Chromosomal instability induced in cancer can enhance macrophage-initiated immune responses that include anti-tumor IgG.

Solid tumors generally exhibit chromosome copy number variation, which is typically caused by chromosomal instability (CIN) in mitosis. The resulting aneuploidy can drive evolution and associates with poor prognosis in various cancer types as well as poor response to T-cell checkpoint blockade in melanoma. Macrophages and the SIRPα-CD47 checkpoint are understudied in such contexts. Here, CIN is induced in poorly immunogenic B16F10 mouse melanoma cells using spindle assembly checkpoint MPS1 inhibitors that generate persistent micronuclei and diverse aneuploidy while skewing macrophages toward a tumoricidal 'M1-like' phenotype based on markers and short-term anti-tumor studies. Mice bearing CIN-afflicted tumors with wild-type CD47 levels succumb similar to controls, but long-term survival is maximized by SIRPα blockade on adoptively transferred myeloid cells plus anti-tumor monoclonal IgG. Such cells are the initiating effector cells, and survivors make de novo anti-cancer IgG that not only promote phagocytosis of CD47-null cells but also suppress tumor growth. CIN does not affect the IgG response, but pairing CIN with maximal macrophage anti-cancer activity increases durable cures that possess a vaccination-like response against recurrence.

Chromosomal instability can favor macrophage-mediated immune response and induce a broad, vaccination-like anti-tumor IgG response.

Chromosomal instability (CIN), a state in which cells undergo mitotic aberrations that generate chromosome copy number variations, generates aneuploidy and is thought to drive cancer evolution. Although associated with poor prognosis and reduced immune response, CIN generates aneuploidy-induced stresses that could be exploited for immunotherapies. In such contexts, macrophages and the CD47-SIRPα checkpoint are understudied. Here, CIN is induced pharmacologically induced in poorly immunogenic B16F10 mouse melanoma cells, generating persistent micronuclei and diverse aneuploidy while skewing macrophages towards an anti-cancer M1-like phenotype, based on RNA-sequencing profiling, surface marker expression and short-term antitumor studies. These results further translate to in vivo efficacy: Mice bearing CIN-afflicted tumors with wild-type CD47 levels survive only slightly longer relative to chromosomally stable controls, but long-term survival is maximized when combining macrophage-stimulating anti-tumor IgG opsonization and some form of disruption of the CD47-SIRPα checkpoint. Survivors make multi-epitope, de novo anti-cancer IgG that promote macrophage-mediated phagocytosis of CD47 knockout B16F10 cells and suppress tumoroids in vitro and growth of tumors in vivo . CIN does not greatly affect the level of the IgG response compared to previous studies but does significantly increase survival. These results highlight an unexpected therapeutic benefit from CIN when paired with maximal macrophage anti-cancer activity: an anti-cancer vaccination-like antibody response that can lead to more durable cures and further potentiate cell-mediated acquired immunity.

Genetic heterogeneity in p53-null leukemia increases transiently with spindle assembly checkpoint inhibition and is not rescued by p53.

Chromosome gains or losses often lead to copy number variations (CNV) and loss of heterozygosity (LOH). Both quantities are low in hematologic "liquid" cancers versus solid tumors in data of The Cancer Genome Atlas (TCGA) that also shows the fraction of a genome affected by LOH is ~ one-half of that with CNV. Suspension cultures of p53-null THP-1 leukemia-derived cells conform to these trends, despite novel evidence here of genetic heterogeneity and transiently elevated CNV after perturbation. Single-cell DNAseq indeed reveals at least 8 distinct THP-1 aneuploid clones with further intra-clonal variation, suggesting ongoing genetic evolution. Importantly, acute inhibition of the mitotic spindle assembly checkpoint (SAC) produces CNV levels that are typical of high-CNV solid tumors, with subsequent cell death and down-selection to novel CNV. Pan-cancer analyses show p53 inactivation associates with aneuploidy, but leukemias exhibit a weaker trend even though p53 inactivation correlates with poor survival. Overexpression of p53 in THP-1 does not rescue established aneuploidy or LOH but slightly increases cell death under oxidative or confinement stress, and triggers p21, a key p53 target, but without affecting net growth. Our results suggest that factors other than p53 exert stronger pressures against aneuploidy in liquid cancers, and identifying such CNV suppressors could be useful across liquid and solid tumor types.

