Adductor Canal Block or Local Infiltrate Analgesia for Pain Control After Total Knee Arthroplasty? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Total knee arthroplasty is a treatment option for debilitating arthritis. In the postoperative period, patients experience moderate to severe pain affecting the rehabilitation, hospital stay, and patient satisfaction. This study aims at utilizing current best evidence to determine whether adductor canal block (ACB) or periarticular injection (PAI) is a better modality for managing short-term postoperative pain and opioid consumption.

Pneumatic sequential-compression boots compared with aspirin prophylaxis of deep-vein thrombosis after total knee arthroplasty

This prospective, randomized study was undertaken to compare the effectiveness of pneumatic sequential-compression boots with that of aspirin in preventing deep-vein thrombosis after total knee arthroplasty. Patients were randomly assigned to one of two prophylactic regimens: compression boots or aspirin. One hundred and nineteen patients completed the study. Seventy-two patients had unilateral arthroplasty and forty-seven, one-stage bilateral arthroplasty. In the unilateral group, the incidence of deep-vein thrombosis was 22 per cent for the patients who used compression boots compared with 47 per cent for those who received aspirin (p less than 0.03). In the bilateral group, the incidence of deep-vein thrombosis was 48 per cent for the patients who used compression boots compared with 68 per cent for those who received aspirin (p less than 0.20). The results confirm the effectiveness of compression boots in the treatment of patients who have had unilateral total knee arthroplasty. Despite the use of compression boots, however, patients who had bilateral arthroplasty were at greater risk for the development of deep-vein thrombosis.     

Survivorship of cemented knee replacements

The survivorship method of analysis has been used to compare the failure rate and overall success of 1,430 cemented primary total knee arthroplasties performed at The Hospital for Special Surgery over a 15-year period. There were 224 total condylar prostheses with a polyethylene tibia, 289 of the posterior stabilised type with an all polyethylene tibia, and 917 posterior stabilised with a metal-backed tibial component. There were 12 failures in the total condylar series, giving an average annual failure rate of 0.65% and a 15-year success rate of 90.56%. The posterior stabilised prosthesis with a polyethylene tibia showed an average annual failure rate of 0.27% and a 10-year success rate of 97.34%, and this prosthesis with a metal-backed tibial component gave an annual failure rate of 0.19% and a seven-year success rate of 98.75%. The overall survival rate was not influenced by sex or age, diagnosis or the percentage of ideal body weight. No metal-backed tibial components have yet needed revision for loosening. It seems that infection will be the major cause of failure.     

The effects of regional and general anesthesia on blood pressure control after carotid endarterectomy

We retrospectively reviewed the influence of preoperative blood pressure control and regional vs. general anesthetic techniques on the incidence of intraoperative and postoperative (recovery room and intensive care unit) hypotension and hypertension in 249 carotid endarterectomy patients. Preoperative blood pressure was classified as uncontrolled hypertension (systolic blood pressure >/= 170 mm Hg and/or diastolic blood pressure >/= 95 mm Hg), controlled hypertension (blood pressure <170/95 mm Hg on chronic antihypertensive therapy), or normotension (blood pressure <170/95 mm Hg without antihypertensive therapy). Hypotension, as defined by the requirement for vasopressor administration to maintain a systolic blood pressure of at least 120 mm Hg, occurred more frequently after regional than after general anesthesia (p < 0.05). Postoperative hypertension was defined as a systolic blood pressure >/= 200 mm Hg and/or a diastolic blood pressure >/= 110 mm Hg in the recovery room or in the Intensive Care Unit. Preoperative hypertension was not associated with acute postoperative hypertension in the intensive care unit in either the regional anesthesia (n = 190) or the general anesthesia (n = 59) groups, although with either type of anesthesia, preoperative hypertension was associated with an increased incidence of hypertension in the recovery room (p < 0.01 regional; p < 0.005 general).     

