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Spine surgery and its corresponding costs have increased in recent years and are variable across geographic regions. Discretionary care is the component of spending variation that is independent of illness severity, age, and regional pricing. It is unknown whether greater discretionary care is associated with improved safety for patients undergoing spine surgery, as we would expect from value-based health care.We conducted an analysis of 5 spine surgery cohorts based on Medicare claims from 2013 to 2017. Patients were grouped into quintiles based on the Dartmouth Atlas End-of-Life Inpatient Care Index (EOL), reflecting regional spending variation attributed to discretionary care. Multivariable regression examined the association between discretionary care and safety measures while controlling for age, sex, race, comorbidity, and hospital features.We observed a threefold to fourfold variation in 90-day episode-of-care cost across regions, depending on the cohort. Spine-specific spending was correlated with EOL quintile, confirming that spending variation is due more to discretionary care than it is to pricing, age, or illness severity. Greater spending across EOL quintiles was not associated with improved safety, and, in fact, was associated with poorer safety in some cohorts. For example, all-cause readmission was greater in the high-spending EOL quintile relative to the low-spending EOL quintile among the "fusion, except cervical" cohort (14.2% vs. 13.1%; OR = 1.10; 95% CI = 1.05 to 1.20), the "complex fusion" cohort (28.0% vs. 25.4%; OR = 1.15; 95% CI = 1.01 to 1.30), and the "cervical fusion" cohort (15.0% vs. 13.6%; OR = 1.12; 95% CI = 1.05 to 1.20).Wide variation in spending was not explained by differences in illness severity, age, or pricing, and increased discretionary care did not enhance safety. These findings point to inefficient use of health-care resources, a potential focus of reform.Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

Anal cancer has increasing incidence and is preceded by high‐grade anal intraepithelial neoplasia (HGAIN; AIN2–3). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV‐positive (HIV+) men who have sex with men (MSM). This study aimed to evaluate these markers in HIV‐negative risk groups. A cross‐sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1 and control biopsies obtained in HIV‐negative women and men was tested for six methylation markers (ASCL1, LHX8, SST, WDR17, ZIC1 and ZNF582). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed‐effect ordinal logistic regression. Methylation levels of all markers increased with increasing severity of disease (P, Host cell DNA methylation plays a role in anal carcinogenesis in HIV‐negative (HIV‐neg) and HIV‐positive (HIV+) individuals, including men who have sex with men (MSM). Methylation levels are increased in high‐grade anal intraepithelial neoplasia at risk of progression towards anal cancer, making methylation markers promising prognostic biomarkers.

Bovine endometrium consists of epithelial and stromal cells that respond to conceptus interferon tau (IFNT), the maternal recognition of pregnancy (MRP) signal, by increasing expression of IFN-stimulated genes (ISGs). Endometrial epithelial and stromal-cell-specific ISGs are largely unknown but hypothesized to have essential functions during pregnancy establishment. Bovine endometrial epithelial cells were cultured in inserts above stromal fibroblast (SF) cells for 6 h in medium alone or with IFNT. The epithelial and SF transcriptomic response was analyzed separately using RNA sequencing and compared to a list of 369 DEGs recently identified in intact bovine endometrium in response to elongating bovine conceptuses and IFNT. Bovine endometrial epithelial and SF shared 223 and 70 DEGs in common with the list of 369 endometrial DEGs. Well-known ISGs identified in the epithelial and SF were ISG15, MX1, MX2, and OAS2. DEGs identified in the epithelial but not SF included a number of IRF molecules (IRF1, IRF2, IRF3, and IRF8), mitochondria SLC transporters (SLC25A19, SLC25A28, and SLC25A30), and a ghrelin receptor. Expression of ZC3HAV1, an anti-retroviral gene, increased specifically within the SF. Gene ontology analysis identified the type I IFN signaling pathway and activation of nuclear factor kappa B transcription factors as biological processes associated with the epithelial cell DEGs. This study has identified biologically relevant IFNT-stimulated genes within specific endometrial cell types. The findings provide critical information regarding the effects of conceptus IFNT on specific endometrial compartments during early developmental processes in cattle.Summary sentenceConceptus-induced, interferon-tau-dependent genes were identified within bovine endometrial epithelial and stromal fibroblast cells providing critical information regarding conceptus-induced modifications to specific endometrial compartments in cattle.

Background Minimal clinically important differences (MCIDs) for different patient outcome scores have been reported for various shoulder diseases, including shoulder arthroplasty and the nonoperative treatment of rotator cuff disease. The purpose of this study was to assess the MCID for the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, the Simple Shoulder Test (SST), and a visual analog scale (VAS) measuring pain, after arthroscopic rotator cuff repair. Methods A total of 202 patients who underwent arthroscopic rotator cuff repair were retrospectively reviewed. ASES, SST, and VAS pain scores were collected preoperatively and at 1 year postoperatively. The MCID was then calculated via a 4-question anchor–based method. Results The MCID results for the ASES, SST, and VAS pain scores were 27.1, 4.3, and 2.4, respectively. Age at time of surgery, sex, anteroposterior tear size, and worker's compensation status were not associated with MCID values (P > .05). Conclusion The MCID values determined in the current study are higher than those previously identified for the nonoperative treatment of rotator cuff disease using the same anchor questions. Use of these higher values should be considered when evaluating improvements of individual patients after rotator cuff repair, to determine comparative effectiveness of various rotator cuff repair techniques and to determine sample sizes for prospective comparative trials of rotator cuff repair methods.

Heat stress and uterine diseases, including metritis and endometritis, both reduce milk yields and reduce reproductive performance. Bacterial growth is promoted by elevated temperature while heat stress reduces host immune cell function, but it is not known whether increased environmental temperature promotes uterine disease by altering host immunity or bacterial growth. We hypothesize that seasonal variations in environmental temperature influence metritis incidence in the dairy cow independent of bacterial prevalence in the reproductive tract. To investigate how environmental temperature may impact metritis incidence, records of 3507 calvings in Florida over a 5-year period were evaluated. The incidence of metritis increased from 21.1% in the cool season (October through March) to 24.2% during the warm season (April through September, P 0.05). To elucidate a link between environmental temperature and uterine disease, 102 cows were enrolled during the warm season (September 2017; n = 51) and cool season (February-March 2018; n = 51). Cows were maintained on pasture during the dry period and moved to free stall barns with fans and water soakers immediately prior to calving and remained in that environment after calving. Vaginal mucus was collected and scored on days 7 (to evaluate metritis) and 21 (to evaluate endometritis) postpartum to evaluate the incidence of uterine disease and quantify bacterial content and species using qPCR. Daily milk yield for the first 60 DIM was reduced during the warm season compared with the cool season (32.6 ± 1.62 vs 37.23 ± 1.60 kg, P 0.05) consistent with effects of prepartum heat stress. Interestingly, more cows had persistent uterine disease on both d 7 and d 21 in the warm season compared with the cool season (58.0 vs 29.4%, P 0.05). Regardless of calving season the total bacterial content in the vagina was greater on d 7 compared to d 21. While metritis incidence was increased in the warm season, the vaginal content of total bacteria, Escherichia coli, Trueperella pyogenes, Fusobacterium necrophorum and Prevotella melaninogenica were similar during the cool season and the warm season. Our data suggests that prepartum heat stress related to season of calving increased the incidence of metritis and persistence of uterine disease in the dairy cow independent of vaginal bacteria content. The possibility that prepartum heat stress perturbs host immune function and increases the risk of metritis when cows are exposed to an equivalent number of pathogenic bacteria requires further investigation.

Pregnancy induces changes in the transcriptome of the bovine endometrium from 15 days after insemination. However, pregnancy is less likely to occur if cows had a postpartum bacterial infection of the uterus, even after the resolution of disease. We hypothesized that uterine bacterial infection alters the endometrial transcriptomic signature of pregnancy after the resolution of disease. To examine the endometrial transcriptomic signature of pregnancy, cows were inseminated 130 days after intrauterine infusion of pathogenic Escherichia coli and Trueperella pyogenes, subsequently endometrium was collected 16 days after insemination for RNA sequencing. We found 171 pregnancy regulated genes in cows 146 days after bacterial infection. When comparing our findings with previous studies that described the endometrial transcriptomic signature of pregnancy in healthy cows, 24 genes were consistently differentially expressed in pregnancy, including MX1, MX2 and STAT1. However, 12 pregnancy regulated genes were found only in the endometrium of healthy cows, including ISG15 and TRANK1. Furthermore, 28 pregnancy regulated genes were found only in the endometrium of cows following bacterial infection and these were associated with altered iNOS, TLR, and IL-7 signaling pathways. Although 94 predicted upstream regulators were conserved amongst the studies, 14 were found only in the endometrium of pregnant healthy cows, and 5 were found only in cows following bacterial infection, including AIRE, NFKBIA, and DUSP1. In conclusion, there were both consistent and discordant features of the endometrial transcriptomic signature of pregnancy 146 days after intrauterine bacterial infusion. These findings imply that there is an essential transcriptomic signature of pregnancy, but that infection induces long-term changes in the endometrium that affect the transcriptomic response to pregnancy.

