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ABSTRACT BACKGROUND It remains unclear if minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is comparable to traditional, open TLIF because of the limitations of the prior small-sample-size, single-center studies reporting comparative effectiveness. OBJECTIVE To compare MI-TLIF to traditional, open TLIF for grade 1 degenerative lumbar spondylolisthesis in the largest study to date by sample size. METHODS We utilized the prospective Quality Outcomes Database registry and queried patients with grade 1 degenerative lumbar spondylolisthesis who underwent single-segment surgery with MI- or open TLIF methods. Outcomes were compared 24 mo postoperatively. RESULTS A total of 297 patients were included: 72 (24.2%) MI-TLIF and 225 (75.8%) open TLIF. MI-TLIF surgeries had lower mean body mass indexes (29.5 ± 5.1 vs 31.3 ± 7.0, P = .0497) and more worker's compensation cases (11.1% vs 1.3%, P < .001) but were otherwise similar. MI-TLIF had less blood loss (108.8 ± 85.6 vs 299.6 ± 242.2 mL, P < .001), longer operations (228.2 ± 111.5 vs 189.6 ± 66.5 min, P < .001), and a higher return-to-work (RTW) rate (100% vs 80%, P = .02). Both cohorts improved significantly from baseline for 24-mo Oswestry Disability Index (ODI), Numeric Rating Scale back pain (NRS-BP), NRS leg pain (NRS-LP), and Euro-Qol-5 dimension (EQ-5D) ( P > .001). In multivariable adjusted analyses, MI-TLIF was associated with lower ODI (β = −4.7; 95% CI = −9.3 to −0.04; P = .048), higher EQ-5D (β = 0.06; 95% CI = 0.01-0.11; P = .02), and higher satisfaction (odds ratio for North American Spine Society [NASS] 1/2 = 3.9; 95% CI = 1.4-14.3; P = .02). Though trends favoring MI-TLIF were evident for NRS-BP ( P = .06), NRS-LP ( P = .07), and reoperation rate ( P = .13), these results did not reach statistical significance. CONCLUSION For single-level grade 1 degenerative lumbar spondylolisthesis, MI-TLIF was associated with less disability, higher quality of life, and higher patient satisfaction compared with traditional, open TLIF. MI-TLIF was associated with higher rates of RTW, less blood loss, but longer operative times. Though we utilized multivariable adjusted analyses, these findings may be susceptible to selection bias.

OBJECTIVELoss to follow-up has been shown to bias outcomes assessment among studies utilizing clinical registries. Here, the authors analyzed patients enrolled in a national surgical registry and compared the baseline characteristics of patients captured with those lost to follow-up at 2 years.METHODSThe authors queried the Quality Outcomes Database for patients with grade I lumbar degenerative spondylolisthesis undergoing a surgical intervention between July 2014 and June 2016. Only those patients enrolled in a multisite study investigating the impact of fusion on clinical and patient-reported outcomes (PROs) among patients with grade I spondylolisthesis were evaluated.RESULTSOf the 608 patients enrolled in the study undergoing 1- or 2-level decompression (23.0%, n = 140) or 1-level fusion (77.0%, n = 468), 14.5% (n = 88) were lost to follow-up at 2 years. Patients who were lost to follow-up were more likely to be younger (59.6 ± 13.5 vs 62.6 ± 11.7 years, p = 0.031), be employed (unemployment rate: 53.3% [n = 277] for successful follow-up vs 40.9% [n = 36] for those lost to follow-up, p = 0.017), have anxiety (26.1% [n = 23] vs 16.3% [n = 85], p = 0.026), have higher back pain scores (7.4 ± 2.9 vs 6.6 ± 2.8, p = 0.010), have higher leg pain scores (7.4 ± 2.5 vs 6.4 ± 2.9, p = 0.003), have higher Oswestry Disability Index scores (50.8 ± 18.7 vs 46 ± 16.8, p = 0.018), and have lower EQ-5D scores (0.481 ± 0.2 vs 0.547 ± 0.2, p = 0.012) at baseline.CONCLUSIONSTo execute future, high-quality studies, it is important to identify patients undergoing surgery for spondylolisthesis who might be lost to follow-up. In a large, prospective registry, the authors found that those lost to follow-up were more likely to be younger, be employed, have anxiety disorder, and have worse PRO scores.

