Tourniquetless Total Knee Arthroplasty With Modern Perioperative Protocols Decreases Pain and Opioid Consumption in Women

Background This study examined whether a modern total knee arthroplasty (TKA) protocol without a tourniquet results in less patient-reported pain and in-hospital opioid consumption compared to TKA with a tourniquet. Methods A retrospective study of 203 primary unilateral cemented TKAs consecutively performed with or without tourniquet was performed. Identical perioperative pain and blood loss protocols were used in all cases. In tourniquetless TKAs, the tourniquet was not inflated at any time, and sterile CO2 gas compression maximized cement interdigitation. Results After exclusions for scientific confounds, 184 TKAs (93 with tourniquet; 91 tourniquetless) were analyzed. Controlling for multiple covariates, females with a tourniquet reported significantly more pain (P = .002) and opioid consumption (P < .001) the first 24 hours after surgery compared to females without a tourniquet. There were no differences in pain (P = .192) or amount of opioids consumed (P = .203) among males with and without a tourniquet. Tourniquet use resulted in a significant reduction in blood loss for both females (P ≤ .040) and males (P ≤ .020), although the total blood savings of approximately 200 mL is of unknown clinical significance. Conclusion Avoiding tourniquet use during TKA for females may be a relatively risk-free adjunct to minimize opioid consumption during hospitalization. Further study is warranted to elucidate the factors accounting for different outcomes in females and males

Cefazolin Prophylaxis for Total Joint Arthroplasty: Obese Patients Are Frequently Underdosed and at Increased Risk of Periprosthetic Joint Infection

Background One of the most effective prophylactic strategies against periprosthetic joint infection (PJI) is administration of perioperative antibiotics. Many orthopedic surgeons are unaware of the weight-based dosing protocol for cefazolin. This study aimed at elucidating what proportion of patients receiving cefazolin prophylaxis are underdosed and whether this increases the risk of PJI. Methods A retrospective study of 17,393 primary total joint arthroplasties receiving cefazolin as perioperative prophylaxis from 2005 to 2017 was performed. Patients were stratified into 2 groups (underdosed and adequately dosed) based on patient weight and antibiotic dosage. Patients who developed PJI within 1 year following index procedure were identified. A bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify risk factors for PJI. Results The majority of patients weighing greater than 120 kg (95.9%, 944/984) were underdosed. Underdosed patients had a higher rate of PJI at 1 year compared with adequately dosed patients (1.51% vs 0.86%, P = .002). Patients weighing greater than 120 kg had higher 1-year PJI rate than patients weighing less than 120 kg (3.25% vs 0.83%, P < .001). Patients who were underdosed (odds ratio, 1.665; P = .006) with greater comorbidities (odds ratio, 1.259; P < .001) were more likely to develop PJI at 1 year. Conclusion Cefazolin underdosing is common, especially for patients weighing more than 120 kg. Our study reports that underdosed patients were more likely to develop PJI. Orthopedic surgeons should pay attention to the weight-based dosing of antibiotics in the perioperative period to avoid increasing risk of PJI

Surgical Treatment of Chronic Periprosthetic Joint Infection: Fate of Spacer Exchanges

Introduction Patients with periprosthetic joint infection (PJI) undergoing two-stage exchange arthroplasty may undergo an interim spacer exchange for a variety of reasons including mechanical failure of spacer or persistence of infection. The objective of this study was to understand the risk factors and outcomes of patients that undergo spacer exchange during the course of a planned two-stage exchange arthroplasty. Methods Our institutional database was used to identify 533 patients who underwent a two-stage exchange arthroplasty for PJI, including 90 patients with a spacer exchange, from 2000-2017. A retrospective review was performed to extract relevant clinical information. Treatment outcomes included 1) progression to reimplantation and 2) treatment success as defined by a Delphi-based criterion. Both univariate and multivariate COX regression models were performed to investigate whether spacer exchange was associated with failure. Additionally, a propensity score analysis was performed based on a 1:2 match. Results A spacer exchange was required in 16.9%. Patients who underwent spacer exchanges had a higher body mass index (BMI) (p<0.001), rheumatoid arthritis (p=0.018), and were more likely to have PJI caused by resistant (0.048) and polymicrobial organisms (p=0.007). Patients undergoing a spacer exchange demonstrated lower survivorship and an increased risk of failure in the multivariate and propensity score matched analysis compared to patients who did not require a spacer exchange. Discussion Despite an additional load of local antibiotics and repeat debridement, patients who underwent a spacer exchange demonstrated poor outcomes, including failure to undergo reimplantation and twice the failure rate. The findings of this study may need to be borne in mind when managing patients who require spacer exchange

Midterm Survivorship and Complications of Total Knee Arthroplasty in Patients with Dwarfism