Colorectal cancer (CRC) is the second leading cause for cancer-related death globally. Clinically, there is an urgent need for non-invasive CRC detection. This study assessed the feasibility of CRC detection by analysis of tumor-derived methylated DNA fragments in urine. Urine samples, including both unfractioned and supernatant urine fractions, of 92 CRC patients and 63 healthy volunteers were analyzed for DNA methylation levels of 6 CRC-associated markers (SEPT9, TMEFF2, SDC2, NDRG4, VIM and ALX4). Optimal marker panels were determined by two statistical approaches. Methylation levels of SEPT9 were significantly increased in urine supernatant of CRC patients compared to controls (p SEPT9 and SDC2 was able to detect up to 70% of CRC cases in urine supernatant at 86% specificity. First evidence is provided for CRC detection in urine by SEPT9 methylation analysis, which combined with SDC2 allows for an optimal differentiation between CRC patients and controls. Urine therefore provides a promising liquid biopsy for non-invasive CRC detection.

OBJECTIVE: To understand whether the Comprehensive Care for Joint Replacement (CJR) program induces participating hospitals to (1) preferentially select lower risk patients, (2) reduce 90‐day episode‐of‐care costs, (3) improve quality of care, and (4) achieve greater cost reduction during its second year, when downside financial risk was applied. DATA SOURCES: We identified beneficiaries of age 65 years or older undergoing hip or knee joint replacement in the 100% sample of Medicare fee‐for‐service inpatient (Part A) claims from January 1, 2013 to August 31, 2017. Cases were linked to subsequent outpatient, Part B, home health agency, and skilled nursing facility claims, as well as publicly available participation status for CJR. STUDY DESIGN: We estimated the effect of CJR for hospitals in the 67 metropolitan statistical areas (MSA) selected to participate in CJR (785 hospitals), compared to those in 104 non‐CJR MSAs (962 hospitals; maintaining fee‐for‐service). A difference‐in‐differences approach was used to detect patient selection, as well as to compare 90‐day episode‐of‐care costs and quality of care between CJR and non‐CJR hospitals over the first two performance years. DATA COLLECTION: We excluded 172 hospitals from our analysis due to their preexisting BPCI participation. We focused on elective admissions in the main analysis. PRINCIPAL FINDINGS: While reductions in 90‐day episode‐of‐care costs were greater among CJR hospitals (−$902, 95% CI: −$1305, −$499), largely driven by a 16.8% (p

STUDY DESIGN Surgeon survey. OBJECTIVE To examine factors influencing surgeons' definition of instability in grade 1 degenerative spondylolisthesis (DS) and assess treatment preferences for both stable and unstable DS. SUMMARY OF BACKGROUND DATA DS treatment options are broadly classified as decompression with or without fusion. In surgical decision-making, "instability" is frequently considered as a key factor. However, no consensus on the definition of instability exists. METHODS A survey was conducted to ascertain the minimum amounts of static translation, dynamic translation, and angulation change that surgeons considered significant for determining instability. The importance of other clinical and radiographic features were also assessed, and respondents' standard treatment for stable and unstable DS. RESULTS Out of 226 respondents, 99% deemed dynamic translation moderately to extremely influential for determining instability, whereas only 55% found static translation as important. The most prevalent cut-off values for dynamic (57%) and static translation (32%) were at least 2-4 mm and for angulation change at least 10-15 degrees (43%). Facet angulation was considered moderately to extremely important to determine instability by 69% of the surgeons, disk height by 67%, patient age by 64%, severity of stenosis by 55%, severity of back pain by 50%, patient-reported function by 49%, pelvic incidence by 47%, and severity of neurogenic claudication by 42%.Decompression with fusion was the preferred treatment method for unstable DS in 99% of the respondents. For stable DS, 40% would still perform fusion, whereas 60% preferred treatment with decompression-alone. Those who preferred fusion for stable DS reported significantly lower thresholds for static (P

Metritis is associated with reduced fertility in dairy cows, but the mechanisms are unclear because the disease resolves several weeks before insemination. One hypothesis is that metritis causes persistent changes in granulosa cells during follicle development, which might be evident in the transcriptome of granulosa cells from dominant follicles weeks after parturition. To test this hypothesis, we collected the follicular fluid and granulosa cells from dominant follicles 63 days post partum from cows previously diagnosed with metritis, at least 6 weeks after resolution of the disease and from cows not diagnosed with metritis (control cows). Bacterial lipopolysaccharide was detected in follicular fluid, and concentrations were associated with follicular fluid IL-8 and glucose concentrations. Transcriptome analysis using RNAseq revealed 177 differentially expressed genes in granulosa cells collected from cows that had metritis compared with control cows. The most upregulated genes wereITLN1,NCF2,CLRN3,FSIP2andANKRD17, and the most downregulated genes wereACSM1,NR4A2,GHITM,CBARPandNR1I3. Pathway analysis indicated that the differentially expressed genes were involved with immune function, cell–cell communication, cell cycle and cellular metabolism. Predicted upstream regulators of the differentially expressed genes included NFκB, IL-21 and lipopolysaccharide, which are associated with infection and immunity. Our data provide evidence for a persistent effect of metritis on the transcriptome of granulosa cells in ovarian follicles after the resolution of disease.

Analysis of National Inpatient Sample (NIS), 2004 to 2015.Describe recent trends in US rates of lumbar fusion procedures and associated costs, by surgical indication.Spinal fusion is appropriate for spinal deformity and instability, but evidence of effectiveness is limited for primary disc herniation and spinal stenosis without instability. It remains controversial for treatment of axial pain secondary to degenerative disc disease. There are potential non-instability, non-deformity indications for fusion surgery, including but not limited to severe foraminal stenosis and third-time disc herniation.Elective lumber fusion trends were reported using Poisson regression, grouped by indication as degenerative scoliosis, degenerative spondylolisthesis, spinal stenosis, disc herniation, and disc degeneration. Generalize linear regression was used to estimate trends in hospital costs, adjusted for age, sex, indication, comorbidity, and inflation.Volume of elective lumbar fusion increased 62.3% (or 32.1% per 100,000 US adults), from 122,679 cases (60.4 per 100,000) in 2004 to 199,140 (79.8 per 100,000) in 2015. Increases were greatest among age 65 or older, increasing 138.7% by volume (73.2% by rate), from 98.3 per 100,000 (95% confidence interval [CI] 97.2, 99.3) in 2004 to 170.3 (95% CI 169.2, 171.5) in 2015. Although the largest increases were for spondylolisthesis (+47,390 operations, 111%) and scoliosis (+16,129 operations, 186.6%), disc degeneration, herniation, and stenosis combined to accounted for 42.3% of total elective lumbar fusions in 2015. Aggregate hospital costs increased 177% during these 12 years, exceeding $10 billion in 2015, and averaging more than $50,000 per admission.While the prevalence of spinal pathologies is not known, the rate of elective lumbar fusion surgery in the United States increased most for spondylolisthesis and scoliosis, indications with relatively good evidence of effectiveness. The proportion of fusions coded for indications with less evidence of effectiveness has slightly decreased in the most recent years.3.

Nasal chondrocytes (NCs) have gained increased recognition for cartilage tissue regeneration. To assess NCs as a source for cell therapy treatment of intervertebral disc (IVD) degeneration, tissue-forming properties of NCs under physiological conditions mimicking the degenerated IVD were compared to those of mesenchymal stromal cells (MSCs) and articular chondrocytes (ACs), two cell sources presently used in clinical trials. Cells were cultured in a combination of low glucose, hypoxia, acidity and inflammation for 28 d. Depending on the conditions, cells were either cultured in the absence of instructive growth factors or underwent chondrogenic instructional priming by addition of transforming growth factor β1 (TGFβ1) for the first 7 d. Histology, immunohistochemistry, biochemistry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses demonstrated limited cell maintenance and accumulation of cartilaginous extracellular matrix for MSCs in IVD conditions. ACs maintained a steady accumulation of glycosaminoglycans (GAGs) throughout all non-acidic conditions, with and without priming, but could not synthesise type II collagen (Col2). NCs accumulated both GAGs and Col2 in all non-acidic conditions, independent of priming, whereas MSCs strongly diminished their GAG and Col2 accumulation in an inflamed environment. Supplementation with inflammatory cytokines or an acidic environment affected NCs to a lower extent than ACs or MSCs. The data, overall indicating that in an inflamed IVD environment NCs were superior to ACs and MSCs, encourage further assessment of NCs for treatment of degenerative disc disease.

Background: Numerous studies have reported the incidence and outcomes of injuries in the men’s and women’s National Basketball Association (NBA and WNBA, respectively). Purpose: To synthesize published data regarding the incidence and outcomes of all injuries in the NBA and WNBA in a comprehensive review. Study Design: Systematic review; Level of evidence, 4. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched 3 electronic databases (PubMed, MEDLINE, Embase) for studies of all levels of evidence since 1990 pertaining to injuries sustained by active players in the NBA and WNBA. Studies were excluded if the cohort of interest included ≤3 active players. Results: The initial search of the 3 databases yielded 1253 unique studies, of which 49 met final inclusion criteria for this review. Only 4 studies included athletes in the WNBA. Based on the mean annual incidence, the 5 most common orthopaedic sports injuries sustained in the NBA were concussions (9.5-14.9 per year), fractures of the hand (3.5-5.5 per year), lower extremity stress fractures (4.8 per year), meniscal tears (2.3-3.3 per year), and anterior cruciate ligament tears (1.5-2.6 per year). Cartilage defects treated using microfracture, Achilles tendon ruptures, and anterior cruciate ligament injuries were 3 injuries that led to significant reductions in performance measurements after injury. Conclusion: With advances in sports technology and statistical analysis, there is rapidly growing interest in injuries among professional basketball athletes. High-quality prospective studies are needed to understand the prevalence and effect of injuries on player performance and career length. This information can inform preventative and treatment measures taken by health care providers to protect players and guide safe return to play at a high level.

