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Background: Pedicle screws are widely used in spinal surgery. There is extensive published literature concerning the use of pedicle screw instrumentation for spinal surgery in adults. Now there is a trend to use pedicle screws in pediatric patients, including the very young. A systematic review of the current English-language literature on the use of pedicle screw instrumentation in the pediatric age group was performed to specifically determine (1) the pedicle screw placement accuracy in patients with spine deformity and (2) the effect size of all-pedicle screw constructs compared with other methods of spinal instrumentation in terms of the percentage of scoliosis correction.Methods: English-language studies of pedicle screw use in pediatric patients (defined as those younger than eighteen years of age) were included. Descriptive statistics synthesized the accuracy of pedicle screw placement. Accuracy rates were compared between pediatric and adult patients. The effect of pedicle screw instrumentation on scoliosis correction was calculated with use of Cobb angle measurements.Results: On the basis of the literature search, 1181 articles were screened, 320 abstracts were examined, and ninety full-text articles representing 5761 patients were reviewed in detail. Seventeen studies met the inclusion criteria for the analysis of pedicle screw placement accuracy. A total of 13,536 pedicle screws were placed in 1353 pediatric patients. The overall placement accuracy rate in pediatric patients was 94.9%, which was higher than the rate of 91.5% reported for adults. The weighted, geometric, and 5% trimmed mean accuracy rates of pedicle screw placement were 91.9%, 88.5%, and 89.1%, respectively (standard deviation = 10%; interquartile range = 10%). Sixteen comparative studies met the inclusion criteria for the analysis of the effect of pedicle screw instrumentation on scoliosis correction. Pedicle screw constructs had a significantly larger percentage of Cobb angle correction compared with hooks (Cohen's d = 1.14) and hybrid constructs (Cohen's d = 0.49).Conclusions: The accuracy of pedicle screw placement in the pediatric spine exceeds the accuracy rate reported in adults. Pedicle screw instrumentation constructs are significantly more effective for scoliosis correction, as determined on the basis of Cobb angle measurements, than are hook constructs and hybrid constructs. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: This is a retrospective cohort study examining 61 patients with neurogenic scoliosis who underwent anterior and/or posterior spinal instrumentation at the age of 18 and younger. OBJECTIVE: The purpose of this study is to investigate this finding further by analyzing the effect of recombinant human erythropoietin (rhEPO) on hematocrit, transfusion and complication rates, and the length of intensive care unit (ICU) days in patients with neurogenic scoliosis. SUMMARY OF BACKGROUND DATA: The preoperative use of rhEPO has been shown to decrease perioperative transfusion requirements in many adult and pediatric patients. A recent study at our institution demonstrated the efficacy of rhEPO in pediatric idiopathic scoliosis patients, but suggested the possibility of an 'erythropoietin resistance' in the pediatric neurogenic scoliosis population. METHODS: The patients' age at the time of surgery, gender, Cobb angle, erythropoietin administration and dosage, hematocrit levels, type of surgery, intraoperative blood loss, duration of surgery, number of vertebrae fused, comorbidities, complications, transfusion status, and the length of ICU days were collected. RESULTS: Thirty-five (57.3%) children received preoperative rhEPO, whereas 26 patients (42.7%) did not receive rhEPO. The mean preoperative and discharge hematocrit levels in the patients treated with rhEPO were significantly higher than the non-rhEPO group (P = 0.05). There were no significant difference in likelihood of transfusion, complications, and the length of ICU days between the rhEPO and the non-rhEPO groups. A multivariate analysis demonstrated that the number of fused vertebral levels maintained its significance (P = 0.044) and surgical time had a trend toward significance (P = 0.051) in predicting likelihood of transfusion. CONCLUSION: The use of rhEPO effectively stimulated erythropoiesis in these patients and yet demonstrated no significant clinical benefit in reducing the likelihood of transfusion in neurogenic patients in this study. More research is necessary to design a transfusion risk reduction protocols that will minimize the exposure of neurogenic scoliosis patients to allogeneic blood products. [ABSTRACT FROM AUTHOR]

Background: Controversy exists regarding the optimal fellowship training experience for surgeons who perform scoliosis surgery in pediatric patients. While many studies have demonstrated that higher surgical volumes are associated with superior outcomes, the volume of scoliosis procedures performed by pediatric orthopaedic-trained surgeons as opposed to spine surgery-trained surgeons has not been reported.Methods: Validated, statewide hospital discharge databases from the states of New York and California were utilized to examine the volume of spinal fusion procedures performed for the treatment of scoliosis in patients who were eighteen years of age or less. Fellowship training of surgeons in New York who had performed more than fifty procedures from 1992 to 2001 (that is, more than five procedures per year) was determined, and the operative volumes of surgeons who had received pediatric orthopaedic as opposed to spine fellowship training were compared. Hospitals in California with either type of fellowship program were identified, and the operative volumes of hospitals and fellows with pediatric orthopaedic or spine fellowship training from 1995 to 1999 were compared.Results: Among the 228 surgeons in New York who had performed one or more spinal fusion procedures in patients eighteen years of age or less from 1992 to 2001, only 13% (thirty) had performed more than five procedures per year. However, these thirty surgeons accounted for 75% (3858) of all 5136 procedures in this age-group. Surgeons who had completed a pediatric orthopaedic fellowship had performed a mean of 14.5 procedures per physician per year, whereas those who had completed a spine fellowship had performed a mean of 10.5 procedures per physician per year. Surgeons who had not completed either type of fellowship had performed a mean of 14.4 procedures per physician per year. In California, the mean annual