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OBJECTIVE Reduction of Meyerding grade is often performed during fusion for spondylolisthesis. Although radiographic appearance may improve, correlation with patient-reported outcomes (PROs) is rarely reported. In this study, the authors’ aim was to assess the impact of spondylolisthesis reduction on 24-month PRO measures after decompression and fusion surgery for Meyerding grade I degenerative lumbar spondylolisthesis. METHODS The Quality Outcomes Database (QOD) was queried for patients undergoing posterior lumbar fusion for spondylolisthesis with a minimum 24-month follow-up, and quantitative correlation between Meyerding slippage reduction and PROs was performed. Baseline and 24-month PROs, including the Oswestry Disability Index (ODI), EQ-5D, Numeric Rating Scale (NRS)–back pain (NRS-BP), NRS-leg pain (NRS-LP), and satisfaction (North American Spine Society patient satisfaction questionnaire) scores were noted. Multivariable regression models were fitted for 24-month PROs and complications after adjusting for an array of preoperative and surgical variables. Data were analyzed for magnitude of slippage reduction and correlated with PROs. Patients were divided into two groups: < 3 mm reduction and ≥ 3 mm reduction. RESULTS Of 608 patients from 12 participating sites, 206 patients with complete data were identified in the QOD and included in this study. Baseline patient demographics, comorbidities, and clinical characteristics were similarly distributed between the cohorts except for depression, listhesis magnitude, and the proportion with dynamic listhesis (which were accounted for in the multivariable analysis). One hundred four (50.5%) patients underwent lumbar decompression and fusion with slippage reduction ≥ 3 mm (mean 5.19, range 3 to 11), and 102 (49.5%) patients underwent lumbar decompression and fusion with slippage reduction < 3 mm (mean 0.41, range 2 to −2). Patients in both groups (slippage reduction ≥ 3 mm, and slippage reduction < 3 mm) reported significant improvement in all primary patient reported outcomes (all p < 0.001). There was no significant difference with regard to the PROs between patients with or without intraoperative reduction of listhesis on univariate and multivariable analyses (ODI, EQ-5D, NRS-BP, NRS-LP, or satisfaction). There was no significant difference in complications between cohorts. CONCLUSIONS Significant improvement was found in terms of all PROs in patients undergoing decompression and fusion for lumbar spondylolisthesis. There was no correlation with clinical outcomes and magnitude of Meyerding slippage reduction.

Objectives: Metastatic cancer has historically been considered fatal; however, there is a paucity of evidence characterizing the epidemiology of incidence, treatment, and outcomes in these patients. Materials and Methods: Incidence rates, annual percent change (APC), descriptive epidemiological statistics, and odds ratios for survival were calculated using registry data from the Surveillance, Epidemiology, and End Results (SEER) and the National Cancer Database (NCDB), 1998 to 2015. Results: There were a total of 1,055,860 patients with metastatic cancer. The most frequent primary cancers were lung (42.6%), colorectal (9.5%), and ovarian (5.5%). Metastatic lung and colorectal cancer incidence decreased, APC: −1.57 (P<0.001) and APC: −1.48 (P<0.001), respectively; metastatic pancreatic cancer incidence increased, APC: 0.62 (P=0.001). The use of local therapies decreased for almost all sites, and the use of systemic therapies increased across multiple sites: single-agent chemotherapy in kidney (2.54% increase/year), female breast (1.14% increase/year), and prostate cancer (1.08% increase/year); multiagent chemotherapy, most notably in pancreas (2.23% increase/year), uterus (1.81% increase/year), and colorectal cancer (1.54% increase/year). Increased utilization of immunotherapy was observed across the majority of sites, most notably in melanoma (2.14% increase/year). Patients diagnosed from 2006 to 2010 had 17.4% higher odds of surviving at least 60 months compared with 1998 to 2002. Conclusions: In this study, metastatic disease has been shown to have unique epidemiological patterns, and survival has improved. Continued research on metastatic disease is important in understanding and addressing the distinct health concerns of this population.

