Comparison of Surgical Burden, Radiographic and Clinical Outcomes According to the Severity of Baseline Sagittal Imbalance in Adult Spinal Deformity Patients.

OBJECTIVE: To determine the clinical impact of the baseline sagittal imbalance severity in patients with adult spinal deformity (ASD). METHODS: We retrospectively reviewed patients who underwent ≥ 5-level fusion including the pelvis, for ASD with a ≥ 2-year follow-up. Using the Scoliosis Research Society-Schwab classification system, patients were classified into 3 groups according to the severity of the preoperative sagittal imbalance: mild, moderate, and severe. Postoperative clinical and radiographic results were compared among the 3 groups. RESULTS: A total of 259 patients were finally included. There were 42, 62, and 155 patients in the mild, moderate, and severe groups, respectively. The perioperative surgical burden was greatest in the severe group. Postoperatively, this group also showed the largest pelvic incidence minus lumbar lordosis mismatch, suggesting a tendency towards undercorrection. No statistically significant differences were observed in proximal junctional kyphosis, proximal junctional failure, or rod fractures among the groups. Visual analogue scale for back pain and Scoliosis Research Society-22 scores were similar across groups. However, severe group's last follow-up Oswestry Disability Index (ODI) scores significantly lower than those of the severe group. CONCLUSION: Patients with severe sagittal imbalance were treated with more invasive surgical methods along with increased the perioperative surgical burden. All patients exhibited significant radiological and clinical improvements after surgery. However, regarding ODI, the severe group demonstrated slightly worse clinical outcomes than the other groups, probably due to relatively higher proportion of undercorrection. Therefore, more rigorous correction is necessary to achieve optimal sagittal alignment specifically in patients with severe baseline sagittal imbalance.

Are Surgical Outcomes Different According to Baseline Balance Status in Elderly Patients with Degenerative Sagittal Imbalance?

STUDY DESIGN: Retrospective study. OBJECTIVE: We sought to compare surgical outcomes according to baseline balance statuses in elderly patients with degenerative sagittal imbalance (DSI). SUMMARY OF BACKGROUND: Although optimal sagittal correction has been emphasized for good surgical outcomes, the effect of the state of preoperative balance on surgical outcome has been adequately described at present. METHODS: Patients aged ≥60 years with DSI who underwent ≥5-level fusion to the sacrum were included. Among them, only those who postoperatively achieved the optimal age-adjusted pelvic incidence (PI) - lumbar lordosis (LL) target were included in this study. Study participants were divided into two groups according to their preoperative sagittal vertical axis (SVA): compensatory balance (SVA <5 cm, group CB) and decompensation (SVA ≥5 cm, group D). Comparisons between the two groups were performed using the chi-squared test or Fisher's exact test for categorical variables and the independent t- test or Wilcoxon rank- sum test for continuous variables. RESULTS: A total of 156 patients whose postoperative sagittal alignment matched the age-adjusted PI-LL target constituted the study cohort. There were 59 patients in group CB and 97 patients in group D. Mean follow-up duration was 50.0 months after surgery. Immediate postoperatively, sacral slope and SVA were significantly greater in group D than in group CB. At last follow-up, the SVA was significantly greater in group D than in group CB (43.6 vs. 22.7 mm), while no significant differences were found in other sagittal parameters. The Oswestry disability index and Scoliosis Research Society -22 scores at the last follow-up were significantly worse in group D than in group CB. CONCLUSION: The SVA tended to experience less correction postoperatively, with evidence of further deterioration during follow-up in group D than in group CB. This suboptimal correction of SVA may contribute to the inferior clinical outcomes encountered in group D relative to group CB. Therefore, we recommend correction of PI-LL as close as possible to the lower limit of the suggested PI-LL target range in patients with evidence of preoperative decompensation.

Discovery of aurones bearing two amine functionalities as SHIP2 inhibitors with insulin-sensitizing effect in rat myotubes.