Differences in cell shape, motility, and growth reflect chromosomal number variations that can be visualized with live-cell ChReporters.

Chromosome numbers often change dynamically in tumors and cultured cells, which complicates therapy as well as understanding genotype-mechanotype relationships. Here we use a live-cell "ChReporter" method to identify cells with a single chromosomal loss in efforts to better understand differences in cell shape, motility, and growth. We focus on a standard cancer line and first show clonal populations that retain the ChReporter exhibit large differences in cell and nuclear morphology as well as motility. Phenotype metrics follow simple rules, including migratory persistence scaling with speed, and cytoskeletal differences are evident from drug responses, imaging, and single-cell RNA sequencing. However, mechanotype-genotype relationships between fluorescent ChReporter-positive clones proved complex and motivated comparisons of clones that differ only in loss or retention of a Chromosome-5 ChReporter. When lost, fluorescence-null cells show low expression of Chromosome-5 genes, including a key tumor suppressor APC that regulates microtubules and proliferation. Colonies are compact, nuclei are rounded, and cells proliferate more, with drug results implicating APC, and patient survival data indicating an association in multiple tumor-types. Visual identification of genotype with ChReporters can thus help clarify mechanotype and mechano-evolution.

Confinement plus myosin-II suppression maximizes heritable loss of chromosomes, as revealed by live-cell ChReporters.

The mechanical environment of a cell can have many effects, but whether it impacts the DNA sequence of a cell has remained unexamined. To investigate this, we developed a live-cell method to measure changes in chromosome numbers. We edited constitutive genes with GFP or RFP tags on single alleles and discovered that cells that lose Chromosome reporters (ChReporters) become non-fluorescent. We applied our new tools to confined mitosis and to inhibition of the putative tumor suppressor myosin-II. We quantified compression of mitotic chromatin in vivo and demonstrated that similar compression in vitro resulted in cell death, but also rare and heritable ChReptorter loss. Myosin-II suppression rescued lethal multipolar divisions and maximized ChReporter loss during three-dimensional (3D) compression and two-dimensional (2D) lateral confinement, but not in standard 2D culture. ChReporter loss was associated with chromosome mis-segregation, rather than just the number of divisions, and loss in vitro and in mice was selected against in subsequent 2D cultures. Inhibition of the spindle assembly checkpoint (SAC) caused ChReporter loss in 2D culture, as expected, but not during 3D compression, suggesting a SAC perturbation. Thus, ChReporters enable diverse studies of viable genetic changes, and show that confinement and myosin-II affect DNA sequence and mechano-evolution.

Face touch monitoring using an instrumented wristband using dynamic time warping and k-nearest neighbours.

One of the main factors in controlling infectious diseases such as COVID-19 is to prevent touching preoral and prenasal regions. Face touching is a habitual behaviour that occurs frequently. Studies showed that people touch their faces 23 times per hour on average. A contaminated hand could transmit the infection to the body by a facial touch. Since controlling this spontaneous habit is not easy, this study aimed to develop and validate a technology to detect and monitor face touch using dynamic time warping (DTW) and KNN (k-nearest neighbours) based on a wrist-mounted inertial measurement unit (IMU) in a controlled environment and natural environment trials. For this purpose, eleven volunteers were recruited and their hand motions were recorded in controlled and natural environment trials using a wrist-mounted IMU. Then the sensitivity, precision, and accuracy of our developed technology in detecting the face touch were evaluated. It was observed that the sensitivity, precision, and accuracy of the DTW-KNN classifier were 91%, 97%, and 85% in controlled environment trials and 79%, 92%, and 79% in natural environment trials (daily life). In conclusion, a wrist-mounted IMU, widely available in smartwatches, could detect the face touch with high sensitivity, precision, and accuracy and can be used as an ambulatory system to detect and monitor face touching as a high-risk habit in daily life.