Complex mosaic structural variations in human fetal brains

Somatic mosaicism, manifesting as single nucleotide variants (SNVs), mobile element insertions, and structural changes in the DNA, is a common phenomenon in human brain cells, with potential functional consequences. Using a clonal approach, we previously detected 200–400 mosaic SNVs per cell in three human fetal brains (15–21 wk postconception). However, structural variation in the human fetal brain has not yet been investigated. Here, we discover and validate four mosaic structural variants (SVs) in the same brains and resolve their precise breakpoints. The SVs were of kilobase scale and complex, consisting of deletion(s) and rearranged genomic fragments, which sometimes originated from different chromosomes. Sequences at the breakpoints of these rearrangements had microhomologies, suggesting their origin from replication errors. One SV was found in two clones, and we timed its origin to ∼14 wk postconception. No large scale mosaic copy number variants (CNVs) were detectable in normal fetal human brains, suggesting that previously reported megabase-scale CNVs in neurons arise at later stages of development. By reanalysis of public single nuclei data from adult brain neurons, we detected an extrachromosomal circular DNA event. Our study reveals the existence of mosaic SVs in the developing human brain, likely arising from cell proliferation during mid-neurogenesis. Although relatively rare compared to SNVs and present in ∼10% of neurons, SVs in developing human brain affect a comparable number of bases in the genome (∼6200 vs. ∼4000 bp), implying that they may have similar functional consequences.

Somatic mosaicism, the presence of more than one genotype in the somatic cells of an individual, is a prominent phenomenon in the human central nervous system. Forms of mosaicism include aneuploidies and smaller copy number variants (CNVs), structural variants (SVs), mobile element insertions, indels, and single nucleotide variants (SNVs). The developing human brain exhibits high levels of aneuploidy compared to other tissues, generating genetic diversity in neurons (Pack et al. 2005; Yurov et al. 2007; Bushman and Chun 2013). Such aneuploidy was suggested to be a natural feature of neurons, rather than a distinctive feature of neurodegeneration. However, the frequency of aneuploidy in neurons has been debated, with a separate study suggesting that aneuploidies occur in only about 2.2% of mature adult neurons (Knouse et al. 2014). They hence infer that such aneuploidy could have adverse effects at the cellular and organismal levels. Additionally, analysis of single cells from normal and pathological human brains identified large, private, and likely clonal somatic CNVs in both normal and diseased brains (Gole et al. 2013; McConnell et al. 2013; Cai et al. 2014; Knouse et al. 2016; Chronister et al. 2019; Perez-Rodriguez et al. 2019), with 3%–25% of human cerebral cortical nuclei carrying megabase-scale CNVs (Chronister et al. 2019) and deletions being twice as common as duplications (McConnell et al. 2013). Given that CNVs often arise from nonhomologous recombination and replication errors, their likely time of origin is during brain development. However, when CNVs first arise in human brain development has not yet been investigated. The present work is the first to examine this question using clonal populations of neuronal progenitor cells (NPCs) obtained from fetal human brains.Detection of CNVs in single neurons is challenging, given the need to amplify DNA. Such amplification may introduce artifacts that could, in turn, be misinterpreted as CNVs. In order to address this technical limitation, Hazen et al. reprogrammed adult postmitotic neurons using somatic cell nuclear transfer (SCNT) of neuronal nuclei into enucleated oocytes (Hazen et al. 2016). These oocytes then made sufficient copies of the neuronal genome allowing for whole-genome sequencing (WGS), thus eliminating the need for amplification in vitro. Using this method, they identified a total of nine structural variants in six neurons from mice, three of which were complex rearrangements. However, it is not possible to extend such studies to humans, given the ethical issues involved, besides the technical challenges in obtaining and cloning adult neurons. To circumvent the need of single-cell DNA amplification or nuclear cloning, we examined clonal cell populations obtained from neural progenitor cells from the frontal region of the cerebral cortex (FR), parietal cortex (PA) and basal ganglia (BG) and describe here the discovery and analysis of mosaic SVs in these NPCs (Bae et al. 2018). These clones were sequenced at 30× coverage (much higher than most previous single-cell studies), allowing identification of SVs other than large deletions and duplications as well as precise breakpoint resolution.     

