Are there differences in the reoperation rates for operative adjacent-segment disease between ALIF+PS, PLIF+PS, TLIF+PS, and LLIF+PS? An analysis of a cohort of 5291 patients.

OBJECTIVE: Biomechanical factors in lumbar fusions accelerate the development of adjacent-segment disease (ASD). Stiffness in the fused segment increases motion in the adjacent levels, resulting in ASD. The objective of this study was to determine if there are differences in the reoperation rates for symptomatic ASD (operative ASD) between anterior lumbar interbody fusion plus pedicle screws (ALIF+PS), posterior lumbar interbody fusion plus pedicle screws (PLIF+PS), transforaminal lumbar interbody fusion plus pedicle screws (TLIF+PS), and lateral lumbar interbody fusion plus pedicle screws (LLIF+PS). METHODS: A retrospective study using data from the Kaiser Permanente Spine Registry identified an adult cohort (≥ 18 years old) with degenerative disc disease who underwent primary lumbar interbody fusions with pedicle screws between L3 to S1. Demographic and operative data were obtained from the registry, and chart review was used to document operative ASD. Patients were followed until operative ASD, membership termination, the end of study (March 31, 2022), or death. Operative ASD was analyzed using Cox proportional hazards models. RESULTS: The final study population included 5291 patients with a mean ± SD age of 60.1 ± 12.1 years and a follow-up of 6.3 ± 3.8 years. There was a total of 443 operative ASD cases, with an overall incidence rate of reoperation for ASD of 8.37% (95% CI 7.6-9.2). The crude incidence of operative ASD at 5 years was the lowest in the ALIF+PS cohort (7.7%, 95% CI 6.3-9.4). In the adjusted models, the authors failed to detect a statistical difference in operative ASD between ALIF+PS (reference) versus PLIF+PS (HR 1.06 [0.79-1.44], p = 0.69) versus TLIF+PS (HR 1.03 [0.81-1.31], p = 0.83) versus LLIF+PS (HR 1.38 [0.77-2.46], p = 0.28). CONCLUSIONS: In a large cohort of over 5000 patients with an average follow-up of > 6 years, the authors found no differences in the reoperation rates for symptomatic ASD (operative ASD) between ALIF+PS and PLIF+PS, TLIF+PS, or LLIF+PS.

Improvements in Quality, Safety and Costs Associated with Use of Implant Registries Within a Health System.

BACKGROUND: Clinical quality registries (CQRs) are intended to enhance quality, safety, and cost reduction using real-world data for a self-improving health system. Starting in 2001, Kaiser Permanente established several medical device CQRs as a quality improvement initiative. This report examines the contributions of these CQRs on improvement in health outcomes, changes in clinical practice, and cost-effectiveness over the past 20 years. METHODS: Eight implant registries were instituted with standardized collection from the electronic health record and other institutional data sources of patient characteristics, medical comorbidities, implant attributes, procedure details, surgical techniques, and outcomes (including complications, revisions, reoperations, hospital readmissions, and other utilization measures). A rigorous quality control system is in place to improve and maintain the quality of data. Data from the Implant Registries form the basis for multiple quality improvement and patient safety initiatives to minimize variation in care, promote clinical best practices, facilitate recalls, perform benchmarking, identify patients at risk, and construct reports about individual surgeons. RESULTS: Following the inception of the Implant Registries, there was an observed (1) reduction in opioid utilization following orthopedic procedures, (2) reduction in use of bone morphogenic protein during lumbar fusion allowing for cost savings, (3) reduction in allograft for anterior cruciate ligament reconstruction and subsequent decrease in organizationwide revision rates, (4) cost savings through expansion of same-day discharge programs for joint arthroplasty, (5) increase in the use of cement fixation in the hemiarthroplasty treatment of hip fracture, and (6) organizationwide discontinuation of an endograft device associated with a higher risk for adverse outcomes following endovascular aortic aneurysm repair. CONCLUSION: The use of Implant Registries within our health system, along with clinical leadership and organizational commitment to a learning health system, was associated with improved quality and safety outcomes and reduced costs. The exact mechanisms by which such registries affect health outcomes and costs require further study.

Primary anterior lumbar interbody fusion, with and without posterior instrumentation: a 1,377-patient cohort from a multicenter spine registry.

