Complications and outcomes after three-column osteotomy: a 5-year follow-up.

BACKGROUND: Three-column spinal osteotomies (3-CO) are powerful techniques used to correct spinal deformity. These surgeries are associated with an elevated risk of complications. While outcomes have been reported in the literature with 2 years follow-up, longer-term outcomes of three-column osteotomies remain understudied. OBJECTIVES: This study aims to examine patient reported outcomes and complications for three-column osteotomies at 5 years. STUDY DESIGN: Retrospective review of a prospectively collected spinal deformity cases database. PATIENT SAMPLE: All consecutive adult patients at a single spine surgery center treated with either a pedicle subtraction osteotomy (PSO) or vertebral column resection (VCR) for spinal deformity, and with a minimum 5-year follow-up were included. OUTCOME MEASURES: Visual-analog scale (VAS) for back pain score (0 to 10), Oswestry Disability Index (ODI) score (0 to 100), number of complications, revision rate, sagittal balance, lumbar lordosis at preoperative and at 5-year visit. METHODS: Data was extracted from a prospectively collected spinal deformity surgery database continuously updated since 2002 with data from operative reports, patients' medical visit notes and patients' self-reported VAS and ODI questionnaires completed at each office visit. Radiographic measurements were performed on standing full-length spine radiographs taken at pre-op and 5-year visits. Descriptive statistics, comparison of means and proportions among groups, and a logistic regression analysis were conducted using the statistical software package SPSS version 28. Statistical significance was set at p<.05. RESULTS: Of 127 consecutive adult patients with minimum of 5-year follow-up undergoing a 3-CO posterior spinal surgery for spinal deformity were identified and included in the study, 79 (62%) were treated with PSO, and 48 (38%) with VCR. Both PSO and VCR groups demonstrated significant improvements in VAS (PSO pre-op: 6.7, 5-year: 4.6, p<.001; VCR pre-op: 7.1, 5-year: 5.2, p<.001), and ODI (PSO pre-op: 52.9, 5-year: 45.4, p<.001; VCR pre-op: 57.5, 5-year 43.0, p<.001) that were maintained at 5 years. Major and minor complications occurring within 5 years were not statistically different between the PSO and VCR groups (major: 59.5% vs 56.3%, p=.85; minor: 45.6% vs 37.5%, p=.46). The rate of revision surgery within 5 years was 39.4% overall. Of the fifty patients requiring revision, 37.5% were for nonunion, 27.1% instrumentation failure, 14.6% proximal junctional kyphosis (PJK), 12.5% vertebral fracture, 6.3% motor weakness, and 2.1% infection. Improvements in lumbar lordosis were maintained at 5 years in both the PSO (29.9° vs 47.2°, p<.001) and VCR (34.6° vs 48.5°, p<.001) groups while sagittal balance maintained significant improvement in the VCR group (9.5 cm vs 6.3 cm, p=.008) but not the PSO (11.4 cm vs 9.3 cm, p=.065). CONCLUSION: Patients undergoing three-column osteotomies had a major complication rate of 57.5% and a minor complication rate of 42.5% after 5 years. Improvements in lumbar lordosis were maintained at 5-year follow-up, but sagittal balance was only maintained in the VCR group. Despite these radiographic findings, both VCR and PSO groups maintained significant clinical improvements in both VAS and ODI scores at 5-year follow up.

Multicenter prospective blinded melanoma detection study with a handheld elastic scattering spectroscopy device.

