Addressing the Impact of Race and Ethnicity on Musculoskeletal Spine Care in the United States.

➤ Despite being a social construct, race has an impact on outcomes in musculoskeletal spine care.➤ Race is associated with other social determinants of health that may predispose patients to worse outcomes.➤ The musculoskeletal spine literature is limited in its understanding of the causes of race-related outcome trends.➤ Efforts to mitigate race-related disparities in spine care require individual, institutional, and national initiatives.

Formal Radiologist Interpretations of Intraoperative Spine Radiographs Have Low Clinical Value.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate the clinical relevance, usefulness, and financial implications of intraoperative radiograph interpretation by radiologists in spine surgery. SUMMARY OF BACKGROUND DATA: Due to rising health care costs, spine surgery is under scrutiny to maximize value-based care. Formal radiographic analysis remains a potential source of unnecessary health care costs, especially for intraoperative radiographs. MATERIALS AND METHODS: A retrospective cohort analysis was performed on all adult elective spine surgeries at a single institution between July 2020 and July 2021. Demographic and radiographic data were collected, including intraoperative localization and post-instrumentation radiographs. Financial data were obtained through the institution's price estimator. Radiographic characteristics included time from radiographic imaging to completion of radiologist interpretation report, completion of radiologist interpretation report before the conclusion of surgical procedure, clinical relevance, and clinical usefulness. Reports were considered clinically relevant if the spinal level of the procedure was described and clinically useful if completed before the conclusion of the procedure and deemed clinically relevant. RESULTS: Four hundred eighty-one intraoperative localization and post-instrumentation radiographs from 360 patients revealed a median delay of 128 minutes between imaging and completion of the interpretive report. Only 38.9% of reports were completed before the conclusion of surgery. There were 79.4% deemed clinically relevant and only 33.5% were clinically useful. Localization reports were completed more frequently before the conclusion of surgery (67.2% vs. 34.4%) but with lower clinical relevance (90.1% vs. 98.5%) and clinical usefulness (60.3% vs. 33.6%) than post-instrumentation reports. Each patient was charged $32 to $34 for the interpretation fee, cumulating a minimum total cost of $15,392. CONCLUSIONS: Formal radiographic interpretation of intraoperative spine radiographs was of low clinical utility for spine surgeons. Institutions should consider optimizing radiology workflows to improve timeliness and clinical relevance or evaluate the necessity of reflexive consultation to radiology for intraoperative imaging interpretation to ensure that value-based care is maximized during spine surgeries. LEVEL OF EVIDENCE: 3.

Modified Clavien-Dindo-Sink Classification System for operative complications in adult spine surgery.

OBJECTIVE: Currently there is no standardized mechanism to describe or compare complications in adult spine surgery. Thus, the purpose of the present study was to modify and validate the Clavien-Dindo-Sink complication classification system for applications in spine surgery. METHODS: The Clavien-Dindo-Sink complication classification system was evaluated and modified for spine surgery by four fellowship-trained spine surgeons using a consensus process. A distinct group of three fellowship-trained spine surgeons completed a randomized electronic survey grading 71 real-life clinical case scenarios. The survey was repeated 2 weeks after its initial completion. Fleiss' and Cohen's kappa (κ) statistics were used to evaluate interrater and intrarater reliabilities, respectively. RESULTS: Overall, interobserver reliability during the first and second rounds of grading was excellent with a κ of 0.847 (95% CI 0.785-0.908) and 0.852 (95% CI 0.791-0.913), respectively. In the first round, interrater reliability ranged from good to excellent with a κ of 0.778 for grade I (95% CI 0.644-0.912), 0.698 for grade II (95% CI 0.564-0.832), 0.861 for grade III (95% CI 0.727-0.996), 0.845 for grade IV-A (95% CI 0.711-0.979), 0.962 for grade IV-B (95% CI 0.828-1.097), and 0.960 for grade V (95% CI 0.826-1.094). Intraobserver reliability testing for all three independent observers was excellent with a κ of 0.971 (95% CI 0.944-0.999) for rater 1, 0.963 (95% CI 0.926-1.001) for rater 2, and 0.926 (95% CI 0.869-0.982) for rater 3. CONCLUSIONS: The Modified Clavien-Dindo-Sink Classification System demonstrates excellent interrater and intrarater reliability in adult spine surgery cases. This system provides a useful framework to better communicate the severity of spine-related complications.

