The cumulative incidence and risk factors associated with 5-year conversion to knee arthroplasty following primary meniscus repair or primary meniscectomy.

Background: This study aimed to observe the 5-year knee arthroplasty conversion incidence rate and associated risk factors in patients who underwent meniscus procedures. Methods: Using a national database, we analyzed patients who had undergone primary meniscus repair or meniscectomy without prior knee surgeries. The cumulative knee arthroplasty conversion incidence was determined via Kaplan Meier analysis. Risk factors for conversion within 5 years were assessed using a Cox proportional hazard ratio model, with results as hazard ratios (HR). Results: 8125 patients had meniscus repair, while 240,209 had meniscectomy. 5-year conversion rates: repair 1.7%, meniscectomy 8.4%. Arthroplasty likelihood decreased as age decreased for repair (70+ [HR: 162.20]; 60-69 [HR: 81.64]; 50-59 [HR: 49.85]; 40-49 [HR: 17.79]; p < 0.001 all). Additional risk factors included male sex (HR: 0.35; p < 0.001) and higher Charlson Comorbidity Index (CCI) (CCI1 [HR: 1.28; p = 0.012]). For meniscectomy, arthroplasty likelihood also decreased with age (70+ [HR: 99.41]; 60-69 [HR: 84.57]; 50-59 [HR: 66.60]; 40-49 [HR: 36.15]; 30-39 [HR: 10.18]; p < 0.001 all). Additional risk factors included male sex (HR: 0.68; p < 0.001), obesity (HR: 1.18; p < 0.001), smoking (HR: 0.1.12; p = 0.010), and higher CCI (CCI1 [HR: 1.25]; CCI2 [HR 1.39]; CCI3+ [HR 1.46]; p < 0.001 all). Conclusion: This study revealed the national 5-year conversion incidence following primary meniscus repair (1.7%) and meniscectomy (8.4%). It also enhanced understanding of age, sex, obesity, smoking, comorbidities (CCI), and knee arthroplasty likelihood after meniscus procedures.

Prior Fragility Fractures are Associated With Higher Risk of Bone Health-Related Complications Within 8-Years Following Lumbar Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: To determine the 8-year risk of revision lumbar fusion, pseudoarthrosis, mechanical failure, fragility fracture, and vertebral compression fracture in patients with a prior fragility fracture compared to those without. SUMMARY OF BACKGROUND DATA: Osteoporosis is a known modifiable risk factor for revision following lumbar fusion due to inadequate fixation. Patients with prior fragility fractures have been shown to have increased bone health-related complications following various orthopedic surgeries, however there is a paucity of literature that identifies these complications in patients undergoing lumbar fusion. METHODS: Patients aged 50 years and older who underwent elective lumbar fusion were identified in a large national database and stratified based on whether they sustained a fragility fracture within 3 years prior to fusion. These patients were propensity-score matched to a control based on age, gender, and Charlson Comorbidity Index (CCI) using a 1:1 ratio. Kaplan-Meier and Cox Proportional Hazards analyses were used to observe the cumulative incidences and risk of complications within 8-years of index surgery. RESULTS: After matching, 8,805 patients were included in both cohorts. Patients who sustained a prior fragility fracture had a higher risk of revision (Hazard Ratio [HR]: 1.46; 95% Confidence Interval [CI]: 1.26-1.69; P<0.001), pseudoarthrosis (HR: 1.31; 95% CI: 1.17-1.48; P<0.001), mechanical failure (HR: 2.08; 95% CI: 1.78-2.45; P<0.001), secondary fragility fracture (HR: 6.36; 95% CI: 5.86-6.90; P<0.001), and vertebral compression fracture (HR: 7.47; 95% CI: 7.68-8.21; P<0.001) when compared to the control cohort. CONCLUSION: Patients who sustain a fragility fracture prior to lumbar fusion have an increased risk of revision, pseudoarthrosis, and mechanical failure within 8 years. Surgeons should be aware of this high-risk patient population and consider bone health screening and treatment to reduce these preventable complications.

The Association of Prior Fragility Fractures on 8-Year Periprosthetic Fracture Risk Following Total Hip Arthroplasty.