Background: The elastic scattering spectroscopy (ESS) device (DermaSensor Inc., Miami, FL) is a noninvasive, painless, adjunctive tool for skin cancer detection. Objectives: To investigate the performance of the ESS device in the detection of melanoma. Methods: A prospective, investigator-blinded, multicenter study was conducted at 8 United States (US) and 2 Australian sites. All eligible skin lesions were clinically concerning for melanoma, examined with the ESS device, subsequently biopsied according to dermatologists' standard of care, and evaluated with histopathology. A total of 311 participants with 440 lesions were enrolled, including 44 melanomas (63.6% in situ and 36.4% invasive) and 44 severely dysplastic nevi. Results: The observed sensitivity of the ESS device for melanoma detection was 95.5% (95% CI, 84.5% to 98.8%, 42 of 44 melanomas), and the observed specificity was 32.5% (95% CI, 27.2% to 38.3%). The positive and negative predictive values were 16.0% and 98.1%, respectively. Limitations: The device was tested in a high-risk population with lesions selected for biopsy based on clinical and dermoscopic assessments of board-certified dermatologists. Most enrolled lesions were pigmented. Conclusion: The ESS device's high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.

Does Laterality Matter? The Effect of Unilateral v. Bilateral Sacroiliac Screw Fixation on Personal Hygiene.

STUDY DESIGN: Retrospective comparative analysis of prospective cohort. OBJECTIVE: To determine whether sacroiliac (SI) screw fixation ipsilateral to hand dominance compared to bilateral fixation impacts personal hygiene (wiping) after toileting. METHODS: Inclusion criteria were adult spinal deformity (ASD) patients with long arthrodesis (≥T12-pelvis) who had undergone primary unilateral or bilateral SI fixation with a minimum of 2-years-follow-up. RESULTS: 117 consecutive patients were included and separated into 2 groups: bilateral SI fixation (BL, n = 61) and unilateral SI fixation (UNI, n = 56), with no difference in age. Of UNI patients, 10.7% (6) performed personal hygiene with a different hand after surgery, compared to 6.6% (4) of patients who received BL fixation (P = 0.422). All UNI patients who switched hands were right-hand dominant, and 5/6 received right-sided fixation. There was no statistical difference found between number of levels fused (<8, 9-11, or >11 levels) and changes in personal hygiene habits. Over a third of patients from both groups had difficulty performing personal hygiene after fusion (UNI = 39.3% BL = 36.1%, P = 0.719). CONCLUSION: SI screws increase the difficulty of performing personal hygiene; yet, the side of unilateral screws does not significantly change personal hygiene habits when compared to bilateral screw placement. Moreover, the length of the construct does not have a significant impact on ability to perform personal hygiene, cause changes in habits, or require the assistance of another individual. However, among our sample of individuals, bilateral fixation did result in a higher rate of revision instrumentation.

A Systematic Review and Meta-Analysis on the Prognostic Value of BRCA Mutations, Homologous Recombination Gene Mutations, and Homologous Recombination Deficiencies in Cancer.

Patients with BRCA1/2 mutations (BRCAm), loss-of-function mutations in other homologous recombination repair (HRRm) genes, or tumors that are homologous recombination deficiency positivity (HRD+) demonstrate a robust response to PARPi therapy. We conducted a systematic literature review and meta-analysis to evaluate the prognostic value of BRCAm, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types. A total of 135 eligible studies were included. Breast cancer (BC) patients with BRCA1/2m had a similar overall survival (OS) to those with wild-type BRCA1/2 (BRCA1/2 wt) across 18 studies. Ovarian cancer (OC) patients with BRCA1/2m had a significantly longer OS than those with BRCA1/2 wt across 24 studies reporting BRCA1m and BRCA2m, with an HR of 0.7 (0.6-0.8). Less OS data were reported for other tumors: 6 studies for BRCA2m compared with BRCA2 wt in prostate cancer with an HR of 1.9 (1.1-3.2) and 2 studies for BRCA1/2m compared with BRCA1/2 wt in pancreatic cancer with an HR of 1.5 (0.8-3.1). Only 4 studies reported HRD+ by either BRCA m or genomic instability score (GIS) ≥ 42 and OS by HRD status. The HR was 0.67 (0.43-1.02) for OS with HRD+ vs. HRD-. A total of 15 studies reported the association between HRRm and OS of cancers in which one or more HRR genes were examined. The HR was 1.0 (0.7-1.4) comparing patients with HRRm to those with HRR wild-type across tumors. Our findings are useful in improving the precision and efficacy of treatment selection in clinical oncology.