Bovine granulosa cells are often exposed to energy stress, due to the energy demands of lactation, and exposed to lipopolysaccharide from postpartum bacterial infections. Granulosa cells mount innate immune responses to lipopolysaccharide, including the phosphorylation of mitogen-activated protein kinases and production of pro-inflammatory interleukins. Cellular energy depends on glycolysis, and energy stress activates intracellular AMPK (AMP-activated protein kinase), which in turn inhibits mTOR (mechanistic target of rapamycin). Here, we tested the hypothesis that manipulating glycolysis, AMPK or mTOR to mimic energy stress in bovine granulosa cells limits the inflammatory responses to lipopolysaccharide. We inhibited glycolysis, activated AMPK or inhibited mTOR in granulosa cells isolated from 4–8mm and from > 8.5 mm diameter ovarian follicles, and then challenged the cells with lipopolysaccharide and measured the production of interleukins IL-1α, IL-1β, and IL-8. We found that inhibiting glycolysis with 2-deoxy-d-glucose reduced lipopolysaccharide-stimulated IL-1α > 80%, IL-1β > 90%, and IL-8 > 65% in granulosa cells from 4–8 mm and from > 8.5 mm diameter ovarian follicles. Activating AMPK with AICAR also reduced lipopolysaccharide-stimulated IL-1α > 60%, IL-1β > 75%, and IL-8 > 20%, and shortened the duration of lipopolysaccharide-stimulated phosphorylation of the mitogen-activated protein kinase ERK1/2 and JNK. However, only the mTOR inhibitor Torin 1, and not rapamycin, reduced lipopolysaccharide-stimulated IL-1α and IL-1β. In conclusion, manipulating granulosa cell energy metabolism with a glycolysis inhibitor, an AMPK activator, or an mTOR inhibitor, limited inflammatory responses to lipopolysaccharide. Our findings imply that energy stress compromises ovarian follicle immune defences.

Supplemental Digital Content is available in the text., Background: In anticipation of a demand surge for hospital beds attributed to the coronavirus pandemic (COVID-19) many US states have mandated that hospitals postpone elective admissions. Objectives: To estimate excess demand for hospital beds due to COVID-19, the net financial impact of eliminating elective admissions in order to meet demand, and to explore the scenario when demand remains below capacity. Research Design: An economic simulation to estimate the net financial impact of halting elective admissions, combining epidemiological reports, the US Census, American Hospital Association Annual Survey, and the National Inpatient Sample. Deterministic sensitivity analyses explored the results while varying assumptions for demand and capacity. Subjects: Inputs regarding disease prevalence and inpatient utilization were representative of the US population. Our base case relied on a hospital admission rate reported by the Center for Disease Control and Prevention of 137.6 per 100,000, with the highest rates in people aged 65 years and older (378.8 per 100,000) and 50–64 years (207.4 per 100,000). On average, elective admissions accounted for 20% of total hospital admissions, and the average rate of unoccupied beds across hospitals was 30%. Measures: Net financial impact of halting elective admissions. Results: On average, hospitals COVID-19 demand for hospital bed-days fell well short of hospital capacity, resulting in a substantial financial loss. The net financial impact of a 90-day COVID surge on a hospital was only favorable under a narrow circumstance when capacity was filled by a high proportion of COVID-19 cases among hospitals with low rates of elective admissions. Conclusions: Hospitals that restricted elective care took on a substantial financial risk, potentially threatening viability. A sustainable public policy should therefore consider support to hospitals that responsibly served their communities through the crisis.

Highlights • Children with COVID 19 disease are less symptomatic but they can be potential agents of transmission. • Most children with symptoms from COVID 19 disease (cough, fever, respiratory difficulties) show bnormalities in CXR. • Findings in CXR are non-specific and superimpose on other viral pneumonias. • Peripheral distribution of lung abnormalities is not a distinctive feature in paediatric population. • CXR have a role in the management of the disease in children., BACKGROUND The outbreak of COVID-19 has become pandemic. Pediatric population has been less studied than adult population and prompt diagnosis is challenging due to asymptomatic or mild episodes. Radiology is an important complement to clinical and epidemiological features. OBJECTIVE To establish the most common CXR patterns in children with COVID-19, evaluate interobserver correlation and to discuss the role of imaging techniques in the management of children. MATERIALS AND METHODS Forty-four patients between 0 and 16 years of age with confirmed SARS-Cov-2 infection and CXR were selected. Two paediatric radiologists independently evaluated the images and assessed the type of abnormality, distribution and evolution when available. RESULTS Median age was 79.8 months (ranging from 2 weeks to 16 years of age). Fever was the most common symptom (43.5 %). 90 % of CXR showed abnormalities. Peribronchial cuffing was the most common finding (86.3 %) followed by GGOs (50 %). In both cases central distribution was more common than peripheral. Consolidations accounted for 18.1 %. Normal CXR, pleural effusion, and altered cardiomediastinal contour were the least common. CONCLUSION The vast majority of CXR showed abnormalities in children with COVID-19. However, findings are nonspecific. Interobserver correlation was good in describing consolidations, normal x-rays and GGOs. Imaging techniques have a role in the management of children with known or suspected COVID-19, especially in those with moderate or severe symptoms or with underlying risk factors.

International audience; Background: Several observational studies have reported elevated baseline D-dimer levels in patients hospitalized for moderate to severe coronavirus disease 2019 (COVID-19). These elevated baseline D-dimer levels have been associated with disease severity and mortality in retrospective cohorts.Objectives: To review current available data on the association between D-Dimer levels and mortality in patients admitted to hospital for COVID-19.Methods: We performed a systematic review of published studies using MEDLINE and EMBASE through 13 April 2020. Two authors independently screened all records and extracted the outcomes. A random effects model was used to estimate the standardized mean difference (SMD) with 95% confidence intervals (CI).Results: Six original studies enrolling 1355 hospitalized patients with moderate to critical COVID-19 (391 in the non-survivor group and 964 in the survivor group) were considered for the final pooled analysis. When pooling together the results of these studies, D-Dimer levels were found to be higher in non-survivors than in-survivors. The SMD in D-Dimer levels between non-survivors and survivors was 3.59μg/L (95% CI 2.79-4.40μg/L), and the Z-score for overall effect was 8.74 (P

Background Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. Methods We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. Results Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p Conclusion SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. Clinical Trial Registration NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883.

We used multicenter international data from the International Society of Heart and Lung Transplantation Mechanically Assisted Circulation Support (IMACS) registry to determine bloodstream infection (BSI) event rate, independent risk factors, and association with mortality.Included were patients registered in IMACS from January 2013 through December 2015, assessed BSI event rate of mechanical circulatory support (MCS) and non-MCS-related BSIs, and conducted univariate and multivariate analyses between BSI with baseline characteristics and mortality.We documented 1,606 BSIs in 1,231 of 10,171 MCS recipients (12%), with an event rate of 2.43 BSIs/100 patient-months within 3 months after implant (early onset) and 1.03 BSIs/100 patient-months after 3 months (late onset). Of these episodes, 1,378 (85.8%) were non- MCS-related BSI. Increasing body mass index and bilirubin were independent correlates of MCS-related BSI. Independent correlates of non-MCS-related BSI included older age, higher body mass index, previous cardiac surgery, baseline chronic renal disease and dialysis, pre-implant frailty, presence of biventricular assist device, total artificial heart or right ventricular assist device, and Interagency Registry for Mechanically Assisted Circulatory Support category 1. Survival after 3 months after implant of patients who developed early-onset BSI was 56.9% at 24 months vs 77.4% in patients without early-onset BSI (p0.001). Early-onset BSI was an independent correlate of mortality at 3 months after implantation (hazard ratio, 2.56; 95% confidence interval, 2.09-3.15; p0.001).Early-onset BSI was associated with significantly increased 24-month mortality. More than 85% of these BSIs were not device related. There is an opportunity for infection prevention practices to decrease the BSI event rate, which may affect 24-month survival. These data can also serve as benchmarking for individual institutions.

