Genome-wide association identifies a BAHD acyltransferase activity that assembles an ester of glucuronosylglycerol and phenylacetic acid.

Genome-wide association studies (GWAS) are an effective approach to identify new specialized metabolites and the genes involved in their biosynthesis and regulation. In this study, GWAS of Arabidopsis thaliana soluble leaf and stem metabolites identified alleles of an uncharacterized BAHD-family acyltransferase (AT5G57840) associated with natural variation in three structurally related metabolites. These metabolites were esters of glucuronosylglycerol, with one metabolite containing phenylacetic acid as the acyl component of the ester. Knockout and overexpression of AT5G57840 in Arabidopsis and heterologous overexpression in Nicotiana benthamiana and Escherichia coli demonstrated that it is capable of utilizing phenylacetyl-CoA as an acyl donor and glucuronosylglycerol as an acyl acceptor. We, thus, named the protein Glucuronosylglycerol Ester Synthase (GGES). Additionally, phenylacetyl glucuronosylglycerol increased in Arabidopsis CYP79A2 mutants that overproduce phenylacetic acid and was lost in knockout mutants of UDP-sulfoquinovosyl: diacylglycerol sulfoquinovosyl transferase, an enzyme required for glucuronosylglycerol biosynthesis and associated with glycerolipid metabolism under phosphate-starvation stress. GGES is a member of a well-supported clade of BAHD family acyltransferases that arose by duplication and neofunctionalized during the evolution of the Brassicales within a larger clade that includes HCT as well as enzymes that synthesize other plant-specialized metabolites. Together, this work extends our understanding of the catalytic diversity of BAHD acyltransferases and uncovers a pathway that involves contributions from both phenylalanine and lipid metabolism.

The impact of asymptomatic human immunodeficiency virus (HIV)-positive disease status on inpatient complications following total joint arthroplasty: a propensity score-matched analysis.

PURPOSE: The number of patients with asymptomatic human immunodeficiency virus (AHIV) is increasing as the efficacy of antiretroviral therapy improves. While there is research on operative risks associated with having HIV, there is a lack of literature describing the impact of well-controlled HIV on postoperative complications. This study seeks to elucidate the impact of AHIV on postoperative outcomes after total hip (THA) and knee (TKA) arthroplasty. METHODS: The Nationwide Inpatient Sample was retrospectively reviewed for patients undergoing TKA and THA from 2005 to 2013. Subjects were subdivided into those with AHIV and those without HIV (non-HIV). Patient demographics, hospital-related parameters, and postoperative complications were all collected. One-to-one propensity score-matching, Chi-square analysis, and multivariate logistical regressions were performed to compare both cohorts. RESULTS: There were no significant differences between AHIV and non-HIV patients undergoing TKA or THA in terms of sex, age, insurance status, or total costs (all, p ≥ 0.081). AHIV patients had longer lengths of stay (4.0 days) than non-HIV patients after both TKA (3.3 days) and THA (3.1 days) (p ≤ 0.011). Both TKA groups had similar postoperative complication rates (p > 0.081). AHIV patients undergoing THA exhibited an increased rate of overall surgical complications compared non-HIV patients (0 vs. 4.5%, p = 0.043). AHIV was not associated with increased complications following both procedures. CONCLUSION: Despite lengthier hospital stays among AHIV patients, baseline AHIV was not associated with adverse outcomes following TKA and THA. This adds to the literature and warrants further research into the impact of asymptomatic, well-controlled HIV infection on postoperative outcomes following total joint arthroplasty.

Venous-plexus-associated lymphoid hubs support meningeal humoral immunity.

