Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.

PURPOSE: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively. METHODS: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID. RESULTS: The ES diagnostic yield was 42 of 74 (57%). GS diagnoses were made in 9 of 32 (28%) ES-unresolved families. Repeated ES with a contemporary pipeline on the GS-diagnosed families identified 8 of 9 single-nucleotide variations/copy-number variations undetected in older ES, confirming a GS-unique diagnostic rate of 1 in 32 (3%). Episignatures contributed diagnostic information in 9% with GS corroboration in 1 of 32 (3%) and diagnostic clues in 2 of 32 (6%). A genetic etiology for ID was detected in 51 of 74 (69%) families. Twelve candidate disease genes were identified. Contemporary ES followed by GS cost US$4976 (95% CI: $3704; $6969) per diagnosis and first-line GS at a cost of $7062 (95% CI: $6210; $8475) per diagnosis. CONCLUSION: Performing GS only in ID trios would be cost equivalent to ES if GS were available at $2435, about a 60% reduction from current prices. This study demonstrates that first-line GS achieves higher diagnostic rate than contemporary ES but at a higher cost.

Direct Trauma Center Access by Helicopter Emergency Medical Services is Associated With Improved Survival After Severe Injury.

OBJECTIVE: Evaluate the association of survival with helicopter transport directly to a trauma center compared with ground transport to a non-trauma center (NTC) and subsequent transfer. SUMMARY BACKGROUND DATA: Helicopter transport improves survival after injury. One potential mechanism is direct transport to a trauma center when the patient would otherwise be transported to an NTC for subsequent transfer. METHODS: Scene patients 16 years and above with positive physiological or anatomic triage criteria within PTOS 2000-2017 were included. Patients transported directly to level I/II trauma centers by helicopter were compared with patients initially transported to an NTC by ground with a subsequent helicopter transfer to a level I/II trauma center. Propensity score matching was used to evaluate the association between direct helicopter transport and survival. Individual triage criteria were evaluated to identify patients most likely to benefit from direct helicopter transport. RESULTS: In all, 36,830 patients were included. Direct helicopter transport was associated with a nearly 2-fold increase in odds of survival compared with NTC ground transport and subsequent transfer by helicopter (aOR 2.78; 95% CI 2.24-3.44, P <0.01). Triage criteria identifying patients with a survival benefit from direct helicopter transport included GCS≤13 (1.71; 1.22-2.41, P <0.01), hypotension (2.56; 1.39-4.71, P <0.01), abnormal respiratory rate (2.30; 1.36-3.89, P <0.01), paralysis (8.01; 2.03-31.69, P <0.01), hemothorax/pneumothorax (2.34; 1.36-4.05, P <0.01), and multisystem trauma (2.29; 1.08-4.84, P =0.03). CONCLUSIONS: Direct trauma center access is a mechanism driving the survival benefit of helicopter transport. First responders should consider helicopter transport for patients meeting these criteria who would otherwise be transported to an NTC.

MIMIC: an optimization method to identify cell type-specific marker panel for cell sorting.

Multi-omics data allow us to select a small set of informative markers for the discrimination of specific cell types and study of cellular heterogeneity. However, it is often challenging to choose an optimal marker panel from the high-dimensional molecular profiles for a large amount of cell types. Here, we propose a method called Mixed Integer programming Model to Identify Cell type-specific marker panel (MIMIC). MIMIC maintains the hierarchical topology among different cell types and simultaneously maximizes the specificity of a fixed number of selected markers. MIMIC was benchmarked on the mouse ENCODE RNA-seq dataset, with 29 diverse tissues, for 43 surface markers (SMs) and 1345 transcription factors (TFs). MIMIC could select biologically meaningful markers and is robust for different accuracy criteria. It shows advantages over the standard single gene-based approaches and widely used dimensional reduction methods, such as multidimensional scaling and t-SNE, both in accuracy and in biological interpretation. Furthermore, the combination of SMs and TFs achieves better specificity than SMs or TFs alone. Applying MIMIC to a large collection of 641 RNA-seq samples covering 231 cell types identifies a panel of TFs and SMs that reveal the modularity of cell type association networks. Finally, the scalability of MIMIC is demonstrated by selecting enhancer markers from mouse ENCODE data. MIMIC is freely available at https://github.com/MengZou1/MIMIC.