Background Utilization of total knee and hip arthroplasty has greatly increased in the past decade in the United States; these are among the most expensive procedures in patients with Medicare. Advances in surgical techniques, anesthesia, and care pathways decrease hospital length of stay. We examined how trends in hospital cost were altered by decreases in length of stay. Methods Procedure, demographic, and economic data were collected on 6.4 million admissions for total knee arthroplasty and 2.8 million admissions for total hip arthroplasty from 2002 to 2013 using the National (Nationwide) Inpatient Sample, a component of the Healthcare Cost and Utilization Project. Trends in mean hospital costs and their association with length of stay were estimated using inflation-adjusted, survey-weighted generalized linear regression models, controlling for patient demographic characteristics and comorbidity. Results From 2002 to 2013, the length of stay decreased from a mean time of 4.06 to 2.97 days for total knee arthroplasty and from 4.06 to 2.75 days for total hip arthroplasty. During the same time period, the mean hospital cost for total knee arthroplasty increased from $14,988 (95% confidence interval [CI], $14,927 to $15,049) in 2002 to $22,837 (95% CI, $22,765 to $22,910) in 2013 (an overall increase of $7,849 or 52.4%). The mean hospital cost for total hip arthroplasty increased from $15,792 (95% CI, $15,706 to $15,878) in 2002 to $23,650 (95% CI, $23,544 to $23,755) in 2013 (an increase of $7,858 or 49.8%). If length of stay were set at the 2002 mean, the growth in cost for total knee arthroplasty would have been 70.8% instead of 52.4% as observed, and the growth in cost for total hip arthroplasty would have been 67.4% instead of 49.8% as observed. Conclusions Hospital costs for joint replacement increased from 2002 to 2013, but were attenuated by reducing inpatient length of stay. With demographic characteristics showing an upward trend in the utilization of joint arthroplasty, including a shift toward younger population groups, reduction in length of stay remains an important target for procedure-level cost containment under emerging payment models.

Background: Class II histone deacetylase (HDAC) inhibitors induce hypoxia-inducible factor-1 and -2α degradation and have antitumour effects in combination with vascular endothelial growth factor (VEGF) inhibitors. In this study, we tested the safety and efficacy of the HDAC inhibitor vorinostat and the VEGF blocker bevacizumab in metastatic clear-cell renal cell carcinoma (ccRCC) patients previously treated with different drugs including sunitinib, sorafenib, axitinib, interleukin-2, interferon, and temsirolimus. Methods: Patients with up to two prior regimens were eligible for treatment, consisting of vorinostat 200 mg orally two times daily × 2 weeks, and bevacizumab 15 mg kg−1 intravenously every 3 weeks. The primary end points were safety and tolerability, and the proportion of patients with 6 months of progression-free survival (PFS). Correlative studies included immunohistochemistry, FDG PET/CT scans, and serum analyses for chemokines and microRNAs. Results: Thirty-six patients were enrolled, with 33 evaluable for toxicity and efficacy. Eighteen patients had 1 prior treatment, 13 patients had 2 prior treatments, and 2 patients were treatment naïve. Two patients experienced grade 4 thrombocytopenia and three patients had grade 3 thromboembolic events during the course of exposure. We observed six objective responses (18%), including one complete response and five partial responses. The proportion of patients with PFS at 6 months was 48%. The median PFS and overall survival were 5.7 months (confidence interval (CI): 4.1–11.0) and 13.9 months (CI: 9.8–20.7), respectively. Correlative studies showed that modulation of specific chemokines and microRNAs were associated with clinical benefit. Conclusions: The combination of vorinostat with bevacizumab as described is relatively well tolerated. Response rate and median PFS suggest clinical activity for this combination strategy in previously treated ccRCC.

What you need to know Postpartum endometritis is a common cause of infertility in dairy cattle, and most vets can discriminate between a normal cow and a cow with endometritis (Fig 1).1 However, vets are less confident when asked how they define endometritis, when cows should be examined, what the best method of diagnosis is and how accurate their diagnosis is. Fig 1: Postpartum endometritis in a dairy cow. The arrow indicates pus discharging from the vulva It is important for vets to be able to diagnose endometritis accurately because the disease can cause infertility in individual cows and reduce the overall reproductive performance of dairy herds.2-4 Endometritis increases the average interval from calving to first insemination by nearly a week compared with normal cows, …

Infection of the postpartum uterus with pathogenic bacteria is associated with infertility months later in dairy cattle. However, it is unclear whether these bacterial infections lead to long-term changes in the reproductive tract that might help explain this infertility. Here we tested the hypothesis that infusion of pathogenic bacteria into the uterus leads to changes in the transcriptome of the reproductive tract 3 months later. We used virgin Holstein heifers to avoid potential confounding effects of periparturient problems, lactation, and negative energy balance. Animals were infused intrauterine with endometrial pathogenic bacteria Escherichia coli and Trueperella pyogenes (n = 4) and compared with control animals (n = 6). Three months after infusion, caruncular and intercaruncular endometrium, isthmus and ampulla of the oviduct, and granulosa cells from ovarian follicles >8 mm diameter were profiled by RNA sequencing. Bacterial infusion altered the transcriptome of all the tissues when compared with control. Most differentially expressed genes were tissue specific, with 109 differentially expressed genes unique to caruncular endometrium, 57 in intercaruncular endometrium, 65 in isthmus, 298 in ampulla, and 83 in granulosa cells. Surprisingly, despite infusing bacteria into the uterus, granulosa cells had more predicted upstream regulators of differentially expressed genes than all the other tissues combined. In conclusion, there were changes in the transcriptome of the endometrium, oviduct and even granulosa cells, 3 months after intrauterine infusion of pathogenic bacteria. These findings imply that long-term changes throughout the reproductive tract could contribute to infertility after bacterial infections of the uterus.

Up to forty percent of dairy cows can develop metritis or endometritis when bacteria infect the uterus after parturition. However, it is unclear why other cows exposed to similar pathogens do not develop uterine disease. We suggest that resilient dairy cows prevent the development of uterine disease using the three complimentary defensive strategies of avoiding, tolerating and resisting infection with pathogenic bacteria. Avoidance maintains health by limiting the exposure to pathogens. Avoidance includes intrinsic behaviors to prevent exposure to pathogens or infected animals, perhaps signaled by the fetid odor of uterine disease. Tolerance improves health by limiting the tissue damage caused by the pathogen burden. Tolerance depends on controlling the tissue damage that pathogens cause in the endometrium by neutralizing bacterial toxins, enhancing tissue repair, and inducing adaptive metabolic responses. Resistance improves health by limiting the pathogen burden. Resistance relies on the immune system generating an inflammatory response in the endometrium to eliminate pathogenic bacteria. People who manage dairy cows can also help prevent uterine disease by using extended lactations, avoiding trauma to the genital tract, maintaining hygiene, and supplying appropriate nutrition during the transition period and after parturition to counter the metabolic stress of lactation. Developing new ways to prevent uterine disease depends on increasing our understanding of the mechanisms of avoidance, tolerance and resistance to pathogens in the postpartum uterus.

PROBLEM ADDRESSED: Adults with intellectual and developmental disabilities (IDD) are a complex population that could benefit from improved care coordination across health and social sectors, as they experience poorer health and have higher rates of emergency department use and hospitalization due to ambulatory care–sensitive conditions. OBJECTIVE OF PROGRAM: To pilot a novel, enhanced model of care coordination for complex patients with IDD. PROGRAM DESCRIPTION: Health Links is a provincial care-coordination program for patients with complex health care needs. This pilot program adapted Health Links to include a guide and training specific to adults with IDD to ensure that these patients’ needs were met and high-quality, efficient care was provided. CONCLUSION: A tailored care-coordination approach for adults with IDD was able to identify complex patients in need and successfully bridge cross-sectoral care.

Study design An analysis of the State Inpatient Database of North Carolina, 2005 to 2012, and the Nationwide Inpatient Sample, including all inpatient lumbar fusion admissions from nonfederal hospitals. Objective The aim of the study was to examine the influence of a major commercial policy change that restricted lumbar fusion for certain indications and to forecast the potential impact if the policy were adopted nationally. Summary of background data Few studies have examined the effects of recent changes in commercial coverage policies that restrict the use of lumbar fusion. Methods We included adults undergoing elective lumbar fusion or re-fusion operations in North Carolina. We aggregated data into a monthly time series to report changes in the rates and volume of lumbar fusion operations for disc herniation or degeneration, spinal stenosis, spondylolisthesis, or revision fusions. Time series regression models were used to test for significant changes in the use of fusion operation following a major commercial coverage policy change initiated on January 1, 2011. Results There was a substantial decline in the use of lumbar fusion for disc herniation or degeneration following the policy change on January 1, 2011. Overall rates of elective lumbar fusion operations in North Carolina (per 100,000 residents) increased from 103.2 in 2005 to 120.4 in 2009, before declining to 101.9 by 2012. The population rate (per 100,000 residents) of fusion among those under age 65 increased from 89.5 in 2005 to 101.2 in 2009, followed by a sharp decline to 76.8 by 2012. There was no acceleration in the already increasing rate of fusion for spinal stenosis, spondylolisthesis, or revision procedures, but there was a coincident increase in decompression without fusion. Conclusion This commercial insurance policy change had its intended effect of reducing fusion operations for indications with less evidence of effectiveness without changing rates for other indications or resulting in an overall reduction in spine surgery. Nevertheless, broader adoption of the policy could significantly reduce the national rates of fusion operations and associated costs. Level of evidence 3.