There is increasing interest in how immune cells in the meninges-the membranes that surround the brain and spinal cord-contribute to homeostasis and disease in the central nervous system1,2. The outer layer of the meninges, the dura mater, has recently been described to contain both innate and adaptive immune cells, and functions as a site for B cell development3-6. Here we identify organized lymphoid structures that protect fenestrated vasculature in the dura mater. The most elaborate of these dural-associated lymphoid tissues (DALT) surrounded the rostral-rhinal confluence of the sinuses and included lymphatic vessels. We termed this structure, which interfaces with the skull bone marrow and a comparable venous plexus at the skull base, the rostral-rhinal venolymphatic hub. Immune aggregates were present in DALT during homeostasis and expanded with age or after challenge with systemic or nasal antigens. DALT contain germinal centre B cells and support the generation of somatically mutated, antibody-producing cells in response to a nasal pathogen challenge. Inhibition of lymphocyte entry into the rostral-rhinal hub at the time of nasal viral challenge abrogated the generation of germinal centre B cells and class-switched plasma cells, as did perturbation of B-T cell interactions. These data demonstrate a lymphoid structure around vasculature in the dura mater that can sample antigens and rapidly support humoral immune responses after local pathogen challenge.

Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity.

Immune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived.

Tumour-retained activated CCR7+ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity.

Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7+ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7+ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7+ DCs co-localise with PD-1+CD8+ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7+ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.

Incidence, risk factors and outcomes of checkpoint inhibitor-induced liver injury: A 10-year real-world retrospective cohort study.

Background & Aims: Checkpoint inhibitors (CPI) account for increasing numbers of drug-induced liver injury (DILI) cases. We aimed to determine the incidence rate and risk factors associated with checkpoint inhibitor-induced liver injury (ChILI). Methods: Prescription event monitoring was performed on all melanoma and renal cancer patients who received CPI at a tertiary centre between 2011 and 2021. ChILI cases were identified using the definitions, grading, and causality assessment methods validated for DILI. We assessed risk factors associated with ChILI in CPI-naive patients using multivariable logistic regression model. Consecutive patients with suspected ChILI from two other tertiary centres were adjudicated and combined for case characterisation and outcomes of ChILI. Results: Out of 432 patients who received CPI over 10 years, ChILI occurred in 38 (8.8%) with an overall incidence rate of 11.5 per 1,000 person-months (95% CI 8.2-15.8). Probability of ChILI was highest in combination therapy (32%) and no new events occurred beyond 135 days of treatment. Risk factor analysis showed that combination therapy, female sex, higher baseline alanine transferase level and lower baseline alkaline phosphatase level were independently associated with higher risk of ChILI. In total, 99 patients were adjudicated to have ChILI from three centres. Although Common Terminology Criteria for Adverse Events classified 20 patients (20.2%) to have 'life-threatening' grade 4 hepatitis, ChILI severity was graded as mild in 45 (45.5%) and moderate in the remaining 54 (54.5%) cases. Conclusions: The real-world risk of ChILI is higher than previously reported. Among patients receiving dual CPI, this risk falls markedly after 4.5 months. As Common Terminology Criteria for Adverse Events overestimates its clinical severity, case-definition, evaluation and management of ChILI should be revised to harmonise care. Impact and implications: Using prescription event monitoring over a 10-year period, the incidence rate of checkpoint inhibitor induced liver injury (ChILI) based on established case definitions for drug-induced liver injury (DILI) is 11.5 per 1,000 person-months. Formal causality assessment identified an alternative cause in 19% of patients with suspected ChILI highlighting the importance of systematic evaluation by clinicians to minimise unnecessary immunosuppression. Intensity of monitoring in patients receiving combination therapy regime after 4.5 months of therapy can be reduced as the risk of new onset ChILI beyond this point is minimal. Current Common Terminology Criteria for Adverse Events (CTCAE) grading overestimates clinical severity of ChILI and hence contributes to avoidable hospitalisation.

Endoscopic surveillance with systematic random biopsy for the early diagnosis of hereditary diffuse gastric cancer: a prospective 16-year longitudinal cohort study.