Background Dwarfism is associated with skeletal dysplasias and joint deformities that frequently result in osteoarthritis requiring treatment with total knee arthroplasty (TKA). These surgeries can be challenging because of alignment deformities, poor bone stock, and smaller components. This study aims to compare TKA implant survivorship and complications between dwarf and nondwarf patients. Methods A retrospective case-control study was performed from 1997-2014 evaluating 115 TKAs in patients under the height threshold of 147.32 cm. This cohort was compared with 164 patients of normal height. Medical records were reviewed for demographics, surgical characteristics, and outcomes. All cases had 2-year minimum follow-up. Results The revision rate was 8.7% in dwarfs compared with 3.7% in controls (P = .08). The 2-, 5-, and 10-year implant survivorship in dwarfs was 96.4%, 92.5%, and 90.2%, respectively; and 96.6%, 95.6%, and 94.8% for controls, respectively (P = .24). Dwarfs underwent significantly more manipulations for arthrofibrosis (P = .002). There was greater femoral (17.4% vs 2.1%, P < .01) and tibial (6.5% vs 2.7%, P < .01) component overhang in dwarfs compared with controls. Conclusion Despite a 2-fold increase in the revision rate of the dwarf cohort, the midterm survivorship is comparable between the dwarf and nondwarf patients. However, dwarfs were more likely to become stiff and undergo manipulation; the increased propensity for stiffness may be associated with oversized components, as evidenced by greater component overhang. Surgeons should be aware of this increased risk and may consider using smaller or customized implants to account for the morphological differences in this patient population

What Are the Economic Consequences of Unplanned Readmissions After TKA?

BACKGROUND: In 2009, the Center for Medicare & Medicaid Services (CMS) began penalizing hospitals with high rates of 30-day readmissions after hospitalizations for certain conditions. This policy will expand to include TKA in 2015. QUESTIONS/PURPOSES: What are the median profits and contribution margins of: (1) Medicare-reimbursed TKA, (2) 30-day TKA readmission, and (3) entire episode of care for readmitted TKA patients within 30 days compared to nonreadmitted patients? (4) Under new CMS guidelines, what financial penalty will the authors' institution face if its arthroplasty readmission rate exceeds the national average? METHODS: A retrospective review of 3218 primary TKAs performed during 2 years at a large urban academic hospital network was conducted using administrative and financial data. RESULTS: The median profit and contribution margins, respectively, were as follows: TKA episode, USD 5209 and USD 11,726; 30-day readmission, USD 608 and USD 3814; TKA visit with readmission, USD 2855 and USD 13,901; TKA visit without readmission, USD 5300 and USD 11,652. Readmission penalties could reach USD 6.21 million per year for the authors' institution. DISCUSSION: If our results are generalizable, unplanned TKA readmissions lead to diminished total profit. Although associated with a positive contribution margin, this is likely to be a short-term phenomenon as the new CMS policy will result in readmissions coming at a steep cost to referral centers

Comparison of new and emerging SARS-CoV-2 variant transmissibility through active contact testing. A comparative cross-sectional household seroprevalence study

Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts; this misses transmission events and identifies only symptomatic contacts who are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding

Comprehensive Study in the Inhibitory Effect of Berberine on Gene Transcription, Including TATA Box

Berberine (BBR) is an established natural DNA intercalator with numerous pharmacological functions. However, currently there are neither detailed reports concerning the distribution of this alkaloid in living cells nor reports concerning the relationship between BBR's association with DNA and the function of DNA. Here we report that the distribution of BBR within the nucleus can be observed 30 minutes after drug administration, and that the content of berberine in the nucleus peaks at around 4 µmol, which is twelve hours after drug administration. The spatial conformation of DNA and chromatin was altered immediately after their association with BBR. Moreover, this association can effectively suppress the transcription of DNA in living cell systems and cell-free systems. Electrophoretic mobility shift assays (EMSA) demonstrated further that BBR can inhibit the association between the TATA binding protein (TBP) and the TATA box in the promoter, and this finding was also attained in living cells by chromatin immunoprecipitation (ChIP). Based on results from this study, we hypothesize that berberine can suppress the transcription of DNA in living cell systems, especially suppressing the association between TBP and the TATA box by binding with DNA and, thus, inhibiting TATA box-dependent gene expression in a non-specific way. This novel study has significantly expanded the sphere of knowledge concerning berberine's pharmacological effects, beginning at its paramount initial interaction with the TATA box

Comparison of new and emerging SARS-CoV-2 variant transmissibility through active contact testing. A comparative cross-sectional household seroprevalence study.

Historically SARS-CoV-2 secondary attack rates (SAR) have been based on PCR positivity on screening symptomatic contacts; this misses transmission events and identifies only symptomatic contacts who are PCR positive at the time of sampling. We used serology to detect the relative transmissibility of Alpha Variant of Concern (VOC) to non-VOC SARS-CoV-2 to calculate household secondary attack rates. We identified index patients diagnosed with Alpha and non-VOC SARS-CoV-2 across two London Hospitals between November 2020 and January 2021 during a prolonged and well adhered national lockdown. We completed a household seroprevalence survey and found that 61.8% of non-VOC exposed household contacts were seropositive compared to 82.1% of Alpha exposed household contacts. The odds of infection doubled with exposure to an index diagnosed with Alpha. There was evidence of transmission events in almost all households. Our data strongly support that estimates of SAR should include serological data to improve accuracy and understanding

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs