Subcutaneous Infliximab (CT-P13) as Maintenance Therapy for Inflammatory Bowel Disease: 2 Randomized Phase 3 Trials.

BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. We aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. Co-primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).

Long-term control of diabetes by tofacitinib-based immunosuppressive regimen after allo islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets.

Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.

Cytokine storm syndrome after anti-thymoglobulin infusion in a cynomolgus monkey with systemic lymphadenopathy caused by follicular hyperplasia: A case report.

Nonhuman primates are widely used in transplantation research as preclinical xeno- or allo-transplantation models. Rabbit anti-thymoglobulin (ATG) is often used for T-cell depletion as an immunosuppressant. T-cell depletion can cause a secondary cytokine storm syndrome that can be minimized/prevented by a prophylactic administration of systemic corticosteroids and antihistamines. We report a case of death due to CSS in a cynomolgus monkey with follicular hyperplasia-induced systemic lymphadenopathy after ATG administration. A 6-year-old female cynomolgus monkey was rendered diabetic and then transplanted with a genetically modified porcine pancreatic islets (PPI) (50 000 IEQ/kg) through the portal vein 22 days later without immunosuppressant. Because graft function was not comparable, we planned re-transplantation of PPI. For re-transplantation of the PPI, we performed an intravenous (IV) ATG infusion for inductive immunosuppression. The monkey died 3 h and 30 min after ATG administration despite cardiopulmonary resuscitation. Systemic lymphadenopathy was observed on submandibular, axillary, inguinal, foregut, colic, and hilar lymph nodes, and splenomegaly was also observed on necropsy. Histopathologic examination of the lymph node revealed follicular hyperplasia. The IL-6 level was higher after ATG infusion compared to before ATG infusion (before vs. after ATG infusion; 14.9 vs. >5000 pg/mL). The death of the cynomolgus monkey was caused by severe CSS because of apoptosis of B cells in the systemic lymph nodes caused by the ATG administration. A thorough physical examination of palpable lymph nodes and pre-ATG sonographic or computed tomographic screening could have identified lymphadenopathy, potentially preventing its infusion and reducing mortality risk.

Association between Cognitive Abilities before the Age of 3 and Those at Least 1 Year Later in Children with Developmental Delay.

AIM: This study investigated whether early cognitive assessment in children with developmental delay (DD) predicts cognitive development. We investigated the correlation between cognitive and language development in children with DD, cerebral palsy (CP), and autism spectrum disorder (ASD). METHODS: Data were collected from children diagnosed with DD who visited the hospital between 2015 and 2023. The assessments included the Korean Bayley Scales of Infant and Toddler Development Second Edition (K-BSID-II) and the Korean Wechsler Preschool Primary Scale of Intelligence Fourth Edition (K-WPPSI-IV). Language development was evaluated using the Sequenced Language Scale for Infants (SELSI) and Preschool Receptive-Expressive Language Scale (PRES). Correlation and multivariate regression analyses were performed. RESULTS: Among 95 children in the study, a significant correlation was discovered between early cognitive assessments (the Mental Developmental Index from the K-BSID-II) and later cognitive development (the Full-Scale Intelligence Quotient from the K-WPPSI-IV) in the DD and CP groups, but not in the ASD group. The DD and CP groups exhibited significant correlations in language development between the SELSI and PRES, whereas the ASD group did not. INTERPRETATION: Early cognitive assessments can predict later cognitive development in children with DD and CP, but not in those with ASD, according to this study. There was a strong correlation between language and cognitive development in the DD and CP groups, highlighting the importance of early intervention and assessment for these children. Further investigation is necessary to address these limitations and refine demographic data.

