Hamouda, Abdelrahman M.

Abstract The development of biocompatible and biologically responsive scaffolds remains a key challenge for bone tissue engineering. Here, we report an enzyme-degradable, metal-free click-cross-linked organic–inorganic nanohybrid (Enz-Deg-Click-ON) scaffold with high biocompatibility for bone repair. The formulation was synthesized using a cyclooctyne-functionalized poly(propylene fumarate) polyphosphoester (PPF-poly(PE-BCN)) and azide-terminated dendritic polycaprolactone (PCL) with a polyhedral oligomeric silsesquioxane core (POSS-PCL-N3) via strain-promoted alkyne-azide cycloaddition (SPAAC) bioorthogonal click chemistry. The incorporation of phosphate-containing linkages enabled alkaline phosphatase (ALP)-responsive degradation. The scaffold exhibited rapid catalyst-free crosslinking, tunable swelling, and suitable mechanical properties. In vitro studies demonstrated excellent cytocompatibility, robust stem cell proliferation, and enhanced osteogenic differentiation with an elevated level of ALP and Runx2 expression. Enzyme-triggered degradation was confirmed in the presence of ALP. In the in vivo rat calvarial defect model, the scaffold significantly improved bone regeneration, as shown by an increased bone volume, mineral density, and defect coverage. Histological and immunofluorescence analyses revealed enhanced collagen deposition, angiogenesis, and osteogenesis. These results indicate that the Enz-Deg-Click-ON system provides a dynamic, bioresponsive platform for bone repair.

Abstract Stroke thrombi are heterogeneous; their composition influences their mechanical properties, including stiffness, elasticity, and adhesiveness, which in turn affect their response to therapy. Systemic characterization of the thrombi components could help select therapeutic techniques and anticipate outcomes. We conducted a systematic review and meta-analysis to evaluate associations between thrombi composition and angiographic and functional outcomes in acute ischemic stroke (AIS). Up to May 2025, relevant studies were sourced from four databases: PubMed, Web of Science, Scopus, and Embase. We included cohort studies whose populations are patients with AIS in relation to thrombi composition. Thirty-six studies involving 5,462 patients matched our eligibility criteria. Angiographic success (Thrombolysis in Cerebral Infarction ≥ 2b/3) did not differ significantly between red blood cell (RBC)-rich and fibrin-rich thrombi (risk ratio [RR] 1.02, 95% confidence interval [CI] 0.85–1.22; p = 0.84; I 2 = 63.8%; very low certainty). However, thrombi from patients with good angiographic outcomes had a significantly higher RBC content compared to patients with poor outcomes (mean difference = 7.22%, 95% CI 3.31–11.13; p < 0.001; low certainty). No significant difference was observed between RBC-rich and fibrin-rich thrombi regarding functional independence at 90 days (modified Rankin Scale 0–2) (RR = 1.22, 95% CI 0.73–2.05; p = 0.31; low certainty). While RBC-rich thrombi are associated with more favorable angiographic performance, thrombus composition alone does not predict functional outcomes. Stroke outcomes remain multifactorial, dominated by time to reperfusion, collateral circulation, and baseline severity. Preinterventional assessment of clot composition via imaging or biomarkers may support individualized therapy but should complement, not replace, other prognostic determinants.