A surgical procedure is a complex behavior that can be constructed from foundation or component behaviors. Both the component and the composite behaviors built from them are much more likely to recur if it they are reinforced (operant learning). Behaviors in humans have been successfully reinforced using the acoustic stimulus from a mechanical clicker, where the clicker serves as a conditioned reinforcer that communicates in a way that is language- and judgment-free; however, to our knowledge, the use of operant-learning principles has not been formally evaluated for acquisition of surgical skills.Two surgical tasks were taught and compared using two teaching strategies: (1) an operant learning methodology using a conditioned, acoustic reinforcer (a clicker) for positive reinforcement; and (2) a more classical approach using demonstration alone. Our goal was to determine whether a group that is taught a surgical skill using an operant learning procedure would more precisely perform that skill than a group that is taught by demonstration alone.Two specific behaviors, "tying the locking, sliding knot" and "making a low-angle drill hole," were taught to the 2014 Postgraduate Year (PGY)-1 class and first- and second-year medical students, using an operant learning procedure incorporating precise scripts along with acoustic feedback. The control groups, composed of PGY-1 and -2 nonorthopaedic surgical residents and first- and second-year medical students, were taught using demonstration alone. The precision and speed of each behavior was recorded for each individual by a single experienced surgeon, skilled in operant learning. The groups were then compared.The operant learning group achieved better precision tying the locking, sliding knot than did the control group. Twelve of the 12 test group learners tied the knot and precisely performed all six component steps, whereas only four of the 12 control group learners tied the knot and correctly performed all six component steps (the test group median was 10 [range, 10-10], the control group median was 0 [range, 0-10], p = 0.004). However, the median "time to tie the first knot" for the test group was longer than for the control group (test group median 271 seconds [range, 184-626 seconds], control group median 163 seconds [range 93-900 seconds], p = 0.017), whereas the "time to tie 10 of the locking, sliding knots" was the same for both groups (test group mean 95 seconds ± SD = 15 [range, 67-120 seconds], control group mean 95 seconds ± SD = 28 [range, 62-139 seconds], p = 0.996). For the low-angle drill hole test, the test group more consistently achieved the ideal six-step behavior for precisely drilling the low-angle hole compared with the control group (p = 0.006 for the median number of technique success comparison with an odds ratio [at the 95% confidence interval] of 82.3 [29.1-232.8]). The mean time to drill 10 low-angle holes was not different between the test group (mean 193 seconds ± SD = 26 [range, 153-222 seconds]) and the control group (mean 146 seconds ± SD = 63 [range, 114-294 seconds]) (p = 0.084).Operant learning occurs as the behavior is constructed and is highly reinforced with the result measured, not in the time saved, but in the ultimate outcome of an accurately built complex behavior.Level II, therapeutic study.

Objective Exposure to persistent organic pollutants is consistently associated with increased diabetes risk in humans. We investigated the short- and long-term impact of transient low-dose dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) exposure during pregnancy and lactation on glucose homeostasis and beta cell function in female mice, including their response to a metabolic stressor later in life. Methods Female mice were injected with either corn oil (CO; vehicle control) or 20 ng/kg/d TCDD 2x/week throughout mating, pregnancy and lactation, and then tracked for 6–10 weeks after chemical exposure stopped. A subset of CO- and TCDD-exposed dams was then transferred to a 45% high-fat diet (HFD) or remained on a standard chow diet for an additional 11 weeks to assess the long-term effects of TCDD on adaptability to a metabolic stressor. To summarize, female mice were transiently exposed to TCDD and then subsequently tracked beyond when TCDD had been excreted to identify lasting metabolic effects of TCDD exposure. Results TCDD-exposed dams were hypoglycemic at birth but otherwise had normal glucose homeostasis during and post-TCDD exposure. However, TCDD-exposed dams on a chow diet were modestly heavier than controls starting 5 weeks after the last TCDD injection, and their weight gain accelerated after transitioning to a HFD. TCDD-exposed dams also had an accelerated onset of hyperglycemia, impaired glucose-induced plasma insulin levels, reduced islet size, increased MAFA-ve beta cells, and increased proinsulin accumulation following HFD feeding compared to controls. Overall, our study demonstrates that low-dose TCDD exposure during pregnancy has minimal effects on metabolism during the period of active exposure, but has detrimental long-term effects on metabolic adaptability to HFD feeding. Conclusions Our study suggests that transient low-dose TCDD exposure in female mice impairs metabolic adaptability to HFD feeding, demonstrating that dioxin exposure may be a contributing factor to obesity and diabetes pathogenesis in females., Highlights • Female mice exposed to TCDD during pregnancy are hypoglycemic at birth. • TCDD exposure promotes weight gain long after exposure ceases. • TCDD-exposed dams fed a high-fat diet have accelerated onset of glucose intolerance. • TCDDHFD dams have defects in islet morphology and beta cell function.

Infections of the female reproductive tract are a major cause of morbidity and mortality in humans, requiring significant investment to sustain treatment and representing a major challenge to health. The increasing prevalence of bacterial resistance, and an almost complete absence of new antibiotic therapies for the past five decades, mean there is a desperate need for novel approaches to the treatment of bacterial infections. Within the present study, we demonstrate the effective ex vivo treatment of bacterial infection of the female reproductive tract using a controlled-release, liquid crystal-based platform. Liquid crystal encapsulation of ciprofloxacin significantly enhanced its bactericidal efficacy and reduced cell toxicity. Liquid crystal structures are low-cost, simple to manufacture and provide a sustained-release profile of encapsulated ciprofloxacin. Treatment of Escherichia coli infected reproductive tract epithelial cells and whole organ cultures with liquid crystal encapsulated ciprofloxacin proved to be an effective strategy for reducing bacterial load and reproductive tract inflammatory responses to infection. These data suggest that such an approach could provide an efficacious treatment modality for enhancing the effectiveness of current antibiotic therapies. Electronic supplementary material The online version of this article (10.1007/s10544-019-0385-x) contains supplementary material, which is available to authorized users.

Communication between the oocyte and cumulus facilitates oocyte growth, cell cycle regulation, and metabolism. This communication is mediated by direct contact between oocytes and cumulus cells, and soluble secreted molecules. Secreted molecules involved in this process are known inflammatory mediators. Lipopolysaccharide (LPS) is detected in follicular fluid and is associated with reduced fertility, whereas accumulation of inflammatory mediators in follicular fluid, including tumor necrosis factor-α (TNF-α), is associated with female infertility. Maturation of oocytes in the presence of LPS or TNF-α reduces meiotic maturation and the capacity to develop to the blastocyst. Here we evaluated the abundance of 92 candidate genes involved immune function, epigenetic modifications, embryo development, oocyte secreted factors, apoptosis, cell cycle, and cell signaling in bovine cumulus cells or zona-free oocytes after exposure to LPS or TNF-α during in vitro maturation. We hypothesize that LPS or TNF-α will alter the abundance of transcripts in oocytes and cumulus cell in a cell type dependent manner. Exposure to LPS altered abundance of 31 transcripts in oocytes (including ACVR1V, BMP15, DNMT3A) and 12 transcripts in cumulus cells (including AREG, FGF4, PIK3IP1). Exposure to TNF-α altered 1 transcript in oocytes (IGF2) and 4 transcripts in cumulus cells (GJA1, PLD2, PTGER4, STAT1). Cumulus expansion was reduced after exposure to LPS or TNF-α. Exposing COCs to LPS had a marked effect on expression of targeted transcripts in oocytes. We propose that altered oocyte transcript abundance is associated with reduced meiotic maturation and embryo development observed in oocytes cultured in LPS or TNF-α.

Bacterial infection of the uterus causes clinical endometritis in 15 to 20% of postpartum dairy cows and reduces fertility, even after the resolution of disease. However, it is difficult to disentangle the mechanisms linking reduced fertility with endometritis because cows have multiple confounding postpartum conditions. The aim of the present experiment was to develop an in vivo model of clinical endometritis in Holstein heifers using pathogenic Escherichia coli and Trueperella pyogenes. Estrous cycles of heifers were synchronized using a 5-d Co-Synch protocol, and subsequently received exogenous progesterone to elevate circulating progesterone at the time of uterine infusion. Endometrial scarification was performed before uterine infusion of live pathogenic Escherichia coli and Trueperella pyogenes, or sterile vehicle. Effects of infusion were evaluated by measuring rectal temperature, plasma haptoglobin, hematology, grading pus in the vaginal mucus, quantifying 16S rRNA in vaginal mucus, and transrectal ultrasonography. Bacterial infusion increased the median vaginal mucus to grade 2 by d 3 postinfusion, and to grade 3 from d 4 to 6 postinfusion. Control heifers maintained a median vaginal mucus grade ≤1 from d 1 to 6. Transrectal ultrasound revealed the accumulation of echogenic fluid in the uterus of heifers following bacterial infusion, which was absent in control heifers. Total 16S rRNA in vaginal mucus was elevated in bacteria-infused heifers compared with control heifers at d 5. Rectal temperature was increased in bacteria-infused heifers. Plasma haptoglobin, general health, and appetite did not differ between groups. As indicated by increased vaginal mucus grade after bacterial infusion and absence of systemic signs of illness, this model successfully induced symptoms resembling clinical endometritis in virgin Holstein heifers. The model allows the isolation of effects of uterine disease on fertility from confounding factors that can occur during the postpartum period in dairy cows.

Bacteria are ubiquitous in the bovine uterus after parturition, but 50 years ago, cows tolerated these bacteria and few animals developed uterine disease. Now, up to 40% of dairy cattle develop postpartum uterine disease. Uterine disease causes infertility by compromising the function of not only the endometrium but also the ovary. Animals defend themselves against pathogens using tolerance and resistance mechanisms. Tolerance is the ability to limit the disease severity induced by a given pathogen burden. Resistance is the ability to limit the pathogen burden and is usually the function of immunity. Endometrial cells contribute to tolerance and have roles in innate immunity and the inflammatory response to pathogens. However, failures in endometrial tolerance and the character of the inflammatory response shape postpartum uterine disease. We propose that uterine health is more dependent on the ability of the endometrium to tolerate pathogens than the ability to resist invading bacteria.

Endometritis is a significant condition in postpartum dairy cattle because it causes infertility.1 Although pathogenic bacteria underlie the aetiology of clinical endometritis (Box 1), peripartum problems such as dystocia and retained placenta increase the risk of disease. Metabolic stress is another risk factor for clinical endometritis2,3 and a recent study by Valdmann and others, summarised on p 126 of this week’s issue of Vet Record ,4 extends this observation to include cytological endometritis. This finding is important because metabolic stress is a common feature of intensive dairy farming, and metabolic demands on cows will rise further because milk yields are expected to double in the next 50 years.5 BOX 1: ### Definitions for postpartum uterine diseases Metritis: An enlarged uterus and a watery red-brown fluid to viscous off-white purulent uterine discharge, within 21 days and usually within 10 days of parturition. Clinical endometritis: The presence of a purulent uterine discharge detectable in the vagina 21 days or more postpartum. Cytological endometritis: The percentage of neutrophils exceeding a threshold, usually between 5 and 18 per cent of cells, in endometrial cytology samples collected 21 days or more postpartum. Subclinical endometritis: The percentage of neutrophils exceeding a threshold, usually between 5 and 18 per cent of cells, in endometrial cytology samples collected 21 days or more postpartum, in the …

Despite widespread use of behavioral observations to evaluate child feeding behaviors in research and clinical practice, few studies have comprehensively characterized mealtimes or identified features that differentiate children with and without disordered feeding; these were the aims of the current study. Mealtime observations were conducted for 18 children with avoidant restrictive food intake disorder (ARFID) and 21 typically developing children. Observations were coded inductively, and associations between disorder and observed mealtime actions were examined. Most behaviors were observed across both clinical and nonclinical mealtimes, and many did not differ in frequency between children with and without ARFID. However, significant group differences were observed in the frequencies of behaviors relating to food intake, visual and physical engagement with feeding, and movement during mealtimes. The comparability of behaviors across clinical and nonclinical groups suggests that eating behaviors exist on a continuum from "normal" to "abnormal," with group differences relating to frequency rather than type of behavior. The behavioral differences observed in this study suggest that identification of children with ARFID should focus on child engagement with food and restlessness during mealtimes. Reliance on emotional and escape-maintained behaviors will lead to underrecognition of families in need of clinical support.

Preventing postpartum uterine disease depends on the ability of endometrial cells to tolerate the presence of the bacteria that invade the uterus after parturition. Postpartum uterine disease and endometrial pathology in cattle are most associated with the pathogen Trueperella pyogenes. Trueperella pyogenes secretes a cholesterol-dependent cytolysin, pyolysin, which causes cytolysis by forming pores in the plasma membrane of endometrial stromal cells. The aim of the present study was to identify cell-intrinsic pathways that increase bovine endometrial stromal cell tolerance to pyolysin. Pyolysin caused dose-dependent cytolysis of bovine endometrial stromal cells and leakage of lactate dehydrogenase into supernatants. Cell tolerance to pyolysin was increased by inhibitors that target the mevalonate and cholesterol synthesis pathway, but not the mitogen-activated protein kinase, cell cycle, or metabolic pathways. Cellular cholesterol was reduced and cell tolerance to pyolysin was increased by supplying the mevalonate-derived isoprenoid farnesyl pyrophosphate, or by inhibiting farnesyl-diphosphate farnesyltransferase 1 or geranylgeranyl diphosphate synthase 1 to increase the abundance of farnesyl pyrophosphate. Supplying the mevalonate-derived isoprenoid geranylgeranyl pyrophosphate also increased cell tolerance to pyolysin, but independent of changes in cellular cholesterol. However, geranylgeranyl pyrophosphate inhibits nuclear receptor subfamily 1 group H receptors (NR1H, also known as liver X receptors), and reducing the expression of the genes encoding NR1H3 or NR1H2 increased stromal cell tolerance to pyolysin. In conclusion, mevalonate-derived isoprenoids increased bovine endometrial stromal cell tolerance to pyolysin, which was associated with reducing cellular cholesterol and inhibiting NR1H receptors.

Background: As the population of older adults continues to increase, the dissemination of strategies to maintain independence of older persons is of critical public health importance. Recent large-scale clinical trial evidence has definitively shown intervention of moderate-intensity physical activity (PA) reduces major mobility disability in at-risk older adults. However, it remains unknown whether structured PA interventions, with demonstrated efficacy in controlled, clinical environments, can be successfully disseminated into community settings to benefit wider populations of older adults. Objective: To assess the dissemination of an evidence-based PA program for older adults by evaluating program participation and its impact on mobility, strength and quality of life. Setting: An urban senior center. Participants: Fifty older adults (71.2 ± 8 years aged; BMI: 30.1 ± 7 kg/m2). Intervention: Average of 8.0 ± 1.8 months of participation in the Fit-4-Life Program, a community-based PA and nutrition counseling intervention. Measurements: Mobility (Short Physical Performance Battery (SPPB)), self-reported physical activity (CHAMPS questionnaire), leg strength, grip strength, and quality of life (Quality of Well-Being Self-Administered (QWB-SA) scale) were assessed at baseline and follow-up. Results: Mean attendance was 55.8%. Fourteen participants were lost to follow-up. Those who dropped-out engaged in less PA at baseline (78 ± 108 mins/wk) compared to those who completed follow-up (203 ± 177 mins/wk, P=0.01). Participants exhibited sustained increases of PA (65 ± 153 mins/wk, P= 0.08), and there were meaningful improvements in SPPB (0.5 ± 0.2, P< 0.01), knee extensor strength (2.6 ± 4.4 kg, P< 0.01) and QWB-SA (0.04 ± 0.09, P= 0.05). Conclusion: The dissemination of a clinically efficacious PA intervention into a community-based setting can improve mobility, strength and quality of life for older adults. This knowledge may be helpful for the design and implementation of larger-scale PA intervention studies designed to preserve mobility in older adults within community-based settings.

Nucleic acid testing (NAT) for hepatitis C virus (HCV) is recommended for screening of organ donors, yet not all donor infections may be detected. We describe three US clusters of HCV transmission from donors at increased risk for HCV infection. Donor's and recipients' medical records were reviewed. Newly infected recipients were interviewed. Donor-derived HCV infection was considered when infection was newly detected after transplantation in recipients of organs from increased risk donors. Stored donor sera and tissue samples were tested for HCV RNA with high-sensitivity quantitative PCR. Posttransplant and pretransplant recipient sera were tested for HCV RNA. Quasispecies analysis of hypervariable region-1 was used to establish genetic relatedness of recipient HCV variants. Each donor had evidence of injection drug use preceding death. Of 12 recipients, 8 were HCV-infected-6 were newly diagnosed posttransplant. HCV RNA was retrospectively detected in stored samples from donor immunologic tissue collected at organ procurement. Phylogenetic analysis showed two clusters of closely related HCV variants from recipients. These investigations identified the first known HCV transmissions from increased risk organ donors with negative NAT screening, indicating very recent donor infection. Recipient informed consent and posttransplant screening for blood-borne pathogens are essential when considering increased risk donors.

Posttransplant lymphoproliferative disorder (PTLD) is an infrequent but serious complication of solid organ transplantation. Early detection and initiation of therapy may improve outcomes. The purpose of this study was to identify human leukocyte antigen (HLA) type as risk and prognostic factors for PTLD.A review was undertaken to identify PTLD cases treated at our institution over the past 25 years. Logistic regression and Cox Proportional Hazards were used to model risk factors for PTLD and clinical outcomes in patients with PTLD.One hundred six cases of PTLD were identified with 1392 solid-organ transplant recipient controls. Epstein-Barr virus (EBV) seronegative status pretransplant (odds ratio [OR] = 7.61, 95% confidence interval [95% CI] = 3.83-15.1) and receipt of a nonkidney transplant were associated with an increased risk of PTLD. Being African American and receipt of a living-related kidney transplant were associated with a decreased risk of PTLD. The HLA-B40 group was a risk factor for PTLD in EBV-seronegative individuals (OR = 8.38, 95% CI = 2.18-32.3), whereas HLA-B8 was a risk factor for PTLD in EBV-seropositive individuals (OR = 3.29, 95% CI = 1.52-7.09). Specific HLA types were not associated with graft failure or mortality after PTLD diagnosis. In PTLD patients, central nervous system (CNS) involvement, bone marrow involvement, T-cell PTLD, and age were associated with increased mortality.Human leukocyte antigen-B40 group and HLA-B8 were identified as novel susceptibility factors for PTLD in EBV-seropositive and EBV-seronegative individuals, respectively. Multicentered, large prospective studies of PTLD with correlative immunologic work are needed to test the significance of these observed associations.