Lateral Distance From the Osteotomy Hinge Point to the Tibial Cortex Is Associated With Lateral Hinge Fracture Type and Fracture Occurrence Time After Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To verify whether the distance from the hinge point to the tibial cortex affects the occurrence time and characteristics of the lateral hinge fracture (LHF) in medial open-wedge high tibial osteotomy. METHODS: We retrospectively reviewed 171 knees in 171 patients (121 women, 50 men; mean age, 53.9 years; range, 36-67 years) who had undergone medial open-wedge high tibial osteotomy with locking plate fixation between January 2011 and December 2020. Osteotomy hinge point and LHFs were identified on intraoperative fluoroscopy and immediate postoperative radiographs. LHF type was classified as suggested by Takeuchi et al. Acute fracture was defined as a fracture that occurred during surgery, and delayed fracture was defined as a fracture observed after 1 month postoperatively. The nearest distances from osteotomy hinge point to lateral, distal, and proximal cortex were measured on postoperative radiographs. We compared the distance between the different types and between acute and delayed LHFs. RESULTS: There were 55 LHFs (32%) (type I, 40 knees; type II, 14 knees; type III, 1 knee) that occurred acutely in 41 knees and were found as delayed fractures in 14 knees. The patient demographics were not significantly different between non-LHFs and each type of LHFs. Proximal and distal distances were not statistically different among fracture types and between occurrence times. However, lateral distances were significantly shorter in type I LHFs (6.2 ± 1.8 mm) and longer in type II LHFs (9.3 ± 2.3 mm) than in non-LHFs (7.1 ± 2.7 mm) (P = .020 and .004, respectively). The lateral cortical distances were also different between acute LHFs (6.4 ± 1.9 mm) and delayed LHF (9.0 ± 2.7 mm) (P < .001). In the case of fracture type, the frequency of type I decreases with increase in the lateral distance, whereas that of type II increases with increase in the lateral cortical distance. In acute fracture, type I was dominant (85.4%), whereas in delayed fracture, type II was dominant (57.2%). CONCLUSIONS: The lateral cortical distance from the hinge point was significantly associated with LHF occurrence. Shorter distance increased the risk for acute type I LHF, whereas longer distance increased the risk for delayed type II LHFs. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

The Impact of an Antimicrobial Stewardship Program on Days of Therapy in the Pediatric Center: An Interrupted Time-Series Analysis of a 19-Year Study.

BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ². RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). CONCLUSION: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Effect of joint-line obliquity on long-term survivorship of total knee arthroplasty: A postoperative phenotype analysis.

PURPOSE: Whether the longevity of total knee arthroplasty (TKA) differs between postoperative phenotypes has not been investigated. This study aims to examine which phenotype has a worse long-term survival rate than the reference phenotype (neutral alignment-parallel joint line), and whether joint-line obliquity (JLO) affects the survivorship of TKA. METHODS: A total of 945 knees that underwent primary TKAs for primary osteoarthritis from January 2000 to January 2009 were included. These were classified into nine postoperative phenotypes based on the combined assessment of the hip-knee-ankle (HKA) angle and JLO, measured on standing radiographs. The 5-, 10- and 15-year survival rates were analysed using Kaplan-Meier methods and log-rank tests. The long-term survival rates of each phenotype were compared with the reference phenotype. RESULTS: There were 55 aseptic mechanical failures within a period of 10.4 ± 5.0 years. The most frequently observed phenotypes were the reference phenotype (n = 527), neutral alignment-lateral joint-line inclination (n = 162), varus alignment-lateral joint-line inclination (n = 104) and varus alignment-parallel joint line (n = 101). The overall failure rate for each phenotype was 3.6%, 3.7%, 18.3% and 7.9%, respectively. Only the 10- and 15-year survival rates of the varus alignment-lateral joint-line inclination phenotype were significantly different from those of the reference phenotype (97%-93% vs. 90%-69%; p = 0.017, <0.001). CONCLUSION: The lateral joint-line inclination phenotype had an inferior long-term survival rate after varus-aligned TKA. This suggested that alignment and JLO affected the long-term survival rate of patients who underwent TKA. LEVEL OF EVIDENCE: Level III, Retrospective cohort study.

Evolution of Local Structural Motifs in Colloidal Quantum Dot Semiconductor Nanocrystals Leading to Nanofaceting.

