HAC Proteins.

Histone acetyltransferases (HATs) are involved in the epigenetic positive control of gene expression in eukaryotes. CREB-binding proteins (CBP)/p300, a subfamily of highly conserved HATs, have been shown to function as acetylases on both histones and non-histone proteins. In the model plant Arabidopsis thaliana among the five CBP/p300 HATs, HAC1, HAC5 and HAC12 have been shown to be involved in the ethylene signaling pathway. In addition, HAC1 and HAC5 interact and cooperate with the Mediator complex, as in humans. Therefore, it is potentially difficult to discriminate the effect on plant development of the enzymatic activity with respect to their Mediator-related function. Taking advantage of the homology of the human HAC catalytic domain with that of the Arabidopsis, we set-up a phenotypic assay based on the hypocotyl length of Arabidopsis dark-grown seedlings to evaluate the effects of a compound previously described as human p300/CBP inhibitor, and to screen previously described cinnamoyl derivatives as well as newly synthesized analogues. We selected the most effective compounds, and we demonstrated their efficacy at phenotypic and molecular level. The in vitro inhibition of the enzymatic activity proved the specificity of the inhibitor on the catalytic domain of HAC1, thus substantiating this strategy as a useful tool in plant epigenetic studies.

Inhibition of Polycomb Repressive Complex 2 activity reduces trimethylation of H3K27 and affects development in Arabidopsis seedlings.

BACKGROUND: Polycomb repressive complex 2 (PRC2) is an epigenetic transcriptional repression system, whose catalytic subunit (ENHANCER OF ZESTE HOMOLOG 2, EZH2 in animals) is responsible for trimethylating histone H3 at lysine 27 (H3K27me3). In mammals, gain-of-function mutations as well as overexpression of EZH2 have been associated with several tumors, therefore making this subunit a suitable target for the development of selective inhibitors. Indeed, highly specific small-molecule inhibitors of EZH2 have been reported. In plants, mutations in some PRC2 components lead to embryonic lethality, but no trial with any inhibitor has ever been reported. RESULTS: We show here that the 1,5-bis (3-bromo-4-methoxyphenyl)penta-1,4-dien-3-one compound (RDS 3434), previously reported as an EZH2 inhibitor in human leukemia cells, is active on the Arabidopsis catalytic subunit of PRC2, since treatment with the drug reduces the total amount of H3K27me3 in a dose-dependent fashion. Consistently, we show that the expression level of two PRC2 targets is significantly increased following treatment with the RDS 3434 compound. Finally, we show that impairment of H3K27 trimethylation in Arabidopsis seeds and seedlings affects both seed germination and root growth. CONCLUSIONS: Our results provide a useful tool for the plant community in investigating how PRC2 affects transcriptional control in plant development.

The value of high-resolution computed tomography (HRCT) to determine exercise ventilatory inefficiency and dynamic hyperinflation in adult patients with cystic fibrosis.

INTRODUCTION: In Cystic Fibrosis (CF), exercise ventilatory inefficiency and dynamic hyperinflation (DH) cause exercise limitation and induce poor exercise tolerance. High-resolution computed tomography (HRCT) of the lung can detect pulmonary abnormalities in CF patients. We aimed to identify the determinants of exercise ventilatory inefficiency and DH using HRCT-derived metrics. METHODS: Fifty-two adult CF patients were prospectively enrolled; all participants underwent cardio-pulmonary exercise test (CPET) and HRCT. Radiological impairment was evaluated by the Brody II scoring system. Slope and intercept of the minute ventilation/CO2 production (V'E/V'CO2) regression line and the ratio of inspiratory capacity/total lung capacity (IC/TLC) at rest and at peak of exercise were measured. RESULTS: Four groups of patients were identified based on the combination of ventilatory efficiency (Vef) or inefficiency (Vin) and the presence/absence of DH. Compared to other groups, CF adults with Vin and DH had worse functional status and higher total (T), bronchiectasis (B) and air trapping (AT) scores at HRCT. Significant correlations were found between V'E/V'CO2 intercept and V'E/V'CO2 slope (ρ - 0.455, p = 0.001) and between V'E/V'CO2 intercept and Δ inspiratory capacity (IC) (ρ - 0.334, p = 0.015). Regression analysis identified AT score (cut-off 7.9, odds ratio-OR 3.50) as the only independent predictor of Vin and T (cut-off 53.6, OR 4.98), B (cut-off 16.1, OR 4.88), airways wall thickening (AWT) (cut-off 13, OR 3.41), and mucous plugging (MP) scores (cut-off 11.7, OR 4.18) as significant predictors of DH. CONCLUSION: In adult CF cohort, values of HRCT metrics are determinants of Vin (AT) and DH (T, B, AWT, MP).