Crosstalk between ERK and MRTF-A signaling regulates TGFß1-induced epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a physiological process that is essential during embryogenesis and wound healing and also contributes to pathologies including fibrosis and cancer. EMT is characterized by marked gene expression changes, loss of cell-cell contacts, remodeling of the cytoskeleton, and acquisition of enhanced motility. In the late stages of EMT, cells can exhibit myofibroblast-like properties with enhanced expression of the mesenchymal protein marker α-smooth muscle actin and contractile activity. Transforming growth factor (TGF)-ß1 is a well-known inducer of EMT and it activates a plethora of signaling cascades including extracellular signal-regulated kinase (ERK). Previous reports have demonstrated a role for ERK signaling in the early stages of EMT, but the molecular impacts of ERK signaling on the late stages of EMT are still unknown. Here, we found that inhibition of the phosphorylation of ERK enhances focal adhesions, stress fiber formation, cell contractility, and gene expression changes associated with TGFß1-induced EMT in mammary epithelial cells. These effects are mediated in part by the phosphorylation state and subcellular localization of myocardin-related transcription factor-A. These findings indicate that the intricate crosstalk between signaling cascades plays an important role in regulating the progression of EMT and suggests new approaches to control EMT processes.

Repigmentation in vitiligo using janus kinase (JAK) inhibitors with phototherapy: systematic review and Meta-analysis.

INTRODUCTION: Vitiligo is an autoimmune disorder characterized by progressive loss of melanocytes, leading to cutaneous depigmentation. Vitiligo has significant psychosocial impacts on patients and is challenging to manage with limited treatment options. Recent studies have suggested promising results for JAK1/3 inhibitors including tofacitinib and ruxolitinib. OBJECTIVE: To determine the expected response of vitiligo to JAK inhibitor therapy and factors which influence response rates. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines. Good response was defined as repigmentation >50% or a 'good' or 'excellent' outcome as described by authors. Partial response was defined as some repigmentation <50%. RESULTS: From the 9 eligible studies, individual patient data from 45 cases were pooled. Good response was achieved in 57.8%, partial response in 22.2%, and none or minimal response in 20% of cases. When subgrouped according to site, facial vitiligo had the highest good response rate (70%), compared to extremities (27.3%) and torso/non-sun exposed areas (13.6%). Concurrent phototherapy was significant associated with higher rates of good overall response (p < .001) and good facial response (p < .001). CONCLUSIONS: There is promising low-quality evidence regarding the effectiveness of JAK inhibitors in vitiligo. Concurrent UVB phototherapy appears to improve efficacy of JAK inhibitors for vitiligo.

Relationship between sagittal balance and adjacent segment disease in surgical treatment of degenerative lumbar spine disease: meta-analysis and implications for choice of fusion technique.

STUDY DESIGN: Meta-analysis. OBJECTIVE: To conduct a meta-analysis investigating the relationship between spinopelvic alignment parameters and development of adjacent level disease (ALD) following lumbar fusion for degenerative disease. ALD is a degenerative pathology that develops at mobile segments above or below fused spinal segments. Patient outcomes are worse, and the likelihood of requiring revision surgery is higher in ALD compared to patients without ALD. Spinopelvic sagittal alignment has been found to have a significant effect on outcomes post-fusion; however, studies investigating the relationship between spinopelvic sagittal alignment parameters and ALD in degenerative lumbar disease are limited. METHODS: Six e-databases were searched. Predefined endpoints were extracted and meta-analyzed from the identified studies. RESULTS: There was a significantly larger pre-operative PT in the ALD cohort versus control (WMD 3.99, CI 1.97-6.00, p = 0.0001), a smaller pre-operative SS (WMD - 2.74; CI - 5.14 to 0.34, p = 0.03), and a smaller pre-operative LL (WMD - 4.76; CI - 7.66 to 1.86, p = 0.001). There was a significantly larger pre-operative PI-LL in the ALD cohort (WMD 8.74; CI 3.12-14.37, p = 0.002). There was a significantly larger postoperative PI in the ALD cohort (WMD 2.08; CI 0.26-3.90, p = 0.03) and a larger postoperative PT (WMD 5.23; CI 3.18-7.27, p < 0.00001). CONCLUSION: The sagittal parameters: PT, SS, PI-LL, and LL may predict development of ALD in patients' post-lumbar fusion for degenerative disease. Decision-making aimed at correcting these parameters may decrease risk of developing ALD in this cohort. These slides can be retrieved under Electronic Supplementary Material.