BACKGROUND CONTEXT: Lumbar interbody instrumentation techniques are common and effective surgical options for a variety of lumbar degenerative pathologies. Anterior lumbar interbody fusion (ALIF) has become a versatile and powerful means of decompression, stabilization, and reconstruction. As an anterior only technique, the integrity of the posterior muscle and ligaments remain intact. Adding posterior instrumentation to ALIF is common and may confer benefits in terms of higher fusion rate but could contribute to adjacent segment degeneration due to additional rigidity. Large clinical studies comparing stand-alone ALIF with and without posterior supplementary fixation (ALIF+PSF) are lacking. PURPOSE: To compare rates of operative nonunion and adjacent segment disease (ASD) in ALIF with or without posterior instrumentation. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients (≥18 years old) who underwent primary ALIF for lumbar degenerative pathology between levels L4 to S1 over a 12-year period. Exclusion criteria included trauma, cancer, infection, supplemental decompression, noncontiguous fusions, prior lumbar fusions, and other interbody devices. OUTCOME MEASURES: Reoperation for nonunion and ASD compared between ALIF only and ALIF+PSF. METHODS: Reoperations were modeled as time-to-events where the follow-up time was defined as the difference between the primary ALIF procedure and the date of the outcome of interest. Crude cumulative reoperation probabilities were reported at 5-years follow-up. Multivariable Cox proportional hazard regression was used to evaluate risk of operative nonunion and for ASD adjusting for patient characteristics. RESULTS: The study consisted of 1,377 cases; 307 ALIF only and 1070 ALIF+PSF. Mean follow-up time was 5.6 years. The 5-year crude nonunion incidence was 2.4% for ALIF only and 0.5% for ALIF+PSF; after adjustment for covariates, a lower operative nonunion risk was observed for ALIF+PSF (HR=0.22, 95% CI=0.06-0.76). Of the patients who are deemed potentially suitable for ALIF alone, one would need to add posterior instrumentation in 53 patients to prevent one case of operative nonunion at a 5-year follow-up (number needed to treat). Five-year operative ASD incidence was 4.3% for ALIF only and 6.2% for ALIF+PSF; with adjustments, no difference was observed between the cohorts (HR=0.96, 95% CI=0.54-1.71). CONCLUSIONS: While the addition of posterior instrumentation in ALIFs is associated with lower risk of operative nonunion compared with ALIF alone, operative nonunion is rare in both techniques (<5%). Accordingly, surgeons should evaluate the added risks associated with the addition of posterior instrumentation and reserve the supplemental posterior fixation for patients that might be at higher risk for operative nonunion. Rates of operative ASD were not statistically higher with the addition of posterior instrumentation suggesting concern regarding future risk of ASD perhaps should not play a role in considering supplemental posterior instrumentation in ALIF.

Risk for surgical interventions following endovascular aneurysm repair with Endologix AFX or AFX2 Endovascular AAA Systems compared with other devices.

OBJECTIVE: To evaluate the risk for 90-day returns to care and long-term subsequent surgical interventions after primary endovascular aneurysm repair (EVAR) with an Endologix AFX Endovascular AAA System compared with three other high-volume endograft devices. METHODS: We conducted a matched cohort study using data from Kaiser Permanente's Endovascular Stent Graft Registry. Patients aged ≥18 years who underwent primary EVAR for AAA in the health care system from January 1, 2011, to December 31, 2017, comprised the eligible study sample. The treatment group included patients who received an Endologix AFX or AFX2 device (n = 470). Patients who received one of three other high-volume endograft devices used within the health care system comprised the eligible comparison group (n = 2122). These patients were 2:1 propensity score matched without replacement to patients who received an Endologix device based on a number of patient and procedural characteristics. After the application of matching, conditional logistic regression was used to evaluate the likelihood for 90-day emergency department visit and readmission. Cause-specific Cox regression was used to evaluate the long-term risk of endoleak, graft revision, secondary reintervention (not including revision), conversion to open repair, and rupture during follow-up. Cox proportional hazards regression was used to evaluate the risk of mortality (overall and aneurysm related). RESULTS: The final matched study sample included 470 patients who received an Endologix AFX or AFX2 device and 940 patients who received a different high-volume device. compared with the other devices, AFX/AFX2 had a higher risk for type III endoleak (hazard ratio [HR], 38.79; 95% confidence interval [CI], 14.51-103.67), revision surgery >1 year after the primary EVAR (HR, 4.50; 95% CI, 3.10-6.54), rupture (HR, 6.52; 95% CI, 1.73-24.63), and aneurysm-related mortality (HR, 2.43; 95% CI, 1.32-4.47) was observed with the use of AFX/AFX2. CONCLUSIONS: In our matched cohort study, patients who received an Endologix AFX System during their primary EVAR had a higher risk for several adverse longitudinal outcomes, as well as aneurysm-related mortality, when compared with patients who received other high-volume devices. Patients who have received these devices should be monitored closely after EVAR.

Lateral Mass Screws Versus Pedicle Screws at C7: Reoperation Rates for Operative Adjacent Segment Disease and Nonunion in Posterior Cervical Fusion.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To determine if there is a difference in reoperation rates for symptomatic adjacent segment disease (operative ASD) and symptomatic nonunions (operative nonunions) in posterior cervical fusions (PCFs) stopping at C7 using either lateral mass screws (LMS) or cervical pedicle screws (CPS) at C7. SUMMARY OF BACKGROUND DATA: Stopping PCFs at C7 has been controversial because of the risks of adjacent segment disease or nonunions. The two commonly used fixation techniques at the C7 level are LMS and CPS. MATERIALS AND METHODS: A retrospective analysis from the Kaiser Permanente Spine Registry identified a cohort of patients with cervical degenerative disk disease who underwent primary PCFs stopping at C7 with either LMS or CPS at C7. Demographic and operative data were extracted from the registry, and operative ASD and operative nonunions were adjudicated through chart review. Patients were followed until validated operative ASD or nonunion, membership termination, death, or end of study (March 31, 2022). Descriptive statistics and multivariable Cox proportional hazards models were calculated for operative ASDs and operative nonunions. RESULTS: We found 481 patients with PCFs stopping at C7 with either LMS (n=347) or CPS (n=134) at C7 with an average follow-up time of 5.6 (±3.8) years, time to operative ASD of 3.0 (±2.8) years, and to operative nonunion of 1.2 (±0.7) years. There were 11 operative ASDs (LMS=8, CPS=3) and eight operative nonunions (LMS=4, CPS=4). There was no statistical difference between patients stopping at C7 with LMS versus CPS for operative ASDs (HR: 0.68, 95% CI=0.17-2.77, P =0.60) or operative nonunions (HR: 2.09, 95% CI=0.45-8.58, P =0.37). CONCLUSION: A large cohort of patients with PCFs stopping at C7 with an average follow-up of > 5 years found no statistical difference in reoperation rates for symptomatic ASD (operative ASD) or operative nonunion using either LMS or CPS at C7.