OBJECTIVE Multisegmental pathological autofusion is a hallmark feature of ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), creating a rigid, brittle spine highly susceptible to three-column fractures and devastating neurological injury. This study aimed to evaluate survival outcomes in this patient population and identify clinical and demographic predictors of mortality. METHODS Adults with DISH or AS who sustained a fracture and were admitted to a single tertiary care center for spinal fracture were retrospectively identified using ICD-10 diagnostic codes. Data were extracted on demographics, clinical presentation, fracture characteristics, and details of treatment. RESULTS A total of 383 patients (median age 78 years, 75.2% male) were included. Over a median follow-up of 17.3 months, overall mortality was 38.1%, in-hospital mortality was 5.2%, 30-day mortality was 5.7%, and 1-year mortality was 18.0%. Initial treatment consisted of external orthosis in 220 (57.4%) and surgery in 144 (37.6%), while 19 (5.0%) were left untreated. Patients who died were older (median 83 vs 74 years, p < 0.001), had a lower BMI (29.4 vs 32.3 kg/m 2 , p < 0.001), had higher frailty on the 5-item modified frailty index (mFI-5), and more commonly had congestive heart failure (CHF), cancer, functional dependency, and chronic kidney disease (CKD) (all p < 0.01). Mortality was not associated with fracture location, mechanism of injury, fracture number, or the presence of neurological deficits. Univariable time-to-event analysis showed that decreased survival was predicted by older age (HR 1.08, p < 0.0001), lower BMI (HR per kg/m 2 0.93, p < 0.0001), functional dependency (HR 2.05, p < 0.001), cancer (HR 1.55 p = 0.01), CKD (HR 1.48, p = 0.019), CHF (HR 2.18, p < 0.001), and higher mFI-5 score (HR per point 1.34, p < 0.001). On multivariable analysis, older age (HR 1.06 per year, p < 0.001), lower BMI (HR per kg/m 2 0.95, p < 0.001), and mFI-5 score (HR per patient 1.37, p < 0.001) remained significant independent predictors of mortality. Treatment modality did not predict mortality. CONCLUSIONS AS- or DISH-associated spinal fractures have a high associated mortality, regardless of mechanism or severity. Treatment modality did not affect odds of survival, suggesting that nonoperative management with an external orthosis may be an appropriate option, particularly in older and medically complex patients.

Background/Objectives: To identify predictors of successful fusion and adjacent segment disease (ASD) following ALIF. Methods: Records of patients undergoing one- or two-level ALIF were queried for baseline and postoperative radiographic data, demographics, operative notes, and implant characteristics. All had ≥1 year of follow-up with CT, and multivariable Cox regression was used to identify predictors of radiographic fusion through the interbody, ASD, and ASD requiring reoperation. Results: In total, 177 patients (median 59 yr; 52.5% male) were treated at 245 unique levels, of which 193 fused (81.3% with posterior fixation and 59.6% with standalone), 43 had ASD (17.6%), and 14 had ASD requiring reoperation (5.7%). Fusion was predicted by anterior cage placement (HR 0.94/mm; 95% CI [0.90, 0.98]; p = 0.003) and BMP use (HR 1.92; [1.15, 3.18]; p = 0.012). Radiographic ASD was predicted by older age (HR 1.08 per year; [1.03, 1.14]; p < 0.001), undergoing a revision [vs. index] fusion operation (HR 3.51; [1.44; 8.59]; p = 0.006), lower preoperative disc height (HR 0.83/mm; [0.74, 0.94]; p = 0.003), and preoperative facet vacuum phenomenon (HR 2.46; [1.18, 5.15]; p = 0.017). None of the extracted variables predicted reoperation for ASD. Conclusions: BMP use along with anterior cage placement and posterior fixation may improve the odds of fusion through the interbody following one- or two-level ALIF. Adjacent segment pathology is more common in patients with greater preoperative degenerative pathology (vacuum sign; more collapsed disc) and advanced age. Pelvic fixation did not improve fusion odds, but the data highlight the benefits of supplementary posterior fixation vs. standalone ALIF.

BACKGROUND AND OBJECTIVES: Ventriculoperitoneal shunt (VPS) placement is a common treatment for idiopathic normal pressure hydrocephalus (iNPH), but patients may require VPS revision. This study aims to evaluate the effectiveness of a standardized VPS placement protocol by comparing indications and rates of shunt revision compared with a historical institutional cohort. METHODS: All patients treated with VPS for “suspected” iNPH at a tertiary care center between January 2000 and January 2023 were retrospectively reviewed and divided into temporally distinct historical (before 2017) and standardized (after 2017) cohorts. Cumulative incidence and timing of VPS revision were compared using competing risks analyses. RESULTS: A total of 561 patients (median age 75.0 years) were identified with 324 (57.8%) in the historical and 237 (42.2%) in the standardized cohorts. Significant variations in surgical technique and shunt hardware were noted between the cohorts. With a median follow-up of 11.4 months for historical and 12.4 months for standardized cohort, shunt revisions occurred in 19.4% and 8.4% of patients in the historical and standardized cohorts, respectively ( P < .001). Revision indications also varied significantly with lower rates of overdrainage ( P < .001), infection ( P < .001), and proximal malfunction ( P = .042) but higher rate of distal malfunction ( P = .03) in the standardized cohort. Notably, no infections were noted in the standardized cohort. CONCLUSION: Risk of shunt revision among iNPH patients may be associated with modifiable factors related to surgical technique and shunt hardware selection. Importantly, no short-term complications such as hemorrhage, infection, or catheter malposition were observed with the standardized protocol. Development and refinement of standardized shunt protocols for iNPH patients should be commonplace to facilitate tracking, identification, and modification of modifiable technical risk factors.