Pharmacological inhibition of the SH2 domain-containing inositol 5-phosphatase 2 (SHIP2) by small-molecule compounds presents an attractive approach to modulate insulin sensitivity. Few drug-like SHIP2 inhibitors have been discovered to date. A series of aurones incorporating key motifs from known SHIP2 inhibitors were synthesized and evaluated for SHIP2-inhibiting activity against a recombinant SHIP2 protein in vitro. Three aurones that inhibited SHIP2 at 15-50 µM were identified. These aurone inhibitors required two amine functionalities, one at ring A and a second at ring B for good inhibitory activity as exemplified by 12a. Mechanistically, molecular dynamics simulations revealed 12a to preferably bind to an allosteric site, restricting the motion of the flexible L4 loop required for SHIP2 phosphatase activity. Additionally, a basic piperidine moiety of 12a interacted with an aspartate residue proximal to the site. At 20-40 µM, 12a significantly enhanced glucose uptake in rat myotubes via increased Akt phosphorylation. 12a showed good permeability across the Caco-2 cell monolayer supporting the aurone chemotype as a new lead to develop drug-like, oral insulin sensitizers.

Hook Fixation at Uppermost Instrumented Vertebra +1 Reduced Proximal Junctional Failure in Adult Patients With Spinal Deformity Having Achieved Optimal Deformity Correction by Sagittal Age-Adjusted Score.

BACKGROUND AND OBJECTIVES: Appropriate correction relative to the age-adjusted sagittal alignment target reduces the proximal junctional failure (PJF) risk. Nonetheless, a considerable number of patients suffer from PJF despite optimal correction. The aim of this study was to identify the risk factors of PJF that occurs despite optimal correction relative to the sagittal age-adjusted score (SAAS) in adult spinal deformity surgery. METHODS: Patients aged 60 years or older with adult spinal deformity who underwent ≥5-level fusion to the sacrum were initially screened. Among them, only patients who achieved optimal sagittal correction relative to the SAAS were included in the study. Optimal correction was defined as the SAAS point between -1 and +1. Various clinical and radiographic factors were compared between the PJF and no PJF groups and were further evaluated using multivariate analysis. RESULTS: The final study cohort comprised 127 patients. The mean age was 67 years, and there were 111 women (87.4%). A mean of total fusion length was 7.2. PJF occurred in 42 patients (33.1%), while 85 patients (66.9%) did not develop PJF. Multivariate analysis showed that a high body mass index (odds ratio [OR] = 1.153, 95% CI = 1.027-1.295, P = .016), a higher lordosis distribution index (LDI) (OR = 1.024, 95% CI = 1.003-1.045, P = .022), and no use of hook fixation (OR = 9.708, 95% CI = 1.121-76.923, P = .032) were significant risk factors of PJF development. In the receiver operating characteristic curve analysis, the cutoff value for the LDI was calculated as 61.0% (area under the curve = 0.790, P < .001). CONCLUSION: PJF developed in a considerable portion of patients despite optimal correction relative to the age-adjusted alignment. The risk factors of PJF in this patient group were high body mass index, high LDI exceeding 61%, and no use of hook fixation. PJF could be further decreased by properly managing these risk factors along with optimal sagittal correction.

Ideal Lumbar Lordosis Correction in Patients with Adult Spinal Deformity Without Adversely Impacting Pelvic Tilt and Pelvic Incidence Minus Lumbar Lordosis: A Study of 426 Cases.

STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the ideal pelvic incidence (PI) - lumbar lordosis (LL) range to prevent pelvic tilt (PT) undercorrection while avoiding PI-LL overcorrection following adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND: PI-LL and PT are the important sagittal parameters to be restored to an adequate range by surgery. Ideal PI-LL target without causing PI-LL overcorrection and PT undercorrection has not been documented. METHODS: We included patients with ASD undergoing ≥5-level fusion including the sacrum. Receiver operating characteristic (ROC) curve analysis was performed to calculate the lower limit of the ideal PI-LL without causing PI-LL overcorrection and the upper limit of ideal PI-LL without causing PT undercorrection. The calculated ideal PI-LL was validated in terms of proximal junctional kyphosis and failure (PJK and PJF) rates and clinical outcomes. Analyses were performed according to age subgroups (<70 and ≥70 y). RESULTS: In total, 426 patients were included in the study. Female patients were predominant (85.4%), with a mean age of 69.8 years. The lower limits of PI-LL were calculated as 4.9° for all patients, 2.3° for patients aged <70 years, and 7.9° for patients aged ≥70 years. Meanwhile, the upper limits of PI-LL were calculated as 12.7° for all patients, 12.5° for patients aged <70 years, and 13.3° for patients aged ≥70 years. There were no significant differences in the PJK and PJF rates among the new three PI-LL groups. Clinical outcomes were significantly better in patients with the ideal PI-LL group than those in patients with overcorrection or undercorrection groups for all age groups. CONCLUSION: The ideal PI-LL correction target without adversely impacting PT and PI-LL was calculated at 2.3°-12.5° for patients aged <70 years and 7.9°-13.3° for patients aged ≥70 years. These guideline parameters may help ensure optimal clinical outcomes without increasing the risk of PJK/F.