Abstract BACKGROUND Trials of lumbar spondylolisthesis are difficult to compare because of the heterogeneity in the populations studied. OBJECTIVE To define patterns of clinical presentation. METHODS This is a study of the prospective Quality Outcomes Database spondylolisthesis registry, including patients who underwent single-segment surgery for grade 1 degenerative lumbar spondylolisthesis. Twenty-four-month patient-reported outcomes (PROs) were collected. A k-means clustering analysis—an unsupervised machine learning algorithm—was used to identify clinical presentation phenotypes. RESULTS Overall, 608 patients were identified, of which 507 (83.4%) had 24-mo follow-up. Clustering revealed 2 distinct cohorts. Cluster 1 (high disease burden) was younger, had higher body mass index (BMI) and American Society of Anesthesiologist (ASA) grades, and globally worse baseline PROs. Cluster 2 (intermediate disease burden) was older and had lower BMI and ASA grades, and intermediate baseline PROs. Baseline radiographic parameters were similar ( P > .05). Both clusters improved clinically ( P < .001 all 24-mo PROs). In multivariable adjusted analyses, mean 24-mo Oswestry Disability Index (ODI), Numeric Rating Scale Back Pain (NRS-BP), Numeric Rating Scale Leg Pain, and EuroQol-5D (EQ-5D) were markedly worse for the high-disease-burden cluster (adjusted- P < .001). However, the high-disease-burden cluster demonstrated greater 24-mo improvements for ODI, NRS-BP, and EQ-5D (adjusted- P < .05) and a higher proportion reaching ODI minimal clinically important difference (MCID) (adjusted- P = .001). High-disease-burden cluster had lower satisfaction (adjusted- P = .02). CONCLUSION We define 2 distinct phenotypes—those with high vs intermediate disease burden—operated for lumbar spondylolisthesis. Those with high disease burden were less satisfied, had a lower quality of life, and more disability, more back pain, and more leg pain than those with intermediate disease burden, but had greater magnitudes of improvement in disability, back pain, quality of life, and more often reached ODI MCID.

AbstractBackgroundThe aim of this study was to investigate the combined effect of mesenchymal stem cells (MSC) and local delivery of tacrolimus (FK506) on nerve regeneration when applied to nerve autografts and decellularized allografts.MethodsA three‐dimensional in vitro compartmented cell culture system consisting of a neonatal dorsal root ganglion adjacent to a nerve graft was used to evaluate the regenerating neurites into the peripheral nerve scaffold. Nerve autografts and allografts were treated with (i) undifferentiated MSCs, (ii) FK506 (100 ng/mL) or (iii) both (N = 9/group). After 48 hours, neurite extension was measured to quantify nerve regeneration and stem cell viability was evaluated.ResultsStem cell viability was confirmed in all MSC‐treated grafts. Neurite extension was superior in autografts treated with FK506, and MSCs and FK506 combined (p < 0.001 and p = 0.0001, respectively), and autografts treated with MSCs (p = 0.12) were comparable to untreated autografts. In allografts, FK506 treatment and combined treatment were superior to controls (p < 0.001 and p = 0.0001, respectively), and treatment with MSCs (p = 0.09) was comparable to controls. All autograft groups were superior compared to their respective allograft treatment group (p < 0.05) in neurite extension.ConclusionsAlone, either MSC or FK506 treatment improved neurite outgrowth, and combined they further enhanced neurite extension in both autografts and allografts.