Evaluate whether mortality after discharge is elevated in geriatric fracture patients whose lower extremity weight-bearing is restricted.Retrospective cohort study SETTING: Urban Level 1 trauma center PATIENTS/PARTICIPANTS: 1746 patients65 years of age INTERVENTION: Post-operative lower extremity weight-bearing status MAIN OUTCOME MEASURE: Mortality, as determined by the Social Security Death Index RESULTS: Univariate analysis demonstrated that patients who were weight-bearing as tolerated on bilateral lower extremities (BLE) had significantly higher 5-year mortality compared to patients with restricted weight-bearing on one lower extremity and restricted weight-bearing on BLE (30%, 21% and 22% respectively, p 0.001). Cox regression analysis controlling for variables including age, Charlson Comorbidity Index, Injury Severity Scale, combined UE/LE injury, injury mechanism (high vs low), sex, BMI and GCS demonstrated that, in comparison to patients who were weight bearing as tolerated on BLE, restricted weight-bearing on one lower extremity had a hazard ratio (HR) of 0.97 (95% confidence interval 0.78 to 1.20, p = 0.76) and restricted weight-bearing in BLE had a HR of 0.91 (95% confidence interval 0.60 to 1.36, p = 0.73).In geriatric patients, prescribed weight-bearing status did not have a statistically significant association with mortality after discharge, when controlling for age, sex, body mass index, medical comorbidities, Injury Severity Scale (ISS), mechanism of injury, nonoperative treatment and admission GCS. This remained true in when the analysis was restricted to operative injuries only.

Study Design. Retrospective analysis of Medicare claims linked to hospital participation in the Center for Medicare and Medicaid Innovation's episode-based Bundled Payment for Care Improvement (BPCI) program for lumbar fusion. Objective. To describe the early effects of BPCI participation for lumbar fusion on 90-day reimbursement, procedure volume, reoperation, and readmission. Summary of Background Data. Initiated on January 1, 2013, BPCI's voluntary bundle payment program provides a predetermined payment for services related to a Diagnosis-Related Group-defined “triggering event” over a defined time period. As an alternative to fee-for-service, these reforms shift the financial risk of care on to hospitals. Methods. We identified fee-for-service beneficiaries over age 65 undergoing a lumbar fusion in 2012 or 2013, corresponding to the years before and after BPCI initiation. Hospitals were grouped based on program participation status as nonparticipants, preparatory, or risk-bearing. Generalized estimating equation models adjusting for patient age, sex, race, comorbidity, and hospital size were used to compare changes in episode costs, procedure volume, and safety indicators based on hospital BPCI participation. Results. We included 89,605 beneficiaries undergoing lumbar fusion, including 36% seen by a preparatory hospital and 7% from a risk-bearing hospital. The mean age of the cohort was 73.4 years, with 59% women, 92% White, and 22% with a Charlson Comorbidity Index of 2 or more. Participant hospitals had greater procedure volume, bed size, and total discharges. Relative to nonparticipants, risk-bearing hospitals had a slightly increased fusion procedure volume from 2012 to 2013 (3.4% increase vs. 1.6% decrease, P = 0.119), did not reduce 90-day episode of care costs (0.4% decrease vs. 2.9% decrease, P = 0.044), increased 90-day readmission rate (+2.7% vs. −10.7%, P = 0.043), and increased repeat surgery rates (+30.6% vs. +7.1% points, P = 0.043). Conclusion. These early, unintended trends suggest an imperative for continued monitoring of BPCI in lumbar fusion. Conclusion. Level of Evidence: 3

Remerciements à Isabelle Hue (INRA, Jouy-en-Josas) et à l'Unité Commune d’Expérimentation Animale (UCEA, INRA, Leudeville) for animal management. Remerciements à Eric Pailhoux et Maëlle Pannetier (INRA, Jouy-en-Josas) for providing us FOXL2-pSG5 and pSG5 plasmids. Remerciements à Kaïs Al-Gubory et Philippe Bolifraud (INRA, Jouy-en-Josas) Remerciements à ICE platform (Claudia Bevilacqua and Nicolas Crapart, INRA, Jouy-en-Josas) for access to the bioanalyzer; International audience; Intensive selection for milk production has led to reduced reproductive efficiency in high-producing dairy cattle. The impact of intensive milk production on oocyte quality as well as early embryo development has been established but few analyses have addressed this question at the initiation of implantation, a critical milestone ensuring a successful pregnancy and normal post-natal development. Our study aimed to determine if contrasted maternal metabolism affects the previously described sensory properties of the endometrium to the conceptus in cattle. Following embryo transfer at Day 7 post-oestrus, endometrial caruncular (CAR) and intercaruncular (ICAR) areas were collected at Day 19 from primiparous postpartum Holstein-Friesian cows that were dried-off immediately after parturition (i.e., never milked; DRY) or milked twice daily (LACT). Gene quantification indicated no significant impact of lactation on endometrial expression of transcripts previously reported as conceptus-regulated (PLET1, PTGS2, SOCS6) and interferon-tau stimulated (RSAD2, SOCS1, SOCS3, STAT1) factors or known as female hormone-regulated genes (FOXL2, SCARA5, PTGS2). Compared with LACT cows, DRY cows exhibited mRNA levels with increased expression for FOXL2 transcription factor and decreased expression for oxidative stress-related genes (CAT, SOD1, SOD2). In vivo and in vitro experiments highlighted that neither interferon-tau nor FOXL2 were involved in transcriptional regulation of CAT, SOD1 and SOD2. In addition, our data showed that variations in maternal metabolism had a higher impact on gene expression in ICAR areas. Collectively, our findings prompt the need to fully understand the extent to which modifications in endometrial physiology drive the trajectory of conceptus development from implantation onwards when maternal metabolism is altered.

Bacterial infections of the uterus after parturition are ubiquitous in dairy cattle and often cause uterine disease, such as metritis or endometritis. However, the metabolic stress associated with milk production increases the risk of developing disease. Resolution of bacterial infections requires rapid and robust innate immune responses, which depend on host cell receptors recognizing pathogen-associated molecular patterns, such as lipopolysaccharide (LPS) from gram-negative bacteria. Here, we argue that metabolic stress impairs the inflammatory response to pathogens. Glucose and glutamine are the major energy sources for cells, but their abundance is reduced in postpartum dairy cows. Furthermore, inflammatory responses exacerbate metabolic stress, with animals and tissues consuming more glucose when challenged with LPS. However, depriving endometrial tissue of glucose or glutamine impairs the secretion of IL-1β, IL-6, and IL-8 in response to pathogen-associated molecular patterns. Glycolysis and the intracellular sensor of energy, AMP-activated protein kinase, are important for the response to LPS because perturbing glycolysis or AMP-activated protein kinase activity reduces the secretion of IL-1β, IL-6, and IL-8 in the endometrium. The mevalonate pathway for cellular cholesterol synthesis may also be linked to immunity, as inhibition of the terminal enzyme in the pathway, squalene synthase, reduces inflammatory responses to pathogenic bacteria and LPS. In contrast, only modest effects on inflammation are found when modulating the sensor of cellular nutrient satiety, mammalian target of rapamycin, or the endocrine regulator of metabolism, insulin-like growth factor-1. We suggest that stressing cellular metabolism increases the risk of uterine disease by impairing endometrial defenses.

The virulence of many Gram-positive bacteria depends on cholesterol-dependent cytolysins (CDCs), which form pores in eukaryotic cell plasma membranes. Pyolysin (PLO) from Trueperella pyogenes provided a unique opportunity to explore cellular responses to CDCs because it does not require thiol activation. Sublytic concentrations of PLO stimulated phosphorylation of MAPK ERK and p38 in primary stromal cells, and induced autophagy as determined by protein light-chain 3B cleavage. Although, inhibitors of MAPK or autophagy did not affect PLO-induced cytolysis. However, 10 μM 3-hydroxynaphthalene-2-carboxylic acid-(3,4-dihydroxybenzylidene)-hydrazide (Dynasore), a dynamin guanosine 5′-triphosphatase inhibitor, protected stromal cells against PLO-induced cytolysis as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (85 ± 17% versus 50 ± 9% cell viability), measuring extracellular ATP, and kinetic assays. This was a generalized mechanism because Dynasore also protected HeLa cells against streptolysin O. Furthermore, the effect was reversible, with stromal cell sensitivity to PLO restored within 30 minutes of Dynasore removal. The protective effect of Dynasore was not conferred by dynamin inhibition, induction of ERK phosphorylation, or Dynasore binding to PLO. Rather, Dynasore reduced cellular cholesterol and disrupted plasma membrane lipid rafts, similar to positive control methyl-β-cyclodextrin. Dynasore is a tractable tool to explore the complexity of cholesterol homeostasis in eukaryotic cells and to develop strategies to counter CDCs.—Preta, G., Lotti, V., Cronin, J. G., and Sheldon, I. M. Protective role of the dynamin inhibitor Dynasore against the cholesterol-dependent cytolysin of Trueperella pyogenes.

This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased adenosine triphosphate (ATP) important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is noninvasive, painless, and non-thermal (cleared by the United States Food and Drug Administration [FDA], an insignificant risk device). Eleven chronic, mTBI participants (26-62 years of age, 6 males) with nonpenetrating brain injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (Monday, Wednesday, Friday, for 6 weeks), starting at 10 months to 8 years post- mTBI (motor vehicle accident [MVA] or sports-related; and one participant, improvised explosive device [IED] blast injury). Four had a history of multiple concussions. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 10 min to each of 11 scalp placements (13 J/cm(2)). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre-LED, and at 1 week, and 1 and 2 months after the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for the Stroop test for Executive Function, Trial 3 inhibition (p=0.004); Stroop, Trial 4 inhibition switching (p=0.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=0.003); and CVLT-II, Long Delay Free Recall (p=0.006). Participants reported improved sleep, and fewer post-traumatic stress disorder (PTSD) symptoms, if present. Participants and family reported better ability to perform social, interpersonal, and occupational functions. These open-protocol data suggest that placebo-controlled studies are warranted.