Skin grafting for the treatment of chronic leg ulcers - a systematic review in evidence-based medicine.

Skin grafting is one of the most common surgical procedures in the area of non-healing wounds by which skin or a skin substitute is placed over a wound to replace and regenerate the damaged skin. Chronic leg ulcers are an important problem and a major source of expense for Western countries and for which many different forms of treatment have been used. Skin grafting is a method of treatment that decreases the area of chronic leg ulcers or heals them completely, thus improving a patient's quality of life. Skin grafting is an old technique, rediscovered during the first and second world wars as the main treatment for wound closure. Nowadays, skin grafting has a pivotal role in the context of modern wound healing and tissue regeneration. The aim of this review was to track and to analyse the specific outcomes this technique achieved, especially in the last decade, in relation to venous, arterial, diabetic, rheumatoid and traumatic leg ulcers. Our main findings indicate that autologous split-thickness skin grafting still remains the gold standard in terms of safety and efficacy for chronic leg ulcers; skin grafting procedures have greater success rates in chronic venous leg ulcers compared to other types of chronic leg ulcers; skin tissue engineering, also supported by genetic manipulation, is quickly expanding and, in the near future, may provide even better outcomes in the area of treatments for long-lasting chronic wounds.

Study on the efficacy of surgery of the superficial venous system and of compression therapy at early stages of chronic venous disease for the prevention of chronic venous ulceration.

The mainstay of treatment of chronic venous ulceration (CVU), as also suggested by current treatment guidelines for chronic venous disease (CVD), is represented by surgery and compression therapy for which there is strong evidence of their role in clinically relevant improvement in wound healing and also in the reduction of CVU recurrence, but no information is available as to whether or not these treatments provide effective protection from the onset of CVU. In our study, we have followed, for a median time of 13 years, a total of 3947 patients with CVD at classes C2-C3 of CEAP classification, treated with our treatment protocol (surgery and compression therapy) in order to track the natural history of these patients with regards to CVU development. We identified four groups of patients: 2354 patients (59·64%) (Group A) fully adherent to protocols; 848 patients (21·48%) (Group B) fully adherent to surgery and non-compliant to compression therapy; 432 patients (10·95%) (Group C) fully adherent to compression therapy and non-compliant to surgery; and 313 patients (7·93%) (Group D) non-compliant to either treatments. Regardless of compliance to treatments, the ulcer development rates were very similar between groups (range: 3·23-4.79%), with no statistical significance (P = 0·1522). Currents treatments used in the early stages of CVD appear to have no effects to progression to CVU. Additional longitudinal studies are required to confirm these findings.

Dual-Energy CT in Oncologic Imaging.

Dual-energy CT (DECT) is an innovative technology that is increasingly widespread in clinical practice. DECT allows for tissue characterization beyond that of conventional CT as imaging is performed using different energy spectra that can help differentiate tissues based on their specific attenuation properties at different X-ray energies. The most employed post-processing applications of DECT include virtual monoenergetic images (VMIs), iodine density maps, virtual non-contrast images (VNC), and virtual non-calcium (VNCa) for bone marrow edema (BME) detection. The diverse array of images obtained through DECT acquisitions offers numerous benefits, including enhanced lesion detection and characterization, precise determination of material composition, decreased iodine dose, and reduced artifacts. These versatile applications play an increasingly significant role in tumor assessment and oncologic imaging, encompassing the diagnosis of primary tumors, local and metastatic staging, post-therapy evaluation, and complication management. This article provides a comprehensive review of the principal applications and post-processing techniques of DECT, with a specific focus on its utility in managing oncologic patients.

Are the criteria for PD-MCI diagnosis comprehensive? A Machine Learning study with modified criteria.