Adenosine Testing After Atrial Fibrillation Ablation: Systematic Review and Meta-Analysis.

BACKGROUND: Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after pulmonary vein isolation (PVI) for the treatment of atrial fibrillation (AF). We performed a systematic review and meta-analysis to assess the impact of adenosine administration in patients undergoing PVI for AF. METHODS: Meta-analysis of 22 studies was performed to assess the rates of freedom from AF in 1) patients with dormant PV conduction versus patients without dormant PV conduction, and 2) patients given routine adenosine post PVI versus patients not given adenosine. Relative-risks (RR) were calculated using random effects modelling. RESULTS: In 18 studies, 3038 patients received adenosine and freedom from AF in those patients with dormant PV reconnection was significantly lower (62.9%) compared to patients without PV reconnection (67.2%) (RR 0.87; 95% CI: 0.78-0.98). In seven studies with 3049 patients, the freedom from AF was significantly higher in patients who received adenosine (67%) versus those patients who did not receive adenosine (63%) (RR: 1.11; 95% CI: 1.01-1.22). CONCLUSIONS: The present study showed clear benefits of adenosine testing for freedom from AF recurrence. Adenosine-guided dormant conduction is associated with higher AF recurrence despite further ablation. Future studies should investigate the optimal methodology, including dosage and waiting time between PVI and adenosine administration.

Implantable cardioverter defibrillator therapy in hypertrophic cardiomyopathy: an updated systematic review and meta-analysis of outcomes and complications.

BACKGROUND: Since the introduction of the implantable cardioverter-defibrillator (ICD) in patients with hypertrophic cardiomyopathy (HCM), the incidence of sudden cardiac death (SCD) has been significantly reduced. Given its widespread use, it is important to identify the outcomes associated with ICD use in patients with HCM. The present paper is a systematic review and meta-analysis of the rates of appropriate and inappropriate interventions, mortality, and device complications in HCM patients with an ICD. METHODS: We conducted a systematic review and meta-analysis on 27 studies reporting outcomes and complications after ICD implantation in patients with HCM. ICD interventions, device complications, and mortality were extracted for analysis. RESULTS: A total of 3,797 patients with HCM and ICD implantation were included (mean age, 44.5 years; 63% male), of which 83% of patients had an ICD for primary prevention of SCD. The cardiac mortality was 0.9% (95% CI: 0.7-1.3) per year and non-cardiac mortality was 0.8% (95% CI: 0.6-1.2) per year. Annualized appropriate intervention rate was 4.8% and annualized inappropriate intervention was 4.9%. The annual incidence of lead malfunction, lead displacement and infection was 1.4%, 1.3%, and 1.1%, respectively. CONCLUSIONS: ICD use in patients with HCM produces low rates of cardiac and non-cardiac mortality, and an appropriate intervention rate of 4.8% per year. However, moderate rates of inappropriate intervention and device complications warrant careful patient selection in order to optimize the risk to benefit ratio in this select group of patients.

A novel technique for placement of sacro-alar-iliac (S2AI) screws by K-wire insertion using intraoperative navigation.

Sacral-iliac fixation techniques may be indicated in the management of various lumbosacral pathologies including spinal degeneration, infection, tumour resection, fracture, pseudarthrosis, correction of spinal deformities involving long fusion constructs to the sacrum and cases with poor sacral fixation. There are a number of options for lumbosacral fixation each with their own advantages and disadvantages. Though S2-alar-iliac (S2AI) have demonstrated promising advantages over alternatives, the complex anatomy of the spinopelvic region demands precise insertion of the screws to create a biomechanically robust construct safely. As such, we present a novel technique of using intra-operative CT navigation and K-wires to establish and secure a planned trajectory, thereby ensuring solid spinopelvic fixation with S2AI screws. This was performed as part of a long fusion construct for correction of kyphosis deformity in a male patient.