BACKGROUND: Fragility fractures are often the initial clinical presentation of osteoporosis. Patients who have a history of fragility fractures undergoing total hip arthroplasty (THA) have an increased risk of 2-year postoperative complications. However, the association of recent fragility fractures with complications beyond 2 years following THA remains unknown. The purpose of this study was to characterize the association of prior fragility fractures with 8-year risks of revision THA, periprosthetic fracture (PPF), and secondary fragility fracture. METHODS: Patients aged 50 years and more who underwent THA for osteoarthritis were identified in a large national database. Patients were stratified based on whether they sustained a fragility fracture within 3 years prior to THA. There were 18,529 patients who had a prior fragility fracture and 408,753 who did not have a prior fragility fracture. Demographics and comorbidities were collected. Kaplan-Meier and Cox Proportional Hazards analyses were used to observe the cumulative incidences of all-cause revision, PPF, and secondary fragility fracture within 8 years of index surgery. RESULTS: Patients who had recent fragility fracture had significantly higher risks of revision THA (Hazard Ratio [HR] 1.7; P < .001), PPF (HR 2.2; P < .001), and secondary fragility fracture (HR 4.9; P < .001). CONCLUSION: Prior fragility fracture was shown to be a significant risk factor for revision THA, PPF, and secondary fragility fracture within 8 years of THA. Identification of these high-risk patients with an emphasis on preoperative and postoperative bone health optimization may help minimize these complications.

Surgical strategies for older patients with glioblastoma.

OBJECTIVE: While adjuvant treatment regimens have been modified for older patients with glioblastoma (GBM), surgical strategies have not been tailored. METHODS: Clinical data of 48 consecutive patients aged 70 years or older, who underwent surgical resection for GBM with intraoperative ultrasonography (IoUS) alone or combination with intraoperative MRI (IoMRI) at Yale New Haven Hospital were retrospectively reviewed. Variables were analyzed, and comparative analyses were performed. RESULTS: The addition of IoMRI was not superior to IoUS alone in terms of overall survival (OS) (P = 0.306), Karnofsky Performance Score (KPS) at postoperative 6 weeks (P = 0.704) or extent of resection (P = 0.263). Length of surgery (LOSx), however, was significantly longer (P = 0.0002) in the IoMRI group. LOSx (P = 0.015) and hospital stay (P = 0.025) were predictors of postoperative complications. Increased EOR (GTR or NTR) (P = 0.030), postoperative adjuvant treatment (P < 0.0001) and postoperative complications (P = 0.006) were predictive for OS. Patients with relatively lower preoperative KPS scores (<70) showed significant improvement at postoperative 6 weeks (P<0.0001). Patients with complications (P = 0.038) were more likely to have lower KPS at postoperative 6 weeks. CONCLUSIONS: Aggressive management with surgical resection should be considered in older patients with GBM, even those with relatively poor KPS. The use of ioMRI in this population does not appear to confer any measurable benefit over ioUS in experienced hands, but prolongs the length of surgery significantly, which is a preventable prognostic factor for impeding care.

The Clinical Implications of Spontaneous Hemorrhage in Vestibular Schwannomas.

Background Spontaneous hemorrhage into vestibular schwannomas (VSs) is rare and can render more rapid symptom onset and a seemingly poorer prognosis for an otherwise benign pathology. We describe our series of hemorrhagic VS (HVSs) and systematically reviewed the literature to better understand relevant clinical factors and outcomes. Methods Retrospective case review series and systematic review of the literature using PRISMA guidelines. Results Fifty-three patients with HVS met inclusion criteria. Compared with historical data for all VS, patients with HVS had relatively higher rates of perioperative mortality, significant preoperative facial weakness, and harbored relatively larger tumors. Regardless of the extent of resection (EOR), surgery for HVS resulted in significant improvement of facial weakness ( p = 0.041), facial numbness ( p < 0.001), vertigo ( p < 0.001), and headache ( p < 0.001). Patients with facial weakness tended to have larger tumors ( p = 0.058) on average and demonstrated significant improvement after surgery, irrespective of EOR ( p < 0.01). The use of blood-thinning medications did not affect patient health outcome. Histopathology of HVS samples showed an increased number of dilated/ectatic thin-walled vascular channels, reflective of potentially increased vascular permeability and hypervascularity. Conclusion HVS may be an aggressive subgroup of VS, associated with a surprisingly high mortality rate. When features of HVS are identified on imaging, these patients should be treated expeditiously, especially given that facial nerve dysfunction, which is identified in more than half of patients with HVS, appears to be reversible. Overall, this study has significant implications in the management of VS, raising awareness of a small, but highly morbid subgroup.

Clinical and genomic factors associated with seizures in meningiomas.

