Poor clinical outcomes and immunoevasive contexture in SIRPα+ tumor-associated macrophages enriched muscle-invasive bladder cancer patients

ObjectivesIn tumor immune microenvironment, the functions of tumor-associated macrophages (TAMs), including phagocytosis and immunomodulatory, have attracted increasing attention recently. With the discovery of CD47–signal regulatory protein-α (SIRPα) as “don't eat me” signaling pathway, the role of novel subpopulation of TAMs expressing SIRPα has not been fully elucidated in a wide spectrum of solid tumors including bladder cancer. In this study, we investigated the prognostic and predictive implication of SIRPα⁺ TAMs regarding clinical outcomes and adjuvant chemotherapeutic benefit in muscle-invasive bladder cancer (MIBC), and preliminarily characterized the phenotypic features of SIRPα⁺ TAMs and its relationship with immune contexture.Materials and methodsA total of 141 histochemical MIBC samples from Zhongshan Hospital (ZS), 45 fresh tissue samples, and 391 MIBC patients from TCGA database were enrolled in this study. SIRPα⁺ TAMs was evaluated by immunohistochemical staining of CD68 and SIRPα, and flow cytometry fluorescence staining.ResultsOur results illustrated that SIRPα⁺ TAMs were enriched in MIBC specimens. Patients with high SIRPα⁺ TAMs infiltration suffered significant poor overall survival and recurrence-free survival (P = 0.0030 and P = 0.0282). SIRPα⁺ TAMs infiltration was an independent prognosticator in multivariate Cox model. Moreover, adjuvant chemotherapy (ACT) application showed significantly survival benefit in patients with low SIRPα⁺ TAMs infiltration (P = 0.0135). SIRPα⁺ TAMs with suppressive phenotype exhibited a positive correlation with immune tolerance and dysfunctional CD8⁺ T cells in MIBC.ConclusionsSIRPα⁺ TAMs infiltration indicated poor prognosis and ACT resistance in MIBC. Immunosuppressive SIRPα⁺ TAMs is closely related to immune evasion with exhausted T cells states, suggesting the prospect of SIRPα⁺ TAMs as a potential therapeutic target in MIBC.     

Risk factors for postoperative ileus after oblique lateral interbody fusion: a multivariate analysis

Background ContextOblique lateral interbody fusion (OLIF)–has become a widely used, efficient surgical tool for various degenerative lumbar conditions. Postoperative ileus (POI) is a relatively common complication after anterior lumbar interbody fusion due to the manipulation of the intestine during the surgical approach. However, to our knowledge, little is known about POI following OLIF even though it also involves bowel manipulation during a surgical procedure.PurposeTo assess the incidence of POI and identify independent risk factors for POI development after OLIF.Study Design/SettingRetrospective cohort study.Patient SampleAll consecutive patients who underwent OLIF and percutaneous pedicle screw instrumentation from August 2012 until October 2019 at a single institutionOutcome MeasuresPatient demographics (sex, age, body weight, height, and body mass index), comorbidities (diabetes mellitus, gastroesophageal reflux disease, antithrombotic medication, previous abdominal surgery, and previous lumbar surgery), and perioperative details (preoperative diagnosis, number of levels fused, inadvertent endplate fracture during cage insertion, type of interbody graft, intraoperative estimated blood loss, duration of surgery and anesthesia, the amount of intraoperative remifentanil and propofol used as anesthetic agents, the total postoperative retroperitoneal closed-suction drainage output, and the cumulative opioid dosage administered in the first 72 hours postoperatively).MethodsPOI was defined as 2 or more of the following at 72 hours postoperatively: (1) ongoing nausea or vomiting postoperatively, (2) the absence of flatus over last 24-hour period, (3) inability to tolerate an oral diet over last 24-hour period, (4) ongoing abdominal distention postoperatively, and (5) radiological confirmation. The subjects were divided into 2 groups: patients with POI and those without POI. Binary logistic regression analyses were performed on demographics, comorbidities, and perioperative factors to identify independent risk factors for POI.ResultsEighteen (3.9%) of 460 patients experienced POI after OLIF and percutaneous pedicle screw instrumentation. Patients with POI had a significantly longer postoperative length of hospital stay than those without POI (8.61 ± 2.66 vs 6.48 ± 2.64, p = .001). Multivariate logistic regression analysis identified inadvertent endplate fracture (adjusted odds ratio = 6.017, p = .001) and the amount of intraoperative remifentanil (adjusted odds ratio = 1.057, p = .024) as independent risk factors for the occurrence of POI following OLIF.ConclusionThis study identified inadvertent endplate fracture and the amount of intraoperative remifentanil as independent risk factors for the development of POI after OLIF.     