AbstractBackgroundThe epithelial cell‐derived danger signal mediators thymic stromal lymphopoietin (TSLP) and IL‐33 are consistently associated with adaptive Th2 immune responses in asthma. In addition, TSLP and IL‐33 synergistically promoted group 2 innate lymphoid cell (ILC2) activation to induce innate allergic inflammation. However, the mechanism of this synergistic ILC2 activation is unknown.MethodsBALB/c WT and TSLP receptor‐deficient (TSLPR−/−) mice were challenged intranasally with Alternaria extract (Alt‐Ext) or PBS for 4 consecutive days to evaluate innate airway allergic inflammation. WT mice pre‐administered with rTSLP or vehicle, TSLPR−/− mice, and IL‐33 receptor‐deficient (ST2−/−) mice were challenged intranasally with Alt‐Ext or vehicle once or twice to evaluate IL‐33 release and TSLP expression in the lung. TSLPR and ST2 expression on lung ILC2 were measured by flow cytometry after treatment of rTSLP, rIL‐33, rTSLP + rIL‐33, or vehicle.ResultsThymic stromal lymphopoietin receptor deficient mice had significantly decreased the number of lung ILC2 expressing IL‐5 and IL‐13 following Alt‐Ext‐challenge compared to WT mice. Further, eosinophilia, protein level of lung IL‐4, IL‐5, and IL‐13, and airway mucus score were also significantly decreased in TSLPR−/− mice compared to WT mice. Endogenous and exogenous TSLP increased Alt‐Ext‐induced IL‐33 release into BALF, and ST2 deficiency decreased Alt‐Ext‐induced TSLP expression in the lung. Further, rTSLP and rIL‐33 treatment reciprocally increased each other's receptor expression on lung ILC2 in vivo and in vitro.ConclusionThymic stromal lymphopoietin and IL‐33 signaling reciprocally enhanced each other's protein release and expression in the lung following Alt‐Ext‐challenge and each other's receptor expression on lung ILC2 to enhance ILC2 activation.

AbstractBuilding on an initiative to enhance clinical trial participation involving the Society for Neuro-Oncology, the Response Assessment in Neuro-Oncology Working Group, patient advocacy groups, clinical trial cooperative groups, and other partners, we evaluate the impact of eligibility criteria and trial conduct on neuro-oncology clinical trial participation. Clinical trials often carry forward eligibility criteria from prior studies that may be overly restrictive and unnecessary and needlessly limit patient accrual. Inclusion and exclusion criteria should be evaluated based on the goals and design of the study and whether they impact patient safety and/or treatment efficacy. In addition, we evaluate clinical trial conduct as a barrier to accrual and discuss strategies to minimize such barriers for neuro-oncology trials.

We investigated the mechanisms involved in the development of airway hyperresponsiveness (AHR) following exposure of mice to halogens. Male mice (C57BL/6; 20–25 g) exposed to either bromine (Br2) or Cl2(600 or 400 ppm, respectively, for 30 min) developed AHR 24 h after exposure. Nifedipine (5 mg/kg body wt; an L-type calcium channel blocker), administered subcutaneously after Br2or Cl2exposure, produced higher AHR compared with Br2or Cl2alone. In contrast, diltiazem (5 mg/kg body wt; a nondihydropyridine L-type calcium channel blocker) decreased AHR to control (air) values. Exposure of immortalized human airway smooth muscle cells (hASMC) to Br2resulted in membrane potential depolarization ( VmAir: 62 ± 3 mV; 3 h post Br2:−45 ± 5 mV; means ± 1 SE; P < 0.001), increased intracellular [Ca2+]i, and increased expression of the calcium-sensing receptor (Ca-SR) protein. Treatment of hASMC with a siRNA against Ca-SR significantly inhibited the Br2and nifedipine-induced Vmdepolarization and [Ca2+]iincrease. Intranasal administration of an antagonist to Ca-SR in mice postexposure to Br2reversed the effects of Br2and nifedipine on AHR. Incubation of hASMC with low-molecular-weight hyaluronan (LMW-HA), generated by exposing high-molecular-weight hyaluronan (HMW-HA) to Br2, caused Vmdepolarization, [Ca2+]iincrease, and Ca-SR expression to a similar extent as exposure to Br2and Cl2. The addition of HMW-HA to cells or mice exposed to Br2, Cl2, or LMW-HA reversed these effects in vitro and improved AHR in vivo. We conclude that detrimental effects of halogen exposure on AHR are mediated via activation of the Ca-SR by LMW-HA.

Abstract Background The proportion of tumors of various histologies that may respond to drugs targeted to molecular alterations is unknown. NCI-MATCH, a collaboration between ECOG-ACRIN Cancer Research Group and the National Cancer Institute, was initiated to find efficacy signals by matching patients with refractory malignancies to treatment targeted to potential tumor molecular drivers regardless of cancer histology. Methods Trial development required assumptions about molecular target prevalence, accrual rates, treatment eligibility, and enrollment rates as well as consideration of logistical requirements. Central tumor profiling was performed with an investigational next-generation DNA–targeted sequencing assay of alterations in 143 genes, and protein expression of protein expression of phosphatase and tensin homolog, mutL homolog 1, mutS homolog 2, and RB transcriptional corepressor 1. Treatments were allocated with a validated computational platform (MATCHBOX). A preplanned interim analysis evaluated assumptions and feasibility in this novel trial. Results At interim analysis, accrual was robust, tumor biopsies were safe (&lt;1% severe events), and profiling success was 87.3%. Actionable molecular alteration frequency met expectations, but assignment and enrollment lagged due to histology exclusions and mismatch of resources to demand. To address this lag, we revised estimates of mutation frequencies, increased screening sample size, added treatments, and improved assay throughput and efficiency (93.9% completion and 14-day turnaround). Conclusions The experiences in the design and implementation of the NCI-MATCH trial suggest that profiling from fresh tumor biopsies and assigning treatment can be performed efficiently in a large national network trial. The success of such trials necessitates a broad screening approach and many treatment options easily accessible to patients.