Examining the safety profile of a standard dose tranexamic acid regimen in spine surgery.

OBJECTIVE: Perioperative blood loss during spinal surgery is associated with complications and in-hospital mortality. Weight-based administration of tranexamic acid (TXA) has the potential to reduce blood loss and related complications in spinal surgery; however, evidence for standardized dosing is lacking. The purpose of this study was to evaluate the impact of a standardized preoperative 2 g bolus TXA dosing regimen on perioperative transfusion, blood loss, thromboembolic events, and postoperative outcomes in spine surgery patients. METHODS: An institutional review board approved this retrospective review of prospectively enrolled adult spine patients (> 18 years of age). Patients were included who underwent elective and emergency spine surgery between September 2018 and July 2021. Patients who received a standardized 2 g dose of TXA were compared to patients who did not receive TXA. The primary outcome measure was perioperative transfusion. Secondary outcomes included estimated blood loss and thromboembolic or other perioperative complications. Descriptive statistics were calculated, and continuous variables were analyzed with the two-tailed independent t-test, while categorical variables were analyzed with the Fisher's exact test or chi-square test. Stepwise multivariate regression analysis was performed to examine independent risk factors for perioperative outcomes. RESULTS: TXA was administered to 353 of 453 (78%) patients, and there were no demographic differences between groups. Although the TXA group had more operative levels and a longer operative time, the transfusion rate was not different between the TXA and no-TXA groups (7.4% vs 8%, p = 0.83). Stepwise multivariate regression found that the number of operative levels was an independent predictor of perioperative transfusion and that both operative levels and operative time were correlated with estimated blood loss. TXA was not identified as an independent predictor of any postoperative complication. CONCLUSIONS: A standardized preoperative 2 g bolus TXA dosing regimen was associated with an excellent safety profile, and despite increased case complexity in terms of number of operative levels and operative time, patients treated with TXA did not require more blood transfusions than patients not treated with TXA.

A Glio-Protective Role of mir-263a by Tuning Sensitivity to Glutamate.

Glutamate is a ubiquitous neurotransmitter, mediating information flow between neurons. Defects in the regulation of glutamatergic transmission can result in glutamate toxicity, which is associated with neurodegeneration. Interestingly, glutamate receptors are expressed in glia, but little is known about their function, and the effects of their misregulation, in these non-neuronal cells. Here, we report a glio-protective role for Drosophila mir-263a mediated by its regulation of glutamate receptor levels in glia. mir-263a mutants exhibit a pronounced movement defect due to aberrant overexpression of CG5621/Grik, Nmdar1, and Nmdar2. mir-263a mutants exhibit excitotoxic death of a subset of astrocyte-like and ensheathing glia in the CNS. Glial-specific normalization of glutamate receptor levels restores cell numbers and suppresses the movement defect. Therefore, microRNA-mediated regulation of glutamate receptor levels protects glia from excitotoxicity, ensuring CNS health. Chronic low-level glutamate receptor overexpression due to mutations affecting microRNA (miRNA) regulation might contribute to glial dysfunction and CNS impairment.

A conformation-induced fluorescence method for microRNA detection.