Subsidence following anterior lumbar interbody fusion (ALIF): a prospective study.

BACKGROUND: Anterior lumbar interbody fusion (ALIF) is a widely used surgical technique for disorders of the lumbar spine. One potential complication is the subsidence of disc height in the post-operative period. Few studies have reported the rate of subsidence in ALIF surgery prospectively. We prospectively evaluated the rate of subsidence in adult patients undergoing ALIF. METHODS: Results were obtained by reviewing scans of 147 patients. Disc heights were measured on radiographic scans taken pre-operatively in addition to post-operatively immediately, at 6 weeks and at 18 months. The anterior and posterior intervertebral disc heights were measured. Subsidence was defined as greater than or equal to 2 mm loss of height. RESULTS: A total of 15 patients (10.2%) had subsidence, with 7 being male. Each case was of delayed cage subsidence (DCS) >6 weeks postoperatively. The mean subsidence was 4.7 mm (range, 2.4-7.8). Mean anterior disc height was 8.6±0.4 mm preoperatively, which improved to 15.1±0.5 mm at latest follow-up. Mean posterior disc height was 4.7±0.2 mm preoperatively, which improved to 8.7±0.4 mm at latest follow-up. The mean lumbar lordosis (LL) angle was 42.5°±10.8° and the mean local disc angle (LDA) was 6.7°±4.0°. The 91.2% (n=114/125) of patients with appropriate radiological follow-up demonstrated fusion by latest follow-up. There was no correlation between subsidence rate with patient reported outcomes [Visual Analog Scale (VAS), Oswestry Disability Index (ODI) and Short Form 12 Item survey (SF-12)] and fusion rates. There was a significant negative correlation between LL and extent of subsidence (Pearson correlation =-0.754, P=0.012). CONCLUSIONS: In conclusion, we found that the subsidence rate at follow-up was generally low following standalone ALIF for this patient series. Patient clinical outcomes and bony fusion rates were not significantly influenced by subsidence.

Flexible band versus rigid ring annuloplasty for tricuspid regurgitation: a systematic review and meta-analysis.

BACKGROUND: Up to 20% of patients have pre-discharge residual moderate to severe tricuspid regurgitation (TR) after tricuspid repair. Reoperations for recurrent TR carry high mortality rates, which emphasizes the importance of identifying the optimal technique for the surgical management of TR. The present study is a systematic review and meta-analysis that aims to compare short and long term survival and freedom from TR of flexible band ring versus rigid ring for annuloplasty of TR. METHODS: We conducted a systematic review and meta-analysis of comparative studies to evaluate these procedures. A systematic search of the literature was performed from six electronic databases. Pooled meta-analysis was conducted using odds ratio (OR) and weighted mean difference (WMD). RESULTS: The rates of in-hospital mortality were not different between the two groups, with cumulative rates of 6.9% for flexible band and 7.3% for rigid ring (OR: 0.92; 95% CI: 0.49-1.71). Rates of stroke were also similar with 1.7% of flexible band and 1.3% of rigid rings suffering a perioperative stroke (OR: 1.29; 95% CI: 0.74-2.23). Rigid ring had significantly better freedom from grade ≥2 TR at 5 years (OR: 0.44; 95% CI: 0.20-0.99) and overall (P=0.005). There was no significant difference in overall rates of reoperation (P=0.232) and survival (P=0.086) between flexible band and rigid ring. CONCLUSIONS: Both rigid ring and flexible band offer acceptable outcomes for the treatment of TR. Compared to flexible band, rates of TR are stable after rigid ring annuloplasty and long term freedom from TR are superior for rigid ring devices. Large prospective randomized trials are required in order to validate these findings and assess for improvements in patient survival.

Reconstruction of Thoracic Spine Using a Personalized 3D-Printed Vertebral Body in Adolescent with T9 Primary Bone Tumor.