BACKGROUND: Mild cognitive impairment in Parkinson's disease (PD-MCI) includes deficits in different cognitive domains, and one domain to explore for neurocognitive impairment following the DSM-V is social cognition. However, this domain is not included in current criteria for PD-MCI diagnosis. Moreover, tests vary across studies. It is, therefore, crucial to optimize cognitive assessment in PD-MCI. We aimed to do so by using Machine Learning. METHODS: 275 PD patients were included. Four cognitive batteries were created: two Standard ones (Levels I and II), applying current criteria and "traditional" tests; two Alternative ones (Levels I and II), which incorporated a test of social cognition. These batteries were included in the Random Forest (RF) classifier. To assess RF performance, the AUC was considered, and the Variable Importance Index was estimated to understand the contribution of each test in PD-MCI classification. RESULTS: Standard Level I and II showed an AUC of 0.852 and 0.892, while Alternative Level I and II showed an AUC of 0.898 and of 0.906. Variable Importance Index revealed that TMT B-A, Ekman test, RAVLT-IR, MoCA, and Action Naming were tests that most contributed to PD-MCI classification. CONCLUSION: The Alternative level I assessment demonstrated a similar classification capacity to the Standard level II assessment. This finding suggests that in the cognitive assessment of PD patients, it is crucial to consider the most affected cognitive domains in this clinical population, including social cognition. Taken together, these results suggest to revise current criteria for the diagnosis of PD-MCI.

When Size Matters: New Insights on How Seed Size Can Contribute to the Early Stages of Plant Development.

The seed habit is the most complex and successful method of sexual reproduction in vascular plants. It represents a remarkable moment in the evolution of plants that afterward spread on land. In particular, seed size had a pivotal role in evolutionary success and agronomic traits, especially in the field of crop domestication. Given that crop seeds constitute one of the primary products for consumption, it follows that seed size represents a fundamental determinant of crop yield. This adaptative feature is strictly controlled by genetic traits from both maternal and zygotic tissues, although seed development and growth are also affected by environmental cues. Despite being a highly exploited topic for both basic and applied research, there are still many issues to be elucidated for developmental biology as well as for agronomic science. This review addresses a number of open questions related to cues that influence seed growth and size and how they influence seed germination. Moreover, new insights on the genetic-molecular control of this adaptive trait are presented.

Artificial intelligence of imaging and clinical neurological data for predictive, preventive and personalized (P3) medicine for Parkinson Disease: The NeuroArtP3 protocol for a multi-center research study.

BACKGROUND: The burden of Parkinson Disease (PD) represents a key public health issue and it is essential to develop innovative and cost-effective approaches to promote sustainable diagnostic and therapeutic interventions. In this perspective the adoption of a P3 (predictive, preventive and personalized) medicine approach seems to be pivotal. The NeuroArtP3 (NET-2018-12366666) is a four-year multi-site project co-funded by the Italian Ministry of Health, bringing together clinical and computational centers operating in the field of neurology, including PD. OBJECTIVE: The core objectives of the project are: i) to harmonize the collection of data across the participating centers, ii) to structure standardized disease-specific datasets and iii) to advance knowledge on disease's trajectories through machine learning analysis. METHODS: The 4-years study combines two consecutive research components: i) a multi-center retrospective observational phase; ii) a multi-center prospective observational phase. The retrospective phase aims at collecting data of the patients admitted at the participating clinical centers. Whereas the prospective phase aims at collecting the same variables of the retrospective study in newly diagnosed patients who will be enrolled at the same centers. RESULTS: The participating clinical centers are the Provincial Health Services (APSS) of Trento (Italy) as the center responsible for the PD study and the IRCCS San Martino Hospital of Genoa (Italy) as the promoter center of the NeuroartP3 project. The computational centers responsible for data analysis are the Bruno Kessler Foundation of Trento (Italy) with TrentinoSalute4.0 -Competence Center for Digital Health of the Province of Trento (Italy) and the LISCOMPlab University of Genoa (Italy). CONCLUSIONS: The work behind this observational study protocol shows how it is possible and viable to systematize data collection procedures in order to feed research and to advance the implementation of a P3 approach into the clinical practice through the use of AI models.

Langerhans cell histiocytosis: unusual dorsal spine localization in an adult male.