A clinical calculator for predicting intraoperative blood loss and transfusion risk in spine tumor patients

BACKGROUND CONTEXTSurgery for vertebral column tumors is commonly associated with intraoperative blood loss (IOBL) exceeding 2 liters and the need for transfusion of allogeneic blood products. Transfusion of allogeneic blood, while necessary, is not benign, and has been associated with increased rates of wound complication, venous thromboembolism, delirium, and death.PURPOSETo develop a prediction tool capable of predicting IOBL and risk of requiring allogeneic transfusion in patients undergoing surgery for vertebral column tumors.STUDY DESIGN/SETTINGRetrospective, single-center study.PATIENT SAMPLEConsecutive series of 274 patients undergoing 350 unique operations for primary or metastatic spinal column tumors over a 46-month period at a comprehensive cancer centerOUTCOME MEASURESIOBL (in mL), use of intraoperative blood products, and intraoperative blood products transfused.METHODSWe identified IOBL and transfusions, along with demographic data, preoperative laboratory data, and surgical procedures performed. Independent predictors of IOBL and transfusion risk were identified using multivariable regression.RESULTSMean age at surgery was 57.0±13.6 years, 53.1% were male, and 67.1% were treated for metastatic lesions. Independent predictors of IOBL included en bloc resection (p<.001), surgical invasiveness (β=25.43 per point; p<0.001), and preoperative albumin (β=?244.86 per g/dL; p=0.011). Predictors of transfusion risk included preoperative hematocrit (odds ratio [OR]=0.88 per %; 95% confidence interval [CI, 0.84, 0.93]; p<0.001), preoperative MCHgb (OR=0.88 per pg; 95% CI [0.78, 1.00]; p=0.048), preoperative red cell distribution width (OR=1.32 per %; 95% CI [1.13, 1.55]; p<0.001), en bloc resection (OR=3.17; 95%CI [1.33, 7.54]; p=0.009), and surgical invasiveness (OR=1.08 per point; [1.06; 1.11]; p<0.001). The transfusion model showed a good fit of the data with an optimism-corrected area under the curve of 0.819. A freely available, web-based calculator was developed for the transfusion risk model (https://jhuspine3.shinyapps.io/TRUST/).CONCLUSIONSHere we present the first clinical calculator for intraoperative blood loss and transfusion risk in patients being treated for primary or metastatic vertebral column tumors. Surgical invasiveness and preoperative microcytic anemia most strongly predict transfusion risk. The resultant calculators may prove clinically useful for surgeons counseling patients about their individual risk of requiring allogeneic transfusion.     

Representative dynamic ranges of spinal alignment during gait in patients with mild and severe adult spinal deformities

BACKGROUND CONTEXTSurgical correction strategies for adult spinal deformity (ASD) relies heavily on radiographic alignment goals, however, there is often debate regarding degree of correction and how static alignment translates to physical ability in daily life. Kinematic analysis has the potential to improve the concept of ideal spinal alignment by providing clinically meaningful estimates of dynamic changes in spinal alignment during activities of daily life.PURPOSEEstimate representative dynamic ranges of spinal alignment during gait among ASD patients using 3D motion tracking; compare dynamic alignment between mild and severe deformity patients and to healthy adults.STUDY DESIGN/SETTINGRetrospective review at a single institution.PATIENT SAMPLEFifty-two ASD patients and 46 healthy adults.OUTCOME MEASURESRadiographic alignment, kinematic spine motion, spatiotemporal gait measures, patient reported outcomes (VAS pain, ODI, SRS-22r).METHODSSpinal alignment was assessed radiographically and during standing and overground walking tests. Dynamic alignment was initialized by linking radiographic alignment to kinematic alignment during standing and at initial heel contact during gait. Dynamic changes in maximums and minimums during gait were made relative to initial heel contact for each gait cycle. Total range-of-motion (RoM) was measured for both ASD and healthy subjects. Dynamic alignment measures included coronal and sagittal vertical axes (CVA, SVA), T1 pelvic angle (TPA), lumbar lordosis (LL), and pelvic tilt (PT). ASD patient's deformities were classified as either Mild or Severe based on the SRS-Schwab ASD classification.RESULTSSevere ASD patients had significantly larger dynamic maximum and minimums for SVA, TPA, LL, and PT (all p<.05) compared with Mild ASD patients. ASD patients exhibited little difference in dynamic alignment compared with healthy subjects. Only PT had a significant difference in dynamic RoM compared with healthy (p<.001).CONCLUSIONSMild and Severe ASD patients exhibited similar global dynamic alignment measures during gait and had comparable RoM to healthy subjects except with greater PT and reduced spatiotemporal performance which may be key compensatory mechanisms for dynamic stabilization.