We clarify that DNA damage triggers autophagy by CHK2-FOXK axis, and misregulation of this pathway leads to chemoresistance.

OBJECTIVEDischarge to an inpatient rehabilitation facility or another acute-care facility not only constitutes a postoperative challenge for patients and their care team but also contributes significantly to healthcare costs. In this era of changing dynamics of healthcare payment models in which cost overruns are being increasingly shifted to surgeons and hospitals, it is important to better understand outcomes such as discharge disposition. In the current article, the authors sought to develop a predictive model for factors associated with nonroutine discharge after surgery for grade I spondylolisthesis.METHODSThe authors queried the Quality Outcomes Database for patients with grade I lumbar degenerative spondylolisthesis who underwent a surgical intervention between July 2014 and June 2016. Only those patients enrolled in a multisite study investigating the impact of fusion on clinical and patient-reported outcomes among patients with grade I spondylolisthesis were evaluated. Nonroutine discharge was defined as those who were discharged to a postacute or nonacute-care setting in the same hospital or transferred to another acute-care facility.RESULTSOf the 608 patients eligible for inclusion, 9.4% (n = 57) had a nonroutine discharge (8.7%, n = 53 discharged to inpatient postacute or nonacute care in the same hospital and 0.7%, n = 4 transferred to another acute-care facility). Compared to patients who were discharged to home, patients who had a nonroutine discharge were more likely to have diabetes (26.3%, n = 15 vs 15.7%, n = 86, p = 0.039); impaired ambulation (26.3%, n = 15 vs 10.2%, n = 56, p < 0.001); higher Oswestry Disability Index at baseline (51 [IQR 42–62.12] vs 46 [IQR 34.4–58], p = 0.014); lower EuroQol-5D scores (0.437 [IQR 0.308–0.708] vs 0.597 [IQR 0.358–0.708], p = 0.010); higher American Society of Anesthesiologists score (3 or 4: 63.2%, n = 36 vs 36.7%, n = 201, p = 0.002); and longer length of stay (4 days [IQR 3–5] vs 2 days [IQR 1–3], p < 0.001); and were more likely to suffer a complication (14%, n = 8 vs 5.6%, n = 31, p = 0.014). On multivariable logistic regression, factors found to be independently associated with higher odds of nonroutine discharge included older age (interquartile OR 9.14, 95% CI 3.79–22.1, p < 0.001), higher body mass index (interquartile OR 2.04, 95% CI 1.31–3.25, p < 0.001), presence of depression (OR 4.28, 95% CI 1.96–9.35, p < 0.001), fusion surgery compared with decompression alone (OR 1.3, 95% CI 1.1–1.6, p < 0.001), and any complication (OR 3.9, 95% CI 1.4–10.9, p < 0.001).CONCLUSIONSIn this multisite study of a defined cohort of patients undergoing surgery for grade I spondylolisthesis, factors associated with higher odds of nonroutine discharge included older age, higher body mass index, presence of depression, and occurrence of any complication.

OBJECTIVES: Preoperative decision-making for differentiating malignant from benign lesions in the gallbladder remains challenging. We aimed to create a diagnostic nomogram to identify gallbladder cancer (GBC), especially for incidental GBC (IGBC), before surgical resection. METHODS: A total of 587 consecutive patients with pathologically confirmed gallbladder lesions from a hospital were randomly assigned to a training cohort (70%) and an internal validation cohort (30%), with 287 patients from other centers as an external validation cohort. Radiological features were developed by the least absolute shrinkage and selection operator logistic regression model. Significant radiological features and independent clinical factors, identified by multivariate analyses, were used to construct a nomogram. RESULTS: A diagnostic nomogram was established by age, CA19.9, and 6 radiological features. The values of area under the curve in the internal and external validation cohorts were up to 0.91 and 0.89, respectively. The calibration curves for probability of GBC showed optimal agreement between nomogram prediction and actual observation. Compared with previous methods, it demonstrated superior sensitivity (91.5%) and accuracy (85.1%) in the diagnosis of GBC. The accuracy using the nomogram was significantly higher in GBC groups compared with that by radiologists in the training cohort ( P < 0.001) and similarly in each cohort. Notably, most of the IGBC, which were misdiagnosed as benign lesions, were successfully identified using this nomogram. DISCUSSION: A novel nomogram provides a powerful tool for detecting the presence of cancer in gallbladder masses, with an increase in accuracy and sensitivity. It demonstrates an unprecedented potential for IGBC identification.