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.

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.

Does previous asbestos exposure increase the risk of a post coronary artery bypass graft (CABG) pleural effusion - a routine data study?

BACKGROUND: Development of pleural effusion (PE) following CABG is common. Post-CABG PE are divided into early- (within 30 days of surgery) and delayed-onset (30 days-1 year) which are likely due to distinct pathological processes. Some experts suggest asbestos exposure may confer an independent risk for late-onset post-CABG PE, however no large studies have explored this potential association. RESEARCH QUESTION: To explore possible association between asbestos exposure and post-CABG PE using routine data. METHODS: All patients who underwent CABG 01/04/2013-31/03/2018 were identified from the Hospital Episode Statistics (HES) Database. This England-wide population was evaluated for evidence of asbestos exposure, pleural plaques or asbestosis and a diagnosis of PE or PE-related procedure from 30 days to 1 year post-CABG. Patients with evidence of PE three months prior to CABG were excluded, as were patients with a new mesothelioma diagnosis. RESULTS: 68,150 patients were identified, of whom 1,003 (1%) were asbestos exposed and 2,377 (3%) developed late-onset PE. After adjusting for demographic data, Index of Multiple Deprivation and Charlson Co-morbidity Index, asbestos exposed patients had increased odds of PE diagnosis or related procedure such as thoracentesis or drainage (OR 1.35, 95% CI 1.03-1.76, p = 0.04). In those with evidence of PE requiring procedure alone, the adjusted OR was 1.66 (95% CI 1.14-2.40, p = 0.01). Additional subgroup analysis of the 518 patients coded for pleural plaques and asbestosis alone revealed an adjusted OR of post-CABG PE requiring a procedure of 2.16 (95% CI 1.38-3.37, p = 0.002). INTERPRETATION: This large-scale study demonstrates prior asbestos exposure is associated with modestly increased risk of post-CABG PE development. The risk association appears higher in patients with assigned clinical codes indicative of radiological evidence of asbestos exposure (pleural plaques or asbestosis). This association may fit with a possible inflammatory co-pathogenesis, with asbestos exposure 'priming' the pleura resulting in greater propensity for PE evolution following the physiological insult of CABG surgery. Further work, including prospective studies and clinicopathological correlation are suggested to explore this further.

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.

Real-world bleeding in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and prescribed different combinations of dual antiplatelet therapy (DAPT) in England: a population-based cohort study emulating a 'target trial'.

OBJECTIVE: To estimate the incidence and HRs for bleeding for different dual antiplatelet therapies (DAPT) in a real-world population with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in England. DESIGN: A retrospective, population-based cohort study emulating a target randomised controlled trial (tRCT). DATA SOURCES: Linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). SETTING: Primary and secondary care. PARTICIPANTS: Patients ≥18 years old with ACS undergoing emergency PCI. INTERVENTIONS: Aspirin and clopidogrel (AC, reference) versus aspirin and prasugrel (AP) or aspirin and ticagrelor (AT); AP evaluated only in patients with ST-elevation myocardial infarction (STEMI). MAIN OUTCOME MEASURES: Primary: any bleeding up to 12 months after the index event (HES- or CPRD- recorded). Secondary: HES-recorded bleeding, CPRD-recorded bleeding, all-cause and cardiovascular mortality, mortality from bleeding, myocardial infarction, stroke, additional coronary intervention and major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: In ACS, the rates of any bleeding for AC and AT were 89 per 1000 person years and 134 per 1000 person years, respectively. In STEMI, rates for AC, AP and AT were 93 per 1000 person years, 138 per 1000 person years and 143 per 100 person years, respectively. In ACS, compared with AC, AT increased the hazard of any bleeding (HR: 1.47, 95% CI 1.19 to 1.82) but did not reduce MACCE (HR: 1.06, 95% CI 0.89 to 1.27). In STEMI, compared with AC, AP and AT increased the hazard of any bleeding (HR: 1.77, 95% CI 1.21 to 2.59 and HR: 1.50, 95% CI 1.10 to 2.05, respectively) but did not reduce MACCE (HR: 1.10, 95% CI 0.80 to 1.51 and HR: 1.21, 95% CI 0.94 to 1.51, respectively). Non-adherence to the prescribed DAPT regimen was 28% in AC (29% in STEMI only), 31% in AP (STEMI only) and 33% in AT (32% in STEMI only). CONCLUSIONS: In a real-world population with ACS, DAPT with ticagrelor or prasugrel are associated with increased bleeding compared with DAPT with clopidogrel. TRIAL REGISTRATION NUMBER: ISRCTN76607611.

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.

Efficacy of Infliximab Dose Escalation in Patients with Refractory Immunotherapy-Related Colitis: A Case Series.

Immune checkpoint inhibitor-related colitis is a common complication of immunotherapy use in patients with cancer. Current guidelines recommend treatment with standard dose infliximab (IFX) for corticosteroid-refractory colitis; however, this case series suggests IFX dose escalation may be a viable treatment option for refractory cases.

Prediction of Bleeding in Pediatric Cardiac Surgery Using Clinical Characteristics and Prospective Coagulation Test Results.