BACKGROUND: Hereditary diffuse gastric cancer, generally caused by germline pathogenic variants in CDH1, presents with early-onset signet ring cell carcinoma. Prophylactic total gastrectomy is the definitive treatment. Endoscopic surveillance can inform the timing of prophylactic total gastrectomy through detection of microscopic signet ring cell carcinoma foci. However, evidence is scarce about the optimal endoscopic sampling technique and characterisation of signet ring cell carcinoma foci in hereditary diffuse gastric cancer. We aimed to formally assess the diagnostic yield of different sampling strategies and to identify criteria for the characterisation of endoscopic lesions. METHODS: For this prospective longitudinal cohort study, we included individuals aged 18 years or older at the Cambridge University Hospitals National Health Service (NHS) Foundation Trust who fulfilled testing criteria for hereditary diffuse gastric cancer between June 1, 2005, and July 31, 2021. The primary outcome was detection of intramucosal signet ring cell carcinoma foci. We assessed the detection rate and anatomical location of signet ring cell carcinoma in random biopsy samples taken according to a systematic protocol compared with biopsies targeted to endoscopic findings. Endoscopic lesions were examined with white-light and narrow band imaging with magnification to assess the likelihood of cancerous foci. FINDINGS: 145 individuals were included, of whom 68 (47%) were male and 92 (63%) carried the CDH1 pathogenic variant. 58 (40%) patients were diagnosed with invasive signet ring cell carcinoma over a median follow-up time of 51 months (IQR 18-80). The first diagnosis of signet ring cell carcinoma was most commonly made from random biopsies (29 [50%] of 58 patients), rather than targeted biopsies (15 [26%] patients). The anatomical distribution of signet ring cell carcinoma foci detected by random biopsies more accurately reflected those identified in prophylactic total gastrectomy specimens than did targeted biopsies. Omitting random biopsies in our cohort would have led to an under-diagnosis rate of 42%. Using a novel panel of endoscopic criteria, gastric lesions containing signet ring cell carcinoma were predicted with a sensitivity of 67·3% and a specificity of 90·2%. INTERPRETATION: Random biopsies enhance the early detection of signet ring cell carcinoma and are complementary to targeted biopsies in surveillance of hereditary diffuse gastric cancer. This sampling method should be the standard of care when performing all surveillance endoscopies for individuals with hereditary diffuse gastric cancer. FUNDING: UK Medical Research Council.

Biosynthesis of tetrahydropapaverine and semisynthesis of papaverine in yeast.

Tetrahydropapaverine (THP) and papaverine are plant natural products with clinically significant roles. THP is a precursor in the production of the drugs atracurium and cisatracurium, and papaverine is used as an antispasmodic during vascular surgery. In recent years, metabolic engineering advances have enabled the production of natural products through heterologous expression of pathway enzymes in yeast. Heterologous biosynthesis of THP and papaverine could play a role in ensuring a stable supply of these clinically significant products. Biosynthesis of THP and papaverine has not been achieved to date, in part because multiple pathway enzymes have not been elucidated. Here, we describe the development of an engineered yeast strain for de novo biosynthesis of THP. The production of THP is achieved through heterologous expression of two enzyme variants with activity on nonnative substrates. Through protein engineering, we developed a variant of N-methylcoclaurine hydroxylase with activity on coclaurine, enabling de novo norreticuline biosynthesis. Similarly, we developed a variant of scoulerine 9-O-methyltransferase capable of O-methylating 1-benzylisoquinoline alkaloids at the 3' position, enabling de novo THP biosynthesis. Flux through the heterologous pathway was improved by knocking out yeast multidrug resistance transporters and optimization of media conditions. Overall, strain engineering increased the concentration of biosynthesized THP 600-fold to 121 µg/L. Finally, we demonstrate a strategy for papaverine semisynthesis using hydrogen peroxide as an oxidizing agent. Through optimizing pH, temperature, reaction time, and oxidizing agent concentration, we demonstrated the ability to produce semisynthesized papaverine through oxidation of biosynthesized THP.

Bromodomain Inhibitors Modulate FcγR-Mediated Mononuclear Phagocyte Activation and Chemotaxis.

IgG antibodies form immune complexes (IC) that propagate inflammation and tissue damage in autoimmune diseases such as systemic lupus erythematosus. IgG IC engage Fcγ receptors (FcγR) on mononuclear phagocytes (MNP), leading to widespread changes in gene expression that mediate antibody effector function. Bromodomain and extra-terminal domain (BET) proteins are involved in governing gene transcription. We investigated the capacity of BET protein inhibitors (iBET) to alter IgG FcγR-mediated MNP activation. We found that iBET dampened IgG IC-induced pro-inflammatory gene expression and decreased activating FcγR expression on MNPs, reducing their ability to respond to IgG IC. Despite FcγR downregulation, iBET-treated macrophages demonstrated increased phagocytosis of protein antigen, IgG IC, and apoptotic cells. iBET also altered cell morphology, generating more amoeboid MNPs with reduced adhesion. iBET treatment impaired chemotaxis towards a CCL19 gradient in IC-stimulated dendritic cells (DC) in vitro, and inhibited IC-induced DC migration to draining lymph nodes in vivo, in a DC-intrinsic manner. Altogether, our data show that iBET modulates FcγR-mediated MNP activation and migration, revealing the therapeutic potential of BET protein inhibition in antibody-mediated diseases.