Colloidal nanocrystals (NCs) have shown remarkable promise for optoelectronics, energy harvesting, photonics, and biomedical imaging. In addition to optimizing quantum confinement, the current challenge is to obtain a better understanding of the critical processing steps and their influence on the evolution of structural motifs. Computational simulations and electron microscopy presented in this work show that nanofaceting can occur during nanocrystal synthesis from a Pb-poor environment in a polar solvent. This could explain the curved interfaces and the olivelike-shaped NCs observed experimentally when these conditions are employed. Furthermore, the wettability of the PbS NCs solid film can be further modified via stoichiometry control, which impacts the interface band bending and, therefore, processes such as multiple junction deposition and interparticle epitaxial growth. Our results suggest that nanofaceting in NCs can become an inherent advantage when used to modulate band structures beyond what is traditionally possible in bulk crystals.

Fermented Protaetia brevitarsis Larvae Improves Neurotoxicity in Chronic Ethanol-Induced-Dementia Mice via Suppressing AKT and NF-κB Signaling Pathway.

This study was investigated to examine the neuroprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced-dementia mice. Consumption of FPB by mice resulted in improved memory dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. FPB significantly decreased oxidative stress by regulating levels of malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) in brain tissues. In addition, FPB restored cerebral mitochondrial dysfunction by modulating levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and ATP. In addition, FPB enhanced the cholinergic system via the regulation of acetylcholine (ACh) content, acetylcholinesterase (AChE) activity, and expressions of AChE and choline acetyltransferase (ChAT) in brain tissues. FPB ameliorated neuronal apoptosis through modulation of the protein kinase B (AKT)/B-cell lymphoma (BCL)-2 signaling pathway. Also, FPB improved inflammation response by down-regulating the toll-like receptor (TLR)-4/nuclear factor (NF)-κB pathway. Additionally, FPB ameliorated synaptic plasticity via the increase of the expressions of synaptophysin (SYP), postsynaptic density protein (PSD)-95, and growth-associated protein (GAP)-43. Treatment with FPB also reinforced the blood-brain barrier by increasing tight junctions including zonula occludens (ZO)-1, occludin, and claudin-1. In conclusion, these results show that FPB can improve cognitive impairment via AKT/NF-κB pathways in ethanol-induced-dementia mice.

Reconstruction of Segmental Bone Defect in Canine Tibia Model Utilizing Bi-Phasic Scaffold: Pilot Study.

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 µm as primary pores, 40-70 µm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

Eucommia ulmoides Leaves Alleviate Cognitive Dysfunction in Dextran Sulfate Sodium (DSS)-Induced Colitis Mice through Regulating JNK/TLR4 Signaling Pathway.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that is characterized by systemic immune system activation. This study was performed to assess the alleviative effect of administering an aqueous extract of Eucommia ulmoides leaves (AEEL) on cognitive dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. The major bioactive compounds of AEEL were identified as a quinic acid derivative, caffeic acid-O-hexoside, and 3-O-caffeoylquinic acid using UPLC Q-TOF/MSE. AEEL administration alleviated colitis symptoms, which are bodyweight change and colon shortening. Moreover, AEEL administration protected intestinal barrier integrity by increasing the tight junction protein expression levels in colon tissues. Likewise, AEEL improved behavioral dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. Additionally, AEEL improved short-chain fatty acid (SCFA) content in the feces of DSS-induced mice. In addition, AEEL improved damaged cholinergic systems in brain tissue and damaged mitochondrial and antioxidant functions in colon and brain tissues caused by DSS. Also, AEEL protected against DSS-induced cytotoxicity and inflammation in colon and brain tissues by c-Jun N-terminal kinase (JNK) and the toll-like receptor 4 (TLR4) signaling pathway. Therefore, these results suggest that AEEL is a natural material that alleviates DSS-induced cognitive dysfunction with the modulation of gut-brain interaction.

Hepatoprotective Effect of Allium ochotense Extracts on Chronic Alcohol-Induced Fatty Liver and Hepatic Inflammation in C57BL/6 Mice.