Are Octogenarians at Higher Risk of Complications After Elective Lumbar Spinal Fusion Surgery? Analysis of a Cohort of 7880 Patients From the Kaiser Permanente Spine Registry.

STUDY DESIGN: A retrospective cohort study with chart review. OBJECTIVE: To determine if there is a difference in risk of adverse outcomes following elective posterior instrumented lumbar spinal fusions for patients aged 80 years and above compared with patients aged 50 to 79 years. SUMMARY OF BACKGROUND DATA: Patients aged 80 years and above are undergoing elective lumbar spinal fusion surgery in increasing numbers. There are conflicting data on the risks of intraoperative and postoperative complications in these patients. MATERIALS AND METHODS: Patients aged 80 years and above were compared with 50 to 79 years (reference group) using time-dependent multivariable Cox proportional hazards regression with a competing risk of death for longitudinal outcomes and multivariable logistic regression for binary outcomes. Outcome measures used were: (1) intraoperative complications (durotomy), (2) postoperative complications: 30-day outcomes (pneumonia); 90-day outcomes (deep vein thrombosis, pulmonary embolism, emergency room visits, readmission, reoperations, and mortality); and two-year outcomes (reoperations and mortality). RESULTS: The cohort consisted of 7880 patients who underwent primary elective posterior instrumented lumbar spinal fusion (L1-S1) for degenerative disk disease or spondylolisthesis. This was subdivided into 596 patients were aged 80 years and above and 7284 patients aged 50 to 79. After adjustment, patients aged 80 years and above had a higher likelihood of durotomy [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.02-2.02] and 30-day pneumonia (OR=1.81, 95% CI=1.01-3.23). However, there was a lower risk of reoperation within two years of the index procedure (hazard ratio=0.69, 95% CI=0.48-0.99). No differences were observed for mortality, readmissions, emergency room visits, pulmonary embolism, or deep vein thrombosis. CONCLUSIONS: In a cohort of 7880 elective posterior instrumented lumbar fusion patients for degenerative disk disease or spondylolisthesis, we did not observe any significant risks of adverse events between patients aged 80 years and above and those aged 50 to 79 except for higher durotomies and 30-day pneumonia in the former. We believe octogenarians can safely undergo lumbar fusions, but proper preoperative screening is necessary to reduce the risks of 30-day pneumonia.

Decreasing trends in reintervention and readmission after endovascular aneurysm repair in a multiregional implant registry.

OBJECTIVE: As endovascular aortic aneurysm repair (EVAR) matures into its third decade, measures such as long-term reintervention and readmission have become a focus of quality improvement efforts. Within a large United States integrated health care system, we describe time trends in the rates of long-term reinterventions utilization measures. METHODS: Data from a United States multiregional EVAR registry was used to perform a descriptive study of 3891 adults who underwent conventional infrarenal EVAR for infrarenal abdominal aortic aneurysm between 2010 and 2019. Three-year follow-up was 96.7%. Outcomes included 1-, 3-, and 5-year graft revision (defined as a procedure involving placement of a new endograft component), secondary interventions (defined as a procedure necessary for maintenance of EVAR integrity [eg, coil embolization and balloon angioplasty/stenting]), conversion to open, interventions for type II endoleaks alone, and 90-day readmission. Crude cause-specific reintervention probabilities were calculated by operative year using the Aalen-Johansen estimator, with death as a competing risk and December 31, 2020 as the study end date. RESULTS: Excluding interventions for type II endoleak alone, 1-year secondary intervention incidence decreased from 5.9% for EVARs in 2010 to 2.0% in 2019 (P < .001) and 3-year incidence decreased from 7.2% to 3.6% from 2010 to 2017 (P = .03). The 3-year incidences of graft revision (mean incidence, 3.4%) and conversion to open remained fairly stable (mean incidence, 0.6%) over time. The 3-year incidence of interventions for type II endoleak alone also decreased from 3.4% in 2010 to 0.7% in 2017 (P = .01). Ninety-day readmission rates decreased from 19.3% for index EVAR in 2010 to 9.2% in 2019 (P = .03). CONCLUSIONS: Comprehensive data from a multiregional health care system demonstrates decreasing long-term secondary intervention and readmission rates over time in patients undergoing EVAR. These trends are not explained by evolving management of type II endoleaks and suggest improving graft durability, patient selection, or surgical technique. Further study is needed to define implant and anatomic predictors of different types of long-term reintervention.