Preliminary Computed Tomography Radiomics Model for Predicting Pretreatment CD8+ T-Cell Infiltration Status for Primary Head and Neck Squamous Cell Carcinoma.

PURPOSE: Immunotherapy has emerged as a treatment option for head and neck squamous cell carcinoma (HNSCC), with tumor response being linked to the CD8+ T-cell inflammation. The purpose of this study is to assess whether computed tomography (CT) radiomic analysis can predict CD8+ T-cell enrichment in HNSCC primary tumors. METHODS: This retrospective study included 71 patients from a head and neck cancer genomics cohort with CD8+ T-cell enrichment status. Pretreatment contrast-enhanced neck CT scans were retrospectively reviewed using 3D Slicer for primary lesion segmentation.The SlicerRadiomics extension was used to extract 107 radiomic features. Ridge regression and lasso regression were applied for feature selection and model construction. RESULTS: Lasso regression defined Coarseness as the most important variable, followed by SmallDependenceEmphasis, SmallAreaLowGrayLevelEmphasis, Contrast.1, and Correlation.Ridge regression defined Coarseness as the most important variable, followed by SmallDependenceLowGrayLevelEmphasis, Contrast.1, DependenceNonUniformityNormalized, and Idmn. These variables identified by lasso and ridge regressions were used to create a combined logistic regression model. The area under the curve (AUC) for the lasso-generated model was 0.786 (95% confidence interval [CI], 0.532-1.000), and the AUC for the ridge-generated model was 0.786 (95% CI, 0.544-1.000). Combining the radiomic variables identified by lasso and ridge regressions with clinical characteristics including alcohol use, tobacco use, anatomic site, and initial T stage produced a model with an AUC of 0.898 (95% CI, 0.731-1.000). CONCLUSIONS: T-cell inflammation status of HNSCC primary tumors can be predicted using radiomic analysis of CT imaging and thereby help identify patients who would respond well to immunotherapy.

Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells.

Hofbauer cells (HBCs) are a population of macrophages found in high abundance within the stroma of the first-trimester human placenta. HBCs are the only fetal immune cell population within the stroma of healthy placenta. However, the functional properties of these cells are poorly described. Aligning with their predicted origin via primitive hematopoiesis, we find that HBCs are transcriptionally similar to yolk sac macrophages. Phenotypically, HBCs can be identified as HLA-DR-FOLR2+ macrophages. We identify a number of factors that HBCs secrete (including OPN and MMP-9) that could affect placental angiogenesis and remodeling. We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal. Finally, we also identify a population of placenta-associated maternal macrophages (PAMM1a) that adhere to the placental surface and express factors, such as fibronectin, that may aid in repair.

Temporary new implant spacers increase post-reimplantation total knee prosthesis survival after periprosthetic joint infection.

PURPOSE: Two-stage exchange arthroplasty is considered the gold standard for treatment of periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). Antibiotic cement spacers can include cement-based spacers (CBS), new components (NEW), and autoclaved components (ACL). The factors that most influence post-reimplantation prosthesis (PRP) survival were determined. METHODS: A retrospective database review of patients undergoing two-stage exchange arthroplasty from 2008 to 2014 was performed. There were 85 patients, 25 patients and 30 patients in CBS, NEW and ACL groups, respectively. Patient, disease and surgical characteristics were collected and analyzed. Post-reimplantation prosthesis (PRP) survival was modeled using the Kaplan-Meier method. Cox proportional hazard modeling was then performed to identify risk factors associated with implant failure. RESULTS: Overall PRP survival was 82% in 140 unilateral TKAs. PRP survival between groups was 81%, 96% and 73% within the minimum 2-year follow-up period, respectively. There was a difference in median interval-to-reimplantation between groups (CBS, 72.0 days; NEW, 111.0 days; ACL, 84.0 days, p = 0.003). Adjusting for time-to-reimplantation, NEW spacers demonstrated greater PRP survival compared with ACL spacers (p = 0.044), and a trend towards greater survival compared with CBS spacers (p = 0.086). Excluding early failures (< 90 days), NEW spacers still demonstrated greater survival than ACL spacers (p = 0.046). Lower volume (≤ 10 within this series) surgeons tended to use more CBS spacers, while higher volume surgeons were comfortable with ACL spacers. CONCLUSIONS: There was greater PRP survival with NEW spacers. NEW spacers also demonstrated an increased inter-stage interval, likely because of increased comfort and motion. There were spacer choice differences between low- and high-volume surgeons. LEVEL OF EVIDENCE: III.

