Acute kidney injury in the context of staged revision arthroplasty and the use of antibiotic-laden cement spacers: a systematic review.

BACKGROUND: The most common cause of revision arthroplasty is prosthetic joint infection (PJI). Chronic PJI is commonly treated with two-stage exchange arthroplasty involving the placement of antibiotic-laden cement spacers (ACS) in the first stage, often containing nephrotoxic antibiotics. These patients often have significant comorbidity burdens and have higher rates of acute kidney injury (AKI). This systematic review aims to assess the current literature to identify (1) AKI incidence, (2) associated risk factors, and (3) antibiotic concentration thresholds in ACS that increase AKI risk following first-stage revision arthroplasty. METHODS: An electronic search was performed of the PubMed database of all studies involving patients undergoing ACS placement for chronic PJI. Studies assessing AKI rates and risk factors were screened by two authors independently. Data synthesis was performed when possible. Significant heterogeneity prevented meta-analysis. RESULTS: Eight observational studies consisting of 540 knee PJIs and 943 hip PJIs met inclusion criteria. There were 309 (21%) cases involving AKI. The most commonly reported risk factors included perfusion-related factors (lower preoperative hemoglobin, transfusion requirement, or hypovolemia), older age, increased comorbidity burden, and nonsteroidal anti-inflammatory drug consumption. Only two studies found increased risk with greater ACS antibiotic concentration (> 4 g vancomycin and > 4.8 g tobramycin per spacer in one study, > 3.6 g of vancomycin per batch or > 3.6 g of aminoglycosides per batch in the other); however, these were reported from univariate analyses not accounting for other potential risk factors. DISCUSSION: Patients undergoing ACS placement for chronic PJI are at an increased risk for AKI. Understanding the risk factors may lead to better multidisciplinary care and safer outcomes for chronic PJI patients.

Not All Patients Need Supervised Physical Therapy After Primary Total Knee Arthroplasty: A Systematic Review and Meta-Analysis.

Although postoperative physical therapy (PT) has long been considered essential to successful total knee arthroplasty (TKA) recovery, recent literature has suggested that unsupervised home exercise regimens may offer similar benefits to formal supervised sessions. We aimed to compare objectively measured physical function and subjective patient-reported outcomes (PROs) between primary TKA patients who received formal supervised physical therapy sessions and those who received unsupervised home exercise regimens after discharge. Six electronic databases were queried to identify randomized controlled trials comparing supervised physical therapy to unsupervised home exercise regimens in primary TKA patients after discharge. Outcomes of interest included change from baseline in objective measures (knee flexion range of motion (ROM), lower extremity strength, and aerobic capacity) and PROs (physical function and quality of life scores). These outcomes were subdivided into short-term (<6 months from surgery; closest data point to three months is used if multiple measurements were made in this time period) and long-term (≥6 months from surgery; closest data point to 12 months is used if multiple measurements were made in this time period) assessments. A total of 1,884 cases performed in 11 studies were included in this review. There were no significant differences between cohorts with regard to short-term knee flexion ROM (p = 0.7), lower extremity strength (p = 0.6), or patient-reported quality of life (p = 0.5), as well as long-term knee flexion ROM (p = 0.7), patient-reported quality of life (p = 0.2), or patient-reported physical outcome scores (p = 0.3). A small difference in short-term patient-reported physical outcomes was observed in favor of the supervised cohort (standardized mean difference (SMD): 0.3 (95% confidence interval (CI): 0.01, 0.6); I2 = 82%; p = 0.04). Formal supervised physical therapy regimens do not confer clinically significant benefits over unsupervised home exercise regimens following primary TKA. The routine use of supervised physical therapy after discharge may not be warranted. Further study is needed to determine the subset of patients that may benefit from supervised care.

Evaluation of the Posterior Tilt Angle in Predicting Failure of Nondisplaced Femoral Neck Fractures After Internal Fixation: A Systematic Review.

OBJECTIVE: To evaluate the posterior tilt angle (PTA) in predicting treatment failure after internal fixation of nondisplaced femoral neck fractures as graded by the Garden classification, which is based solely on anterior-posterior radiographic evaluation. DATA SOURCES: A search was conducted of all published literature in the following databases from inception to December 20, 2021: PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov . STUDY SELECTION: We included English-language randomized controlled trials, prospective and retrospective cohort studies that reported malunion/nonunion, avascular necrosis, fixation failure, or reoperations in patients with nondisplaced femoral neck fractures treated with internal fixation who were evaluated for PTA using either lateral radiograph or computed tomography. DATA EXTRACTION: All abstract, screening, and quality appraisal was conducted independently by 2 authors. Data from included studies were extracted manually and summarized. The Methodological Index for Non-Randomized Studies criteria was used for quality appraisal. DATA SYNTHESIS: Odds ratios with 95% confidence intervals were calculated for treatment failure, defined as nonunion/malunion, avascular necrosis, fixation failure, or reoperation, in cases involving preoperative PTA ≥20-degrees and <20-degrees. Statistical significance was set at P < 0.05. RESULTS: Nondisplaced femoral neck fractures with PTA >20-degrees had a 24% rate of treatment failure compared with 12% for those <20-degrees [odds ratios, 3.21 (95% confidence intervals, 1.95-5.28); P < 0.001]. CONCLUSION: PTA is a predictor of treatment failure in nondisplaced femoral neck fractures treated with internal fixation. Nondisplaced femoral neck fractures with a PTA >20-degrees may warrant alternative treatment modalities. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Unsupervised Home Exercises Versus Formal Physical Therapy After Primary Total Hip Arthroplasty: A Systematic Review.