Bleeding caused by coagulopathy is common in children undergoing cardiac surgery and causes adverse outcomes. Coagulation testing assists selection of treatments to stop bleeding but has an uncertain role for predicting bleeding. We aimed to evaluate how well prospective coagulation testing predicted excessive bleeding during and after cardiac surgery compared to prediction using clinical characteristics alone. The study was a single-center, prospective cohort study in children having a range of cardiac surgery procedures with coagulation testing at anesthetic induction and immediately after cardiopulmonary bypass. The primary outcome was clinical concern about bleeding (CCB), a composite of either administration of prohemostatic treatments in response to bleeding or a high chest drain volume after surgery. In 225 children, CCB occurred in 26 (12%) during surgery and in 68 (30%) after surgery. Multivariable fractional polynomial models using the clinical characteristics of the children alone predicted CCB during surgery (c-statistic 0.64; 95% confidence interval 0.53, 0.76) and after surgery (0.74; 0.67, 0.82). Incorporating coagulation test results into these models improved prediction (c-statistics 0.79; 0.70, 0.87, and 0.80; 0.74, 0.87, respectively). However, this increased the overall proportion of children classified correctly as CCB or not CCB during surgery by only 0.9% and after surgery by only 0.4%. Incorporating coagulation test results into predictive models had no effect on prediction of blood transfusion or postoperative complications. Prospective coagulation testing marginally improves prediction of CCB during and after cardiac surgery but the clinical impact of this is small when compared to prediction using clinical characteristics.

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.

Efficacy and safety of vedolizumab and infliximab treatment for immune-mediated diarrhea and colitis in patients with cancer: a two-center observational study.

BACKGROUND: Current treatment guidelines for immune-mediated diarrhea and colitis (IMDC) recommend steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) for refractory cases. We aimed to compare the efficacy of these two SITs and their impact on cancer outcomes. METHODS: We performed a two-center, retrospective observational cohort study of patients with IMDC who received SITs following steroids from 2016 to 2020. Patients' demographic, clinical, and overall survival data were collected and analyzed. RESULTS: A total of 184 patients (62 vedolizumab, 94 infliximab, 28 combined sequentially) were included. The efficacy of achieving clinical remission of IMDC was similar (89% vs 88%, p=0.79) between the two groups. Compared with the infliximab group, the vedolizumab group had a shorter steroid exposure (35 vs 50 days, p<0.001), fewer hospitalizations (16% vs 28%, p=0.005), and a shorter hospital stay (median 10.5 vs 13.5 days, p=0.043), but a longer time to clinical response (17.5 vs 13 days, p=0.012). Longer durations of immune checkpoint inhibitors treatment (OR 1.01, p=0.004) and steroid use (OR 1.02, p=0.043), and infliximab use alone (OR 2.51, p=0.039) were associated with higher IMDC recurrence. Furthermore, ≥3 doses of SIT (p=0.011), and fewer steroid tapering attempts (p=0.012) were associated with favorable overall survival. CONCLUSIONS: Treatment with vedolizumab as compared with infliximab for IMDC led to comparable IMDC response rates, shorter duration of steroid use, fewer hospitalizations, and lower IMDC recurrence, though with slightly longer time to IMDC response. Higher number of SIT doses was associated with better survival outcome, while more steroid exposure resulted in worse patient outcomes.

Pre-admission interventions (prehabilitation) to improve outcome after major elective surgery: a systematic review and meta-analysis.

OBJECTIVE: To determine the benefits and harms of pre-admission interventions (prehabilitation) on postoperative outcomes in patients undergoing major elective surgery. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs) (published or unpublished). We searched Medline, Embase, CENTRAL, DARE, HTA and NHS EED, The Cochrane Library, CINAHL, PsychINFO and ISI Web of Science (June 2020). SETTING: Secondary care. PARTICIPANTS: Patients (≥18 years) undergoing major elective surgery (curative or palliative). INTERVENTIONS: Any intervention administered in the preoperative period with the aim of improving postoperative outcomes. OUTCOMES AND MEASURES: Primary outcomes were 30-day mortality, hospital length of stay (LoS) and postoperative complications. Secondary outcomes included LoS in intensive care unit or high dependency unit, perioperative morbidity, hospital readmission, postoperative pain, heath-related quality of life, outcomes specific to the intervention, intervention-specific adverse events and resource use. REVIEW METHODS: Two authors independently extracted data from eligible RCTs and assessed risk of bias and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation. Random-effects meta-analyses were used to pool data across trials. RESULTS: 178 RCTs including eight types of intervention were included. Inspiratory muscle training (IMT), immunonutrition and multimodal interventions reduced hospital LoS (mean difference vs usual care: -1.81 days, 95% CI -2.31 to -1.31; -2.11 days, 95% CI -3.07 to -1.15; -1.67 days, 95% CI -2.31 to -1.03, respectively). Immunonutrition reduced infective complications (risk ratio (RR) 0.64 95% CI 0.40 to 1.01) and IMT, and exercise reduced postoperative pulmonary complications (RR 0.55, 95% CI 0.38 to 0.80, and RR 0.54, 95% CI 0.39 to 0.75, respectively). Smoking cessation interventions reduced wound infections (RR 0.28, 95% CI 0.12 to 0.64). CONCLUSIONS: Some prehabilitation interventions may reduce postoperative LoS and complications but the quality of the evidence was low. PROSPERO REGISTRATION NUMBER: CRD42015019191.

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.

A family with partially penetrant multicentric carpotarsal osteolysis due to gonadal mosaicism: First reported case.

Multicentric carpotarsal osteolysis (MCTO) is an autosomal dominant condition characterized by carpal-tarsal abnormalities; over half of affected individuals also develop renal disease. MCTO is caused by mutations of MAFB; however, there is no clear phenotype-genotype correlation. We describe the first reported family of variable MCTO phenotype due to mosaicism: the proband had classical skeletal features and renal involvement due to focal segmental glomerulosclerosis (FSGS), and the father had profound renal impairment due to FSGS, necessitating kidney transplantation. Mosaicism was first suspected in this family due to unequal allele ratios in the sequencing chromatograph of the initial blood sample of proband's father and confirmed by sequencing DNA extracted from the father's hair, collected from different bodily parts. This case highlights the need for a high index of clinical suspicion to detect low-level parental mosaicism, as well as a potential role for MAFB mutation screening in individuals with isolated FSGS.

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.

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.