A numerical investigation of passive acoustic mapping for monitoring bubble-mediated focused ultrasound treatment of the spinal cord.

Focused ultrasound (FUS) combined with intravenous microbubbles (MBs) has been shown to increase drug delivery to the spinal cord in animal models. Eventual clinical translation of such a technique in the sensitive spinal cord requires robust treatment monitoring to ensure efficacy, localization, safety, and provide key intraprocedural feedback. Here, the use of passive acoustic mapping (PAM) of MB emissions with a spine-specific detector array in the context of transvertebral FUS sonications is investigated in silico. Using computed tomography-derived human vertebral geometry, transvertebral detection of MBs is evaluated over varying source locations with and without phase and amplitude corrections (PACs). The impact of prefocal cavitation is studied by simulating concurrent cavitation events in the canal and pre-laminar region. Spatially sensitive application of phase and amplitude is used to balance signal strengths emanating from different axial depths in combination with multiple dynamic ranges to elicit multisource viewing. Collectively, the results of this study encourage the use of PAM in transvertebral FUS applications with PACs to not only localize sources originating in the spinal canal but also multiple sources of innate amplitude mismatches when corrective methods are applied.

Maximal and Submaximal Intensity Isometric Knee Extensions Induce an Underestimation of Time Estimates with Both Younger And Older Adults: A Randomized Crossover Trial.

Our perception of time plays a critical role in nearly all daily activities and especially in sports. There are no studies that have investigated and compared time perception during exercise in young and older adults. Thus, this study aimed to compare the effects of exercise on time perception between younger and older adult populations. Thirty-three recreationally active participants were recruited and assigned to either the younger (university students, 9 males and 10 females) or older adults (>60 years, 8 males and 6 females). All participants completed four exercise conditions over two sessions on separate days: approximately 30-seconds of knee extensors 100%, 60% and 10% of maximum voluntary isometric contraction (MVIC), and control (no contractions). Prospective time perception was estimated (at 5-, 10-, 20-, and 30-seconds) at the beginning of each session and while performing the exercise. A main effect for condition (p < 0.001, d = 1.06) with subsequent post-hoc tests indicated participants significantly underestimated (estimated time was shorter than chronological time) time in all three exercise conditions compared to the control. There were no significant age group differences. In conclusion, exercise underestimated time estimates regardless of intensity or age. This questions the postulated intensity-dependent relationship between exercise and time perception. While older adults were expected to be less accurate in their time estimates, they may have been able to adopt alternative strategies for age-related changes in their internal clock, resulting in no significant age group differences.

The effects of sequencing depth on the assembly of coding and noncoding transcripts in the human genome.

Investigating the functions and activities of genes requires proper annotation of the transcribed units. However, transcript assembly efforts have produced a surprisingly large variation in the number of transcripts, and especially so for noncoding transcripts. This heterogeneity in assembled transcript sets might be partially explained by sequencing depth. Here, we used real and simulated short-read sequencing data as well as long-read data to systematically investigate the impact of sequencing depths on the accuracy of assembled transcripts. We assembled and analyzed transcripts from 671 human short-read data sets and four long-read data sets. At the first level, there is a positive correlation between the number of reads and the number of recovered transcripts. However, the effect of the sequencing depth varied based on cell or tissue type, the type of read and the nature and expression levels of the transcripts. The detection of coding transcripts saturated rapidly with both short and long-reads, however, there was no sign of early saturation for noncoding transcripts at any sequencing depth. Increasing long-read sequencing depth specifically benefited transcripts containing transposable elements. Finally, we show how single-cell RNA-seq can be guided by transcripts assembled from bulk long-read samples, and demonstrate that noncoding transcripts are expressed at similar levels to coding transcripts but are expressed in fewer cells. This study highlights the impact of sequencing depth on transcript assembly.

The diverse pleiotropic effects of spliceosomal protein PUF60: A case series of Verheij syndrome.