Baseline Computed Tomography Radiomic and Genomic Assessment of Head and Neck Squamous Cell Carcinoma.

PURPOSE: To determine the relationship between computed tomography (CT) radiomic features and gene expression levels in head and neck squamous cell carcinoma (HNSCC). METHODS: This retrospective study included 66 patients with HNSCC primary lesions (36 oropharyngeal, 6 hypopharyngeal, 10 laryngeal, 14 oral cavity). Gene expression information for 6 targetable genes (fibroblast growth factor receptor [FGFR]1, epidermal growth factor receptor [EGFR], FGFR2, FGFR3, EPHA2, PIK3CA) was obtained via Agilent microarrays from samples collected between 1997 and 2010. Pretreatment contrast-enhanced soft tissue neck CT scans were reviewed, and 142 radiomics features were derived. R was used to calculate Pearson correlation coefficients were calculated between gene expression levels and each radiomic feature. P values were adjusted using the false discovery rate (FDR) method. RESULTS: There were significant correlations between FGFR1 and 5 gray level cooccurrence matrix (GLCM) features with FDR-adjusted P values less than 0.05: inertia (r = 0.366, FDR-adjusted P = 0.006), absolute value (r = 0.31, FDR-adjusted P = 0.024), contrast (r = 0.366, FDR-adjusted P = 0.006), difference average (r = 0.31, FDR-adjusted P = 0.024), and difference variance (r = 0.37, FDR-adjusted P = 0.005). There was 1 correlated feature for FGFR2 with an FDR-adjusted P value less than 0.05: fractal dimension box-coarse (r = 0.33, FDR-adjusted P = 0.018). There was 1 correlated feature for EPHA2 with an FDR-adjusted P value less than 0.05: GLCM entropy (r = -0.28, FDR-adjusted P = 0.049). Six of the 7 features that showed significant correlation belonged to the GLCM class of features. CONCLUSIONS: The CT radiomic features demonstrate correlations with FGFR1 status in HNSCC and should be further investigated for their potential to predict FGFR1 status.

Neuroimaging of septo-optic dysplasia-plus with midbrain hypoplasia and ophthalmoplegia.

Septo-optic dysplasia is a rare brain malformation that can be associated with anomalous cortical development, such as schizencephaly, which is referred to as septo-optic dysplasia plus. This report describes septo-optic dysplasia-plus associated with unilateral atrophy of the midbrain and oculomotor nerve deficiency, which was diagnosed on MRI in a teenage male who presented with ophthalmoplegia.

Días de gestación ganados con diferentes técnicas de cerclaje en pacientes con insuficiencia cervical / Gestational days gained with different cerclage techniques in patients with cervical incompetence