Background: Anterior cervical discectomy and fusion (ACDF) is a widely performed procedure for treating degenerative cervical spine conditions. While it effectively addresses neural decompression and restores segmental alignment, the interplay of baseline alignment and implant-specific factors on postoperative segmental alignment remains underexplored. This study evaluates the influence of preoperative cervical alignment and interbody cage design on segmental alignment changes following 1- to 3-level ACDF. Methods: Following institutional review board approval, we identified 258 patients undergoing ACDF for degenerative pathology between 1 January 2010 and 31 December 2023. Preoperative and postoperative radiographs were analyzed for cervical alignment, disc height, and segmental lordosis. Cage dimensions, lordosis, and positioning relative to vertebral landmarks were recorded. Multivariable linear regression models evaluated predictors of postoperative disc height, segmental lordosis, and their respective changes. Results: Postoperative disc height was positively associated with greater cage height (β = 1.13 mm per mm, p < 0.001) and negatively associated with greater cage lordosis (β = −0.10 mm per °, p = 0.001). Segmental lordosis was positively influenced by cage height (β = 0.78° per mm, p = 0.002) and lordosis (β = 0.42° per °, p = 0.002) but was negatively correlated with the distance of the cage from the anterior edge of the cranial vertebra (β = −1.76° per mm, p = 0.004). Greater preoperative segmental kyphosis predicted more significant postoperative lordosis correction (β = −1.07° per °, p < 0.001). Conclusions: This study underscores the importance of preoperative alignment and interbody cage design in achieving optimal segmental correction following ACDF. While cage height primarily drives disc height restoration, surgical technique, particularly anterior placement of the cage, is pivotal for enhancing segmental lordosis. These findings support personalized surgical planning to optimize alignment and patient outcomes.

Abstract Background The associations between bilateral oophorectomy or hysterectomy with ovarian conservation and the risk of Parkinson's disease (PD) remain inconclusive. Objectives To evaluate the evidence on these two associations. Methods We conducted a systematic search across Embase, PubMed, Scopus, MEDLINE, and Web of Science through May 15, 2024. Data were extracted independently by two reviewers, and random‐effects meta‐analyses were performed. Results Eight studies with a total of 242,275 women were included. For bilateral oophorectomy, the effect size (ES) was greater than 1.0 in 5 of 8 studies. The pooled analysis showed a significant association between premenopausal bilateral oophorectomy and an increased risk of PD in cohort studies (hazard ratio [HR] 1.32; 95% CI 1.12–1.56) but not in case–control studies or combining both cohort and case–control studies. There was a suggestive trend of increasing risk with younger age at bilateral oophorectomy. For hysterectomy with ovarian conservation, the ES was greater than 1.0 in all six studies. The pooled analysis showed a non‐significant association in cohort studies and in case–control studies; however, the association was significant when combining both cohort studies and case–control studies (ES 1.19; 95% CI 1.01–1.41). Conclusions Current studies provided low to moderate evidence for the associations between bilateral oophorectomy and hysterectomy with ovarian conservation and increased risk of PD. However, the evidence was only observational and there was important heterogeneity across the case–control studies. Future studies should focus on surgeries performed at younger ages and on the possible effects of estrogen replacement therapy.