Percutaneous endobiliary radiofrequency ablation with stent placement in type IV hilar cholangiocarcinoma: A prospective comparison with stent placement alone.

OBJECTIVES: This study aimed to compare the safety and effectiveness of percutaneous endobiliary radiofrequency ablation with stent placement (RFA group) versus stent placement alone (stent group) in patients with type IV hilar cholangiocarcinoma. METHODS: This prospective nonrandomized study was conducted between October 2021 and April 2023. The study included 56 participants (33 men and 23 women, median age 73 years) who underwent percutaneous endobiliary RFA with stent placement (n = 25) or stent placement alone (n = 31) for type IV hilar cholangiocarcinoma. The primary end point was stent patency, while the secondary end points were procedure-related adverse events (AE) and overall survival. RESULTS: The percutaneous endobiliary RFA and/or stent placement were successfully completed in all patients in both groups. The median stent patency rate was higher in the RFA group than the stent group (188 days vs. 155 days, p = 0.048). There were no differences in AEs (grade 1 [5 in RFA group vs. 5 in stent group, p = 0.74] and grade 2 AEs [2 vs. 4, p = 0.68]) and patients' survival (median 222 days vs. 214 days, p = 0.49) between the two groups. CONCLUSIONS: In patients with type IV hilar cholangiocarcinoma, percutaneous endobiliary RFA with stent placement may improve stent patency without increasing the risk of AEs compared to stent placement alone.

A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory.

BACKGROUND & AIMS: Hepatocellular Carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma (AHCC) trials group (NCT03267641), we recruited one of the largest prospective cohorts of HCC with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provided a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort) IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected HCC, reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of Hepatocellular Carcinoma (HCC). These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for developing personalized therapies tailored to specific tumor evolutionary and transcriptomic profiles. The co-existence of multiple sub-types within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making.

Superselective Ablative Chemo-ethanol Embolization for Recurrent Single Hepatocellular Carcinoma: A Six-Month Outcome Analysis.

Background/Aim: To evaluate the safety and effectiveness of superselective ablative chemoethanol embolization (SACE) for the treatment of patients with recurrent single hepatocellular carcinoma (rHCC). Materials and Methods: This retrospective study included 22 patients (19 men, median age 63 [range 38-86 y]) with Child-Pugh class of A/B/C (16/3/3) that underwent SACE between January and June 2023 for recurrent single HCCs measuring ≤ 5 cm in diameter using a mixture of 99% Ethanol and ethiodized oil/doxorubicin emulsion. The primary endpoint was the 6-month tumor response, and the secondary endpoints were the 1-month tumor response and treatment-related safety. This study was approved by our institutional review board, and the requirement for informed consent was waived. Results: SACE was successfully performed in 22 (95.2%) patients. The complete response rates at 1-month and 6-month after treatment were 100% and 83.3%, respectively. At 6-month, local tumor progression occurred in one patient and intrahepatic distant metastasis was found in 6 (30%) patients. No 6-month mortalities were reported. No adverse events greater than grade 2 or laboratory deteriorations were observed. Biliary complications or liver abscesses were not observed. Conclusion: SACE for a single rHCC was highly effective in achieving a favorable 6-month tumor response and showed acceptable adverse events. However, further prospective studies are required to verify these findings.

Development of a Rabbit Iliac Arterial Stenosis Model Using a Controlled Cholesterol Diet and Pullover Balloon Injury.