No Difference in Reoperation Rates for Adjacent Segment Disease (Operative Adjacent Segment Disease) in Posterior Cervical Fusions Stopping at C7 Versus T1/T2: A Cohort of 875 Patients-Part 1.

STUDY DESIGN: A retrospective cohort study with chart review. OBJECTIVE: To determine whether there is a difference in reoperation rates for adjacent segment disease ([ASD] operative ASD) in posterior cervical fusions (PCFs) that stop at -C7 versus -T1/T2. SUMMARY OF BACKGROUND DATA: There are surgical treatment challenges to the anatomical complexities of the cervicothoracic junction. Current posterior cervical spine surgery is based on the belief that ASD occurs if fusions are stopped at C7 although there is varying evidence to support this assumption. METHODS: Patients were followed until validated reoperations for ASD, membership termination, death, or March 31, 2020. Descriptive statistics and 5-year crude incidence rates and 95% confidence intervals for operative ASD for PCF ending at -C7 or -T1/T2 were reported. Time-dependent crude and adjusted multivariable Cox-Proportional Hazards models were used to evaluate operative ASD rates with adjustment for covariates or risk change estimates more than 10%. RESULTS: We identified 875 patients with PCFs (beginning at C3 or C4 or C5 or C6) stopping at either -C7 (n = 470) or -T1/T2 (n = 405) with average follow-up time of 4.6 (±3.3) years and average time to operative ASD of 2.7 (±2.8) years. Crude overall incidence rates for stopping at -C7 (2.12% [1.02%-3.86%]) and -T1/T2 (2.48% [1.25%-4.40%]) were comparable with no statistical difference in risk (adjusted hazard ratio = 1.47, 95% confidence interval = 0.61-3.53, P = 0.39). In addition, we observed no differences in the probability of operative ASD in competing risk time-dependent models (Grey test P  = 0.448). CONCLUSION: A large cohort of 875 patients with PCFs stopping at -C7 or -T1/T2 with an average follow-up of more than 4 years found no statistical difference in reoperation rates for ASD (operative ASD).Level of Evidence: 3.

No difference in reoperation rates for nonunions (operative nonunions) in posterior cervical fusions stopping at C7 versus T1/2: a cohort of 875 patients.

OBJECTIVE: The challenges of posterior cervical fusions (PCFs) at the cervicothoracic junction (CTJ) are widely known, including the development of adjacent-segment disease by stopping fusions at C7. One solution has been to cross the CTJ (T1/T2) rather than stopping at C7. This approach may have undue consequences, including increased reoperations for symptomatic nonunion (operative nonunion). The authors sought to investigate if there is a difference in operative nonunion in PCFs that stop at C7 versus T1/T2. METHODS: A retrospective analysis identified patients from the authors' spine registry (Kaiser Permanente) who underwent PCFs with caudal fusion levels at C7 and T1/T2. Demographics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Operative nonunion was adjudicated via chart review. Patients were followed until validated operative nonunion, membership termination, death, or end of study (March 31, 2020). Descriptive statistics and 2-year crude incidence rates and 95% confidence intervals for operative nonunion for PCFs stopping at C7 or T1/T2 were reported. Time-dependent crude and adjusted multivariable Cox proportional hazards models were used to evaluate operative nonunion rates. RESULTS: The authors identified 875 patients with PCFs (beginning at C3, C4, C5, or C6) stopping at either C7 (n = 470) or T1/T2 (n = 405) with a mean follow-up time of 4.6 ± 3.3 years and a mean time to operative nonunion of 0.9 ± 0.6 years. There were 17 operative nonunions, and, after adjustment for age at surgery and smoking status, the cumulative incidence rates were similar between constructs stopping at C7 and those that extended to T1/T2 (C7: 1.91% [95% CI 0.88%-3.60%]; T1/T2: 1.98% [95% CI 0.86%-3.85%]). In the crude model and model adjusted for age at surgery and smoking status, no difference in risk for constructs extended to T1/T2 compared to those stopping at C7 was found (adjusted HR 1.09 [95% CI 0.42-2.84], p = 0.86). CONCLUSIONS: In one of the largest cohort of patients with PCFs stopping at C7 or T1/T2 with an average follow-up of > 4 years, the authors found no statistically significant difference in reoperation rates for symptomatic nonunion (operative nonunion). This finding shows that there is no added risk of operative nonunion by extending PCFs to T1/T2 or stopping at C7.

Germline ERBB3 mutation in familial non-small-cell lung carcinoma: expanding ErbB's role in oncogenesis.