volume of scoliosis procedures from 1995 to 1999 was 59.0 procedures per year at hospitals with pediatric orthopaedic fellowship programs and 15.7 procedures per year at those with spine surgery programs. The mean number of procedures per fellow at hospitals with pediatric orthopaedic fellowship programs was 31.6 procedures per fellow per year, and the mean number at hospitals with spine surgery programs was 12.7 procedures per fellow per year. Over time, there was a significant increase in the number of procedures per year at hospitals with both types of fellowship programs, but the percentage increase was greater for hospitals with pediatric orthopaedic fellowship programs than for hospitals with spine surgery fellowship programs (45.2% compared with 13.5%).Conclusions: These data indicate that, on the average, a large number of surgeons in New York performed five scoliosis procedures per year or fewer. Among higher-volume surgeons in New York, those with pediatric orthopaedic fellowship training performed more scoliosis procedures on children and adolescents than those with orthopaedic spine training did. In California, the volume of scoliosis procedures at hospitals with pediatric orthopaedic fellowship programs was nearly four times greater than that at hospitals with spine fellowship programs and the volume of procedures per fellow was more than two times greater, and this disparity is widening over time. These data are an important element in establishing what type of fellowship best prepares surgeons for scoliosis surgery. [ABSTRACT FROM AUTHOR]

Purpose: Despite the introduction of "standardized counting" methods, errors in counting spinal levels and subsequent wrong-level surgery (WLS) remain critically important patient safety concerns. Previous work by our group has documented inconsistency in the identification of T12 despite the use of these systems including the Spinal Deformity Study Group (SDSG) conventions. To assist with consistent and repeatable identification of proposed preoperative surgical levels, the current study investigates a new strategy: utilization of a "landmark vertebra". It was hypothesized that individuals using a "landmark vertebra" strategy will achieve high concordance with target level identification between distinct time points as compared to conventional methods defining T12., Methods: Survey participants analyzed 99 pre-op radiographs, identifying and naming a "landmark vertebra" with concise descriptions like "last bilaterally ribbed vertebra." They then noted the proposed lowest instrumented vertebra's (LIV) distance relative to landmark (i.e., one below landmark). After a waiting period, participants used their written descriptions of the landmark and distance to LIV to reidentify these vertebrae. Cohen's Kappa (k) was used to measure intra-rater agreeability. The landmark strategy was compared to our previous work evaluating consistency in defining T12 based on the SDSG system., Results: All raters showed perfect to near-perfect agreement when re-identifying the landmark and target vertebrae (k = 0.819-1.00; Table 1A). Raters at all training levels had higher agreeability in naming the landmark vertebra and target when compared to raters at similar training levels defining T12 (k = 0.34-0.91; Table 1B). This high agreement across training demonstrates the strategy's versatility and generalizability., Conclusion: Utilization of a landmark strategy proved to be highly effective in reducing intra-rater variability, with perfect to near-perfect agreement among all raters and consistently higher agreeability when compared to defining T12., Level of Evidence: Level II-prospective survey., Competing Interests: Declarations. Conflict of interest: RRG has no conflicts of interest to disclose. MSM has no conflicts of interest to disclose. KL has no conflicts of interest to disclose. AM has no conflicts of interest to disclose. NB has no conflicts of interest to disclose. TMZ has no conflicts of interest to disclose. BDR has received grants from the Pediatric Orthopaedic Society of North America, Scoliosis Research Society, and Orthopedic Science Research Foundation. LGL has received royalties from Medtronic and Acuity Surgical and is a consultant for Medtronic and Acuity Surgical. He has received grants from the Setting Scoliosis Straight (SSS) Foundation, International Spine Study Group (ISSG) Foundation, and AOSpine. LGL has served on the board of the National Spine Health Foundation (NSHF), Global Spine Outreach (GSO), and Setting Scoliosis Straight Foundation (SSSF). He has also received funding/support from the Fox Family (Prospective Pediatric Spinal Deformity study), AOSpine, Scoliosis Research Society (SRS) and BroadWater. MGV has received grants from the Pediatric Orthopaedic Society of North America, Orthopedic Science Research Foundation, Pediatric Spine Foundation, and Setting Scoliosis Straight Foundation and royalties from Biomet. He is a paid consultant for Stryker, Biomet, and NuVasive. MGV is on the Board of Directors of Pediatric Spine Foundation, Pediatric Spine Study Group, and C4K. He is former president of Pediatric Orthopaedic Society of North America and is a Board Member, Chair Emeritus of the International Pediatric Orthopaedic Symposium. Ethical approval: This study was approved by the Columbia University Institutional Review Board under protocol AAAU3144. It was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication: No patient identifying information is included in the article. Not applicable., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Background: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable BRAF V600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients., Methods: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C)., Results: Brain metastases were discovered during the trial in 23/69 patients in arm A, 11/69 in arm B, and 9/68 in arm C. At a median follow-up of 56 months, the 60-month brain metastases-free survival rates were 56% for arm A, 80% for arm B (hazard ratio [HR] vs. A: 0.40, 95% confidence interval [CI] 0.23 to 0.58), and 85% for arm C (HR vs. A: 0.35, 95% CI 0.16 to 0.76)., Conclusions: In patients with unresectable metastatic melanoma, the treatment sequence of immune checkpoint inhibition followed by BRAF/MEK inhibitors was associated with longer periods of new brain metastases-free survival than the reverse sequence. A regimen in which immune checkpoint inhibition was sandwiched between BRAF/MEK inhibition also appeared to be protective against brain metastases. (ClinicalTrials.gov number NCT02631447.).