This study was performed to investigate the protective effects of Allium ochotense on fatty liver and hepatitis in chronic alcohol-induced hepatotoxicity. The physiological compounds of a mixture of aqueous and 60% ethanol (2:8, w/w) extracts of A. ochotense (EA) were identified as kestose, raffinose, kaempferol and quercetin glucoside, and kaempferol di-glucoside by UPLC Q-TOF MSE. The EA regulated the levels of lipid metabolism-related biomarkers such as total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL)-cholesterol in serum. Also, EA ameliorated the levels of liver toxicity-related biomarkers such as glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total bilirubin in serum. EA improved the antioxidant system by reducing malondialdehyde contents and increasing superoxide dismutase (SOD) levels and reduced glutathione content. EA improved the alcohol metabolizing enzymes such as alcohol dehydrogenase, acetaldehyde dehydrogenase, and cytochrome P450 2E1 (CYP2E1). Treatment with EA alleviated lipid accumulation-related protein expression by improving phosphorylation of AMP-activated protein kinase (p-AMPK) expression levels. Especially, EA reduced inflammatory response by regulating the toll-like receptor-4/nuclear factor kappa-light-chain-enhancer of activated B cells (TLR-4/NF-κB) signaling pathway. EA showed an anti-apoptotic effect by regulating the expression levels of B-cell lymphoma 2 (BCl-2), BCl-2-associated X protein (BAX), and caspase 3. Treatment with EA also ameliorated liver fibrosis via inhibition of transforming growth factor-beta 1/suppressor of mothers against decapentaplegic (TGF-ß1/Smad) pathway and alpha-smooth muscle actin (α-SMA). Therefore, these results suggest that EA might be a potential prophylactic agent for the treatment of alcoholic liver disease.

Altered Brain Glymphatic Flow at Diffusion-Tensor MRI in Rapid Eye Movement Sleep Behavior Disorder.

Background Brain glymphatic dysfunction may contribute to the development of α-synucleinopathies. Yet, noninvasive imaging and quantification remain lacking. Purpose To examine glymphatic function of the brain in isolated rapid eye movement sleep behavior disorder (RBD) and its relevance to phenoconversion with use of diffusion-tensor imaging (DTI) analysis along the perivascular space (ALPS). Materials and Methods This prospective study included consecutive participants diagnosed with RBD, age- and sex-matched control participants, and participants with Parkinson disease (PD) who were enrolled and examined between May 2017 and April 2020. All study participants underwent 3.0-T brain MRI including DTI, susceptibility-weighted and susceptibility map-weighted imaging, and/or dopamine transporter imaging using iodine 123-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane SPECT at the time of participation. Phenoconversion status to α-synucleinopathies was unknown at the time of MRI. Participants were regularly followed up and monitored for any signs of α-synucleinopathies. The ALPS index reflecting glymphatic activity was calculated by a ratio of the diffusivities along the x-axis in the projection and association neural fibers to the diffusivities perpendicular to them and compared according to the groups with use of the Kruskal-Wallis and Mann-Whitney U tests. The phenoconversion risk in participants with RBD was evaluated according to the ALPS index with use of a Cox proportional hazards model. Results Twenty participants diagnosed with RBD (12 men; median age, 73 years [IQR, 66-76 years]), 20 control participants, and 20 participants with PD were included. The median ALPS index was lower in the group with RBD versus controls (1.53 vs 1.72; P = .001) but showed no evidence of a difference compared with the group with PD (1.49; P = .68). The conversion risk decreased with an increasing ALPS index (hazard ratio, 0.57 per 0.1 increase in the ALPS index [95% CI: 0.35, 0.93]; P = .03). Conclusion DTI-ALPS in RBD demonstrated a more severe reduction of glymphatic activity in individuals with phenoconversion to α-synucleinopathies. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Filippi and Balestrino in this issue.

Ocular Motor Findings Aid in Differentiation of Spinocerebellar Ataxia Type 17 from Huntington's Disease.

Differentiation of spinocerebellar ataxia type 17 (SCA17) from Huntington's disease (HD) is often challenging since they share the clinical features of chorea, parkinsonism, and dystonia. The ocular motor findings remain to be elucidated in SCA17, and may help differentiating SCA17 from HD. We retrospectively compared the ocular motor findings of 11 patients with SCA17 with those of 10 patients with HD. In SCA17, abnormal ocular motor findings included impaired smooth pursuit (9/11, 82%), dysmetric saccades (9/11, 82%), central positional nystagmus (CPN, 7/11, 64%), abnormal head-impulse tests (4/11, 36%), and horizontal gaze-evoked nystagmus (GEN, 3/11, 27%). Among these, CPN was more frequently observed in SCA17 than in HD (7/11 (64%) vs. 0/10 (0%), p = 0.004) while saccadic slowing was more frequently observed in HD than in SCA17 (8/10 (80%) vs. 2/11 (18%), p = 0.009). Of six patients with follow-up evaluation, five later developed bilateral saccadic hypermetria (n = 4), GEN (n = 1), CPN (n = 1), bilaterally abnormal smooth pursuit (n = 1), and hyperactive head-impulse responses (n = 1) along with a clinical decline. Ocular motor abnormalities can be utilized as a diagnostic marker for differentiation of SCA17 from HD as well as a surrogate marker for clinical decline in SCA17.