This case report describes the clinical, imaging, and pathological features of a case of Langerhans cell histiocytosis affecting a patient suffering from chronic thoracic spine pain. Spinal localizations of Langerhans cell histiocytosis have been rarely described and they are usually characterized by involvement of vertebral bodies with osteolytic lesions. Our case presented with several unusual features that delayed the diagnosis, including the age of patient and the involvement of left T10 costovertebral junction with relative sparing of vertebral body and costal bone. The clues for diagnosis were represented by increased signal intensity both on T 2W fat-saturated and T 1W images after administration of gadolinium. The diagnosis was finally confirmed by means of percutaneous biopsy with subsequent histological/immunohistochemical study.

Quantitative Assessment of Lung Volumes and Enhancement in Patients with COVID-19: Role of Dual-Energy CT.

Dual-energy computed tomography (DECT) has been used for detecting pulmonary embolism, but the role of lung perfusion DECT as a predictor of prognosis of coronavirus disease 2019 (COVID-19) has not been defined yet. The aim of our study was to explore whether the enhancement pattern in COVID-19+ patients relates to the disease outcome. A secondary aim was to compare the lung volumes in two subgroups of patients. In this observational study, we considered all consecutive COVID-19+ patients who presented to the emergency room between January 2021 and December 2021 with respiratory symptoms (with mild to absent lung consolidation) and were studied by chest contrast-enhanced DECT to be eligible. Two experienced radiologists post-processed the images using the "lung-analysis" software (SyngoVia). Absolute and relative enhancement lung volumes were assessed. Patients were stratified in two subgroups depending on clinical outcome at 30 days: (i) good outcome (i.e., discharge, absence of clinical or imaging signs of disease); (ii) bad outcome (i.e., hospitalization, death). Patient sub-groups were compared using chi-square test or Fisher test for qualitative parameters, chi-square test or Spearman's Rho test for quantitative parameters, Students' t-test for parametric variables and Wilcoxon test for non-parametric variables. We enrolled 78 patients (45M), of whom, 16.7% had good outcomes. We did not observe any significant differences between the two groups, both in terms of the total enhancement evaluation (p = 0.679) and of the relative enhancement (p = 0.918). In contrast, the average lung volume of good outcome patients (mean value of 4262 mL) was significantly larger than that of bad outcome patients (mean value of 3577.8 mL), p = 0.0116. All COVID-19+ patients, with either good or bad outcomes, presented similar enhancement parameters and relative enhancements, underlining no differences in lung perfusion. Conversely, a significant drop in lung volume was identified in the bad outcome subgroup eligible compared to the good outcome subgroup.

Ultrasound-Guided Percutaneous Bone Biopsy: Feasibility, Diagnostic Yield and Technical Notes.

While nowadays, CT-guided bone biopsy represents the gold standard tool for histopathological and microbiological diagnosis of skeletal lesions, the role of US-guided bone biopsy has not yet been fully explored. US-guided biopsy offers several advantages, such as the absence of ionizing radiation, fast acquisition time, as well as good intra-lesional echo, and structural and vascular characterization. Despite that, a consensus in regard to its applications in bone neoplasms has not been established. Indeed CT-guided technique (or fluoroscopic ones) still represents the standard choice in clinical practice. This review article aims to review the literature data about US-guided bone biopsy, underlying clinical-radiological indications, advantages of the procedure and future perspectives. Bone lesions taking the best advantages of the US-guided biopsy are osteolytic, determining the erosion of the overlying bone cortex and/or with an extraosseous soft-tissue component. Indeed, osteolytic lesions with extra-skeletal soft-tissue involvement represent a clear indication for US-guided biopsy. Moreover, even lytic bone lesions with cortical thinning and/or cortical disruption, especially located in the extremities or pelvis, can be safely sampled with US guidance with very good diagnostic yield. US-guided bone biopsy is proven to be fast, effective and safe. Additionally, it offers real-time needle evaluation, an advantage when compared to CT-guided bone biopsy. In the current clinical settings, it seems relevant to select the exact eligibility criteria for this imaging guidance since the effectiveness can vary depending on the type of lesion and body site involved.

Which components of famous people recognition are lateralized? A study of face, voice and name recognition disorders in patients with neoplastic or degenerative damage of the right or left anterior temporal lobes.

