The purpose was to describe cervical sagittal alignment in adolescent idiopathic scoliosis (AIS) compared to a normal group of adolescents and young adults, seeking for differences by Lenke type. Radiographs of 1779 AIS patients and 1115 controls were analyzed. Lenke types were determined. Spinopelvic parameters, thoracic kyphosis (TK), lumbar lordosis and sagittal vertical axis (SVA) CAM, C2, and C7 were measured. Cervical parameters included McGregor slope, C1–C2 and McGregor–C2 lordosis, C2–C7 lordosis (subdivided into cranial and caudal arches), C7 and T1 slopes. Cervical alignment patterns were classified as lordotic, kyphotic or sigmoid shapes. Lenke 1, 2, 3 and 6 curves showed decreased C2–C7 and caudal arch lordosis associated with decreased C7 and T1 slopes and TK (p < 0.001) compared to normal. Cranial cervical parameters were comparable to the normal group. Lenke 5 patients demonstrated TK, C7 and T1 slopes, and cervical alignment parameters close to the normal group. In AIS, TK correlated with caudal cervical (r = 0.76) and C2-C7 lordosis (r = 0.52), but only weakly with cranial cervical parameters. Cervical sagittal alignment compensatory changes in AIS predominantly involve the caudal cervical segment and are closely related to TK, while cranial alignment remains close to normal, supporting horizontal gaze. As opposed to other AIS types with thoracic deformity, Lenke 5 patients had no cervical compensation, and sagittal alignment was close to normal. Distinguishing normative from pathologic compensation across AIS curve types may help optimize surgical planning and restoration of TK to indirectly improve cervical alignment.
ABSTRACT:Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive pediatric myeloproliferative neoplasm for which hematopoietic stem cell transplantation (HSCT) is currently the only established curative therapy. However, a watch-and-wait (W&W) approach has shown promise for long-term survival in selected cases. In this real-world study, we analyzed outcomes of patients with JMML initially managed with a W&W strategy within a nationwide cohort of 161 genetically characterized cases. W&W was chosen for 35 patients, with increasing adoption over time, reaching 39% in the 2016-to-2021 period. Most patients carried mutations in CBL (43%), NRAS (34%), or homozygous germ line SH2B3 (14%). Over a median follow-up of 6.5 years, 30 of 35 (86%) achieved long-term survival with partial or complete resolution of myeloproliferative symptoms, although clonal hematopoiesis persisted in nearly all survivors (18/20). Disease progression occurred in 5 patients (CBL, n = 3; NRAS, n = 1; PTPN11, n = 1), mostly within 2 years after diagnosis. Overall, in the W&W cohort, the 5-year overall and event-free survivals were 93.1% and 84.5%, respectively. In NRAS-mutated cases, age of <30 months, normal to slightly elevated fetal hemoglobin, platelet counts of >45 × 109/L, the absence of additional somatic mutations, and low DNA methylation profile were associated with favorable outcomes. In CBL-driven JMML, no predictive factor of adverse evolution was identified. Notably, W&W was effective in all patients with homozygous germ line SH2B3. These findings support W&W as a viable alternative in up to 30% of patients with JMML, potentially sparing them from HSCT-associated risks. Given the persistence of clonal hematopoiesis and the risk of extrahematological complications, long-term monitoring remains essential.
