Citations

ABSTRACT Long segment losses exceeding 10 cm in the sciatic nerve are challenging in both the reconstructive techniques and optimizing sensory and motor function recovery. This case report and literature review describes our experience of using a pedicled vascularized common peroneal nerve graft to repair a 14‐cm sciatic nerve defect, involving L4 , L5 , and S1 nerve roots. Additionally, we conducted a literature review of various types of nerve autografts for large sciatic nerve defects, summarizing their characteristics and outcomes to aid clinicians in decision‐making and expected results in different scenarios. The patient, a 23‐year‐old female diagnosed with neurofibromatosis type I, underwent R0 tumor resection of the proximal left sciatic nerve due to a malignant peripheral nerve sheath tumor. She received an ipsilateral pedicled vascularized common peroneal nerve graft. The reconstruction included the L4 , L5 , and S1 nerve roots beyond the greater sciatic foramen into the inner pelvis. The patient's postoperative course was uneventful. At the 26‐month follow‐up, she showed MRC grade 4/5 strength in hamstrings with 90°knee flexion and a steady gait pattern. At the 32‐month follow‐up, she could ambulate very well with an ankle‐foot orthosis. The outcomes support the use of a pedicled vascularized common peroneal nerve graft in a single‐staged surgery to restore motor function for large sciatic nerve defects. Our literature review revealed that in cases where sural nerves are insufficient or injured for sciatic nerve reconstruction, the common peroneal nerve is a viable alternative to help patients regain functional independence.

Objective: The fulcrum as a structure that has been described in human and mammalian hearts as ossa cordis; the aim of the present study is to demonstrate its existence in the fetal heart, using ultrasonographic techniques and macro and microscopic anatomy. Methods: Ultrasound images of the fulcrum were obtained in 240 normal fetal hearts between 26 and 37 weeks of gestation, using 2D ultrasound and TM mode in 201 cases. Speckle tracking alone was used in 58 cases to demonstrate the triphasic movements of the fulcrum. Macroscopic anatomical dissection and histological study were performed in eight fetal hearts from spontaneous abortions (20-22 weeks). Results: We demonstrated the presence of the cardiac fulcrum, on which myocardial tissue fibers are inserted as a tendon constituting a unit that serves as a pivot for cardiac contraction, resulting in a three-phase displacement of the fulcrum. Values and displacement curves were obtained as a function of gestational age, adjusted to the cubic regression model and bivariate correlation (p < 0.001). Macroscopic anatomy and histology results are presented. Conclusions: The present study demonstrated the myocardial fulcrum in the fetal heart, a structure composed of myxo-chondroid tissue, being able to be visualized by ultrasound. This structure that acts as a lever has a mixed displacement that can be quantified in terms of vertical, rotational, angular and deformation displacement. Its existence could be proved in macro and histological dissections demonstrating the anchorage of cardiac fibers at the ends of this structure.

ABSTRACT Background Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra‐rare, acquired non‐malignant haematological disorder characterised by thrombosis risk, serious complications and debilitating symptoms in untreated patients. Objective This anchored indirect treatment comparison (ITC) evaluated efficacy data between proximal complement 3 inhibitor (C3i) pegcetacoplan and factor B inhibitor, iptacopan, in patients with PNH previously treated with complement 5 inhibitors (C5i; eculizumab, ravulizumab). Methods Respective pivotal studies provided patient‐level trial data for pegcetacoplan (16‐week PEGASUS [NCT03500549]) and published data for iptacopan (24‐week APPLY PNH [NCT04558918]). Differences in study design, duration and statistical methods between PEGASUS and APPLY PNH necessitated the comparative analyses to be conducted on secondary measures based on haemoglobin (Hb) levels, absolute reticulocyte count (ARC), lactate dehydrogenase (LDH) levels, and patient‐reported outcomes on the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐Fatigue) scale scores. The availability of a common reference C5i treatment group in both PEGASUS and APPLY PNH studies allowed anchored ITC (Bucher method). Simulated treatment comparison (STC) assessed the robustness of the main analysis. Results Overall, baseline characteristics of the populations in the PEGASUS and APPLY PNH studies were broadly comparable. Anchored ITC showed comparable outcomes (mean difference, [95% CI]) on change‐from‐baseline to end of study for pegcetacoplan versus C5i, and iptacopan versus C5i, respectively, across endpoints: Hb level ( − 0.49 g/dL [ − 1.78, 0.80]); ARC ( – 34.41 × 10 9 /L [ − 90.02, 21.21]); LDH level ( − 115.16 U/L [ − 244.40, 14.01]); FACIT‐Fatigue score (3.57 [ − 5.60, 12.73]). Finally, the STC produced results consistent with the main Bucher analyses across all clinical endpoints and patient‐reported fatigue, providing similar point estimates and confidence intervals. Conclusion This anchored ITC, based on data from pivotal trials, did not indicate significant differences in clinical or patient‐reported outcomes between pegcetacoplan and iptacopan in PNH treatment. The findings suggest that PNH treatment decisions should also consider individualised disease‐ and patient‐related factors. Trial Registration: ClinicalTrials.gov identifier: NCT03500549.