Lung cancer is the commonest cause of cancer deaths worldwide. Although strongly associated with smoking, predisposition to lung cancer is also heritable, with multiple common risk variants identified. Rarely, dominantly inherited non-small-cell lung cancer (NSCLC) has been reported due to somatic mutations in EGFR/ErbB1 and ERBB2. Germline exome sequencing was performed in a multi-generation family with autosomal dominant NSCLC, including an affected child. Tumour samples were also sequenced. Full-length wild-type (wtErbB3) and mutant ERBB3 (mutErbB3) constructs were transfected into HeLa cells. Protein expression, stability, and subcellular localization were assessed, and cellular proliferation, pAkt/Akt and pERK levels determined. A novel germline variant in ERBB3 (c.1946 T > G: p.Iso649Arg), coding for receptor tyrosine-protein kinase erbB-3 (ErbB3), was identified, with appropriate segregation. There was no loss-of-heterozygosity in tumour samples. Both wtErbB3 and mutErbB3 were stably expressed. MutErbB3-transfected cells demonstrated an increased ratio of the 80 kDa form (which enhances proliferation) compared with the full-length (180 kDa) form. MutErbB3 and wtErbB3 had similar punctate cytoplasmic localization pre- and post-epidermal growth factor stimulation; however, epidermal growth factor receptor (EGFR) levels decreased faster post-stimulation in mutErbB3-transfected cells, suggesting more rapid processing of the mutErbB3/EGFR heterodimer. Cellular proliferation was increased in mutErbB3-transfected cells compared with wtErbB3 transfection. MutErbB3-transfected cells also showed decreased pAkt/tAkt ratios and increased pERK/tERK 30 min post-stimulation compared with wtErbB3 transfection, demonstrating altered signalling pathway activation. Cumulatively, these results support this mutation as tumorogenic. This is the first reported family with a germline ERBB3 mutation causing heritable NSCLC, furthering understanding of the ErbB family pathway in oncogenesis.

Do PEEK Rods for Posterior Instrumented Fusion in the Lumbar Spine Reduce the Risk of Adjacent Segment Disease?

BACKGROUND: Polyetheretherketone (PEEK) rods were clinically introduced in the mid-2000s as an alternative to titanium (Ti) rods for posterior instrumented lumbar spine fusion, theorized to reduce the risk of adjacent segment disease (ASD). However, few studies have follow-up beyond 2 years. Consequently, we conducted a matched cohort study using data from Kaiser Permanente's spine registry to compare the 2 rod systems and risk for outcomes. METHODS: Patients aged ≥18 undergoing first posterior lumbar fusion for a degenerative diagnosis from 2009 to 2018 using either a PEEK or a Ti rod were identified. Fusions using Ti rods were 2:1 propensity score matched to PEEK rods on the following factors: patient age, body mass index, smoking, American Society of Anesthesiologists classification, diagnosis, interbody use, bone morphogenic protein use, number of levels fused, fusion levels, and operative year. The matched sample included 154 PEEK and 308 Ti fusions. We used Cox regression to evaluate ASD and nonunion, and logistic regression to evaluate 90-day emergency department (ED) visit, readmission, and complication. RESULTS: We did not observe a difference in risk for ASD (hazard ratio = 1.02, 95% confidence interval [CI] = 0.66-1.59) or ED visit (odds ratio [OR] = 0.88, 95% CI = 0.48-1.59). A lower likelihood of readmission (OR = 0.34, 95% CI = 0.13-0.94) was observed following PEEK fusion compared with Ti. No nonunions or 90-day complications were observed for the PEEK group; 5 (2-year cumulative incidence = 0.7%) nonunions and 4 (1.3%) complications were observed for the Ti group. CONCLUSIONS: Our multicenter study did not support the hypothesis that PEEK rods are associated with a lower ASD risk. Reasons for readmission need to be identified to better understand the differences observed here. Further study of patients with TLIF using Ti and PEEK rods and posterolateral fusion with Ti and PEEK rods is needed. CLINICAL RELEVANCE: The present study adds to the literature supporting their midterm effectiveness of PEEK rods compared with Ti rods for both their safety and their effectiveness at the 5-7-year follow-up. LEVEL OF EVIDENCE: 3.

PLF+PS or ALIF+PS: which has a lower operative nonunion rate? Analysis of a cohort of 2,061 patients from a National Spine Registry.

BACKGROUND CONTEXT: Although fusion rates in posterolateral lumbar fusions with pedicle screws (PLF+PS) and anterior lumbar interbody fusions with pedicle screws (ALIF+PS) have been reported, there has been no consensus on superiority with respect to clinical outcome and nonunion rates. Most studies determine nonunion rates based on radiographic studies; however, many of these nonunions are asymptomatic and may not require reoperations. Hence, a potentially more clinically useful measure is the reoperation rate for symptomatic nonunions, which we term the operative nonunion rate. PURPOSE: To determine if there is a difference in operative nonunion rates between PLF+PS versus ALIF+PS. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients (≥18 years old) with the diagnosis of lumbar spondylolisthesis or lumbar spinal stenosis who underwent primary elective PLF+PS and ALIF+PS for 1-level and 2-level fusions (L4-S1) between 2009 and 2018. OUTCOME MEASURES: Reoperation rates for symptomatic nonunions (ie, operative nonunion rates). METHODS: Patients were followed until validated operative nonunions, membership termination, death, or 03/31/2019. Descriptive statistics and 2-year incidence rates for operative nonunions were calculated by fusion-level, fusion type, and levels fused. Time-dependent multivariable Cox-Proportional Hazards regression was used to evaluate operative nonunion rates with adjustment for covariates or risk change estimates more than 10%. RESULTS: We identified 2,061 patients (PLF+PS:1,491, ALIF+PS:570) with average follow-up time of 4.8 (±3.1) years and average time to operative nonunion of 1.3 (±1.2) yrs. Comparatively, unadjusted 1-level and 2-level incidence rates for operative nonunions were higher in PLF+PS versus ALIF+PS. For 1-level procedures these were 0.9% (95% CI=0.4-1.6) versus 0.6% (95% CI=0.1-2.1); 2-level, 2.0% (95% CI=0.8-4.0) versus 0.9% (95% CI=0.1-3.3). However, there were no observed significant differences in risks for operative nonunions in multivariable models comparing PLF+PS versus ALIF+PS (HR=0.3, 95% CI=0.1-1.1), 1-level versus 2-level fusions (HR=1.8, 95% CI=0.8-4.3), or by fusion level (L4-L5: HR=1.0, 95% CI=0.4-2.7; L5-S1: HR=2.0, 95% CI=0.7-5.4). CONCLUSIONS: A large cohort of patients with lumbar fusions between L4 to S1 and an average follow-up of >4 years found that although there was a trend for higher operative nonunions in PLF+PS compared with ALIF+PS, this was not statistically significant. The role of spinal alignment was not investigated.