Background and Objective: Papillary renal cell carcinoma (pRCC) is the most frequent histological subtype of non-clear cell RCC (nccRCC). Owing to the heterogeneity of nccRCC, patients are often excluded from large phase 3 trials focused on clear cell RCC, so treatment options for nccRCC remain limited. Our aim was to investigate the efficacy of first-line treatment with tyrosine kinase inhibitors (TKIs) or immuno-oncology (IO)-based combinations in patients with pRCC., Methods: We performed a multicenter retrospective analysis of real-world data collected for patients with advanced pRCC treated in 40 centers in 12 countries as part of the ARON-1 project (NCT05287464). The primary endpoints were overall survival (OS), progression-free survival (PFS), the overall response rate (ORR), and time to second progression (PFS2). OS, PFS, and PFS2 were estimated using the Kaplan-Meier method and results were compared between the treatment groups using a log-rank test. Univariate and multivariable analyses were carried out using Cox proportional-hazard models., Key Findings and Limitations: We included 200 patients with metastatic pRCC, of whom 73 were treated with IO-based combinations and 127 with TKIs. Median OS was 22.5 mo in the TKI group 28.8 mo in the IO group (p = 0.081). Median PFS was 6.4 mo in the TKI group and 17.4 mo in the IO group (p < 0.001). The ORR was higher in the IO group than in the TKI group (41% vs 27%; p = 0.037)., Conclusions and Clinical Implications: Our results show that IO-based combinations have superior efficacy outcomes to TKIs for first-line treatment of metastatic pRCC., Patient Summary: The ARON-1 project collects clinical data for patients with kidney cancer treated in multiple centers worldwide to assess outcomes in the real-world setting. We analyzed data for patients with metastatic kidney cancer of a specific subtype to evaluate the efficacy of different first-line treatments. Patients treated with immune-based combinations had better outcomes than patients treated with tyrosine kinase inhibitors., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Teamwork and communication are important components of any surgical team. This study uses a simple, reproducible, and quantitative "team consistency score" and a nodal-based model for examining prior interactions amongst team members to represent and quantify the regularity of an OR team for a specific surgical case., Methods: The electronic medical record (EMR) at our institution was queried for pediatric patients undergoing spinal surgery from January 2021 through December 2023. The number of prior interactions between individuals filling distinct roles in the OR for each case was recorded. A metric coined the consistency score was developed representing the sum total of these prior interactions standardized to a reference case. Spearman's Correlation as well as the Mann-Whitney comparison test were used to analyze the associations between case team consistency score and efficiency measures., Results: 154 cases were included for analysis. There was a statistically significant negative correlation between case consistency score and both anesthesia time (rho = -0.159; p < 0.05) and patient preparation time (rho = -0.218; p < 0.01). When looking at the consistent (above median consistency score of 0.46) vs. inconsistent cohorts, the inconsistent cohort had a higher mean patient preparation time (53.3 ± 14.0 min vs. 49.0 ± 9.3 min; p < 0.05), as well as a higher overall mean case length (336.6 ± 47.4 min vs. 321.9 ± 42.4 min; p < 0.05)., Conclusion: The findings suggest that increased team consistency, as measured by a "team consistency score" metric, is related to heightened efficiency and reduced intraoperative times., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

The standard of care for advanced or metastatic urothelial carcinoma (mUC) was historically identified with platinum-based chemotherapy. Thanks to the advances in biological and genetic knowledge and technologies, new therapeutic agents have emerged in this setting recently: the immune checkpoint inhibitors and the fibroblast growth factor receptor inhibitors as the target therapy for patients harboring alterations in the fibroblast growth factor receptor (FGFR) pathway. However, chasing a tumor's tendency to recur and progress, a new class of agents has more recently entered the scene, with promising results. Antibody-drug conjugates (ADCs) are in fact the latest addition, with enfortumab vedotin being the first to receive accelerated approval by the U.S. Food and Drug Administration in December 2019, followed by sacituzumab govitecan. Many other ADCs are still under investigation. ADCs undoubtedly represent the new frontier, with the potential of transforming the management of mUC treatment in the future. Therefore, we reviewed the landscape of mUC treatment options, giving an insight into the molecular basis and mechanisms, and evaluating new therapeutic strategies in the perspective of more and more personalized treatments.