Cumulative Erythemal Ultraviolet Radiation and Risk of Cancer in 3 Large US Prospective Cohorts.

Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and noncutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined 3 US prospective cohorts, the Health Professionals Follow-up Study (HPFS) (1986) and Nurses' Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding nonmelanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 men; 212,449 women) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as referent, for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared with the lowest quintile, risk of any cancer was slightly increased across all other quintiles (highest quintile hazard ratio (HR) = 1.04, 95% confidence interval (CI): 1.01, 1.07; P for heterogeneity = 0.41). All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR = 1.17, 95% CI: 1.04, 1.31; P for heterogeneity = 0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and noncutaneous cancers.

Characterizing negative reviews of orthopedic spine surgeons and practices.

Background: Recent evidence suggests that patients prefer subjective and crowd-sourced information over data-driven or quality-based outcomes when choosing a surgeon. Online physician rating and review websites continue to increase in popularity, and over half of patients use them to research physicians. Specifically, Yelp.com is the most frequently utilized online resource by patients. Data regarding the characteristics of negative reviews for spine surgeons and practices is lacking. Methods: Orthopedic Spine surgeons and practices in 8 major US metropolitan regions were surveyed for one-star reviews on Yelp.com. The factors noted in the reviews were recorded and they were classified according to their clinical or nonclinical nature. Reviews were also subclassified into nonsurgical or surgical episodes of care. Results: A total of 6,286 Yelp reviews were discovered, 671 (10.6%) of which were rated one-star. The majority of negative reviews (76.4%) were from patients who did not report surgery by the surgeon or practice. Of all comments, 491 (77.6%) related to nonclinical complaints. The most common factors noted in negative reviews were related to bedside manner, rude or unprofessional staff, and wait time. Conclusion: Choosing a surgeon is a complex process for patients. The large majority of negative reviews were related to nonclinical issues such as poor bedside manner or rude staff and most of these were written by patients that did not undergo a surgical procedure. This may explain the large discrepancy that has been observed between quality metrics and online crowd-sourced reviews. Paying attention to these nonclinical factors may represent the most feasible and valuable targets to improve a surgeon's practice and attract future patients.

Increased relative proportions of advanced melanoma among veterans: A comparative analysis with the Surveillance, Epidemiology, and End Results registry.

BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) program reflects a third of the population of the United States. However, SEER may not be generalizable to the veteran population. Because veterans comprise a high-risk population, this discrepancy may limit our understanding of the epidemiology of melanoma in such high-risk populations. OBJECTIVES: To assess differences in demographics, tumor characteristics, and melanoma-specific survival (MSS) in veterans compared to the general population. METHODS: Data were collected from the Veterans Affairs Cancer Registry (VACR) and SEER (18 registries) from 2009 to 2017. RESULTS: We identified 15,334 veterans and 166,265 SEER patients with melanoma. Veterans were more likely to present with regional or distant disease (17.5% vs 13.0% in SEER). In VACR relative to SEER, the 5-year MSS was lower across all ages, except those diagnosed at ≥80 years. From 2009 to 2017, MSS by stage was lower across all stages in VACR. However, for stage IV melanomas diagnosed in 2015 to 2017 compared to 2011-2014, 2-year MSS increased from 37.8% to 51.5% in VACR versus 36.4% to 44.8% in SEER. LIMITATIONS: Unique veteran demographics and missing data inherent to VACR. CONCLUSION: Compared to SEER, veterans with melanoma were diagnosed at later stages; however, both exhibited recent improvement in stage IV MSS.

Dynamic genome-wide gene expression and immune cell composition in the developing human placenta.