Purpose: This study aimed to develop a rabbit iliac stenosis model and evaluate the effects of different mechanical injury techniques on the degree of arterial stenosis. Materials and Methods: Eighteen rabbits were divided into three groups: cholesterol-fed with pullover balloon injury (group A; n = 6), cholesterol-fed with localized balloon dilatation (group B; n = 6), and chow-diet with pullover balloon injury (group C; n = 6). After baseline angiography, the left iliac arteries of all rabbits were injured with a 3 × 10 mm noncompliant balloon using either a wide pullover technique (groups A and C) or a localized balloon dilatation technique (group B). A nine-week follow-up angiography was performed, and the angiographic late lumen loss and percentage of stenosis were compared. Results: Group A exhibited the most severe late lumen loss (A vs. B, 0.67 ± 0.13 vs. 0.04 ± 0.13 mm, p < 0.0001; A vs. C, 0.67 ± 0.13 vs. 0.26 ± 0.29 mm, p < 0.05; stenosis percentage 32.02% ± 6.54%). In contrast, group B showed a minimal percentage of stenosis (1.75% ± 6.55%). Conclusion: Pullover-balloon injury can lead to significant iliac artery stenosis in rabbits with controlled hypercholesterolemia. This model may be useful for elucidating the pathogenesis of atherosclerosis and for evaluating the efficacy of novel therapeutic interventions.

Copper/Polyaniline Interfaces Confined CO2 Electroreduction for Selective Hydrocarbon Production.

Polyaniline (PANI) provides an attractive organic platform for CO2 electrochemical reduction due to the ability to adsorb CO2 molecules and in providing means to interact with metal nanostructures. In this work, a novel PANI supported copper catalyst has been developed by coupling the interfacial polymerization of PANI and Cu. The hybrid catalyst demonstrates excellent activity towards production of hydrocarbon products including CH4 and C2H4, compared with the use of bare Cu. A Faradaic efficiency of 71.8 % and a current density of 16.9 mA/cm2 were achieved at -0.86 V vs. RHE, in contrast to only 22.2 % and 1.0 mA/cm2 from the counterpart Cu catalysts. The remarkably enhanced catalytic performance of the hybrid PANI/Cu catalyst can be attributed to the synergistic interaction between the PANI underlayer and copper. The PANI favours the adsorption and binding of CO2 molecules via its nitrogen sites to form *CO intermediates, while the Cu/PANI interfaces confine the diffusion or desorption of the *CO intermediates favouring their further hydrogenation or carbon-carbon coupling to form hydrocarbon products. This work provides insights into the formation of hydrocarbon products on PANI-modified Cu catalysts, which may guide the development of conducting polymer-metal catalysts for CO2 electroreduction.

Opicapone to Treat Early Wearing-off in Parkinson's Disease Patients: The Korean ADOPTION Trial.

BACKGROUND: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients. OBJECTIVES: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients. METHODS: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. RESULTS: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. CONCLUSIONS: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off.

Rosuvastatin Enhances Lymphangiogenesis after Myocardial Infarction by Regulating the miRNAs/Vascular Endothelial Growth Factor Receptor 3 (miRNAs/VEGFR3) Pathway.

BACKGROUND: Several clinical studies have suggested that the early administration of statins could reduce the risk of in-hospital mortality in acute myocardial infarction (AMI) patients. Recently, some studies have identified that stimulating lymphangiogenesis after AMI could improve cardiac function by reducing myocardial edema and inflammation. This study aimed to identify the effect of rosuvastatin on postinfarct lymphangiogenesis and to identify the underlying mechanism of this effect. METHOD: Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery in mice orally administered rosuvastatin for 7 days. The changes in cardiac function, pathology, and lymphangiogenesis following MI were measured by echocardiography and immunostaining. EdU, Matrigel tube formation, and scratch wound assays were used to evaluate the effect of rosuvastatin on the proliferation, tube formation, and migration of the lymphatic endothelial cell line SVEC4-10. The expression of miR-107-3p, miR-491-5p, and VEGFR3 was measured by polymerase chain reaction (PCR) and Western blotting. A gain-of-function study was performed using miR-107-3p and miR-491-5p mimics. RESULTS: The rosuvastatin-treated mice had a significantly improved ejection fraction and increased lymphatic plexus density 7 days after MI. Rosuvastatin also reduced myocardial edema and inflammatory response after MI. We used a VEGFR3 inhibitor to partially reverse these effects. Rosuvastatin promoted the proliferation, migration, and tube formation of SVEC4-10 cells. PCR and Western blot analyses revealed that rosuvastatin intervention downregulated miR-107-3p and miR-491-5p and promoted VEGFR3 expression. The gain-of-function study showed that miR-107-3p and miR-491-5p could inhibit the proliferation, migration, and tube formation of SVEC4-10 cells. CONCLUSION: Rosuvastatin could improve heart function by promoting lymphangiogenesis after MI by regulating the miRNAs/VEGFR3 pathway.