Resumen OBJETIVO: Reportar la experiencia en la práctica de cerclajes con indicación profiláctica y terapéutica en pacientes con embarazo único o múltiple, con insuficiencia cervical. Además, informar los días de gestación ganados y comparar las técnicas quirúrgicas con los cerclajes. MATERIALES Y MÉTODOS: Estudio retrospectivo, descriptivo, comparativo y transversal efectuado entre enero de 2011 y enero de 2018. Criterios de inclusión: pacientes a quienes se efectuó un cerclaje y el embarazo finalizó en nuestra unidad. Variables de estudio: edad, IMC, embarazos, abortos, días de gestación ganados, días en que se efectuó el procedimiento quirúrgico, semanas de gestación cumplidas a la finalización del embarazo, tiempo quirúrgico, medicamentos (tocolíticos y antibióticos), complicaciones a partir del cerclaje hasta la finalización del embarazo. Para el análisis descriptivo se utilizó el paquete estadístico IBM SPSS (versión 22); la distribución se obtuvo con t de Student, se aplicó la prueba de normalidad Shapiro-Wilk y las variables con distribución normal se analizaron, comparativamente, con ANOVA y las de distribución anormal con la prueba Kruskal-Wallis. RESULTADOS: Se analizaron 37 casos en los que el cerclaje prolongó 116.14 ± 47.4 días la gestación, con finalización promedio del embarazo a los 246.41 ± 26.54 días. El cerclaje Shirodkar fue superior: prolongó la gestación 134.69 días con finalización del embarazo a las 36 ± 2 semanas. CONCLUSIONES: En pacientes con insuficiencia cervical el cerclaje es una opción para prolongar el embarazo. La técnica Shirodkar tuvo márgenes de mayor seguridad hasta la finalización del embarazo (más de 34 semanas). El comportamiento en embarazos múltiples es similar, por lo que en caso de insuficiencia cervical debe aplicarse.

Abstract OBJECTIVE: To report the experience in the practice of cerclages with prophylactic and therapeutic indication in patients with single or multiple pregnancy, with cervical incompetence. In addition, report the days of pregnancy gained, compare surgical techniques and cerclages in single and multiple gestations. MATERIALS AND METHODS: Retrospective, descriptive, comparative and cross-sectional study carried out between January 2011 and January 2018. Inclusion criteria: patients who had a cerclage and the pregnancy ended in our unit. Study variables: age, BMI, pregnancies, abortions, days of gestation earned, days in which they were placed, weeks of gestation completed at the end of pregnancy, surgical time, medications (tocolytics and antibiotics), complications from the placement of the cerclage until the end of pregnancy. For the descriptive analysis the statistical package IBM SPSS (version 22) was used; the distribution was obtained with Student's t test, the Shapiro-Wilk normality test was applied and the variables with normal distribution were analyzed, comparatively, with ANOVA and those with abnormal distribution with the Kruskal-Wallis test. RESULTS: 37 cases were analyzed in which the placement of cerclage prolonged 116.14 ± 47.4 days gestation, with an average termination of pregnancy at 246.41 ± 26.54 days. The Shirodkar cerclage was superior: it extended gestation 134.69 days with the end of pregnancy at 36 ± 2 weeks. CONCLUSIONS: In patients with cervical incompetence cerclages are an option to prolong pregnancy. The Shirodkar technique had higher safety margins until the end of pregnancy (more than 34 weeks). The behavior in multiple pregnancies is similar, so in case of cervical incompetence should be applied.

Dynamic sensor-balanced knee arthroplasty: can the sensor "train" the surgeon?

BACKGROUND: Dynamic tibial tray sensors are playing an increasing role in total knee arthroplasty (TKA) coronal balancing. Sensor balance is proposed to lead to improved patient outcomes compared with sensor-unbalanced TKA, and traditional manual-balanced TKA. However, the "learning curve" of this technology is not known, and also whether sensor use can improve manual TKA balance skills once the sensor is taken away, effectively "training" the surgeon. METHODS: We conducted a single-surgeon prospective study on 104 consecutive TKAs. In Nonblinded Phase I (n = 49), sensor-directed releases were performed during trialing and final intercompartmental load was recorded. In Blinded Phase II (n = 55), manual-balanced TKA was performed and final sensor readings were recorded by a blinded observer after cementation. We used cumulative summation analysis and sequential probability ratio testing to analyze the surgeon learning curve in both phases. RESULTS: In Nonblinded Phase I, sensor balance proficiency was attained most easily at 10°, followed by 90°, and most difficult to attain at 45° of flexion. In Blinded Phase II, manual balance was lost most quickly at 45°, followed by 90°, and preserved for longest at 10° of flexion. The number of cases in the steady state periods (early phase periods where there is a mix of sensor balance and sensor imbalance) for both phases is similar. CONCLUSIONS: A surgeon who consistently uses the dynamic sensor demonstrates a learning curve with its use, and an "attrition" curve once it is removed. Consistent sensor balance is more predictable with constant sensor use.