OBJECTIVE: The association of seizures with meningiomas is poorly understood. Moreover, any relationship between seizures and the underlying meningioma genomic subgroup has not been studied. Herein, the authors report on their experience with identifying clinical and genomic factors associated with preoperative and postoperative seizure presentation in meningioma patients. METHODS: Clinical and genomic sequencing data on 394 patients surgically treated for meningioma at Yale New Haven Hospital were reviewed. Correlations between clinical, histological, or genomic variables and the occurrence of preoperative and postoperative seizures were analyzed. Logistic regression models were developed for assessing multiple risk factors for pre- and postoperative seizures. Mediation analyses were also conducted to investigate the causal pathways between genomic subgroups and seizures. RESULTS: Seventeen percent of the cohort had presented with preoperative seizures. In a univariate analysis, patients with preoperative seizures were more likely to have tumors with a somatic NF2 mutation (p = 0.020), WHO grade II or III tumor (p = 0.029), atypical histology (p = 0.004), edema (p < 0.001), brain invasion (p = 0.009), and worse progression-free survival (HR 2.68, 95% CI 1.30-5.50). In a multivariate analysis, edema (OR 3.11, 95% CI 1.46-6.65, p = 0.003) and atypical histology (OR 2.00, 95% CI 1.03-3.90, p = 0.041) were positive predictors of preoperative seizures, while genomic subgroup was not, such that the effect of an NF2 mutation was indirectly mediated through atypical histology and edema (p = 0.012). Seizure freedom was achieved in 83.3% of the cohort, and only 20.8% of the seizure-free patients, who were more likely to have undergone gross-total resection (p = 0.031), were able to discontinue antiepileptic drug use postoperatively. Preoperative seizures (OR 3.54, 95% CI 1.37-9.12, p = 0.009), recurrent tumors (OR 2.89, 95% CI 1.08-7.74, p = 0.035), and tumors requiring postoperative radiation (OR 2.82, 95% CI 1.09-7.33, p = 0.033) were significant predictors of postoperative seizures in a multivariate analysis. CONCLUSIONS: Seizures are relatively common at meningioma presentation. While NF2-mutated tumors are significantly associated with preoperative seizures, the association appears to be mediated through edema and atypical histology. Patients who undergo radiation and/or have a recurrence are at risk for postoperative seizures, regardless of the extent of resection. Preoperative seizures may indeed portend a more potentially aggressive molecular entity and challenging clinical course with a higher risk of recurrence.

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

OBJECTIVE: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. METHODS: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. RESULTS: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. CONCLUSIONS: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

Bee pathogen transmission dynamics: deposition, persistence and acquisition on flowers.

Infectious diseases are a primary driver of bee decline worldwide, but limited understanding of how pathogens are transmitted hampers effective management. Flowers have been implicated as hubs of bee disease transmission, but we know little about how interspecific floral variation affects transmission dynamics. Using bumblebees ( Bombus impatiens), a trypanosomatid pathogen ( Crithidia bombi) and three plant species varying in floral morphology, we assessed how host infection and plant species affect pathogen deposition on flowers, and plant species and flower parts impact pathogen survival and acquisition at flowers. We found that host infection with Crithidia increased defaecation rates on flowers, and that bees deposited faeces onto bracts of Lobelia siphilitica and Lythrum salicaria more frequently than onto Monarda didyma bracts . Among flower parts, bracts were associated with the lowest pathogen survival but highest resulting infection intensity in bee hosts. Additionally, we found that Crithidia survival across flower parts was reduced with sun exposure. These results suggest that efficiency of pathogen transmission depends on where deposition occurs and the timing and place of acquisition, which varies among plant species and environmental conditions. This information could be used for development of wildflower mixes that maximize forage while minimizing disease spread.

Rev7 and 53BP1/Crb2 prevent RecQ helicase-dependent hyper-resection of DNA double-strand breaks.

Poly(ADP ribose) polymerase inhibitors (PARPi) target cancer cells deficient in homology-directed repair of DNA double-strand breaks (DSBs). In preclinical models, PARPi resistance is tied to altered nucleolytic processing (resection) at the 5' ends of a DSB. For example, loss of either 53BP1 or Rev7/MAD2L2/FANCV derepresses resection to drive PARPi resistance, although the mechanisms are poorly understood. Long-range resection can be catalyzed by two machineries: the exonuclease Exo1, or the combination of a RecQ helicase and Dna2. Here, we develop a single-cell microscopy assay that allows the distinct phases and machineries of resection to be interrogated simultaneously in living S. pombe cells. Using this assay, we find that the 53BP1 orthologue and Rev7 specifically repress long-range resection through the RecQ helicase-dependent pathway, thereby preventing hyper-resection. These results suggest that 'rewiring' of BRCA1-deficient cells to employ an Exo1-independent hyper-resection pathway is a driver of PARPi resistance.