The objectives of this study were (1) to identify distinct subtypes of older Korean immigrants based on their levels of religiosity/spirituality (R/S) and (2) to determine if the identified subtypes differed by demographic characteristics, perceived health, depression, and life satisfaction.Factor mixture models were evaluated with a nonprobability sample of older Korean immigrants (N=200) residing in the New York City area in 2009 to classify typologies of R/S. Multiple regression was used to test the associations between the R/S subtypes and outcomes (perceived health, depression, and life satisfaction) while controlling for demographics.Two substantively distinct latent profiles were identified: normally religious/spiritual ('average R/S') and minimally religious/spiritual ('low R/S'). The average R/S subgroup (74.4%) showed higher means than those in the low R/S subgroup (25.6%) on all six R/S class indicators. Subtypes did not differ on age, education, income, marital status, living arrangements, or years in the USA. However, males were more likely than females to be 'average R/S.' The 'average R/S' subtype had significantly greater life satisfaction than their 'low R/S' counterpart. No differences between the two subtypes were found on perceived health or depression.Findings highlight the importance of the classifications of R/S for mental health outcomes, and they indicate that relationships among R/S, various demographic characteristics, and physical/mental health are complex. Future research should validate and refine this classification of R/S in order to help identify particular sources of health risks/behaviors, relevant treatments, and health-promoting interventions within homogenous subtypes of older Korean immigrants.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. This study assessed the specificity and sensitivity of two commonly used psychometric methods to assess ARFID in children. To achieve this, a sample of 329 mothers and one father completed the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) and the Child Food Neophobia Scale (CFNS). A Receiver Operating Characteristic (ROC) analysis indicated that both measures were able to successfully differentiate a known clinical sample from those of typically developing population. Although the BPFAS was more accurate at differentiating ARFID from the general population, the CFNS was acceptable and on some metrics better than its longer counterpart. The ability of a food neophobia scale to differentiate clinical and population samples, and detect gradation of food avoidance within the population sample, suggests that the multitude of psychometric measures available may be measuring similar constructs. Therefore, confidence can be expected in cross-site comparisons despite each using different psychometric measures of food avoidance in children.

Regionalization of perinatal care has been developed to improve the survival of preterm babies. The mortality rate is higher among very premature infants born outside level-3 maternity units. The objective of this study was to evaluate the preventability of these very premature births occurring outside recommendations within level-2B maternity units. The secondary objective was to describe the care of premature infants between 23 and 24 weeks.This is a single-center retrospective qualitative study of the care delivery pathways. Thirty-one deliveries in which the fetus was alive between 23 and 30 weeks+6 days occurred in a level-2B maternity unit in Thionville, France, between 1 January 2013 and 31 December 2015. After oral presentation of the cases, a level 2-3 multidisciplinary committee of experts in Lorraine evaluated the preventability criteria and reasons, and divided the deliveries into three groups: (i) birth in level-2B institutions avoidable, (ii) inevitable with factors related to the mother or the organization of care, (iii) with no inevitable factors.Out of the 31 deliveries included, the committee classified six deliveries as preventable, 14 as inevitable with factors, and 11 as inevitable with no factors. The criteria for preventability of birth in a level-2B unit were underestimation of maternal and fetal risk, an erroneous initial estimate of term or preterm labor, and two births in the upper limits of the French recommendations for in utero transfer. Nineteen of the 35 premature infants before 31 weeks' gestation died, 16 children were transferred to a level-3 maternity ward, and 16 children were allowed to go home.Analysis of the obstetrical-pediatric care course by an expert committee determined the preventability of the average birth and prematurity in level-2B maternity units in Lorraine for a small but significant number of cases. The local regionalization of neonatal care could be improved by the application of this method of analysis to other maternity wards in the Lorraine network.

Bacteria infect the endometrium lining the uterus of cattle after parturition, and clearance of these microbes depends on a robust innate immune response to bacterial molecules, such as the endotoxin lipopolysaccharide (LPS). Endometrial inflammation is characterized by secretion of the cytokines IL-1β and IL-6 and the chemokine IL-8. However, animals often fail to clear invading bacteria and develop uterine disease if they are in negative energy balance, with reduced abundance of glucose and glutamine, which are substrates for energy in tissues. Depletion of glucose blunts inflammatory responses in the endometrium, but the role of glutamine is not clear. The present study tested the hypothesis that depletion of glutamine compromises inflammatory responses to LPS in endometrial tissue. Ex vivo organ cultures of endometrium were challenged with LPS, and culture supernatants accumulated IL-1β, IL-6, and IL-8, as expected. However, reducing the availability of glutamine in culture medium containing glucose reduced the accumulation of IL-1β, IL-6, and IL-8 by50%. Surprisingly, in the absence of glucose, supplying increasing amounts of glutamine was not sufficient to augment inflammatory responses to LPS, whereas, in the absence of glutamine, supplying more glucose increased inflammation. Furthermore, inhibiting glycolysis reduced the accumulation of IL-1β, IL-6, and IL-8 by50%, even when glutamine and glucose were abundant. In conclusion, depletion of glutamine reduces inflammatory responses to LPS in the endometrium, and the activity of glutamine depends on glucose and glycolysis. These data provide mechanistic insights into how negative energy balance may be linked to postpartum uterine disease.

Background Context Minimally invasive lumbar spinal stenosis procedures have uncertain long-term value. Purpose This study sought to characterize factors affecting the long-term cost-effectiveness of such procedures using interspinous spacer devices (“spacers”) relative to decompression surgery as a case study. Study Design Model-based cost-effectiveness analysis. Patient Sample The Medicare Provider Analysis and Review database for the years 2005–2009 was used to model a group of 65-year-old patients with spinal stenosis who had no previous spine surgery and no contraindications to decompression surgery. Outcome Measures Costs, quality-adjusted life years (QALYs), and cost per QALY gained were the outcome measures. Methods A Markov model tracked health utility and costs over 10 years for a 65-year-old cohort under three care strategies: conservative care, spacer surgery, and decompression surgery. Incremental cost-effectiveness ratios (ICER) reported as cost per QALY gained included direct medical costsfor surgery. Medicare claims data were used to estimate complication rates, reoperation, and related costs within 3 years. Utilities and long-term reoperation rates for decompression were derived frompublished studies. Spacer failure requiring reoperation beyond 3 years and post-spacer health utilities are uncertain and were evaluated through sensitivity analyses. In the base-case, the spacer failure rate was held constant for years 4–10 (cumulative failure: 47%). In a “worst-case” analysis, the 10-year cumulative reoperation rate was increased steeply (to 90%). Threshold analyses were performed to determine the impact of failure and post-spacer health utility on the cost-effectiveness of spacer surgery. Results The spacer strategy had an ICER of $89,500/QALY gained under base-case assumptions, and remained under $100,000 as long as the 10-year cumulative probability of reoperation did not exceed 54%. Under worst-case assumptions, the spacer ICER was $482,000/QALY and fell below $100,000 only if post-spacer utility was 0.01 greater than post-decompression utility or the cost of spacer surgery was $1,600 less than the cost of decompression surgery. Conclusions Spacers may provide a reasonably cost-effective initial treatment option for patients with lumbar spinal stenosis. Their value is expected to improve if procedure costs are lower in outpatient settings where these procedures are increasingly being performed. Decision analysis is useful for characterizing the long-term cost-effectiveness potential for minimally invasive spinal stenosis treatments and highlights the importance of complication rates and prospective health utility assessment.

Retrospective analysis of patients undergoing elective lumbar fusion operations, comparing rates of repeat spine surgery based on method of ascertainment. We report the accuracy of a claims-based approach for reporting repeat surgery compared to medical records abstraction as the “gold standard.” Previous studies have reported the validity of a claims-based algorithm for grouping patients by surgical indication and classifying operative features, but their accuracy in measuring surgical quality indicators has not been widely examined. We identified a subset of patients undergoing elective lumbar fusion operations at a single institution from 1996–2011, excluding those with spinal fracture, spinal cord injury, or cancer. From the medical record we abstracted the incidence of repeat spine operation or re-hospitalization at one-year. We cross-classified each event record with its corresponding value derived from claims. The sensitivity and specificity of the claims-based approach were calculated for reoperation within 30, 90, and 365 days, and all-cause hospital readmission within 30 days. Medical records linked to claims data were obtained for 520 patients undergoing elective lumbar fusion. Reoperation rates based on chart review were 1.0%, 1.3%, 3.6%, compared to 0.8%, 1.7%, and 3.8% based on the final claims methods at 30, 90, and 365 days, respectively. The claims-based algorithm had sensitivities of 80.0%, 100%, and 94.1% and specificities of 100%, 99.6%, 99.2% for repeat surgery within 30, 90, and 365 days, respectively. The sensitivity for all-cause readmission was 50%. Health care quality improvement efforts often rely on administrative data to report surgical safety. We found that claims-based ascertainment of safety at a single institution was very accurate. However, accuracy depended on careful attention to the timing of outcomes, as well as the definitions and coding of repeat surgery, including how orthopaedic device removal codes are classified. Level of Evidence: 3