Deep learning regressor model based on nigrosome MRI in Parkinson syndrome effectively predicts striatal dopamine transporter-SPECT uptake.

PURPOSE: Nigrosome imaging using susceptibility-weighted imaging (SWI) and dopamine transporter imaging using 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) single-photon emission computerized tomography (SPECT) can evaluate Parkinsonism. Nigral hyperintensity from nigrosome-1 and striatal dopamine transporter uptake are reduced in Parkinsonism; however, quantification is only possible with SPECT. Here, we aimed to develop a deep-learning-based regressor model that can predict striatal 123I-FP-CIT uptake on nigrosome magnetic resonance imaging (MRI) as a biomarker for Parkinsonism. METHODS: Between February 2017 and December 2018, participants who underwent 3 T brain MRI including SWI and 123I-FP-CIT SPECT based on suspected Parkinsonism were included. Two neuroradiologists evaluated the nigral hyperintensity and annotated the centroids of nigrosome-1 structures. We used a convolutional neural network-based regression model to predict striatal specific binding ratios (SBRs) measured via SPECT using the cropped nigrosome images. The correlation between measured and predicted SBRs was evaluated. RESULTS: We included 367 participants (203 women (55.3%); age, 69.0 ± 9.2 [range, 39-88] years). Random data from 293 participants (80%) were used for training. In the test set (74 participants [20%]), the measured and predicted 123I-FP-CIT SBRs were significantly lower with the loss of nigral hyperintensity (2.31 ± 0.85 vs. 2.44 ± 0.90) than with intact nigral hyperintensity (4.16 ± 1.24 vs. 4.21 ± 1.35, P < 0.01). The sorted measured 123I-FP-CIT SBRs and the corresponding predicted values were significantly and positively correlated (ρc = 0.7443; 95% confidence interval, 0.6216-0.8314; P < 0.01). CONCLUSION: A deep learning-based regressor model effectively predicted striatal 123I-FP-CIT SBRs based on nigrosome MRI with high correlation using manually-measured values, enabling nigrosome MRI as a biomarker for nigrostriatal dopaminergic degeneration in Parkinsonism.

Sex differences in gastrointestinal dysfunction among patients with Parkinson's disease.

BACKGROUND AND OBJECTIVE: Sex differences in gastrointestinal dysfunction have not been systematically analyzed in patients with Parkinson's disease (PD). This study was aimed to investigate the sex differences in gastrointestinal dysfunctions among the patients with PD using a multicenter trial dataset. METHODS: We analyzed the baseline data of prospectively enrolled set of patients with gastrointestinal dysfunctions. Possible sex differences in gastrointestinal symptoms assessed on the Nepean Dyspepsia Index-Korean Version (NDI-K), gastrointestinal symptom diary, and Bristol stool scale were analyzed in association with clinical PD severity and antiparkinsonian drug dosages by multiple linear regression models. We also performed post hoc analysis of the dyspepsia symptom sub-items, adjusting for multiple comparisons. RESULTS: Sixty-six of the 144 participants were female (45.8%). There were no differences in age, PD duration, Hoehn and Yahr stage, and daily dopaminergic medication dosages between sexes. NDI-K symptom and dyspepsia scores were correlated with the activity of daily living in females but not in males. In the multiple regression analysis controlling for all possible variables, female patients were shown to have worse gastrointestinal symptoms than males. When we performed post hoc analysis of the dyspepsia symptoms, inability to finish a regular meal and nausea were significantly worse in female patients. Gastrointestinal symptom diary supported that female patients more frequently complained of early fullness and bloating in the upper abdomen after meals than males, and burning pain in upper abdomen was more severe in female patients. CONCLUSION: Gastrointestinal dysfunctions may differentially affect female and male PD patients.