Background Context: Intraoperative neurophysiological monitoring (IONM) is used to reduce the risk of spinal cord injury during pediatric spinal deformity surgery. Significant reduction and/or loss of IONM signals without immediate recovery may lead the surgeon to acutely abort the case. The timing of when monitorable signals return remains largely unknown., Purpose: The goal of this study was to investigate the correlation between IONM signal loss, clinical examination, and subsequent normalization of IONM signals after aborted pediatric spinal deformity surgery to help determine when it is safe to return to the operating room., Study Design/setting: This is a multicenter, multidisciplinary, retrospective study of pediatric patients (<18 years old) undergoing spinal deformity surgery whose surgery was aborted due to a significant reduction or loss of IONM potentials., Patient Sample: Sixty-six patients less than 18 years old who underwent spinal deformity surgery that was aborted due to IONM signal loss were enrolled into the study., Outcome Measures: IONM data, operative reports, and clinical examinations were investigated to determine the relationship between IONM loss, clinical examination, recovery of IONM signals, and clinical outcome., Methods: Information regarding patient demographics, deformity type, clinical history, neurologic and ambulation status, operative details, IONM information (eg, quality of loss [SSEPs, MEPs], laterality, any recovery of signals, etc.), intraoperative wake-up test, postoperative neurologic exam, postoperative imaging, and time to return to the operating were all collected. All factors were analyzed and compared with univariate and multivariate analysis using appropriate statistical analysis., Results: Sixty-six patients were enrolled with a median age of 13 years [IQR 11-14], and the most common sex was female (42/66, 63.6%). Most patients had idiopathic scoliosis (33/66, 50%). The most common causes of IONM loss were screw placement (27/66, 40.9%) followed by rod correction (19/66, 28.8%). All patients had either complete bilateral (39/66, 59.0%), partial bilateral (10/66, 15.2%) or unilateral (17/66, 25.8%) MEP loss leading to termination of the case. Overall, when patients were returned to the operating room 2 weeks postoperatively, nearly 75% (40/55) had monitorable IONM signals. Univariate analysis demonstrated that bilateral SSEP loss (p=.019), bilateral SSEP and MEP loss (p=.022) and delayed clinical neurologic recovery (p=.008) were significantly associated with having unmonitorable IONM signals at repeat surgery. Multivariate regression analysis demonstrated that delayed clinical neurologic recovery (> 72 hours) was significantly associated with unmonitorable IONM signals when returned to the operating room (p=.006). All patients ultimately made a full neurologic recovery., Conclusions: In children whose spinal deformity surgery was aborted due to intraoperative IONM loss, there was a strong correlation between combined intraoperative SSEP/MEP loss, the magnitude of IONM loss, the timing of clinical recovery, and the time of electrophysiological IONM recovery. The highest likelihood of having a prolonged postoperative neurological deficit and undetectable IONM signals upon return to the OR occurs with bilateral complete loss of SSEPs and MEPs., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: New evidence highlights the significance of 3D in-brace correction for Adolescent Idiopathic Scoliosis (AIS) patients. This study explores how axial parameters relate to treatment failure in braced AIS patients., Methods: AIS patients (Sanders 1-5) undergoing Rigo-Chêneau bracing at a single institution were included. Axial vertebral rotation (AVR) was determined by utilizing pre-brace and in-brace 3D reconstructions from EOS® radiographs. The primary outcome was treatment failure: surgery or coronal curve progression > 5°. Minimum follow-up was two years., Results: 75 patients (81% female) were included. Mean age at bracing initiation was 12.8 ± 1.3 years and patients had a pre-brace major curve of 31.0° ± 6.5°. 25 patients (76% female) experienced curve progression > 5°, and 18/25 required surgical intervention. The treatment failure group had larger in-brace AVR than the success group (5.8° ± 4.1° vs. 9.9° ± 7.6°, p = 0.003), but also larger initial coronal curve measures. In-brace AVR did not appear to be associated with treatment failure after adjusting for the pre-brace major curve (Hazard Ratio (HR):0.99, 95% Confidence Interval (CI):0.94-1.05, p = 0.833). Adjusting for pre-brace major curve, patients with AVR improvement with bracing had an 85% risk reduction in treatment failure versus those without (HR:0.15, 95% CI:0.02-1.13, p = 0.066). At the final follow-up, 42/50 (84%) patients without progression had Sanders ≥ 7., Conclusions: While in-brace rotation was not an independent predictor of curve progression (due to its correlation with curve magnitude), improved AVR with bracing was a significant predictor of curve progression. This study is the first step toward investigating the interplay between 3D parameters, skeletal maturity, compliance, and brace efficacy, allowing a future prospective multicenter study., Level of Evidence: Retrospective study; Level III., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Purpose: Early onset scoliosis (EOS) patient diversity makes outcome prediction challenging. Machine learning offers an innovative approach to analyze patient data and predict results, including LOS in pediatric spinal deformity surgery., Methods: Children under 10 with EOS were chosen from the American College of Surgeon's NSQIP database. Extended LOS, defined as over 5 days, was predicted using feature selection and machine learning in Python. The best model, determined by the area under the curve (AUC), was optimized and used to create a risk calculator for prolonged LOS., Results: The study included 1587 patients, mostly young (average age: 6.94 ± 2.58 years), with 33.1% experiencing prolonged LOS (n = 526). Most patients were female (59.2%, n = 940), with an average BMI of 17.0 ± 8.7. Factors influencing LOS were operative time, age, BMI, ASA class, levels operated on, etiology, nutritional support, pulmonary and neurologic comorbidities. The gradient boosting model performed best with a test accuracy of 0.723, AUC of 0.630, and a Brier score of 0.189, leading to a patient-specific risk calculator for prolonged LOS., Conclusions: Machine learning algorithms accurately predict extended LOS across a national patient cohort and characterize key preoperative drivers of increased LOS after PSIF in pediatric patients with EOS., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Metastatic renal cell carcinoma (mRCC) carrying sarcomatoid features (sRCC) has aggressive biology and poor prognosis. First-line immunotherapy (IO)-based combinations have improved the outcome of clear cell RCC patients, including that of sRCC. Real-world data confirming the adequate first-line management of sRCC is largely lacking. We investigated the clinical features and the outcome of sRCC patients treated with IO-based combinations within the ARON-1 study population (NCT05287464). The primary objective was to define the incidence and baseline clinical characteristics of sRCC compared with non-sRCC patients. The secondary objective was to describe the outcome of sRCC patients based on type of first-line treatment (IO + IO vs. IO + tyrosin kinase inhibitor [TKI]). We identified 1362 mRCC patients with IMDC intermediate or poor risk, 226 sRCC and 1136 non-sRCC. These two subgroups did not differ in terms of baseline characteristics. The median overall survival (OS) was 26.8 months (95%CI 21.6-44.2) in sRCC and 35.3 months (95%CI 30.2-40.4) in non-sRCC patients (p = .013). The median progression-free survival (PFS) was longer in non-sRCC patients compared to sRCC (14.5 vs. 12.3 months, p = .064). In patients treated with first-line IO + TKI the median OS was 34.4 months compared to 26.4 months of those who received IO + IO (p = .729). The median PFS was 12.4 months with IO + TKI and 12.3 months with IO + IO (p = .606). In conclusion, we confirm that sRCC are aggressive tumors with poor prognosis. IO-based combinations improve survival outcomes of sRCC patients, regardless from the type of strategy (IO + IO versus IO + TKI) adopted., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Study Design: Retrospective, Multicenter., Objective: Determine if posterior column osteotomies (PCO) at time of conversion from growth friendly instrumentation (GFI) to definitive fusion in early onset scoliosis (EOS) graduates impacts outcomes., Summary of Background Data: Increasing spinal rigidity following treatment of EOS with GFI can limit curve correction at time of conversion to definitive spinal fusion. PCO are often employed at the time of fusion to improve flexibility. This technique's efficacy has not been studied., Methods: EOS patients with GFI undergoing conversion to fusion were grouped by those that did or did not have PCO. Patients with inadequate radiographs, <2 years follow-up, or three-column osteotomies at time of fusion were excluded., Results: 832 patients met inclusion criteria. 175 (21%) patients had PCO. Age at index surgery was younger (6.6 vs. 7.4 y, P =0.0009) and the mean duration of GFI was greater (6.2 vs. 5.5 y, P =0.009) in the PCO group. Prior to fusion, curve magnitude was similar between the groups (PCO=61.9 degrees, no PCO=59.3 degrees, P=0.18). On average 4.4 osteotomies (range: 1 - 12) were performed for the PCO group and EBL (PCO=820 cc vs no PCO=752 cc, P<0.01) and surgical time (PCO=403 min vs no PCO=349 min, P<0.01) were greater. Postoperatively, mean curve correction (PCO=16.6, no PCO=14.4 degrees, P=0.18) was similar. Accounting for preoperative curve magnitude, there was a relationship between number of PCOs and curve correction (P=0.04). There was no relationship between degrees of correction per osteotomy and duration of GFI (P=0.12). Postoperative complications at 2 years were similar (PCO=25% vs no PCO=27%, P=0.63)., Conclusion: EOS graduates achieve minimal correction at time of conversion regardless of whether PCOs are performed. PCOs increase EBL and operative time but have a similar complication rate. More PCOs resulted in more correction, though less than that anticipated in a previously uninstrumented spine., Level of Evidence: III., Competing Interests: Although the authors have no disclosures related to the study, please find the Conflicts of Interests as follows: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival., (© 2024. The Author(s).)