Despite the central role of the placenta in supporting a pregnancy, relatively little is known about transcriptomic and immune-cell changes that occur across gestation. To generate a reference gene expression map of first (T1), second (T2) and third (T3) trimester human placenta, and assess differences in transcriptome in maternal versus fetal side tissues sections of full-term placenta, we performed RNA-Seq analysis on 64 biopsy samples from 18 placentas across all three gestations. We identified 1120 differentially expressed genes in placenta tissues from T1 and T3 samples using a generalized linear model within DESeq2. In total, 411 and 709 genes were positively associated with T1 and T3 placenta, respectively. Comparison of the top 200 differentially expressed genes in the T1 placenta with T3 showed that most of the top enriched biological processes were related to cell division and proliferation. T1 and T2 tissues shared expression of fibroblast-specific COL6A2, HGF, and SPP1 genes. In T3 samples, the expression of genes relating to vasculature development and regulation were highly enriched. Monocytes and NK cell population increased in T3 compared to T1 and T2, whereas Hofbauer cell proportion expanded significantly in T2 and then decreased in T3 samples. There were no significant gene expression differences in the maternal vs. fetal side in T3 placentas. Gene expression patterns shift temporally across trimesters but not spatially across the placenta, at least at the resolution of the biopsy samples. The genes and gene set we identified here represent a valuable resource for studying pathology in pregnancy-related disorders.

Cutaneous Squamous Cell Carcinoma: The Frontier of Cancer Immunoprevention.

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer, with its incidence rising steeply. Immunosuppression is a well-established risk factor for cSCC, and this risk factor highlights the critical role of the immune system in regulating cSCC development and progression. Further highlighting the nature of cSCC as an immunological disorder, substantial evidence demonstrates a tight association between cSCC risk and age-related immunosenescence. Besides the proven efficacy of immune checkpoint blockade therapy for advanced cSCC, novel immunotherapy that targets cSCC precursor lesions has shown efficacy for cSCC prevention. Furthermore, the appreciation of the interplay between keratinocytes, commensal papillomaviruses, and the immune system has revealed the possibility for the development of a preventive cSCC vaccine. cSCC shares fundamental aspects of its origin and pathogenesis with mucosal SCCs. Therefore, advances in the field of cSCC immunoprevention will inform our approach to the management of mucosal SCCs and potentially other epithelial cancers.

Identifying Brigham and Women's Hospital stage T2a cutaneous squamous cell carcinomas at risk of poor outcomes.

BACKGROUND: Although most of the poor outcomes with cutaneous squamous cell carcinoma (CSCC) occur in high-stage tumors, 26% of nodal metastases and 8% of disease-specific deaths develop in Brigham and Women's Hospital (BWH) T2a tumors. OBJECTIVE: To determine risk factors associated with poor outcomes (nodal metastasis, distant metastases, and disease-specific deaths) in BWH T2a CSCC. METHODS: A 17-year retrospective multi-institutional cohort study of primary CSCC BWH T2a tumors. A predictive model based on tumor characteristics was developed to identify those at higher risk of poor outcomes. RESULTS: Presence of 1 major criterion (primary tumor diameter ≥40 mm, invasion depth beyond subcutaneous fat, poor differentiation, or large-caliber perineural invasion) and ≥ 1 minor criterion (invasion depth in subcutaneous fat, moderate differentiation, small-caliber perineural invasion, or lymphovascular invasion) was most predictive of developing poor outcomes (area under the curve, 0.53; C-statistic, 0.60). This model has a sensitivity of 7.7%, specificity of 97.4%, and a positive and negative predictive value of 33.3% and 86.1%, respectively. The 5-year cumulative incidence of poor outcomes in these tumors is 8.0% (95% CI, 5.1-13.7) compared to 2.8% (95% CI, 1.9-4.1) in other T2a tumors (sub-hazard ratio, 3.0; 95% CI, 1.5-5.8). LIMITATIONS: Multi-institutional cohort study was not externally validated. CONCLUSIONS: BWH T2a-high CSCCs have an 8% chance of developing poor outcomes.