Verheij syndrome (VRJS) is a rare craniofacial spliceosomopathy presenting with craniofacial dysmorphism, multiple congenital anomalies and variable neurodevelopmental delay. It is caused by single nucleotide variants (SNVs) in PUF60 or interstitial deletions of the 8q24.3 region. PUF60 encodes a splicing factor which forms part of the spliceosome. To date, 36 patients with a sole diagnosis of VRJS due to disease-causing PUF60 SNVs have been reported in peer-reviewed publications. Although the depth of their phenotyping has varied greatly, they exhibit marked phenotypic heterogeneity. We report 10 additional unrelated patients, including the first described patients of Khmer, Indian, and Vietnamese ethnicities, and the eldest patient to date, with 10 heterozygous PUF60 variants identified through exome sequencing, 8 previously unreported. All patients underwent deep phenotyping identifying variable dysmorphism, growth delay, neurodevelopmental delay, and multiple congenital anomalies, including several unique features. The eldest patient is the only reported individual with a germline variant and neither neurodevelopmental delay nor intellectual disability. In combining these detailed phenotypic data with that of previously reported patients (n = 46), we further refine the known frequencies of features associated with VRJS. These include neurodevelopmental delay/intellectual disability (98%), axial skeletal anomalies (74%), appendicular skeletal anomalies (73%), oral anomalies (68%), short stature (66%), cardiac anomalies (63%), brain malformations (48%), hearing loss (46%), microcephaly (41%), colobomata (38%), and other ocular anomalies (65%). This case series, incorporating three patients from previously unreported ethnic backgrounds, further delineates the broad pleiotropy and mutational spectrum of PUF60 pathogenic variants.

Enhancement of stratum corneum lipid structure improves skin barrier function and protects against irritation in adults with dry, eczema-prone skin.

BACKGROUND: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens. OBJECTIVES: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation. METHODS: A randomized observer-blind intrapatient-controlled study in 34 adults with dry, eczema-prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier-transform infrared spectroscopy using a novel interface. RESULTS: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve -162, 95% confidence interval (CI) -206 to -118]. Skin sensitivity to sodium lauryl sulfate was reduced (-0·5 points visual redness, 97·57% CI -1·00 to -0·25), as was transepidermal water loss (-15·3 g m-2 h-1 , 95% CI -20·3 to -10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61-10·6) and decreased signs of dryness. CONCLUSIONS: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin.

Different types of emollient cream exhibit diverse physiological effects on the skin barrier in adults with atopic dermatitis.

BACKGROUND: Eczema (atopic dermatitis; AD) is a very common itchy skin condition affecting 1 in 5 children and up to 1 in 10 adults worldwide. The skin of eczema sufferers is prone to redness, irritation and dryness because it does not form an effective barrier, i.e. the ability of the skin to stop irritants, allergens and microorganisms getting into the body. Skin barrier dysfunction is a hallmark of AD. The regular and liberal (600 g/week for an adult) use of emollients is recommended for all patients with eczema), even between episodes of itching and redness, to soften and soothe the skin. In England alone, almost 9 million prescriptions for emollient creams were issued in 2018, at a cost of over £50 million. Despite this widespread use, relatively little is known about how commonly prescribed emollient creams affect the skin's barrier, and thus the role of moisturizers in AD development and progression remains unclear. We set out to compare three different types of emollient cream and a no-treatment control. AIM: To compare the barrier-strengthening properties of a new moisturizer containing urea and glycerol (urea-glycerol cream; UGC), with those of a glycerol-containing moisturizer (glycerol cream; GC), a simple paraffin cream (PC) with no humectant, and a no-treatment control (NTC). METHODS: This was an observer-blinded prospective Phase 2 within-subject multilateral single-centre randomized controlled trial in adults with AD (Clinical Trials #NCT03901144). The intervention involved 4 weeks of treatment, twice daily, with the three products applied to one of four areas on the forearms the (the fourth area was the untreated control, randomized allocation). Skin properties [dryness, transepidermal water loss (TEWL), hydration and natural moisturizing factor (NMF) levels] were assessed before, during and after treatment to see what happened to the skin's barrier. The primary outcome was skin sensitivity to the irritant sodium lauryl sulfate (SLS) after treatment. We performed tests on the skin before and after treatment to see what happened to the skin's barrier. RESULTS: In total, 49 patients were randomized, completed treatment and included in the analysis. UGC significantly reduced the response to SLS as indicated by a reduction in TEWL compared with NTC (-9.0 g/m2 /h; 95% CI -12.56 to -5.49), with PC (-9.0 g/m2 /h; 95% CI -12.60 to -5.44) and with GC -4.2 g/m2 /h; 95% CI 7.76 to -0.63). Skin moisturization improved at sites treated with UGC compared with NTC and PC, and this was accompanied by concordant changes in dryness and NMF levels. Subgroup analysis suggested FLG-dependent enhancement of treatment effects. CONCLUSION: The study showed that not all emollient creams for eczema are equal. The simple paraffin-based emollient, which represents the most widely prescribed type of emollient cream in England, had no effect on the skin's barrier and reduced the skin's NMF. UGC markedly improved the skin's barrier and protected against irritation. GC performed better than PC, but not as well as UGC. UGC strengthened the skin barrier through a mechanism involving increased NMF levels in the skin, and imparted protection from SLS-induced irritation. By helping correct a major pathophysiological process, UGC has the potential to improve the long-term control of AD. The results show that different emollient creams have different effects on our skin, and only certain types have the ability to improve the skin's barrier and protect against irritants that trigger eczema.