Post-infarction ventricular septal rupture complicated with cardiogenic shock and multiple organ hemorrhage: An autopsy case report.

Ventricular septal rupture (VSR) is a catastrophic mechanical complication of acute myocardial infarction (AMI) that can result in acute heart failure. Delaying operative intervention frequently leads to cardiogenic shock and multi-organ failure. Here we report a case of massive anterior MI complicated with VSR that was discovered through cardiac Doppler ultrasound and suspected multiple organ hemorrhage. The patient showed signs of rapid cardiogenic shock and eventually died. The morphological changes of VSR and MI were identified during necropsy, and microscopic examinations of the heart, brain, and kidney revealed multiple organ hemorrhage. This autopsy case suggested that the complication of VSR caused by AMI results in a reduction of oxygen and nutrient content of the circulating blood throughout the body and, eventually, functional failure of multiple organs. We provide clinical and pathological evidence elucidating changes in multiple organs under the severe condition of post-infarction VSR and demonstrate the consequences of a lack of immediate surgery and sufficient medical intervention for a patient suffering from AMI with VSR.

Risk factors of adjacent-segment disease after short-segment fusion in patients with de novo degenerative lumbar scoliosis.

OBJECTIVE: Short-segment fusion (SSF) is an effective surgical option for appropriately selected patients with de novo degenerative lumbar scoliosis (DNDLS). Considering that DNDLS is frequently accompanied by multisegment degeneration and potential instability across the entire lumbar segments, it is inevitable that unhealthy segments remain after SSF, thereby increasing the potential risk of adjacent-segment disease (ASD) occurrence. Therefore, the authors aimed to identify the risk factors for ASD in patients with DNDLS who underwent SSF. METHODS: This retrospective study included 80 patients with DNDLS (Cobb angle > 10°) who underwent SSF (1 or 2 levels) between December 2010 and July 2018 with a minimum follow-up duration of 5 years. The participants were divided into two groups: ASD and non-ASD. ASD was defined as clinical ASD rather than radiographic ASD. Various patient and operative variables were compared between the groups. Global and regional radiographic parameters (preoperatively and postoperatively) were also compared between the two groups using plain radiography and MRI. Consequently, univariate and multivariate analyses were conducted to identify the risk factors for ASD occurrence. The receiver operating characteristic (ROC) curve was used to calculate the cutoff values. RESULTS: The mean ± SD age was 67.7 ± 7.2 years at the time of SSF, and there were 62 women (77.5%) enrolled in the study. Thirty patients (37.5%) were in the ASD group and 50 patients (62.5%) were in the non-ASD group. The mean time from the surgery to ASD diagnosis was 34.9 ± 28.2 months in ASD group. Thirteen patients required revision surgery at a mean time of 8.8 ± 7.0 months after ASD occurrence. Multivariate logistic regression analysis demonstrated that preoperative disc wedging angle (OR 1.806, 95% CI 1.255-2.598, p = 0.001), presence of facet tropism (defined as ≥ 10° difference between the facet joint angles of the right and left sides) (OR 5.534, 95% CI 1.528-20.040, p = 0.009), and foraminal stenosis ≥ grade 2 (OR 5.935, 95% CI 1.253-28.117, p = 0.025) were significant risk factors for ASD development. The cutoff value of the preoperative disc wedging angle was calculated to be 2.5° using the ROC curve. CONCLUSIONS: Preoperative disc wedging angle ≥ 2.5°, presence of facet tropism, and foraminal stenosis ≥ grade 2 were identified as significant risk factors for ASD development after SSF in patients with DNDLS.

Transcatheter management of pure native aortic valve regurgitation in patients with left ventricular assist device.