BACKGROUND: Neurosurgery and spine surgery have the potential to benefit from the use of 3-dimensional printing (3DP) technology due to complex anatomic considerations and the delicate nature of surrounding structures. We report a procedure that uses a 3D-printed titanium T9 vertebral body implant post T9 vertebrectomy for a primary bone tumor. CASE DESCRIPTION: A 14-year-old female presented with progressive kyphoscoliosis and a pathologic fracture of the T9 vertebra with sagittal and coronal deformity due to a destructive primary bone tumor. Surgical resection and reconstruction was performed in combination with a 3D-printed, patient-specific implant. Custom design features included porous titanium end plates, corrective angulation of the implant to restore sagittal balance, and pedicle screw holes in the 3D implant to assist with insertion of the device. In addition, attachment of the anterior column construct to the posterior pedicle screw construct was possible due to the customized features of the patient-specific implant. CONCLUSIONS: An advantage of 3DP is the ability to manufacture patient-specific implants, as in the current case example. Additionally, the use of 3DP has been able to reduce operative time significantly. Surgical procedures can be preplanned using 3DP patient-specific models. Surgeons can train before performing complex procedures, which enhances their presurgical planning in order to maximize patient outcomes. When considering implants and prostheses, the use of 3DP allows a superior anatomic fit for the patient, with the potential to improve restoration of anatomy.

Evaluating Outcomes of Stand-Alone Anterior Lumbar Interbody Fusion: A Systematic Review.

BACKGROUND: Stand-alone anterior lumbar interbody fusion (ALIF) is an effective surgical approach for selected spinal pathologies. It avoids the morbidity and complications associated with instrumented ALIF, such as plate fixation and the traditionally used posterior approach. Despite improved disc space visualization and clearance, the associated posterior instability and increased risk of nonfusion present major challenges to this approach. The integral cage design aims to address these challenges by providing the necessary stabilization through intracorporeal screws. However, there is limited and controversial data available for stand-alone ALIF and integral cage fixation. To our knowledge, this is the first systematic review to evaluate recent findings on outcomes of stand-alone ALIF devices to explore areas of controversy and identify directions for future research. METHODS: Two reviewers conducted independent, systematic literature searches for appropriate studies in 5 electronic databases as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were filtered by the use of specified selection criteria, particularly exclusion of studies with supplementary fixation to ALIF and studies published before the year 2000. A total of 17 studies met the criteria, and their data were comprehensively extracted and analyzed. RESULTS: The current literature is supportive of stand-alone ALIF due to acceptable clinical outcomes, promising fusion rates and disc height restoration. However, data and outcomes remain preliminary, and there are numerous areas of controversy. CONCLUSIONS: There is evidence for the efficacy and safety of stand-alone ALIF. However, the extent of improvement based on specific indications for surgery remains unclear. Further investigation utilizing more methodologically rigorous studies of long-term outcomes is necessary to address these issues.

Impact of Elderly Age on Complications and Clinical Outcomes Following Anterior Lumbar Interbody Fusion Surgery.

BACKGROUND: Anterior lumbar interbody fusion (ALIF) is a surgical technique used to treat patients with a variety of lumbar pathologies. Identification of risk factors leading to complication following ALIF surgery may allow surgeons to better judge candidacy and optimize care for high-risk patients. METHODS: A retrospective analysis was conducted on a prospectively collected database of 137 patients who all underwent ALIF surgery by a single primary spine surgeon. Patients were separated into age-based cohorts (≤49, 50-63, and ≥64 years of age). Chi-squared, Fisher exact test, and multivariate logistic regression models were used to identify independent risk factors. RESULTS: A total of 137 patients met the inclusion criteria. Patients were divided into age-based tertiles as follows: Group 1 (<49 years old, n = 45, 32.8%), Group 2 (50-63 years old, n = 46, 33.6%), and Group 3 (64 years old, n = 46, 33.6%). Univariate analysis revealed increasing age (relative to Group 1) to be an independent risk factor for postoperative hematoma and delayed subsidence at 6 weeks and 12 weeks postoperatively compared with immediately post operation (all P < 0.05). No significant differences were found among the groups in terms of clinical outcome. Multivariate analysis also demonstrated increased age to be independently associated with greater prevalence of delayed subsidence (odds ratio 9.174, P = 0.029). CONCLUSIONS: Increased age was not associated with adverse perioperative outcomes and complications of ALIF. However, there was an increased incidence of delayed subsidence in patients ≥64 years old.