The Financial Impact of an Inpatient Diabetes Management Service.

CONTEXT: Diabetes is a leading metabolic disorder with a substantial cost burden, especially in inpatient settings. The complexity of inpatient glycemic management has led to the emergence of inpatient diabetes management service (IDMS), a multidisciplinary team approach to glycemic management. OBJECTIVE: To review recent literature on the financial and clinical impact of IDMS in hospital settings. METHODS: We searched PubMed using a combination of controlled vocabulary and keyword terms to describe the concept of IDMS and combined the search terms with a comparative effectiveness filter for costs and cost analysis developed by the National Library of Medicine. FINDINGS: In addition to several improved clinical endpoints such as glycemic management outcomes, IDMS implementation is associated with hospital cost savings through decreased length of stay, preventing hospital readmissions, hypoglycemia reduction, and optimizing resource allocation. There are other downstream potential cost savings in long-term patient health outcomes and avoidance of litigation related to suboptimal glycemic management. CONCLUSION: IDMS may play an important role in helping both academic and community hospitals to improve the quality of diabetes care and reduce costs. Clinicians and policymakers can utilize existing literature to build a compelling business case for IDMS to hospital administrations and state legislatures in the era of value-based healthcare.

The Whole is Greater Than the Sum of its Parts: GCS Versus GCS-Motor for Triage in Geriatric Trauma.

BACKGROUND: Trauma field triage matches injured patients to the appropriate level of care. Prior work suggests the Glasgow Coma Scale motor (GCSm) is as accurate as the total GCS (GCSt) and easier to use. However, older patients present with higher GCS for a given injury, and as such, it is unclear if this substitution is advisable. Our objective was to compare the GCS deficit patterns between geriatric and adult patients presenting with severe traumatic brain injury (TBI), as well as the diagnostic performance of the GCSm versus GCSt within the field triage criteria in these populations. MATERIALS AND METHODS: We conducted a retrospective, observational cohort study of patients ≥16 y in the National Trauma Data Bank 2007-2015. GCS deficit patterns were compared between adults (16-65) and geriatric patients (>65). Measures of diagnostic performance of GCSt≤13 versus GCSm≤5 criteria to predict trauma center need (TCN) were compared. RESULTS: In total, 4,480,185 patients were analyzed (28% geriatric). Geriatric patients more frequently presented with non-motor-only deficits than adults (16.4% versus 12.4%, P < 0.001), and these patients demonstrated higher severe TBI (40.3% versus 36.7%, P < 0.001) and craniotomy (5.8% versus 5.1%, P < 0.001) rates. GCSt was more sensitive and accurate in predicting TCN for geriatric patients and had lower rates of undertriage as compared to GCSm. CONCLUSIONS: Geriatric patients more frequently present with non-motor-only deficits after injury, and this is associated with severe head injury. Substitution of GCSm for GCSt would exacerbate undertriage in geriatric patients and, thus, the total GCS should be maintained for field triage in geriatric patients.