MicroRNAs play important roles in a large variety of biological systems and processes through their regulation of target mRNA expression, and show promise as clinical biomarkers. However, their small size presents challenges for tagging or direct detection. Innovation in techniques to sense and quantify microRNAs may aid research into novel aspects of microRNA biology and contribute to the development of diagnostics. By introducing an additional stem loop into the fluorescent RNA Spinach and altering its 3' and 5' ends, we have generated a new RNA, Pandan, that functions as the basis for a microRNA sensor. Pandan contains two sequence-variable stem loops that encode complementary sequence for a target microRNA of interest. In its sensor form, it requires the binding of a target microRNA in order to reconstitute the RNA scaffold for fluorophore binding and fluorescence. Binding of the target microRNA resulted in large changes in fluorescence intensity. The median fold change in fluorescence observed for the sensors tested was ∼50-fold. Pandan RNA sensors exhibit good signal-to-noise ratios, and can detect their target microRNAs within complex RNA mixtures.

Identifying the prevalence, trajectory, and determinants of psychological distress in extremity sarcoma.

Objective. Extremity sarcoma (ES) is a rare cancer that presents with unique challenges. This study was performed to identify the prevalence, trajectory, and determinants of distress and characterise sources of stress in this cohort. Methods. Consecutive patients with ES were prospectively recruited between May 2011 and December 2012. Questionnaires were administered during initial diagnosis and then six months and one year after surgery. Results. Distress was reported by about a third of our cohort and associated with poorer physical function, poorer quality of life, and pain. In addition to fears regarding mortality and life role changes, the most common sources of stress were centered on dissatisfaction with the healthcare system, such as frustrations with a lack of communication with the hospital regarding appointments and lack of education regarding management and outcomes. Conclusions. Psychological distress presents early in the cancer journey and persists up to one year after surgery. Distress is associated with negative outcomes. Active screening and effective interventions are necessary to improve outcomes. Sources of stress have been identified that may be amenable to targeted interventions.

The DNA damage response induces antigen presenting cell-like functions in fibroblasts.

The DNA damage response (DDR) alerts the immune system to the danger posed by DNA damage through the induction of damage-associated molecular pattern molecules, chemokines, and ligands for activating immune receptors such as lymphocyte function-associated antigen 1 (LFA-1), NKG2D, and DNAX accessory molecule 1 (DNAM-1). Here we provide evidence that OVA(257-264) -pulsed fibroblasts gain the ability to activate naïve OT-I CD8(+) T cells in response to DNA damage. The ability of fibroblasts to activate OT-I CD8(+) T cells depended on the upregulation of ICAM-1 on fibroblasts and DNAM-1 expression of CD8(+) T cells. OVA(257-264) -pulsed fibroblasts were able to induce a protective T-cell response against B16-OVA cells in a DDR-dependent manner. Hence, the DDR may alert the immune system to the presence of potentially dangerous cells by upregulating the expression of ligands that can induce the activation of innate and adaptive immune cells.

ATM activation mediates anticancer immunosurveillance by natural killer and T cells.

The DNA damage response (DDR), which is frequently activated in cancer cells, has been proposed to operate as an early barrier against oncogenesis. We have recently shown that ATM mediates the spontaneous regression of Eµ-myc-driven murine B-cell leukemia in a natural killer and T cell-dependent manner. The DDR partially enhanced immune recognition by stimulating the expression of the DNAM-1 ligand CD155.

Autonomic neuropathy in young people with type 1 diabetes: a systematic review.

Autonomic neuropathy is an under-recognized complication of diabetes, although it affects multiple organ systems and has widespread clinical manifestations including orthostatic hypotension, exercise intolerance, gastroparesis, diarrhea, constipation, and urinary incontinence. The most severe consequences include hypoglycemia unawareness and cardiovascular dysfunction. Autonomic neuropathy is also implicated in sudden unexplained deaths in otherwise healthy young people--the 'dead in bed syndrome'. In adults, cardiovascular autonomic neuropathy is an independent predictor of mortality, predominantly due to cardiovascular disease, nephropathy, and hypoglycemia. While overt autonomic neuropathy is rare in childhood and adolescence, subclinical signs of autonomic dysfunction are common, and can be found soon after diabetes diagnosis. Risk factors for autonomic neuropathy in young people include diabetes duration, poor glycemic control, and presence of aldose reductase gene (AKR1B1) polymorphisms, specifically the Z-2/Z-2 genotype. Autonomic dysfunction is accelerated by puberty.