Ravitch versus Nuss procedure for pectus excavatum: systematic review and meta-analysis.

BACKGROUND: Pectus excavatum is the most common congenital chest wall deformity. The two most common surgical techniques for its correction are the modified Ravitch technique and the minimally invasive Nuss technique. Despite both procedures being used widely, data comparing them are scarce. METHODS: We conducted a systematic review and meta-analysis of comparative studies to evaluate these procedures. A systematic search of the literature was performed from six electronic databases. Pooled meta-analysis was conducted using odds ratio (OR) and weighted mean difference (WMD). RESULTS: A total of 13 studies comprising 1,432 pediatric (79.3%) and adult (20.7%) patients were identified, including 912 patients undergoing the Nuss procedure compared to 520 patients undergoing the Ravitch procedure. There was no significant difference found between the Nuss group versus Ravitch group in pediatric patients with regard to overall complications (OR =1.16; 95% CI: 0.61-2.19; I2=56%; P=0.65), reoperations (6.1% vs. 6.4%; OR =1.00; 95% CI: 0.40-2.50; I2=0%; P=1.00), wound infections (OR =0.58; 95% CI: 0.23-1.46; I2=0%; P=0.25), hemothorax (1.6% vs. 1.3%; OR =0.74; 95% CI: 0.21-2.65; I2=12%; P=0.64), pneumothorax (3.4% vs. 1.5%; OR =1.11; 95% CI: 0.42-2.93; I2=0%; P=0.83) or pneumonia (OR =0.15; 95% CI: 0.02-1.48; I2=0%; P=0.10). Adult patients undergoing the Nuss procedure had a higher incidence of overall complications (OR =3.26; 95% CI: 1.01-10.46; I2=0%; P=0.05), though there were far fewer studies that reported data. CONCLUSIONS: These results suggest no difference between the Nuss and Ravitch procedures for pediatric patients, while in adults the Ravitch procedure resulted in fewer complications.

Meta-analysis of stent-assisted coiling versus coiling-only for the treatment of intracranial aneurysms.

Endovascular coil embolization is a widely accepted and useful treatment modality for intracranial aneurysms. However, the principal limitation of this technique is the high aneurysm recurrence. The adjunct use of stents for coil embolization procedures has revolutionized the field of endovascular aneurysm management, however its safety and efficacy remains unclear. Two independent reviewers searched six databases from inception to July 2015 for trials that reported outcomes according to those who received stent-assisted coiling versus coiling-only (no stent-assistance). There were 14 observational studies involving 2698 stent-assisted coiling and 29,388 coiling-only patients. The pooled immediate occlusion rate for stent-assisted coiling was 57.7% (range: 20.2%-89.2%) and 48.7% (range: 31.7%-89.2%) for coiling-only, with no significant difference between the two (odds ratio [OR}=1.01; 95% confidence intervals [CI}: 0.68-1.49). However, progressive thrombosis was significantly more likely in stent-assisted coiling (29.9%) compared to coiling-only (17.5%) (OR=2.71; 95% CI: 1.95-3.75). Aneurysm recurrence was significantly lower in stent-assisted coiling (12.7%) compared to coiling-only (27.9%) (OR=0.43; 95% CI: 0.28-0.66). In terms of complications, there was no significant difference between the two techniques for all-complications, permanent complications or thrombotic complications. Mortality was significantly higher in the stent-assisted group 1.4% (range: 0%-27.5%) compared to the coiling-only group 0.2% (range: 0%-19.7%) (OR=2.16; 95% CI: 1.33-3.52). Based on limited evidence, stent-assisted coiling shows similar immediate occlusion rates, improved progressive thrombosis and decreased aneurysm recurrence compared to coiling-only, but is associated with a higher mortality rate. Future randomized controlled trials are warranted to clarify the safety of stent-associated coiling.