We administered to large groups of patients with neoplastic or degenerative damage affecting the right or left ATL, the 'Famous People Recognition Battery' (FPRB), in which subjects are required to recognize the same 40 famous people through their faces, voices and names, to clarify which components of famous people recognition are lateralized. At the familiarity level, we found, as expected, a dissociation between a greater impairment of patients with right ATL lesions on the non-verbal (face and voice) recognition modalities and of those with left ATL lesions on name familiarity. Equally expected were results obtained at the naming level, because the worse naming scores for faces and voices were observed in left-sided patients. Less foregone were, for two reasons, results obtained at the semantic level. First, no difference was found between the two hemispheric groups when scores obtained on the verbal (name) and non-verbal (face and voice) recognition modalities were account for. Second, the face and voice recognition modalities showed a different degree of right lateralization. All groups of patients showed, indeed, both at the familiarity and at the semantic level, a greater difficulty in the recognition of voices regarding faces, but this difference reached significance only in patients with right ATL lesions, suggesting a greater right lateralization of the more complex task of voice recognition. A model aiming to explain the greater right lateralization of the more perceptually demanding voice modality of person recognition is proposed.

Osteomyelitis of the Lower Limb: Diagnostic Accuracy of Dual-Energy CT versus MRI.

BACKGROUND: MRI is the preferred imaging technique for the identification of osteomyelitis. The key element for diagnosis is the presence of bone marrow edema (BME). Dual-energy CT (DECT) is an alternative tool which is able to identify BME in the lower limb. PURPOSE: To compare the diagnostic performance of DECT and MRI for osteomyelitis, using clinical, microbiological, and imaging data as reference standards. MATERIALS AND METHODS: This prospective single-center study enrolled consecutive patients with suspected bone infections undergoing DECT and MRI imaging from December 2020 to June 2022. Four blinded radiologists with various experience levels (range of 3-21 years) evaluated the imaging findings. Osteomyelitis was diagnosed in the presence of BMEs, abscesses, sinus tracts, bone reabsorption, or gaseous elements. The sensitivity, specificity, and AUC values of each method were determined and compared using a multi-reader multi-case analysis. A p value < 0.05 was considered significant. RESULTS: In total, 44 study participants (mean age 62.5 years ± 16.5 [SD], 32 men) were evaluated. Osteomyelitis was diagnosed in 32 participants. For the MRI, the mean sensitivity and specificity were 89.1% and 87.5%, while for the DECT they were 89.0% and 72.9%, respectively. The DECT demonstrated a good diagnostic performance (AUC = 0.88), compared with the MRI (AUC = 0.92) (p = 0.12). When considering each imaging finding alone, the best accuracy was achieved by considering BME (AUC for DECT 0.85 versus AUC of MRI of 0.93, with p = 0.07), followed by the presence of bone erosions (AUC 0.77 for DECT and 0.53 for MRI, with p = 0.02). The inter-reader agreement of the DECT (k = 88) was similar to that of the MRI (k = 90). CONCLUSION: Dual-energy CT demonstrated a good diagnostic performance in detecting osteomyelitis.

Dose escalation of adalimumab as a strategy to overcome anti-drug antibodies: A case report of infantile-onset inflammatory bowel disease.

BACKGROUND: Treatment of infantile-onset inflammatory bowel disease (IO-IBD) is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics. Secondary loss of response is frequently caused by the production of anti-drug antibodies, a well-known problem in IBD patients on biologic treatment. We present a case of IO-IBD treated with therapeutic drug monitoring (TDM)-guided high-dose anti-tumor necrosis factor therapy, in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies. CASE SUMMARY: A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life, as well as relapsing perianal abscess and growth failure. Hypoalbuminemia, anemia, and elevated inflammatory markers were also present. Endoscopic assessment revealed skip lesions with deep colic ulcerations, inflammatory anal sub-stenosis, and deep fissures with persistent abscess. A diagnosis of IO-IBD Crohn-like was made. The patient was initially treated with oral steroids and fistulotomy. After the perianal abscess healed, adalimumab (ADA) was administered with concomitant gradual tapering of steroids. Clinical and biochemical steroid-free remission was achieved with good trough levels. After 3 mo, antibodies to ADA (ATA) were found with undetectable trough levels; therefore, we optimized the therapy schedule, first administering 10 mg weekly and subsequently up to 20 mg weekly (2.8 mg/kg/dose). After 2 mo of high-dose treatment, ATA disappeared, with concomitant high trough levels and stable clinical and biochemical remission of the disease. CONCLUSION: TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production. This strategy could be a good alternative to combination therapy, especially in very young patients.