ATM-dependent spontaneous regression of early Eµ-myc-induced murine B-cell leukemia depends on natural killer and T cells.

Mechanisms of spontaneous tumor regression have been difficult to characterize in a systematic manner due to their rare occurrence and the lack of model systems. Here, we provide evidence that early-stage B cells in Eµ-myc mice are tumorigenic and sharply regress in the periphery between 41 and 65 days of age. Regression depended on CD4(+), CD8(+), NK1.1(+) cells and the activation of the DNA damage response, which has been shown to provide an early barrier against cancer. The DNA damage response can induce ligands that enhance immune recognition. Blockade of DNAM-1, a receptor for one such ligand, impaired tumor regression. Hence, Eµ-myc mice provide a model to study spontaneous regression and possible mechanisms of immune evasion or suppression by cancer cells.

A systematic review of the recent quality of life studies in adult extremity sarcoma survivors.

Background. Extremity sarcoma represents a heterogeneous group of rare cancers that carries a relatively high morbidity with regards to physical function. Quality of Life (QoL) as an outcome is an important consideration in this cohort. We aimed to identify the correlates of QoL in extremity sarcoma cohorts. Methods. A systematic review of the literature on extremity sarcoma in adults from five databases over the last ten years was undertaken. Results. Twelve articles were chosen and assessed for quality. Physical and social function of extremity sarcoma survivors is below that of the general population. Overall QoL scores of these patients are comparable to those of the general population. Studies that used more recently treated cohorts found that patients who had limb sparing surgery displayed superior functional outcomes over those that underwent amputations. Pain and perceiving that the cancer negatively influenced opportunities was associated with poor outcomes. Conclusion. The available literature regarding QoL in extremity sarcoma patients is heterogeneous in terms of aims and assessment tools. Results need to be interpreted in light of the improved management of extremity sarcoma in more recent patient cohorts.

Single motherhood versus poor partner relationship: outcomes for antenatal mental health.

OBJECTIVE: In the transition to parenthood, lack of social support significantly impacts on maternal mood. This paper compares the influence of single-mother status and level of partner support in a partnered relationship, on antenatal emotional health. METHODS: Antenatal demographic, psychosocial and mental health data, as determined by Edinburgh Postnatal Depression Scale (EPDS) score, were collected from 1578 women. The association between these variables, and marital status, was investigated using logistic regression. RESULTS: Sixty-two women (3.9%) were identified as single/unpartnered. Elevated EPDS scores (>12) were found in 15.2% (240/1578) of the total cohort and 25.8% (16/62) of the single/unpartnered women. EPDS scores were significantly lower for single/unpartnered women than for women with unsupportive partners (8.9+/-5.3 vs 11.9+/-6.5, p<0.001). Compared to the partnered cohort, single/unpartnered women were more likely to have experienced >or=2 weeks of depression before the current pregnancy (p<0.05), a previous psychopathology (p<0.001), emotional problems during the current pregnancy (p<0.01) and major life events in the last year (p<0.01). Binary logistic regression modelling to predict antenatal EPDS scores suggests that this is mediated by previous psychiatric history (p<0.001) and emotional problems during pregnancy (p=0.02). CONCLUSION: Women in a partnered-relationship with poor partner-derived support were at an increased risk of elevated antenatal EPDS scores compared to single/unpartnered women. A previous history of depression and current emotional problems, rather than single mother status, were significant risk factors for elevated EPDS scores. The present study reiterates the contribution of psychosocial risk factors as important mediators of antenatal emotional health.