Abstract Background Early tumor shrinkage and depth of response have emerged as potential prognostic indicators in metastatic colorectal cancer (CRC). However, their associations with overall survival, progression-free survival (PFS), and postprogression survival in patients receiving anti–epidermal growth factor receptor (EGFR) antibodies or bevacizumab remain unclear. Methods We analyzed 3219 treatment-naive patients with RAS wild-type metastatic CRC from 8 randomized studies (CRYSTAL, OPUS, PRIME, CAIRO2, CALGB80405, WJOG4407G, ATOM, PARADIGM) in the Aid and Research in Digestive Cancerology database. Early tumor shrinkage was defined as a 20% or more reduction in tumor size at 8 ± 2 weeks, whereas depth of response was assessed by maximum tumor shrinkage at nadir. Cox regression models evaluated the associations of early tumor shrinkage and depth of response with overall survival, PFS, and postprogression survival, adjusting for confounders. A 2-sided test was conducted with a significance level of .05. Results Early tumor shrinkage and depth of response substantially stratified overall survival, PFS, and postprogression survival outcomes across all treatment groups. Early tumor shrinkage positivity was associated with improved overall survival, PFS, and postprogression survival in anti-EGFR and bevacizumab-based therapies, with a trend toward better outcomes in the anti-EGFR group. The depth of response analysis revealed optimal cutoff values of 0.55 for anti-EGFR–based therapy and 0.47 for bevacizumab-based therapy to achieve a median overall survival of approximately 32 months. Conclusions Early tumor shrinkage and depth of response serve as valuable prognostic markers in RAS wild-type metastatic CRC, particularly for patients treated with anti-EGFR antibodies. These findings highlight the potential role of early tumor shrinkage and depth of response in guiding treatment strategies and improving outcomes for patients with CRC.

Abstract Background: Metabolic-associated fatty liver disease (MAFLD) is a common liver disease and may become the leading cause of severe liver disease in the future. The Global Burden of Disease (GBD) study assesses MAFLD’s impact in countries and regions worldwide, providing insights into its prevalence. Methods: Prevalence data for MAFLD from 1990 to 2021 by country and region in all sex and age groups were collected from the Global Health Data Exchange. The categorization of countries and geographic areas by development was performed using the Sociodemographic Index (SDI). Results: Between 1990 and 2021, the global crude prevalence rate of MAFLD increased from 10.6% to 16.1% (beta-coefficient: 0.2%, 95% confidence interval [CI]: 0.2–0.2%, P <0.001), and the age-standardized prevalence rate was increased from 12.1% to 15.0% (beta-coefficient: 0.1%, 95% CI: 0.1–0.1%, P <0.001). In 2021, MAFLD was estimated to have affected 1.3 billion people worldwide. Significant uptrends were observed in all regions, super regions, and SDI categories. The fastest increase from 1990 to 2021 and the highest prevalence rate in 2021 were experienced by countries and territories with high–middle and middle SDI. An increase in the prevalence of MAFLD from 1990 to 2021 was demonstrated in all but six countries. Conclusions: In 2021, the number of patients affected by MAFLD was doubled compared to 1990, and the prevalence rate increased by over 50%. The burden of MAFLD, as measured by prevalence, was more prominent in countries and territories with middle SDI and in those located in North African and Middle Eastern, possibly due to changes in lifestyle in these areas over the past 30 years.

OBJECTIVE Despite the known negative physiological impact of repeated mild head trauma events, their multiplicative impact on long-term seizure risk remains unclear. The objective of this study was to evaluate how multiple mild traumatic brain injuries (mTBIs) impact long-term seizure risk by testing 3 distinct machine learning approaches. Baseline and injury-specific characteristics were incorporated to enhance prognostication of individual seizure risk. METHODS Children with at least 1 mTBI event without prior evidence of seizure or antiepileptic drug treatment, from 2003 to 2021, were identified from a nationally sourced administrative claims database. The primary outcome of interest was a seizure event after mTBI, defined by qualifying principal diagnosis codes. Time-varying multivariable Cox regression was used to assess the impact of repeated mTBI. RESULTS A total of 156,118 children (mean age 11.7 ± 4.7 years) were included, with a median follow-up duration of 22.6 months (IQR 9.2–45.4 months). Among patients who experienced seizure after mTBI, the median time to seizure was 306 days. Seizures among those with radiographic findings and/or loss of consciousness occurred earlier (median time to seizure 112.5 days [imaging findings only, IQR 5–526.25 days], 80 days [loss of consciousness only, IQR 7–652 days], 22 days [both, IQR 5–192 days]). Both mTBI without and with short-term loss of consciousness resulted in increasing seizure risk with repeated trauma (HR 1.196, 95% CI 1.082–1.322; HR 2.025, 95% CI 1.828–2.244; respectively). The random survival forest approach achieved fixed-time areas under the receiver operating characteristic curve of 0.780 and 0.777 at 30 and 90 days after mTBI, and children predicted at high risk by the final model experienced a significantly higher burden of early seizure after mTBI (46.7% within the first 30 days vs 17.7% and 19.9% of children at low and medium risk). A simplified model using the top 12 contributing features achieved 95% of the full model’s performance in the validation set. CONCLUSIONS A novel machine learning model was developed and validated for personalized prediction of long-term seizure risk following multiple mTBIs. Model performance remained robust with a limited feature set, suggesting the feasibility of real-time incorporation into clinical workflows for individualized prognostication following each repeat mTBI event. In children predicted to be at high risk, early intervention should be considered.