Remote Patient Monitoring with Wearable Sensors Following Knee Arthroplasty.

(Background) Inertial Measurement Units (IMUs) provide a low-cost, portable solution to obtain functional measures similar to those captured with three-dimensional gait analysis, including spatiotemporal gait characteristics. The primary aim of this study was to determine the feasibility of a remote patient monitoring (RPM) workflow using ankle-worn IMUs measuring impact load, limb impact load asymmetry and knee range of motion in combination with patient-reported outcome measures. (Methods) A pilot cohort of 14 patients undergoing primary knee arthroplasty for osteoarthritis was prospectively enrolled. RPM in the community was performed weekly from 2 up to 6 weeks post-operatively using wearable IMUs. The following data were collected using IMUs: mobility (Bone Stimulus and cumulative impact load), impact load asymmetry and maximum knee flexion angle. In addition, scores from the Oxford Knee Score (OKS), EuroQol Five-dimension (EQ-5D) with EuroQol visual analogue scale (EQ-VAS) and 6 Minute Walk Test were collected. (Results) On average, the Bone Stimulus and cumulative impact load improved 52% (p = 0.002) and 371% (p = 0.035), compared to Post-Op Week 2. The impact load asymmetry value trended (p = 0.372) towards equal impact loading between the operative and non-operative limb. The mean maximum flexion angle achieved was 99.25° at Post-Operative Week 6, but this was not significantly different from pre-operative measurements (p = 0.1563). There were significant improvements in the mean EQ-5D (0.20; p = 0.047) and OKS (10.86; p < 0.001) scores both by 6 weeks after surgery, compared to pre-operative scores. (Conclusions) This pilot study demonstrates the feasibility of a reliable and low-maintenance workflow system to remotely monitor post-operative progress in knee arthroplasty patients. Preliminary data indicate IMU outputs relating to mobility, impact load asymmetry and range of motion can be obtained using commercially available IMU sensors. Further studies are required to directly correlate the IMU sensor outputs with patient outcomes to establish clinical significance.

The changing face of clinical genetics service delivery in the era of genomics: a framework for monitoring service delivery and data from a comprehensive metropolitan general genetics service.

PURPOSE: Clinical genetics is an evolving specialty impacted by the availability of increasingly sophisticated investigational technologies. Methods for monitoring the changes in workload and workflow are necessary to ensure adequate service resourcing. METHODS: A literature search of known workload and workflow studies was completed, identifying metrics of value. A framework of metrics to allow consistent capture in clinical genetics practice was developed. This framework was then applied to local general genetics service data to evaluate recent changes in service delivery. RESULTS: Literature regarding service delivery metrics in clinical genetics services is limited and inconsistent in application. The metric framework generated is a useful tool for consistent and ongoing evaluation of general genetics services. Through application of the framework, new service delivery trends and significant changes in workload were identified. CONCLUSION: Studies of clinical genetics service delivery suffer from the use of inconsistent metrics. This framework will allow for monitoring of changes to service delivery, caseload volume, caseload complexity, and workforce over time. Local data presented demonstrate the significant effect that implementing clinical genomic sequencing has had on clinical service delivery. Applying this framework produces a comprehensive service characterization, enabling funding bodies to justify resourcing that addresses the growing demand of clinical genetics.

Change in matrix metalloproteinase 2, 3, and 9 levels at the time of and after acute atherothrombotic myocardial infarction.