Increased fibronectin production by cell lines from hypertrophic scar and keloid

Primary cell lines of fibroblasts from 8 tissues were established--three from hypertrophic scars (HS), one keloid (K) and four from the normal uninvolved dermis adjacent to each lesion. The objective was to quantify and compare all eight cell lines on the basis of fibronectin (FN) produced per cell and per total protein (PR). Two hypertrophic scars and their adjacent skin cell lines were evaluated by the ELISA method for FN and a micro Lowry assay for PR. The scar lines showed statistically significant increases in the amount of FN/cell compared to the cell lines from their adjacent normal dermis. The third hypertrophic scar and the keloid with their adjacent skin cell lines were assayed for FN and PR by radioimmunoprecipitation. Subconfluent cells were metabolically labeled with 35S-methionine for 20 hours. Harvested media and cell monolayers were assayed for radioactivity incorporated into FN and PR. The percentage of FN/PR was significantly higher in media for HS and K compared to the adjacent normal skin lines in the three passages tested. These results support our previous immunofluorescence studies and demonstrate that a fibroblast-type cell line from a hypertrophic scar or keloid produces more FN/PR over time than the normal fibroblast-type cell line from adjacent uninvolved dermis.     

Pharmacokinetics of dopamine in healthy male subjects

BACKGROUND: Dopamine is an agonist of alpha, beta, and dopaminergic receptors with varying hemodynamic effects depending on the dose of drug being administered. The purpose of this study was to measure plasma concentrations of dopamine in a homogeneous group of healthy male subjects to develop a pharmacokinetic model for the drug. Our hypothesis was that dopamine concentrations can be predicted from the infusion dose using a population-based pharmacokinetic model. METHODS: Nine healthy male volunteers aged 23 to 45 yr were studied in a clinical research facility within our academic medical center. After placement of venous and arterial catheters, dopamine was infused at 10 microg x kg(-1) x min(-1) for 10 min, followed by a 30-min washout period. Subsequently, dopamine was infused at 3 microg x kg(-1) x min(-1) for 90 min, followed by another 30-min washout period. Timed arterial blood samples were centrifuged, and the plasma was analyzed by high-performance liquid chromatography. Mixed-effects pharmacokinetic models using NONMEM software (NONMEM Project Group, University of California, San Francisco, CA) were used to determine the optimal compartmental pharmacokinetic model for dopamine. RESULTS: Plasma concentrations of dopamine varied from 12,300 to 201,500 ng/l after 10 min of dopamine infusion at 10 microg x kg(-1) x min(-1). Similarly, steady-state dopamine concentrations varied from 1,880 to 18,300 ng/l in these same subjects receiving 3-microg x kg(-1) x min(-1) infusions for 90 min. A two-compartment model adjusted for body weight was the best model based on the Schwartz-Bayesian criterion. CONCLUSIONS: Despite a homogeneous population of healthy male subjects and weight-based dosing, there was 10- to 75-fold intersubject variability in plasma dopamine concentrations, making standard pharmacokinetic modeling of less utility than for other drugs. The data suggest marked intraindividual and interindividual variability in dopamine distribution and/or metabolism. Thus, plasma dopamine concentrations in patients receiving dopamine infusion at identical rates may vary profoundly. Our data suggest that dosing dopamine based on body weight does not yield predictable blood concentrations.     

Clinical Outcomes in Critically Ill Patients Associated With the Use of Complex vs Weight‐Only Predictive Energy Equations

Background: The energy intake goal is important to achieving energy intake in critically ill patients, yet clinical outcomes associated with energy goals have not been reported. Methods: This secondary analysis used the Improving Nutrition Practices in the Critically III International Nutrition Surveys database from 2007–2009 to evaluate whether mortality or time to discharge alive is related to use of complex energy prediction equations vs weight only. The sample size was 5672 patients in the intensive care unit (ICU) ≥4 days and a subset of 3356 in the ICU ≥12 days. Mortality and time to discharge alive were compared between groups by regression, controlling for age, sex, admission type, Acute Physiology and Chronic Health Evaluation II score, ICU geographic region, actual energy intake, and obesity. Results: There was no difference in mortality between the use of complex and weight‐only equations (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.86–1.15), but obesity (OR, 0.83; 95% CI, 0.71–0.96) and higher energy intake (OR, 0.65; 95% CI, 0.56–0.76) had lower odds of mortality. Time to discharge alive was shorter in patients fed using weight‐only equations (hazard ratio [HR], 1.11; 95% CI, 1.01–1.23) in patients staying ≥4 days and with greater energy intake (HR, 1.19; 95% CI, 1.06–1.34) in patients in the ICU ≥12 days. Conclusion: These data suggest that higher energy intake is important to survival and time to discharge alive. However, the analysis was limited by actual energy intake <70% of goal. Delivery of full goal intake will be needed to determine the relationship between the method of determining energy goal and clinical outcomes.