Midterm outcomes for 605 patients receiving Endologix AFX or AFX2 Endovascular AAA Systems in an integrated healthcare system.

BACKGROUND: Endologix issued important safety updates for the AFX Endovascular AAA System in 2016 and 2018 owing to the risk of type III endoleaks. Outcomes with these devices are limited to small case series with short-term follow-up. We describe the midterm outcomes for a large cohort of patients who received an Endologix AFX or AFX2 device. STUDY DESIGN: Data from an integrated healthcare system's implant registry, which prospectively monitors all patients after endovascular aortic repair, was used for this descriptive study. Patients undergoing endovascular aortic repair with three AFX System variations (Strata [AFX-S], Duraply [AFX-D], and AFX2 with Duraply [AFX2]) were identified (2011-2017). Crude cumulative event probabilities for endoleak (types I and III), major reintervention, conversion to open, rupture, and mortality (aneurysm related and all cause) were estimated. RESULTS: Among 605 patients, 375 received AFX-S, 197 received AFX-D, and 33 received AFX2. Median follow-up for the cohort was 3.9 (interquartile range, 2.5-5.1) years. The crude 2-year incidence of overall endoleak, any subsequent reintervention or conversion, and mortality was 8.8% (95% confidence interval [CI], 6.3-12.3), 12.0% (95% CI, 9.1-15.9), and 8.8% (95% CI, 6.3-12.2) for AFX-S. Respective estimates for AFX-D were 7.9% (95% CI, 4.8-13.0), 10.6% (95% CI, 6.9-16.1), and 9.7% (95% CI, 6.3-14.7); for AFX2, they were 14.1% (95% CI, 4.7-38.2), 16.2% (95% CI, 6.4-37.7), and 21.2% (95% CI, 10.7-39.4). CONCLUSIONS: The midterm outcomes of a large U.S. patient cohort with an Endologix AFX or AFX2 System demonstrate a concerning rate of adverse postoperative events. Patients with these devices should receive close clinical surveillance to prevent device-related adverse events.

Operative Nonunion Rates in Posterolateral Lumbar Fusions: Analysis of a Cohort of 2591 Patients from a National Spine Registry.

OBJECTIVE: Radiographic nonunion rates in the literature for posterolateral lumbar fusions with pedicle screws (PLFs) range from 8.1% to 43.3% but may not represent nonunion rates. A few small studies have reported reoperations for symptomatic nonunions (operative nonunions) to range from 3.2% to 13.9%. The objective of this study is to determine operative nonunion rates for 1-level, 2-level, 3-level, and ≥4-level PLFs and to determine the risks for these nonunions. METHODS: A retrospective cohort study, using data from the Kaiser Permanente Spine Registry, identified adult patients (≥18 years old) who underwent PLFs for degenerative disc disease. Multivariable Cox proportional hazards regression and Kaplan-Meier survival estimates using the log-rank statistic were used to evaluate operative nonunion rates. RESULTS: The cohort consisted of 2591 patients with single-level and multilevel PLFs with mean follow-up of 4.6 years, time to operative nonunion of 1.52 years, and 2-year operative nonunion rate of 1.08%. Compared with single-level fusions, patients with 3-level and ≥4-level fusion had 2.8 and 3.7 times higher risk of operative nonunions. Patients with PLFs involving L5-S1 had 2.5 times the risk of an operative nonunion compared with those without. CONCLUSIONS: Our study reports results from one of the largest cohort of patients for the first time with single-level and multilevel instrumented PLFs and found a 2-year operative nonunion rate of 1.08% with increased risk of nonunion for constructs that included L5-S1 and ≥3-level fusions. Operative nonunion combines clinical and radiographic data and provides an alternative measure of fusion rates.

Multiple Endocrine Tumors Associated with Germline MAX Mutations: Multiple Endocrine Neoplasia Type 5?

CONTEXT: Pathogenic germline MAX variants are associated with pheochromocytoma and paraganglioma (PPGL), pituitary neuroendocrine tumors and, possibly, other endocrine and nonendocrine tumors. OBJECTIVE: To report 2 families with germline MAX variants, pheochromocytomas (PCs) and multiple other tumors. METHODS: Clinical, genetic, immunohistochemical, and functional studies at University hospitals in Australia on 2 families with germline MAX variants undergoing usual clinical care. The main outcome measures were phenotyping; germline and tumor sequencing; immunohistochemistry of PC and other tumors; functional studies of MAX variants. RESULTS: Family A has multiple individuals with PC (including bilateral and metastatic disease) and 2 children (to date, without PC) with neuroendocrine tumors (paravertebral ganglioneuroma and abdominal neuroblastoma, respectively). One individual has acromegaly; immunohistochemistry of PC tissue showed positive growth hormone-releasing hormone staining. Another individual with previously resected PCs has pituitary enlargement and elevated insulin-like growth factor (IGF-1). A germline MAX variant (c.200C>A, p.Ala67Asp) was identified in all individuals with PC and both children, with loss of heterozygosity in PC tissue. Immunohistochemistry showed loss of MAX staining in PCs and other neural crest tumors. In vitro studies confirmed the variant as loss of function. In Family B, the proband has bilateral and metastatic PC, prolactin-producing pituitary tumor, multigland parathyroid adenomas, chondrosarcoma, and multifocal pulmonary adenocarcinomas. A truncating germline MAX variant (c.22G>T, p.Glu8*) was identified. CONCLUSION: Germline MAX mutations are associated with PCs, ganglioneuromas, neuroblastomas, pituitary neuroendocrine tumors, and, possibly, parathyroid adenomas, as well as nonendocrine tumors of chondrosarcoma and lung adenocarcinoma, suggesting MAX is a novel multiple endocrine neoplasia gene.

PLF Versus PLIF and the Fate of L5-S1: Analysis of Operative Nonunion Rates Among 3065 Patients with Lumbar Fusions from a Regional Spine Registry.

STUDY DESIGN: A retrospective cohort study with chart review. OBJECTIVE: The aim of this study was to compare the reoperation rates for symptomatic nonunions (operative nonunion rates) between posterolateral fusions with pedicle screws (PLFs) and posterior interbody fusion with pedicle screws (PLIFs). SUMMARY OF BACKGROUND DATA: Although radiographic nonunions in PLFs and PLIFs are well documented in the literature, there is no consensus on which technique has lower nonunions. Since some radiographic nonunions may be asymptomatic, a more clinically useful measure is operative nonunions, of which there is minimal research. METHODS: A retrospective cohort study, using data from the Kaiser Permanente Spine Registry, identified adult patients (≥18 years' old) who had elective single and multilevel PLFs and PLIFs. Descriptive statistics and 2-year incidence rates for operative nonunions were calculated by fusion-level (1-3), fusion type (PLF vs. PLIF), and levels fused (L3 to S1). Time-dependent multivariable Cox-Proportional Hazards regression was used to evaluate nonunion reoperation rates with adjustment for covariates. RESULTS: The cohort consisted of 3065 patients with PLFs (71.6%) and PLIFs (28.4%). Average age was 65.0 ±â€Š11.7, average follow-up time was 4.8 ±â€Š3.1 years, and average time to operative nonunion was 1.6 (±1.3) years. Single and multilevel incidence rates for nonunions after PLF versus PLIF were similar except for three-level fusions (2.9% [95% confidence interval, CI = 1.0-6.7] vs. 7.1% [95% CI = 0.2-33.9]). In adjusted models, there was no difference in risk of operative nonunions in PLIF compared to PLF (hazard ratio [HR]: 0.8, 95% CI = 0.4-1.6); however, patients with L5-S1 constructs with PLFs had 2.8 times the risk of operative nonunion compared to PLIFs (PLF: HR = 2.8, 95% CI = 1.3-6.2; PLIF: HR = 1.5, 95% CI = 0.4-5.1). CONCLUSION: In a large cohort of patients with >4 years of follow-up, we found no difference in operative nonunions between PLF and PLIF except for constructs that included L5-S1 in which the risk of nonunion was limited to PLF patients.Level of Evidence: 3.

Early revision in anatomic total shoulder arthroplasty in osteoarthritis: a cross-registry comparison.

BACKGROUND: We evaluated anatomic total shoulders undergoing early revision (less than two years) in the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and the Kaiser Permanente Shoulder Arthroplasty Registry (KPSAR). METHODS: A cross-sectional comparison of both registries was performed between the years of 2009 and 2012. Only patients who underwent anatomic total shoulder arthroplasty for a primary diagnosis of osteoarthritis were included. Aggregate-level data of patients undergoing early revisions done within two years of index arthroplasty were evaluated, and descriptive analysis was conducted. RESULTS: During the study period, 4614 patients were identified in the AOANJRR compared to 2036 in the KPSAR. Rotator cuff pathology, component loosening, and prosthetic instability were among the most common reasons for revision in both registries. A higher rate of revision in the AOANJRR was found to be secondary to the failure of one specific prosthesis, which has since been discontinued. DISCUSSION: Comparing reasons for early revision in total shoulder arthroplasty revealed several similarities between the AOANJRR and KPSAR. Differences were also noted, and this study served to highlight the importance prosthesis selection can play in determining outcomes. Cooperation among registries may allow for earlier identification of risk factors for failure in shoulder arthroplasty.

Does the use of preoperative bisphosphonates in patients with osteopenia and osteoporosis affect lumbar fusion rates? Analysis from a national spine registry.