Purpose: To review the current options in the management of Warthin tumors (WTs) and to propose a working management protocol. Methods: A systematic literature search was conducted using PubMed and ScienceDirect database. A total of 141 publications were selected and have been included in this review. Publications were selected based on relevance, scientific evidence, and actuality. Results: The importance of parotid WTs is increasing due to its rising incidence in many countries, becoming the most frequently encountered benign parotid tumor in certain parts of the world. In the past, all WTs were treated with surgery, but because of their slow growth rate, often minimal clinical symptoms, and the advanced age of many patients, active observation has gradually become more widely used. In order to decide on active surveillance, the diagnosis of WT must be reliable, and clinical, imaging, and cytological data should be concordant. There are four clear indications for upfront surgery: uncertain diagnosis; cosmetic problems; clinical complaints, such as pain, ulceration, or recurrent infection; and the patient’s wish to have the tumor removed. In the remaining cases, surgery can be elective. Active surveillance is often suggested as the first approach, with surgery being considered if the tumor progresses and/or causes clinical complaints. The extent of surgery is another controversial topic, and the current trend is to minimize the resection using partial parotidectomies and extracapsular dissections when possible. Recently, non-surgical options such as microwave ablation, radiofrequency ablation, and ultrasound-guided ethanol sclerotherapy have been proposed for selected cases. Conclusions: The management of WT is gradually shifting from superficial or total parotidectomy to more conservative approaches, with more limited resections, and to active surveillance in an increasing number of patients. Additionally, non-surgical treatments are emerging, but their role needs to be defined in future studies.

Abstract Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5–52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13). MAPK pathway activating alterations were identified in all 13 cases. Fusions were present in the 7 youngest patients: FGFR2-CTNNA3 (n = 2), FGFR2-KIAA1598 (FGFR2-SHTN1) (n = 1), FGFR2-INA (n = 1), FGFR2-MPRIP (n = 1), QKI-NTRK2 (n = 1), and KIAA1549-BRAF (n = 1). BRAF V600E mutation was present in 6 patients (17 years or older). Two fusion-positive cases additionally harbored TP53/RB1 abnormalities suggesting biallelic inactivation. Copy number changes predominantly involving whole chromosomes were observed in all 10 evaluated cases, with losses of chromosome 10q occurring with FGFR2-KIAA1598 (SHTN1)/CTNNA3 fusions. The KIAA1549-BRAF and QKI-NTRK2 fusions were associated respectively with a 7q34 deletion and 9q21 duplication. This study shows that despite its name, PLNTY also occurs in older adults, who frequently show BRAF V600E mutation. It also expands the spectrum of the MAPK pathway activating alterations associated with PLNTY and demonstrates recurrent chromosomal copy number changes consistent with chromosomal instability.

Abstract This study evaluated neoadjuvant niraparib antitumor activity and safety in patients with localized HER2-negative, BRCA-mutated breast cancer. Twenty-one patients received niraparib 200 mg once daily in 28-day cycles. After 2 cycles, tumor response (≥30% reduction from baseline) by MRI was 90.5% and 40.0% (6/15) of patients who only received niraparib (2–6 cycles) had pathological complete response. No new safety signals were identified and high niraparib intratumoral concentration was observed.

Abstract In the present study, acute onset of severe lupus nephritis was successfully treated in mice using a new, benzamide‐linked, small molecule that targets immune modulation and the NLRP3 inflammasome. Specifically, 6‐(2,4‐difluorophenyl)‐3‐(3‐(trifluoromethyl)phenyl)‐2H‐benzo[e][1,3]oxazine‐2,4(3H)‐dione (Cf‐02) (a) reduced serum levels of IgG anti‐dsDNA, IL‐1β, IL‐6, and TNF‐α, (b) inhibited activation of dendritic cells and differentially regulated T cell functions, and (c) suppressed the NF‐κB/NLRP3 inflammasome axis, targeting priming and activating signals of the inflammasome. Moreover, treatment with Cf‐02 significantly inhibited secretion of IL‐1β in lipopolysaccharide‐stimulated macrophages, but this effect was abolished by autophagy induction. These results recommend Cf‐02 as a promising drug candidate for the serious renal conditions associated with systemic lupus erythematosus. Future investigations should examine whether Cf‐02 may also be therapeutic in other types of chronic kidney disease involving NLRP3 inflammasome‐driven signaling.