Lateral Meniscal Allograft Transplantation Provides a Chondroprotective Effect on Articular Cartilage: Quantitative 3-T Magnetic Resonance Imaging T2 Mapping.

PURPOSE: This study aimed to assess the cartilage status in patients who underwent isolated lateral meniscus allograft transplantation (MAT) using preoperative and postoperative quantitative 3-T magnetic resonance imaging T2 mapping at midterm follow-up period. METHODS: Patients who underwent lateral MAT without cartilage treatment procedures between 2010 and 2019 were assessed by quantitative magnetic resonance imaging preoperatively and postoperatively. On the sagittal section image following the center of the lateral femoral condyle, the weight-bearing area of the articular cartilage was divided into 6 segments based on the meniscal coverage area from anterior to posterior direction. The mean T2 values of each of the 6 segments were measured for 3 regions of interest: overall, deep, and superficial layers. The change in T2 values was statistically analyzed by paired t-tests. The Lysholm score was used to evaluate clinical function. RESULTS: A total of 105 patients were included in the study. The mean follow-up period was 3.2 years (range 2.0-5.4 years). Among the 6 segments, the mean T2 value showed significant improvement in the overall layer of F2 (the middle weight-bearing area of femoral condyle) and TP3 (the posterior weight-bearing area of tibia condyle) segments (P = .013 and .021, respectively) and the superficial layer of the F3 (the posterior weight-bearing area of femoral condyle) segments (P = .028). The mean T2 value of all the other segments did not show a statistically significant change. The mean Lysholm score significantly improved from 66.5 ± 15.8 to 89.3 ± 10.0 (P < .001). Overall, 73.3% and 96.2% of the patients met the minimal clinically important difference and patient acceptable symptomatic state, respectively. CONCLUSIONS: The mean T2 value of the articular cartilage of the weight-bearing area was either maintained or showed statistically significant improvement depending on the location following isolated lateral MAT. Thus, the transplanted meniscus seems to have a chondroprotective effect on the weight-bearing cartilage. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic case series.

Lateral Meniscal Allograft Transplantation Shows a Long-Term Chondroprotective Effect on Quantitative MRI T2 Mapping at 7 Years' Minimum Follow-Up.

PURPOSE: The purpose of this study was to assess the long-term chondroprotective effect of lateral meniscal allograft transplantation (MAT) using quantitative magnetic resonance imaging (MRI) T2 mapping. METHODS: In patients who underwent isolated lateral MAT, quantitative MRI T2 mapping was conducted preoperatively and postoperatively with at minimum follow-up of 7 years to assess the articular cartilage status. On the sagittal section image bisecting the lateral femoral condyle, the weight-bearing portions of the femoral and tibial articular cartilage were divided into 3 segments each-6 segments in total-based on the meniscal coverage area. The regions of interest analysis were performed on the 6 segments to measure the mean T2 value. Then, the whole layer was divided into deep and superficial layers for further zonal analysis. The longitudinal change in T2 values was statistically analyzed using paired t-tests. Clinical outcome was evaluated using the Lysholm score. RESULTS: A total of 31 patients were included in the study, with the MRI follow-up period of a minimum follow-up of 7 years (mean: 8.9 ± 1.3 years; range: 7.0-11.2 years). The mean T2 value of the whole layer showed significant improvement in all segments of the femoral cartilage and the posterior segment of tibial cartilage. In the zonal analysis, the mean T2 value of the tibial cartilage showed significant improvement in the superficial layer of the mid to posterior portion, while the deep layer remained stable. In contrast, the mean T2 value of the femoral cartilage showed significant improvement in the superficial and deep layers in all segments. The mean Lysholm score significantly improved from 62.6 ± 12.8 to 90.9 ± 10.5 (P < .001). CONCLUSION: This study suggests that MAT appears to have a long-term chondroprotective effect on the articular cartilage as judged by quantitative T2 mapping. LEVEL OF EVIDENCE: Level Ⅳ, case series.