BACKGROUND AND OBJECTIVES: Anterior lumbar interbody fusion (ALIF) is a powerful procedure for sagittal correction and indirect decompression in the lumbar spine, though aggressive correction can cause stretch neuropraxia and implant subsidence. The aim of this study was to identify radiographic and clinical predictors of segmental correction, as well as to evaluate the degree to which segmental correction on supine intraoperative radiographs translates to postoperative upright alignment changes. METHODS: We identified patients treated with 1- or 2-level ALIF at a tertiary care center and extracted data on demographics, spinopelvic parameters, and surgical details. Patients treated with isolated ALIF and ALIF with supplementary posterior instrumentation were compared on pre- and postoperative intradiscal lordosis (IDL) and change in IDL. Multivariable linear regression was performed to identify independent predictors of postoperative IDL. RESULTS: We included 204 patients (median age 57 years, 55.4% male) treated at 258 levels, of whom 114 (55.9%) underwent supplementary posterior fixation and 150 (73.5%) underwent single-level implantation. Across all patients, postoperative IDL was significantly greater than preoperative segmental lordosis (25.4° vs 15.3°; P < .001). Standalone ALIF achieved less ΔIDL than circumferential fusion for L5/S1 procedures (7.4° vs 11.6°; P < .001), though ΔIDL for L3/4 and L4/5 was similar between the standalone and circumferential groups. Multivariable analysis showed postoperative IDL to be predicted by greater preoperative IDL (β = 0.26° per degree; [0.15, 0.36]; P < .001), L5/S1 [vs L4/5] implantation (β = 3.97°; [2.72, 5.21]; P < .001), use of supplementary posterior fixation (β = 1.80°; [0.70, 2.89]; P < .001), and greater implant lordosis (β = 0.62° per degree; [0.44, 0.79]; P < .001). CONCLUSION: Postoperative IDL after 1- or 2-level ALIF is best predicted by placement of larger interbody sizes, L5/S1 implantation, greater baseline IDL, and use of adjunct posterior fixation. Patients with higher preoperative lordosis experienced smaller postoperative increases in IDL, though this was likely influenced by a treatment bias.

Background Delayed aneurysm rupture (DAR) is a potentially devastating complication after flow-diverters (FD) deployment and their exact mechanisms are still unclear. The purpose of this meta-analysis is to synthesize the latest evidence on DAR after FD treatment and identify predictive factors. Methods A systematic review and meta-analysis were conducted according to established protocols. Searches were conducted in PubMed, Scopus, Web of Science, and Embase databases up to June 2024 using variations of “aneurysm “and “delayed aneurysm rupture” terms. Original studies reporting DAR and including more than five patients were included. All analyses were conducted in R software (version 4.4.2), employing the “meta” and “tableone” packages. Results 64 studies with 9820 patients were included, large aneurysm size (OR=1.08, 95% CI (1.02, 1.14), P value=0.008), intra-aneurysmal thrombus (OR=1.05, 95% CI (1.01, 1.09), P value=0.010) and posterior circulation location (OR=1.02, 95% CI (1.00, 1.04), P value=0.014) were significant risk factors for DAR. The pooled prevalence of DAR was 1.40%, with a rate of 1.18% after removing outliers. DAR occurred within 30 days in 66.7% of cases, with a mortality rate of 73.3% at discharge. Conclusion DAR following flow diversion treatment is an uncommon but devastating complication and remains a limitation of the technique. It is influenced by factors such as large aneurysm size, intra-aneurysmal thrombosis, and posterior circulation involvement. The first 30 days post-procedure represent a particularly high-risk period. Despite advancements in FD technology, significant gaps remain, highlighting the need for further research to improve risk assessment and treatment strategies.

Background Mechanical thrombectomy (MT) is a well-established treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, its role in cervical artery dissection-related (CeAD) LVO remains debated due to anatomical complexities and procedural challenges. This systematic review and meta-analysis aims to evaluate the safety, efficacy, and clinical outcomes of MT in patients with AIS due to CeAD-related LVO compared with other AIS etiologies. Methods PubMed, Embase, and Scopus were systematically searched from inception to March 2025. Comparative observational studies evaluating the use of MT in adult patients with AIS due to LVO were included, specifically those comparing outcomes in patients with CeAD versus non-CeAD etiologies. Results MT for CeAD-related AIS showed no statistically significant difference in successful recanalization compared with non-CeAD cases (OR 0.81 (95% CI 0.63 to 1.04), P=0.10). However, patients with CeAD-related AIS had significantly higher rates of 90-day functional independence (modified Rankin Scale score 0–2) (OR 2.17 (95% CI 1.55 to 3.05), P<0.01) and lower 90-day mortality (OR 0.34 (95% CI 0.22 to 0.53), P<0.01). Rates of distal embolization (OR 1.60 (95% CI 0.69 to 3.70), P=0.27), symptomatic intracranial hemorrhage (OR 0.84 (95% CI 0.51 to 1.38), P=0.49), or iatrogenic dissection (OR 1.58 (95% CI 0.59 to 4.22), P=0.36) did not differ significantly between patient groups. Conclusions MT in patients with CeAD-related LVO is safe, effective, and associated with improved functional outcomes and lower mortality compared with patients with non-CeAD acute ischemic causes.