OBJECTIVES: Aortic valve regurgitation (AR) frequently complicates the clinical course after left ventricular assist device (LVAD) implantation. Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement (SAVR) in this cohort with a mostly high surgical risk profile. The unique challenges in LVAD patients, such as presence of non-calcified aortic valves and annular dilatation, raise concerns about device migration and paravalvular leakage (PVL) leading to missing device success. This study evaluates procedural outcomes and survival rates in LVAD patients who underwent TAVI, emphasizing strategies to enhance device success. METHODS: Between January 2017 and April 2023, 27 LVAD patients with clinically significant AR underwent elective or urgent TAVI at our centre. Primary end-points were procedural success rates, without the need for a second transcatheter heart valve (THV) and postprocedural AR/PVL. Secondary outcomes included survival rates and adverse events. RESULTS: Among the cohort, 14.8% received AR-dedicated TAVI devices, with none requiring a second THV. There was no intraprocedural AR, and 1 patient (25%) had AR > 'trace' at discharge. Additionally, 25.9% underwent device landing zone (DLZ) pre-stenting with a standard TAVI device, all without needing a second THV. There was no intraprocedural AR, and none to trace AR at discharge. Among the 59.3% receiving standard TAVI devices, 37.5% required a second THV. In this subgroup, intraprocedural AR > 'trace' occurred in 12.5%, decreasing to 6.25% at discharge. In-hospital mortality was 3.7%, and median follow-up survival was 388 days (interquartile range 208-1167 days). CONCLUSIONS: TAVI yields promising procedural outcomes and early survival rates in LVAD patients with AR. Tailored TAVI devices and pre-stenting techniques enhance procedural success. Continued research into these strategies is essential to optimize outcomes in this complex patient cohort.

Physiochemical Coupled Dynamic Nanosphere Lithography Enabling Multiple Metastructures from Single Mask.

Metastructures are widely used in photonic devices, energy conversion, and biomedical applications. However, to fabricate multiple patterns continuously in single etching protocol with highly tunable photonic properties is challenging. Here, a simple and robust dynamic nanosphere lithography is proposed by inserting a spacer between the nanosphere assembly and the wafer. The nanosphere diameter decrease and uneven penetration of the spacer during etching lead to a dynamic masking process. Coupled anisotropic physical ion sputtering and ricocheting with isotropic chemical radical etching achieve highly tunable structures with various 3D patterns continuously forming through a single etching process. Specifically, the nanosphere diameters define the periodicity, the etched spacer forms the upper parts, and the wafer forms the lower parts. Each part of the structure is highly tunable through changing nanosphere diameter, spacer thickness, and etch conditions. Using this protocol, numerous structures of varying sizes including nanomushrooms, nanocones, nanopencils, and nanoneedles with diverse shapes are realized as proof of concepts. The broadband antireflection ability of the nanostructures and their use in surface-enhanced Raman spectroscopy are also demonstrated for practical application. This method substantially simplifies the fabrication procedure of various metastructures, paving the way for its application in multiple disciplines especially in photonic devices.

Predictor of Postoperative Ambulatory Recovery in Metastatic Spinal Cord Compression with Delayed Surgical Timing and Progressive Paraplegia.

OBJECTIVE: To analyze preoperative predictors of ambulatory recovery after surgical treatment in metastatic spinal cord compression (MSCC) patients with delayed surgical timing and progressive paraplegia. METHODS: We reviewed patients with a preoperative lower-extremity motor grade of ≤3 and surgical timing ≥48 hours after the nonambulatory status. The recovery group (group R) and nonrecovery group (group NR) were classified according to ambulation assessment during follow-up. The data on patient demographics, origin of the primary tumor, pre and postoperative chemotherapy and radiation therapy, surgical procedures, Tokuhashi score, Karnofsky score, preoperative lower-extremity motor grade, and surgical timing were collected for analyzing predictors of postoperative ambulatory recovery. RESULTS: Of the 55 patients, 24 (43.6%) were group R and 31 patients were group NR. The preoperative motor grade of the lower extremities was the only predictive factor (P < 0.05). The mean hip flexor and knee extensor motor grades in group R were 2.0 ± 1.0 and 2.4 ± 1.1 respectively, while in group NR, they were 1.2 ± 1.0 and 1.3 ± 1.0. The odds ratios for failing to regain ambulatory ability were 12.6 in the knee extensor and 4.8 in the hip flexor when the motor grades 0-2 and 3 groups were compared. The rescue ratio of the preoperative hip flexor and knee extensor motor grade 0-2 group were 34.1% and 21.2%, grades 3 group were 71.4% and 77.3%, respectively. CONCLUSIONS: The significant predictive factor for ambulatory recovery was the preoperative lower-extremity motor grade. The preoperative knee extensor motor grade was identified as a more important factor than hip flexor motor grade in predicting ambulatory recovery.

Assessing the impact of direct-acting antivirals on hepatitis C complications: a systematic review and meta-analysis.

Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.