Graft Extrusion of 3 Millimeters Is Acceptable at a Minimum of 5-Year Outcomes for Lateral Meniscal Allograft Transplantation.

PURPOSE: To determine the acceptable amount of graft extrusion based on long-term radiographic outcomes in lateral meniscal allograft transplantation (MAT). METHODS: 94 lateral MAT patients with a minimum 5-year follow-up period were reviewed. Graft extrusion was measured on MRI scans taken 1 year after surgery, and the study population was divided according to the amount of extrusion: group A, extrusion <3 mm; group B, 3 mm ≤ extrusion <5 mm; and group C, extrusion ≥5 mm. For radiographic evaluation, the bilateral lateral joint space widths (JSWs) were measured on a standing 45° flexion posteroanterior radiograph. To standardize the measurements, the affected JSW was divided by the contralateral JSW. The change in the standardized JSW (ΔJSWstd) between the preoperative and latest follow-up assessments was analyzed according to the three groups. Multiple regression analysis was performed to control other related factors, such as lower limb alignment and cartilage status at the time of MAT. The acceptable amount of graft extrusion was calculated using a receiver operating characteristic (ROC) curve for the third quartile of ΔJSWstd. Clinical outcomes were evaluated using the Lysholm score and were compared among the groups. RESULTS: The mean follow-up duration was 8.3 ± 3.1 years. There were 54, 25, and 15 patients in group A, group B, and group C, respectively. In multiple regression analysis, both group B and group C had significant associations with ΔJSWstd and their beta coefficients were comparable (group B, P < .001, ß = .642; group C, P < .001, ß = 0.613). No significant difference in ΔJSWstd was found between group B and group C (P = .494). On the basis of the ROC curve, the acceptable amount of graft extrusion was 3.74 mm (sensitivity, 81.8%; specificity, 77.8%). There were no differences in the Lysholm scores among the three groups (P = .329). CONCLUSIONS: ΔJSWstd differed between graft extrusion <3 mm (group A) and graft extrusion ≥3 mm (group B and group C). However, there was no significant difference in ΔJSWstd between group B and group C. No significant difference in clinical outcomes was found according to graft extrusion. This study gave supporting evidence for the currently recognized acceptable amount of graft extrusion (3 mm). LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Tear patterns and locations are different between lateral and medial compartments in patients with early anatomical failure after meniscal allograft transplantation.

PURPOSE: To investigate the characteristics of anatomically failed grafts within 1 year after meniscal allograft transplantation (MAT) and compare the differences between lateral and medial MATs. METHODS: The records of consecutive patients with anatomically failed grafts within 1 year after primary MAT between 2005 and 2018 were reviewed. Anatomical failure was defined as a tear covering > 50% of the allograft or an unstable peripheral rim. The pattern and location of the graft tears were analyzed using magnetic resonance imaging or arthroscopy. RESULTS: A total of 21 patients were included. All 21 patients had anatomical failure with tears involving > 50% of the allograft, whereas 15 had an unstable peripheral rim of the allograft. The mean failure time was 6.6 ± 3.6 months in all patients (lateral MAT, n = 15; medial MAT, n = 6). In the lateral MAT group, meniscocapsular separation was the most common pattern (n = 10, 66.7%), followed by complex (n = 3, 20.0%), radial (n = 1, 6.7%), and longitudinal (n = 1, 6.7%) tear. In the medial MAT group, a root tear was the most common pattern (n = 5, 83.3%), followed by a complex tear (n = 1, 16.7%). Meanwhile, in the lateral MAT, the midbody was the most frequently affected location (n = 9, 60.0%), followed by the posterior (n = 5, 33.3%) and anterior (n = 1, 6.7%) areas; in the medial MAT group, the posterior (n = 5, 83.3%) was the most frequently affected location, followed by the anterior area (n = 1, 16.7%). Significant differences in the pattern (P = 0.002) and location (P = 0.043) of the graft tears were found between lateral and medial MATs. CONCLUSION: In patients with early failure after MAT, meniscocapsular separation in the midbody of the lateral compartment and root tears in the posterior area of the medial compartment were the most common. Thus, surgeons are encouraged to pay extra attention to these vulnerable areas during the early period after MAT. LEVEL OF EVIDENCE: IV.