Elevated measures of matrix metalloproteinases (MMPs) are associated with acute myocardial infarction (MI), but it is not known how long these changes persist post-MI or if these measures differ between atherothrombotic versus non-atherothrombotic MI. MMPs-2, 3, and 9 were measured in 80 subjects with acute MI (atherothrombotic and non-atherothrombotic MI) or stable coronary artery disease (CAD). Measurements were made at, the time of acute MI, and > 3-month following acute MI (quiescent phase). Outcome measures were compared between groups and between time of acute MI and quiescent post-MI follow-up using Wilcoxon's and repeated measures analysis of variance. Forty-nine subjects met the criteria for acute MI with clearly defined atherothrombotic (n = 22) and non-atherothrombotic (n = 12) subsets. Fifteen subjects met criteria for stable CAD. MMP-3 was higher in acute MI versus stable CAD subjects at the time of acute MI: (453 vs. 217 pg/mL, p = 0.010) but not at quiescent phase follow-up (p > 0.05). MMP-9 was higher in acute MI versus stable CAD subjects at the time of acute MI: (412 vs. 168 pg/mL, p = 0.002) but not at the quiescent phase follow-up (p > 0.05). MMP-9 was higher at the time of acute MI versus quiescent phase follow-up in acute MI (412 vs. 213 pg/mL, p = 0.001) and atherothrombotic MI specifically (458 vs. 212 pg/mL, p = 0.001). No difference in MMP-2, 3, or 9 was observed between atherothrombotic versus non-atherothrombotic MI subgroups. MMPs-3 and 9 are significantly elevated in acute MI verses stable CAD subjects at time of acute MI but not different at quiescent phase follow-up. MMP-9 is elevated at the time of acute MI and specifically in acute atherothrombotic MI at time of MI versus quiescent phase follow-up.

Allogeneic Leukocyte-Reduced Red Blood Cell Transfusion Is Associated with Postoperative Infectious Complications and Cancer Recurrence after Colon Cancer Resection.

BACKGROUND/AIMS: Transfusion rates in colon cancer surgery are traditionally very high. Allogeneic red blood cell (RBC) transfusions are reported to induce immunomodulation that contributes to infectious morbidity and adverse oncologic outcomes. In an effort to attenuate these effects, the study institution implemented a universal leukocyte reduction protocol. The purpose of this study was to examine the impact of leukocyte-reduced (LR) transfusions on postoperative infectious complications, recurrence-free survival, and overall survival (OS). METHODS: In a retrospective study, patients with stage I-III adenocarcinoma of the colon from 2003 to 2010 who underwent elective resection were studied. The primary outcome measures were postoperative infectious complications and recurrence-free and OS in patients that received a transfusion. Bivariate and multivariable regression analyses were performed for each endpoint. RESULTS: Of 294 patients, 66 (22%) received a LR RBC transfusion. After adjustment, transfusion of LR RBCs was found to be independently associated with increased infectious complications (OR 3.10, 95% CI 1.24-7.73), increased odds of cancer recurrence (hazard ratio [HR] 3.74, 95% CI 1.94-7.21), and reduced OS when ≥3 units were administered (HR 2.24, 95% CI 1.12-4.48). CONCLUSION: Transfusion of LR RBCs is associated with an increased risk of infectious complications and worsened survival after elective surgery for colon cancer, irrespective of leukocyte reduction.

Arthroscopic partial meniscectomy for meniscal tears of the knee: a systematic review and meta-analysis.