Case: Spinal deformity associated with Guillain-Barre syndrome (GBS) is not commonly reported. We present a 6-year-old girl who developed kyphoscoliosis after being diagnosed GBS. She had extensive motor deficits requiring 2 hospitalizations and treatment with IV immunoglobulin therapy. Five months after diagnosis, she presented to our clinic with a 15° coronal scoliosis and a 65° thoracic kyphosis. At 6-month follow-up, kyphosis progressed to 77° with no significant change in the coronal curve. At 1 year, sagittal alignment was within normal limits and the coronal curve had completely resolved., Conclusion: Spinal deformity in GBS can resolve spontaneously., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C409)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: Severe scoliosis can affect thoracic organs, potentially leading to cardiovascular abnormalities. Thus, echocardiograms have been suggested for use in preoperative screening in patients with significant scoliosis. However, the utility of preoperative heart screenings in patients without known or suspected heart problems is not well understood. This study aims to find the incidence of cardiac findings in patients with severe scoliosis ≥90° without cardiac history., Methods: A single-institution retrospective chart review was performed. Inclusion criteria were scoliosis patients with curves ≥90 degrees and a screening echocardiogram performed within 6 months of spine surgery. Patients with a previous cardiac history, diagnosis associated with cardiac comorbidities (eg, connective tissue disease), or major coronal curves <90 degrees were excluded. Echocardiogram reports and perioperative clinical notes from involved services (including orthopaedics, cardiology, and anesthesia) were reviewed. Any postoperative use of vasopressors and reasons for their use were recorded., Results: Overall, 50 patients met the inclusion criteria. The mean age at surgery was 14.0 ± 4.9 years old (range: 2 to 33). The mean major curve was 108 ± 19 degrees (range: 90 to 160 degrees). A normal echocardiogram was seen in 38 (76%), whereas 6 patients (12%) had mild dilation of the aortic sinus or root, 4 (8%) had mild valvular regurgitation, 1 patient had a small atrial septal defect, and 1 had a trace pericardial effusion. No patient had any changes made to their perioperative plan and one patient was advised to see a cardiologist postoperatively. Postoperatively, 8 patients (16%) received vasopressors to raise blood pressure to meet preset goal MAP, but only one of these 8 had a positive echocardiogram (mild valvular insufficiency), which was not seen as a contributing factor to the use of pressors., Conclusions: This study suggests that screening echocardiograms for patients without a cardiac history or related symptoms does not contribute to the evaluation of perioperative risk or anesthetic management. Creating clear, evidence-based guidelines for the utilization of perioperative testing, like echocardiograms, can reduce the social, time, and financial burdens on families. Such guidelines are vital for appropriate risk assessment and proper utilization of health care resources., Level of Evidence: Level III., Competing Interests: M.G.V. has received grants from the Pediatric Orthopaedic Society of North America, Orthopaedic Science Research Foundation, Pediatric Spine Foundation, and Setting Scoliosis Straight Foundation and royalties from Biomet. He is a paid consultant for Stryker, Biomet, and NuVasive. Also, he is on the Board of Directors of Pediatric Spine Foundation, Pediatric Spine Study Group, and C4K. He is former president of Pediatric Orthopaedic Society of North America and is a Board Member, Chair Emeritus of the International Pediatric Orthopaedic Symposium. B.D.R. has received grants from the Pediatric Orthopaedic Society of North America and Orthopaedic Science Research Foundation. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The complexity of health care delivery systems presents a unique challenge for the perioperative space. In the area of arthroplasty procedures, the shift of complex patients into ambulatory surgery centers and reimbursement that is no longer commensurate with the inflated costs of performing these procedures have created difficulties for hospitals and physicians alike. Thus, there is a critical need to optimize perioperative workflows while maintaining high-quality care provision., Methods: Our institution implemented the Comprehensive Unit-based Safety Program (CUSP) to improve the quality and efficiency of total knee and hip arthroplasties (TKAs and THAs). This initiative involved extensive collaboration with clinical and administrative teams, as well as 5 intervention-driven workgroups. First-case on-time start rates and duration of first-case delays, case length, anesthesia preparation, in-room patient preparation, operation, patient exit, and room turnover after CUSP implementation were analyzed using independent samples median testing, Mann-Whitney U testing, and a percentage-point difference calculation., Results: After CUSP arthroplasty implementation, first-case on-time start rates increased from 43 to 81%. Statistically significant decreases were observed in median times for first-case delays, case length, in-room patient preparation, operation, patient exit, and room turnover for TKAs and THAs, but not anesthesia preparation., Conclusions: The implementation of CUSP arthroplasty for TKAs and THAs resulted in significant improvements in nearly all efficiency metrics, as well as preventions of patient safety missteps. These results exemplify the versatility of CUSP as a quality improvement method that can maintain patient safety and perioperative efficiency in the arthroplasty service of a large-scale medical center., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: In 2018, Best Practice Guidelines (BPGs) were published for preventing wrong-level surgery in pediatric spinal deformity, but successful implementation has not been established. The purpose of this study was to evaluate BPG compliance 5 years after publication. We hypothesized higher compliance among BPG authors and among surgeons with more experience, higher caseload, and awareness of the BPGs., Methods: We queried North American and European surgeons, authors and nonauthors, and members of pediatric spinal study groups on adherence to BPGs using an anonymous survey consisting of 18 Likert scale questions. Respondents provided years in practice, yearly caseload, and guideline awareness. Mean compliance scores (MCS) were developed by correlating Likert responses with MCS scores ("None of the time" = no compliance = MCS 0, "Sometimes" = weak to moderate = MCS 1, "Most of the time" = high = MCS 2, and "All the time" = perfect = MCS 3)., Results: Of the 134 respondents, 81.5% reported high or perfect compliance. Average MCS for all guidelines was 2.4 ± 0.4. North American and European surgeons showed no compliance differences (2.4 vs. 2.3, p = 0.07). Authors and nonauthors showed significantly different compliance scores (2.8 vs 2.4, p < 0.001), as did surgeons with and without knowledge of the BPGs (2.5 vs 2.2, p < 0.001). BPG awareness and compliance showed a moderate positive correlation (r = 0.48, p < 0.001), with non-significant associations between compliance and both years in practice (r = 0.41, p = 0.64) and yearly caseload (r = 0.02, p = 0.87)., Conclusion: Surgeons reported high or perfect compliance 81.5% of the time with BPGs for preventing wrong-level surgery. Authorship and BPG awareness showed increased