Aspirin Alone Is Not Enough to Prevent Deep Venous Thrombosis After Total Joint Arthroplasty.

Thromboembolic events after total joint arthroplasty are potentially devastating complications. This study evaluated the efficacy of 4 different anticoagulants in preventing deep venous thrombosis and pulmonary embolism after total joint arthroplasty. The demographics and anticoagulant use (warfarin, enoxaparin, and aspirin with and without outpatient mechanical pumps) for patients who underwent primary unilateral total joint arthroplasties performed by a single surgeon from January 2013 to October 2014 were retrospectively reviewed. All patients underwent lower extremity ultrasound at the 3-week postoperative visit. A total of 613 primary unilateral total joint arthroplasties met the study inclusion criteria. There were 288 primary total knee arthroplasties and 325 primary total hip arthroplasties. The patients were 62.2% female, having a mean age of 67.6±10.6 years and a mean body mass index of 30.2±5.9 kg/m2. There were 119 patients in group 1 (aspirin alone), 40 patients in group 2 (aspirin plus pumps), 246 patients in group 3 (warfarin), and 208 patients in group 4 (enoxaparin). The overall 3-week symptomatic and asymptomatic deep venous thrombosis and symptomatic pulmonary embolism rates in the entire cohort were 5.7% and 0.3%, respectively. The venous thromboembolism rate was significantly affected by the anticoagulant of choice (P<.01). Compared with aspirin alone, warfarin decreased the risk of venous thromboembolism (P<.01). Increasing age led to increased risk of venous thromboembolism (P=.05). This study indicated that aspirin chemoprophylaxis alone was not as efficacious as warfarin and enoxaparin in preventing asymptomatic and symptomatic venous thromboembolism found during routine postoperative surveillance with lower extremity ultrasound. Aspirin alone may be inadequate and should be augmented with an outpatient mechanical pump as part of multimodal prophylaxis. [Orthopedics. 2019; 42(1):48-55.].

Return to the operating room after patellofemoral arthroplasty versus total knee arthroplasty for isolated patellofemoral arthritis-a systematic review.

PURPOSE: Patellofemoral arthroplasty (PFA) and total knee arthroplasty (TKA) are accepted treatments for end-stage isolated patellofemoral osteoarthritis (PFOA). However, complications and re-operations have historically differed between the two procedures. We performed a systematic review to report on the re-operation rates between TKA and modern PFA for isolated PFOA. METHODS: Systematically identified publications reporting on patients that underwent either TKA or modern PFA for isolated PFOA were reviewed. Meta-analysis software was used to screen potential articles with at least one year follow-up that detailed reasons for re-operation. Data was extracted and analyzed for all re-operations. Survival of the implant was used as the primary outcome; return to the operating room (OR) for any reason was used as a secondary outcome. RESULTS: The weighted rate of either conversion or revision arthroplasty in the PFA group and the TKA group was 6.34 and 0.11, respectively. The weighted rate of return to the OR for bony and soft tissue procedures was 1.06 and 0.79, respectively. The weighted rate of manipulation under anaesthesia (MUA) was 0.32 and 1.23, respectively. CONCLUSION: Patients who undergo PFA may be more likely to return to the operating room for conversion to TKA and/or revision surgery than those who undergo TKA.

Total Hip Arthroplasty and Hemiarthroplasty: US National Trends in the Treatment of Femoral Neck Fractures.

There is controversy regarding whether total hip arthroplasty (THA) or hemiarthroplasty (HA) is the treatment preferred for displaced intracapsular femoral neck fractures (FNFs). Using the US National Hospital Discharge Survey, we found that, of 12,757 patients admitted for FNF between 2001 and 2010, 4.6% underwent THA and 52.5% underwent HA. More of both procedures were performed over time. Mean age was higher for HA patients. Hospitalization duration and blood transfusion rates were higher for THA. There were region-based differences in frequency of THA and significant hospital-size-based differences in frequency of HA, possibly because of differences in regional training and subspecialist availability. In addition, a larger proportion of THA patients was covered by private insurance.