OBJECTIVE: To assess the benefit of arthroscopic partial meniscectomy (APM) in adults with a meniscal tear and knee pain in three defined populations (taking account of the comparison intervention): (A) all patients (any type of meniscal tear with or without radiographic osteoarthritis); (B) patients with any type of meniscal tear in a non-osteoarthritic knee; and (C) patients with an unstable meniscal tear in a non-osteoarthritic knee. DESIGN: Systematic review and meta-analysis. DATASOURCES: A search of MEDLINE, Embase, CENTRAL, Scopus, Web of Science, Clinicaltrials.gov and ISRCTN was performed, unlimited by language or publication date (inception to 18 October 2018). ELIGIBILITYCRITERIA: Randomised controlled trials performed in adults with meniscal tears, comparing APM versus (1) non-surgical intervention; (2) pharmacological intervention; (3) surgical intervention; and (4) no intervention. RESULTS: Ten trials were identified: seven compared with non-surgery, one pharmacological and two surgical. Findings were limited by small sample size, small number of trials and cross-over of participants to APM from comparator interventions. In group A (all patients) receiving APM versus non-surgical intervention (physiotherapy), at 6-12 months, there was a small mean improvement in knee pain (standardised mean difference [SMD] 0.22 [95% CI 0.03 to 0.40]; five trials, 943 patients; I2 48%; Grading of Recommendations Assessment, Development and Evaluation [GRADE]: low), knee-specific quality of life (SMD 0.43 [95% CI 0.10 to 0.75]; three trials, 350 patients; I2 56%; GRADE: low) and knee function (SMD 0.18 [95% CI 0.04 to 0.33]; six trials, 1050 patients; I2 27%; GRADE: low). When the analysis was restricted to people without osteoarthritis (group B), there was a small to moderate improvement in knee pain (SMD 0.35 [95% CI 0.04 to 0.66]; three trials, 402 patients; I2 58%; GRADE: very low), knee-specific quality of life (SMD 0.59 [95% CI 0.11 to 1.07]; two trials, 244 patients; I2 71%; GRADE: low) and knee function (SMD 0.30 [95% CI 0.06 to 0.53]; four trials, 507 patients; I2 44%; GRADE: very low). There was no improvement in knee pain, function or quality of life in patients receiving APM compared with placebo surgery at 6-12 months in group A or B (pain: SMD 0.08 [95% CI -0.24 to 0.41]; one trial, 146 patients; GRADE: low; function: SMD -0.08 [95% CI -0.41 to 0.24]; one trial, 146 patients; GRADE: high; quality of life: SMD 0.05 [95% CI -0.27 to 0.38]; one trial; 146 patients; GRADE: high). No trials were identified for people in group C. CONCLUSION: Performing APM in all patients with knee pain and a meniscal tear is not appropriate, and surgical treatment should not be considered the first-line intervention. There may, however, be a small-to-moderate benefit from APM compared with physiotherapy for patients without osteoarthritis. No trial has been limited to patients failing non-operative treatment or patients with an unstable meniscal tear in a non-arthritic joint; research is needed to establish the value of APM in this population. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42017056844.

No difference in revision rates between anteromedial portal and transtibial drilling of the femoral graft tunnel in primary anterior cruciate ligament reconstruction: early results from the New Zealand ACL Registry.

PURPOSE: The use of an accessory anteromedial portal to drill the femoral graft tunnel in primary anterior cruciate ligament (ACL) reconstruction was introduced in the 2000s in an effort to achieve a more anatomic femoral tunnel position. However, some early studies reported an increase in revision ACL reconstruction compared to the traditional transtibial technique. The aim of this study was to analyse recent data recorded by the New Zealand ACL Registry to compare outcomes of ACL reconstruction performed using the anteromedial portal and transtibial techniques. METHODS: Analysis was performed on primary isolated single-bundle ACL reconstructions recorded between 2014 and 2018 by the New Zealand ACL Registry. Patients were categorised into two groups according to whether an anteromedial portal or transtibial technique was used to drill the femoral graft tunnel. The primary outcome was revision ACL reconstruction and was compared between both groups through univariate and multivariate survival analyses. The secondary outcomes that were analysed included subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Marx activity score. RESULTS: Six thousand one hundred and eighty-eight primary single-bundle ACL reconstructions were performed using either the anteromedial portal or transtibial drilling techniques. The mean time of follow-up was 23.3 (SD ± 14.0) months. Similar patient characteristics such as mean age (29 years, SD ± 11), sex (males = 58% versus 57%) and time to surgery (median 4 months, IQR 5) were observed between both groups. The rate of revision ACL reconstruction was 2.6% in the anteromedial portal group and 2.2% in the transtibial group (n.s.). The adjusted risk of revision ACL reconstruction was 1.07 (95% CI 0.62-1.84, n.s.). Patients in the anteromedial portal group reported improved scores for subscales of the KOOS and higher Marx activity scores at 1-year post-reconstruction. CONCLUSION: There was no difference in the risk of revision ACL reconstruction between the two femoral tunnel drilling techniques at short-term follow-up. We observed minor differences in patient-reported outcomes at 1-year follow-up favouring the anteromedial portal technique, which may not be clinically relevant. Surgeons can achieve good clinical outcomes with either drilling technique. LEVEL OF EVIDENCE: III.