Historically, postoperative exercise and physical therapy (PT) have been viewed as crucial to a successful outcome following primary total hip arthroplasty (THA). This systematic review and meta-analysis aimed to assess differences in both short- and long-term objective and self-reported measures between primary THA patients with formal supervised physical therapy versus unsupervised home exercises after discharge. A search was conducted of six electronic databases from inception to December 14, 2020, for randomized controlled trials (RCTs) comparing changes from baseline in lower extremity strength (LES), aerobic capacity, and self-reported physical function and quality of life (QoL) between supervised and unsupervised physical therapy/exercise regimens following primary THA. Outcomes were separated into short-term (<6 months from surgery, closest to 3 months) and long-term (≥6 months from surgery, closest to 12 months) measures. Meta-analyses were performed when possible and reported in standardized mean differences (SMDs) with 95% confidence intervals (CI). Seven studies (N=398) were included for review. No significant differences were observed with regard to lower extremity strength (p=0.85), aerobic capacity (p=0.98), or short-term quality of life scores (p=0.18). Although patients in supervised physical therapy demonstrated improved short-term self-reported outcomes compared to those performing unsupervised exercises, this was represented by a small effect size (SMD 0.23 [95% CI, 0.02-0.44]; p=0.04). No differences were observed between groups regarding long-term lower extremity strength (p=0.24), physical outcome scores (p=0.37), or quality of life (p=0.14). The routine use of supervised physical therapy may not provide any clinically significant benefit over unsupervised exercises following primary THA. These results suggest that providers should reconsider the routine use of supervised physical therapy after discharge.

A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study.

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. RESULTS: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19. CONCLUSIONS: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.

A Dual-Center Cohort Study on The Association Between Early Deep Sedation and Clinical Outcomes in Mechanically Ventilated Patients During the COVID-19 Pandemic: the COVID-SED Study.

Background : Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. Study Design and Methods : Dual-center, retrospective cohort study conducted over six months (March - August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 hours were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Riker Sedation-Agitation Scale of 1 - 3. To examine impact of early sedation depth on hospital mortality (primary outcome) we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. Results : 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation ( p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65 - 7.17; p <0.01). These results were stable in the subgroup of patients with COVID-19. Conclusions : The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach. Clinical Trial Registration : Not applicable.

Fusion versus fixation in complex comminuted C3-type tibial pilon fractures: a systematic review.

BACKGROUND: Comminuted intra-articular tibial pilon fractures can be challenging to manage, with high revision rates and poor functional outcomes. This study reviewed [1] treatment, complications, and clinical outcomes in studies of complex comminuted tibial pilon fractures (type AO43-C3); and [2] primary ankle arthrodesis as a management option for these types of complex injuries. METHODS: A systematic literature search was performed on PubMed from 1990 to 2020 to determine complications and outcomes after staged fracture fixation and primary ankle joint arthrodesis for comminuted C3-type tibial pilon fractures. The search was conducted in compliance with the PRISMA guidelines, using the following MeSH terms: "tibial pilon"/"pilon fracture"/"plafond fracture"/"distal tibial"/"43-C3"/"ankle fracture"/"ankle fusion"/"primary ankle arthrodesis"/"pilon fracture staged"/"pilon external fixation" and "pilon open reduction internal fixation." Inclusion criteria were restricted to original articles in English language on adult patients ≥18 years of age. Eligibility criteria for retrieved publications were determined using a "PICO" approach (population, intervention/exposure, comparison, outcomes). Weighted analysis was used to compare treatment groups on time to definitive treatment, follow-up time, range of motion, fracture classification, and complications. RESULTS: The systematic literature review using the defined MeSH terms yielded 72 original articles. Of these, 13 articles met the eligibility criteria based on the PICO statements, of which 8 publications investigated the outcomes of a staged fixation approach in 308 cumulative patients, and 5 articles focused on primary ankle arthrodesis in 69 cumulative patients. For staged treatment, the mean wound complication rate was 14.6%, and the malunion/nonunion rate was 9.9%. For primary arthrodesis, the mean wound complication rate was 2.9%, and the malunion/nonunion rate was 2.9%. After risk stratification for fracture type and severity, the small cumulative cohort of patients included in the primary arthrodesis publications did not provide sufficient power to determine a clinically relevant difference in complications and long-term patient outcomes compared to the staged surgical fixation group. CONCLUSIONS: At present, there is insufficient evidence in the published literature to provide guidance towards consideration of ankle arthrodesis for complex comminuted C3-type tibial pilon fractures, compared to the standard treatment by staged surgical fracture fixation.