BACKGROUND:More high-quality evidence for stent-assisted coiling (SAC) of cerebral aneurysms is needed. Randomized controlled trials have shown lower recurrence with the HydroCoil Embolic System (HES) compared with bare platinum coils, and self-adjudicated LVIS Evo SAC studies have demonstrated favorable safety and technical success. The objective of the SEALANT study is to investigate the safety and effectiveness of this device combination. METHODS:SEALANT is an open-label, prospective, single-arm, multicenter study including patients with aneurysms up to a maximum size of 12 mm. The primary effectiveness endpoint was complete occlusion on digital subtraction angiography (DSA), and the primary safety endpoint was major ipsilateral stroke or neurological death. Adverse events and imaging were independently adjudicated. RESULTS:206 patients were enrolled; 193 had follow-up imaging for outcome assessment; and 164 satisfied all criteria, were treated with both study devices (including ≥90% HES), and had DSA follow-up. The participants' mean age was 56.8±11.6 years; 65% were female. Of 212 aneurysms, 86.3% were bifurcation and 13.2% sidewall; 25.0% were previously treated and 17.9% previously ruptured; 89.6% were anterior circulation, 34.0% at the anterior communicating artery, and 30.7% at the middle cerebral artery; and 84.9% were wide-necked (neck ≥4 mm or dome/neck ratio <2). The primary effectiveness endpoint of complete occlusion was achieved in 82.1% (95% CI 76.4% to 87.9%) of aneurysms. 2.4% (95% CI 0.3% to 4.5%) of patients met the primary safety endpoint of major ipsilateral stroke or neurological death. The primary safety endpoint was significantly associated with baseline modified Rankin Scale and history of previous stroke. CONCLUSION:1-year SEALANT results confirm the safety and effectiveness of SAC using LVIS Evo and HES. TRIAL REGISTRATION NUMBER:NCT04999423.
Carotid artery stenting has become a widely used treatment for carotid artery stenosis, whether symptomatic or asymptomatic. This procedure can be challenging in specific anatomies, especially when the vessels are tortuous or present an uncommon orientation. We describe a fully endovascular technique to mitigate the lack of support by using a stiff wire in the distal brachial artery to allow a safe catheterization of the brachiocephalic trunk with an 8F sheath. The procedure is then performed with a lower risk of backing out of the brachiocephalic trunk, thereby minimizing surgical risk.Clinical ImpactWe report a safe technical tip that eases catheterization of the brachiocephalic trunk in difficult anatomy, mitigating the lack of support encountered with a standard femoral approach and reducing the risk of kickback during maneuvers.
Background and ObjectivesDevelopmental and epileptic encephalopathies (DEEs) with early burst-suppression EEG (EIDEE-BS) are among the most severe neonatal epileptic syndromes, typically presenting in the first months of life with refractory seizures and profound neurodevelopmental impairment. Although variants in the KCNQ2, STXBP1, and SCN2A genes are recognized as major causes, the full genetic spectrum remains uncertain. We aimed to delineate the electroclinical characteristics, genetic etiologies, and long-term outcomes in a large MRI-negative EIDEE-BS cohort.MethodsWe retrospectively analyzed 110 patients with BS EEG enrolled from a database of 1,540 individuals with suspected genetic epilepsies (2008-2023). Clinical, EEG, and genetic data were systematically collected. Patients were stratified into 4 groups: KCNQ2, STXBP1, "other pathogenic variants," and "without a genetic diagnosis." EEG traces were reviewed independently, and outcomes were assessed through long-term follow-up.ResultsPathogenic or likely pathogenic variants were identified in 62.7% of patients and involved 23 genes, including 2 copy number variants. KCNQ2 (n = 24) and STXBP1 (n = 16) accounted for one-third of diagnoses, whereas SCN2A (n = 3) and KCNT1 (n = 2) were less frequent. In KCNQ2 cases, seizures and BS onset occurred earlier than in STXBP1 cases: mean 2 days vs 6 weeks for seizures and 3 days vs 2 months for BS, respectively. A typical BS pattern (bursts longer than suppressions) strongly correlated with KCNQ2 and STXBP1 variants. Novel associations were found with DPM1, GRIN2A, KCNT2, PIGO, PURA, WWOX, and candidate genes (KMT2E, SNAP25, and SYT1). Most variants were de novo heterozygous; however, recessive and X-linked inheritance patterns were also observed. Mortality was high (25%), primarily from status epilepticus and complications of severe disability. Most patients (72.5%) had persistent seizures at follow-up (a mean of 6.5 years), as well as profound intellectual disabilities, irrespective of genotype.DiscussionThis large series highlights the strong monogenic basis of EIDEE-BS. KCNQ2, STXBP1, and SCN2A were the most commonly affected genes. Early EEG features, particularly BS timing and morphology, can help anticipate the underlying genotype and guide precision therapy, including the early use of sodium channel blockers in selected cases. These findings support recent ILAE reclassification efforts and underscore the importance of comprehensive genomic testing for improved diagnosis and counseling.