compliance. Location, study group membership, years in practice, and yearly caseload did not affect compliance., Level of Evidence: Level V-expert opinion., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Background: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care., Objective: This retrospective study focused on the impact of upfront CN on metastatic nccRCC outcomes with first-line immune checkpoint inhibitor (IO) combinations or tyrosine kinase inhibitor (TKI) monotherapy., Methods: The study included 221 patients with nccRCC and synchronous metastatic disease, treated with IO combinations or TKI monotherapy in the first line. Baseline clinical characteristics, systemic therapy, and treatment outcomes were analyzed. The primary objective was to assess clinical outcomes, including progression-free survival (PFS) and overall survival (OS). Statistical analysis involved the Fisher exact test, Pearson's correlation coefficient, analysis of variance, Kaplan-Meier method, log-rank test, and univariate/multivariate Cox proportional hazard regression models., Results: Median OS for patients undergoing upfront CN was 36.8 (95% confidence interval [CI] 24.9-71.3) versus 20.8 (95% CI 12.6-24.8) months for those without CN (p = 0.005). Upfront CN was significantly associated with OS in the multivariate Cox regression analysis (hazard ratio 0.47 [95% CI 0.31-0.72], p < 0.001). In patients without CN, the median OS and PFS was 24.5 (95% CI 18.1-40.5) and 13.0 months (95% CI 6.6-23.5) for patients treated with IO+TKI versus 7.5 (95% CI 4.3-22.4) and 4.9 months (95% CI 3.0-8.1) for those receiving the IO+IO combination (p = 0.059 and p = 0.032, respectively)., Conclusions: Our study demonstrates the survival benefits of upfront CN compared with systemic therapy without CN. The study suggests that the use of IO+TKI combination or, eventually, TKI monotherapy might be a better choice than IO+IO combination for patients who are not candidates for CN regardless of IO eligibility. Prospective trials are needed to validate these findings and refine the role of CN in current mRCC management., (© 2024. The Author(s).)

Treatment duration with checkpoint inhibitors must be optimized to prevent unjustified toxicity, but evidence for the management of cutaneous squamous cell carcinoma is lacking. A retrospective study was performed to evaluate the survival of patients with cutaneous squamous cell carcinoma (CSCC) who discontinued cemiplimab due to different causes and without progression. Among 95 patients with CSCC who received cemiplimab, 22 (23%) patients discontinued immunotherapy due to causes other than progression, such as comorbidities, toxicity, complete response or lack of compliance (group that discontinued before censoring [DBC]), then 73 patients had standard treatment scheduled (STS). The overall survival was 25.2 months (95% CI: 8.9-29.4) in STS group and 28.3 months (95% CI: 12.7-28.3) in the DBC group; deaths for all causes were 11/22 (50%) in the DBC group and 34/73 (46.6%) in the STS group (p = 0.32). 10/22 (45.4%) subjects died due to CSCC in the DBC after discontinuation and 34/73 (46.6%) in the STS group, and the difference between groups was not significant (p = 0.230). Duration of treatment was significantly lower in subjects with stable disease versus those with complete or partial response (16.9, 30.6 and 34.9 months, respectively; p = 0.004). Among the 22 STS patients, 12 received cemiplimab for less than 12 months (10 [83%] died) and 10 for at least 12 months (1 [10%] died). Our observation, finding no outcome difference between DBC and STS groups, suggests that ICI treatment after one year might expose patients to further treatment related events without efficacy advantages., (© 2024. The Author(s).)

Introduction: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors., Patients and Methods: Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis. From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy., Results: In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death. Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83)., Conclusion: In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes., Competing Interests: Disclosure The other authors declare no conflict of interest. Francesco Pierantoni: Advisory board: Eli Lilly; Speaker and travel fees: Pfizer, BMS, MSD, AstraZeneca, Jannsen, Takeda, Merck, Astellas, Ipsen. Paola Ermacora: MSD, BMS, AAA, Astellas, Recordati, Eisai (advisory board), Jansenn (travel grant)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Mehta casting is a potentially curative intervention for early-onset scoliosis (EOS) that typically requires multiple anesthetics. The Food and Drug Administration (FDA) reported that >3 hours of anesthesia under the age of 3 years old may alter brain development; however, no standard exists for the duration of anesthesia during casting. The purpose of this study is to quantify the variability in anesthesia during Mehta casting. We hypothesize that significant institutional variability exists and may be attributed to modifiable factors., Methods: An EOS registry was used to identify patients who underwent at least one Mehta casting procedure. Anesthesia exposure was quantified, and site variability was assessed by patient characteristics, cast placement, procedure type, and equipment used., Results: Our cohort consisted of 208 patients from 5 institutions (age 2.6±1.4 y). There were 1097 Mehta casting procedures, with 5.4±3.6 castings per patient. Of these patients, 106 (51%) were female, with an average age of 2.11±1.29 years old at the time casting was initiated. Patient etiologies included 154 idiopathic (74.0%), 22 syndromic (10.6%), 18 congenital (8.7%), 11 neuromuscular (5.3%), and 3 unknown (1.4%). Anesthesia time was 69±31 minutes and varied significantly between sites (59±14 to 117±46 min; P <0.001). Cumulative anesthesia time for patients under 3 years was 320±197 minutes with 120/161 (74.5%) patients exceeding 3 hours. Anesthesia time was lower after the FDA warning in 2016 compared with pre-2016 (71±30 vs. 66±32, P =0.008)., Conclusions: Patients undergoing Mehta casting are at significant risk of exceeding 3 hours of anesthesia, which the FDA has stated may be harmful for children <3 years. Significant site variability indicates that standardization protocols should be developed to encourage best practices and minimize anesthetic times., Level of Evidence: Prognostic Level II., Competing Interests: L.B.O. received a grant by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number TL1TR001875. P.S. received consulting fees from Nuvasive and Depuy Synthes Spine. J.M.P. received consulting fees from Nuvasive, Depuy Synthes, and Zimmer Biomet. A.N.L. consulted unrelated to this submitted work with all funds directed to Mayo Clinic Orthopedics research. M.G.V. has received grants from the Pediatric Orthopaedic Society of North America, Orthopedic Science Research Foundation, Pediatric Spine Foundation, and Setting Scoliosis Straight Foundation and royalties from Biomet. He is a paid consultant for Stryker, Biomet, and NuVasive. M.G.V. is on the Board of Directors of Pediatric Spine Foundation, Pediatric Spine Study Group, and C4K. He is former president of Pediatric Orthopaedic Society of North America and is a Board Member, Chair Emeritus of the International Pediatric Orthopaedic Symposium. B.D.R. has received grants from the Pediatric Orthopaedic Society of North America and Orthopedic Science Research Foundation. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript.