Rates of revision and surgeon-reported graft rupture following ACL reconstruction: early results from the New Zealand ACL Registry.

PURPOSE: There remains a lack of consensus on the patient factors associated with graft rupture following anterior cruciate ligament (ACL) reconstruction. This study aimed to identify the rate of revision and surgeon-reported graft rupture and clarify the patient risk factors for failure. METHODS: Analysis was conducted on prospective data captured by the New Zealand ACL registry. All primary isolated ACL reconstructions recorded between April 2014 and December 2018 were reviewed to identify the rate of revision and surgeon-reported graft rupture. Univariate and multivariate survival analysis was performed to identify patient factors associated with revision and graft rupture. RESULTS: A total of 7402 primary isolated ACL reconstructions were reviewed and had a mean follow-up time of 23.1 (SD ± 13.9) months. There were 258 surgeon-reported graft ruptures (3.5%) of which 175 patients underwent subsequent revision ACL reconstruction (2.4%). Patients younger than 18 years had the highest risk of revision (adjusted HR = 7.29, p < 0.001) and graft rupture (adjusted HR = 4.26, p < 0.001) when compared to patients aged over 36 years. Male patients had a higher risk of revision (adjusted HR = 2.00, p < 0.001) and graft rupture (adjusted HR = 1.70, p < 0.001) when compared to their female counterparts. Patients who underwent ACL reconstruction within 6 months of their injury had a two times increased risk of revision compared to patients who had surgery after 12 months (adjusted HR = 2.15, p = 0.016). CONCLUSION: Younger age, male sex and a shorter injury-to-surgery time interval increased the risk of revision, while younger age and male sex increased the risk of surgeon-reported graft rupture. LEVEL OF EVIDENCE: II.

Needlestick injuries: the role of safety-engineered devices in prevention.

The first documented mention of a needlestick injury (NSI) in the medical literature appeared in 1906. Despite growth in academic and clinical interest for NSI prevention, a global report identified that approximately 3 million healthcare workers have suffered percutaneous exposure to blood-borne pathogens. Legislation is an important component of NSI prevention. Unfortunately, the impact of legislation may not always reduce the incidence of NSI as much as expected. Safety-engineered device (SED) implementation has demonstrated a substantial reduction in NSI rates compared with non-SEDs. More importantly, passive SEDs are 10 times less likely to be connected with an NSI incident.

The impact of postreperfusion syndrome during liver transplantation using livers with significant macrosteatosis.

The impact of postreperfusion syndrome (PRS) during liver transplantation (LT) using donor livers with significant macrosteatosis is largely unknown. Clinical outcomes of all patients undergoing LT with donor livers with moderate macrosteatosis (30%-60%) (N = 96) between 2000 and 2017 were compared to propensity score matched cohorts of patients undergoing LT with donor livers with mild macrosteatosis (10%-29%) (N = 96) and no steatosis (N = 96). Cardiac arrest at the time of reperfusion was seen in eight (8.3%) of the patients in the moderate macrosteatosis group compared to one (1.0%) of the patients in the mild macrosteatosis group (P = .02) and zero (0%) of the patients in the no steatosis group (P = .004). Patients in the moderate macrosteatosis group had a higher rate of PRS (37.5% vs 18.8%; P = .004), early allograft dysfunction (EAD) (76.4% vs 25.8%; P < .001), renal dysfunction requiring continuous renal replacement therapy following transplant (18.8% vs 8.3%; P = .03) and return to the OR within 30 days (24.0% vs 7.3%; P = .002), than the no steatosis group. Both long-term patient (P = .30 and P = .08) and graft survival (P = .15 and P = .12) were not statistically when comparing the moderate macrosteatosis group to the mild macrosteatosis and no steatosis groups. Recipients of LT using livers with moderate macrosteatosis are at a significant increased risk of PRS. If patients are able to overcome the initial increased perioperative risk of using these donor livers, long-term graft survival does not appear to be different than matched recipients receiving grafts with no steatosis.