OBJECTIVE: Bisphosphonates are used to increase bone strength in treating osteopenia and osteoporosis, but their use for increasing lumbar fusion rates has been controversial. The objective of this study was to determine if preoperative treatment with bisphosphonates affects the reoperation rates for nonunions (operative nonunion rates) following lumbar fusions in patients with osteopenia or osteoporosis. METHODS: The authors conducted a cohort study using data from the Kaiser Permanente Spine Registry. Patients (aged ≥ 50 years) with a diagnosis of osteopenia or osteoporosis who underwent primary elective lumbar fusions for degenerative disc disease, deformity, or spondylolisthesis were included in the cohort. Repeated spinal procedures at the index lumbar levels were noted through chart review. Reoperations for symptomatic nonunions (operative nonunions), time to nonunion, and the nonunion spine level(s) were also identified. The crude 2-year cumulative incidence of operative nonunions was calculated as 1 minus the Kaplan-Meier estimator. Cox proportional hazard regression was used to evaluate the association between preoperative bisphosphonate use and operative nonunion after adjustment for covariates. Analysis was stratified by osteopenia and osteoporosis diagnosis. RESULTS: The cohort comprised 1040 primary elective lumbar fusion patients, 408 with osteopenia and 632 with osteoporosis. Ninety-seven (23.8%) patients with osteopenia and 370 (58.5%) patients with osteoporosis were preoperative bisphosphonate users. For the osteopenia group, no operative nonunions were observed in patients with preoperative bisphosphonate, while the crude 2-year incidence was 2.44% (95% CI 0.63-4.22) in the nonuser group. For the osteoporotic group, after adjustment for covariates, no difference was observed in risk for operative nonunions between the preoperative bisphosphonate users and nonusers (HR 0.96, 95% CI 0.20-4.55, p = 0.964). CONCLUSIONS: To the authors' knowledge, this study presents one of the largest series of patients with the diagnosis of osteopenia or osteoporosis in whom the effects of preoperative bisphosphonates on lumbar fusions were evaluated using operative nonunion rates as an outcome measure. The results indicate that preoperative bisphosphonate use had no effect on the operative nonunion rates for patients with osteoporosis. Similar indications were not confirmed in osteopenia patients because of the low nonunion frequency. Further studies are warranted to the determine if preoperative and postoperative timing of bisphosphonate use has any effect on lumbar fusion rates.

Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant mutations in one of 13 confirmed genes. Estimates of MODY prevalence vary widely, as genetic screening is usually restricted based on clinical features, even in population studies. We aimed to determine prevalence of MODY variants in a large and unselected pediatric diabetes cohort. METHODS: MODY variants were assessed using massively parallel sequencing in the population-based diabetes cohort (n = 1363) of the sole tertiary pediatric diabetes service for Western Australia (population 2.6 million). All individuals were screened, irrespective of clinical features. MODY variants were also assessed in a control cohort (n = 993). RESULTS: DNA and signed consent were available for 821 children. Seventeen children had pathogenic/likely pathogenic variants in MODY genes, two diagnosed with type 2 diabetes, four diagnosed with antibody-negative type 1 diabetes (T1DM), three diagnosed with antibody-positive T1DM, and eight previously diagnosed with MODY. Prevalence of MODY variants in the sequenced cohort was 2.1%, compared to 0.3% of controls. CONCLUSIONS: This is the first comprehensive study of MODY variants in an unselected population-based pediatric diabetes cohort. The observed prevalence, increasing access to rapid and affordable genetic screening, and significant clinical implications suggest that genetic screening for MODY could be considered for all children with diabetes, irrespective of other clinical features.

Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia.

BACKGROUND: Acromelic dysplasias are a group of disorders characterised by short stature, brachydactyly, limited joint extension and thickened skin and comprises acromicric dysplasia (AD), geleophysic dysplasia (GD), Myhre syndrome and Weill-Marchesani syndrome. Mutations in several genes have been identified for these disorders (including latent transforming growth factor ß (TGF-ß)-binding protein-2 (LTBP2), ADAMTS10, ADAMSTS17 and fibrillin-1 (FBN1) for Weill-Marchesani syndrome, ADAMTSL2 for recessive GD and FBN1 for AD and dominant GD), encoding proteins involved in the microfibrillar network. However, not all cases have mutations in these genes. METHODS: Individuals negative for mutations in known acromelic dysplasia genes underwent whole exome sequencing. RESULTS: A heterozygous missense mutation (exon 14: c.2087C>G: p.Ser696Cys) in latent transforming growth factor ß (TGF-ß)-binding protein-3 (LTBP3) was identified in a dominant AD family. Two distinct de novo heterozygous LTPB3 mutations were also identified in two unrelated GD individuals who had died in early childhood from respiratory failure-a donor splice site mutation (exon 12 c.1846+5G>A) and a stop-loss mutation (exon 28: c.3912A>T: p.1304*Cysext*12). CONCLUSIONS: The constellation of features in these AD and GD cases, including postnatal growth retardation of long bones and lung involvement, is reminiscent of the null ltbp3 mice phenotype. We conclude that LTBP3 is a novel component of the microfibrillar network involved in the acromelic dysplasia spectrum.