Convection-Enhanced Delivery and Principles of Extracellular Transport in the Brain.

Stereotactic neurosurgery involves a targeted intervention based on congruence of image guidance to a reference fiducial system. This discipline has widespread applications in radiosurgery, tumor therapy, drug delivery, functional lesioning, and neuromodulation. In this article, we focused on convection-enhanced delivery to deliver therapeutic agents to the brain addressing areas of research and clinical development. We performed a robust literature review of all relevant articles highlighting current efforts and challenges of making this delivery technique more widely understood. We further described key biophysical properties of molecular transport in the extracellular space that may impact the efficacy and control of drug delivery using stereotactic methods. Understanding these principles is critical for further refinement of predictive models that can inform advances in stereotactic techniques for convection-enhanced delivery of therapeutic agents to the brain.

Estimating relative bioavailability of soil lead in the mouse.

Lead (Pb) in soil is an important exposure source for children. Thus, determining bioavailability of Pb in soil is critical in evaluating risk and selecting appropriate strategies to minimize exposure. A mouse model was developed to estimate relative bioavailability of Pb in NIST SRM 2710a (Montana 1 Soil). Based on Pb levels in tissues, the mean relative bioavailability of this metal in this soil was 0.5. Estimates of relative bioavailabilities derived from mouse compared favorably with those obtained in juvenile swine. The mouse model is thus an efficient and inexpensive method to obtain estimates of relative bioavailability of soil Pb.

Long-Term Survival After Lung Transplantation in Patients with Silicosis and Other Occupational Lung Disease.

BACKGROUND: Survival after lung transplantation (LTx) for patients with occupational lung disease (OLD) is not well studied. METHODS: The United Network for Organ Sharing (UNOS) database was queried from 2005 to 2013 to assess survival after LTx in patients with silicosis and non-silicotic OLD compared to non-OLD patients. RESULTS: Of 7273 adult LTx recipients, 7227 (24 with silicosis and 29 with non-silicotic OLD) were included in our univariate and Kaplan-Meier function analysis and 6370 for multivariate Cox models. Univariate Cox models did not identify survival differences in silicosis (HR 0.717; 95 % CI 0.358-1.435; p = 0.347) and non-silicotic OLDs (HR 0.934; 95 % CI 0.486-1.798; p = 0.839). Kaplan-Meier function analysis did not identify a survival disadvantage for either silicosis or non-silicotic OLD (log-rank test: χ (2) 0.93, p = 0.627). Patients with non-silicotic OLD were at risk for worse survival for the first 2.5 years post-transplant; however, at the conclusion of the study, this group had the highest survival rate. Multivariate Cox models confirmed no increased risk for mortality for silicosis (HR 1.264; 95 % CI 0.631-2.534; p = 0.509) and non-silicotic OLD (HR 1.114; 95 % CI 0.578-2.147; p = 0.747). CONCLUSION: Long-term survival for adult patients with silicosis and non-silicotic OLD after LTx is not significantly different compared to the general lung transplant population.

Incidence and severity of potential drug-dietary supplement interactions in primary care patients: an exploratory study of 2 outpatient practices.

BACKGROUND: To explore the incidence and severity of potential interactions between prescription medications and dietary supplements. METHODS: A survey was conducted on dietary supplement use in 458 veteran outpatients currently taking prescription medications. Self-reported dietary supplement use was cross-referenced with each patient's prescription medication list, and potential interactions were identified from several tertiary sources and medical literature searches. RESULTS: One hundred ninety-seven patients (43%) were currently taking at least 1 dietary supplement with prescription medication(s). The most common products included vitamins and minerals, garlic, Ginkgo biloba, saw palmetto, and ginseng. Among these, 89 (45%) had a potential for drug-dietary supplement interactions of any significance. Most of these interactions (n = 84 [94%]) were not serious based on limited available evidence, giving an incidence of 6% (5/89) of potentially severe interactions among patients taking interacting drugs and dietary supplements and 3% (5/197) among patients taking coincident dietary supplements and medications. CONCLUSIONS: Although the use of dietary supplements appears to be very common among patients who also take prescription medications, most potential drug-dietary supplement interactions found were not serious. However, literature support was sparse at best. Health care providers should continue to inquire about dietary supplement use and consider the potential for interactions, regardless of their severity.