Background: The treatment of heavily pretreated patients with metastatic renal cell carcinoma (mRCC) represents an unmet medical need and is still challenging., Objectives: The primary objective was to assess the effectiveness of the lenvatinib plus everolimus combination and the secondary objective was the toxicity profile of this combination., Design: We conducted a longitudinal retrospective study examining mRCC patients pre-treated with one or more lines of therapy among different cancer centers in Italy., Methods: The study included patients who received the combination of lenvatinib plus everolimus as either a second-line treatment or beyond. We assessed progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), response rate (RR), and toxicity profile. In addition, we explored the potential relationship between treatment effectiveness and clinical and laboratory parameters., Results: In all, 33 patients were assessed, the median age was 60 years, 57% had an Eastern Cooperative Oncology Group performance status of 1-2 and. 63% received ⩾ 3 prior lines of therapy. 62% were 'intermediate risk' according to the International Metastatic Renal Cell Carcinoma Database Consortium and 30% were 'poor risk'. The RR was 42% (no complete response), 18% stable disease. Median OS was 11.2 months (95% CI 6.8-19.9), median PFS was 6.7 months (95% CI 0.6-30.8), and median TTF was 6.7 months (95% CI 4.8-16.6). A shorter OS was significantly associated with lymph node metastases ( p  = 0.043, 95% CI), neutrophils/ lymphocytes ratio (NLR) ⩾ 3 ( p  = 0.007), hemoglobin/red cell distribution width ratio cutoff value <0.7 was significant ( p  = 0.03) while a shorter PFS was associated with lung ( p  = 0.048) and brain metastases ( p  = 0.023). The most frequent G1 toxicity was diarrhea (24%), G2 was fatigue (30%), and hypertension and skin toxicity (6%) for G3., Conclusion: Our findings suggest a clinically relevant effectiveness of lenvatinib plus everolimus combination with an acceptable toxicity profile for heavily pretreated patients with mRCC., Competing Interests: V.C. has served as a consultant/advisory board member for Janssen, Astellas, Merck, AstraZeneca, Amgen, and Bayer and has received speaker honoraria or travel support from Astellas, Janssen, Ipsen, Bayer, and Sanofi. E.R. had a role as consultant for Bristol Meyers Squibb, MSD, Novartis, Pierre Fabre, Immunocore, and Pfizer., (© The Author(s), 2024.)

Background: Ipilimumab plus nivolumab (COMBO) is the standard treatment in asymptomatic patients with melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO outside clinical trials., Methods: Consecutive patients treated with COMBO have been included. Demographics, steroid treatment, Central Nervous System (CNS)-related symptoms, BRAF status, radiotherapy or surgery, response rate (RR), progression-free (PFS) and overall survival (OS) have been analyzed., Results: 376 patients were included: 262 received COMBO as first-line and 114 as a subsequent line of therapy, respectively. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) (≥1 vs 0) [HR 1.97 (1.46-2.66)], extracerebral metastases [HR 1.92 (1.09-3.40)], steroid use at the start of COMBO [HR 1.59 (1.08-2.38)], CNS-related symptoms [HR 1.59 (1.08-2.34)], SRS (Stereotactic radiosurgery) [HR 0.63 (0.45-0.88)] and surgery [HR 0.63 (0.43-0.91)] were associated with OS. At a median follow-up of 30 months, the median OS (mOS) in the overall population was 21.3 months (18.1-24.5), whilst OS was not yet reached in treatment-naive patients, steroid-free at baseline. In patients receiving COMBO after BRAF/MEK inhibitors(i) PFS at 1-year was 15.7%. The dose of steroids (dexamethasone < vs ≥ 4 mg/day) was not prognostic. SRS alongside COMBO vs COMBO alone in asymptomatic patients prolonged survival. (p = 0.013). Toxicities were consistent with previous studies. An independent validation cohort (n = 51) confirmed the findings., Conclusions: Our results demonstrate remarkable long-term survival in treatment-naïve, asymptomatic, steroid-free patients, as well as in those receiving SRS plus COMBO. PFS and OS were poor in patients receiving COMBO after progressing to BRAF/MEKi., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)