How Has the Total Hip Arthroplasty Patient Population Changed? A Ten-Year Analysis of Total Hip Arthroplasty Patients From 2013 to 2022: A Retrospective, Single-Center Study.

BACKGROUND: Over the past decades, utilization of total hip arthroplasty (THA) has steadily increased. Understanding the demographic trends of THA patients can assist in projecting access to care. This study sought to assess the temporal trends in THA patient baseline characteristics and socioeconomic factors. METHODS: We retrospectively analyzed 16,296 patients who underwent primary elective THA from January 1, 2013, to December 31, 2022. Demographic data, including age, sex, race, body mass index (BMI), Charlson comorbidity index, insurance, and socioeconomic status, as determined by median income by patients' zip code, were collected. The trends of these data were analyzed using the Mann-Kendall test. RESULTS: Over the past decade at our institution, patient age (2013: 62.1 years to 2022: 65.1 years, P = .001), BMI (2013: 29.0 to 2022: 29.5, P = .020), and mean Charlson comorbidity index (2013: 2.4 to 2022: 3.1, P = .001) increased. The proportion of Medicare patients increased from 48.4% in 2013 to 54.9% in 2022 (P = .001). The proportion of African American patients among the THA population increased from 11.3% in 2013 to 13.0% in 2022 (P = .012). Over this period, 90-day readmission and 1-year revision rates did not significantly change (2013: 4.8 and 3.0% to 2022: 3.4 and 1.4%, P = .107 and P = .136, respectively). The proportion of operations using robotic devices also significantly increased (2013: 0% to 2022: 19.1%; P < .001). CONCLUSIONS: In the past decade, the average age, BMI, and comorbidity burden of THA patients have significantly increased, suggesting improved access to care for these populations. Similarly, there have been improvements in access to care for African American patients. Along with these changes in patient demographics, we found no change in 90-day readmission or 1-year revision rates. Continued characterization of the THA patient population is vital to understanding this demographic shift and educating future strategies and improvements in patient care.

Opioid Use Disorder Is Associated with an Increased Risk of Infection after Total Joint Arthroplasty: A Large Database Study.

BACKGROUND: Recent studies have shown that patients with opioid use disorder have impaired immunity. However, few studies with large patient populations have evaluated the risks of surgical site infection (SSI) and prosthetic joint infection (PJI) with opioid use disorder after total joint arthroplasty (TJA), and there is a lack of evidence for revision TJA in particular. QUESTIONS/PURPOSES: Are patients with opioid use disorder who undergo (1) primary THA, (2) primary TKA, (3) revision THA, or (4) revision TKA at a higher risk of experiencing SSIs 90 days after surgery or PJIs 2 years after surgery than those who do not have opioid use disorder? METHODS: All primary and revision TJAs performed between 2005 and 2014 were identified from the Medicare Analytical Files of the PearlDiver Supercomputer using ICD-9 codes. This database is one of the largest nationwide databases; it comprehensively and longitudinally tracks patients based on all insurance claims rather than particular hospital visits, and has a low error rate (estimated at 1.3%). Boolean command operators were used to form a study group of patients with a history of opioid use disorder before surgery. ICD-9 diagnosis codes 304.00 to 304.02 and 305.50 to 305.52 were used to identify patients with opioid use disorder. Study group patients were matched 1:1 to control participants without opioid use disorder undergoing TJA, according to age, sex, and comorbidity burden (Elixhauser comorbidity index [ECI]). The ECI is comprised of 31 different comorbidities and can be used for large administrative databases. The query yielded a study population of 54,332 patients: 14,944 undergoing primary THA (opioid use disorder: n = 7472), 23,680 undergoing primary TKA (opioid use disorder: n = 11,840), 8116 undergoing revision THA (opioid use disorder: n = 4058), and 7592 undergoing revision TKA (opioid use disorder: n = 3796). The primary outcomes analyzed were SSI at 90 days and PJI at 2 years postoperatively, which were identified with ICD-9 codes. Logistic regression analyses were performed to calculate the risk that an infection would develop in a patient with opioid use disorder compared with the matched control patients without opioid use disorder. RESULTS: Patients with opioid use disorder undergoing primary THA had an increased risk of SSI at 90 days (OR 1.85 [95% CI 1.51 to 2.25]; p < 0.001) and PJI at 2 years (OR 1.66 [95% CI 1.42 to 1.93]; p < 0.001). Compared with matched controls, opioid use disorder patients undergoing primary TKA had an increased risk of SSI at 90 days (OR 1.72 [95% CI 1.46 to 2.02]; p < 0.001) and PJI at 2 years (OR 1.31 [95% CI 1.16 to 1.47]; p < 0.001). Similarly, for revision THAs, there was an increase in 90-day SSIs (OR 1.89 [95% CI 1.53 to 2.32]; p < 0.001) and 2-year PJIs (OR 4.24 [95% CI 3.67 to 4.89]; p < 0.001). The same held for revision TKAs for 90-day SSIs (OR 1.88 [95% CI 1.53 to 2.29]; p < 0.001) and 2-year PJIs (OR 4.94 [95% CI 4.24 to 5.76]; p < 0.001). CONCLUSIONS: After accounting for age, sex, and comorbidity burden, these results revealed that patients with opioid use disorder undergoing TJA were at increased risk of having SSIs and PJIs. Based on these findings, healthcare systems and/or administrators should recognize the increased associated PJI and SSI risks in patients with opioid use disorder and enact clinical policies that reflect these associated risks. Additionally, these findings should encourage surgeons to pursue multidisciplinary approaches to help patients reduce their opioid consumption before their arthroplasty procedure. LEVEL OF EVIDENCE: Level III, therapeutic study.

What Are Risk Factors for Infection after Primary or Revision Total Joint Arthroplasty in Patients Older Than 80 Years?

BACKGROUND: Patients older than 80 years of age form an increasing proportion of the patient population undergoing total joint arthroplasty (TJA). With increasing life expectancy and the success of TJA, orthopaedic surgeons are more likely to operate on patients older than 80 years than ever before. Given that most other studies focus on younger populations, only evaluate primary TJA, or limit patient populations to institutional or regional data, we felt a large-database, nationwide analysis of this demographic cohort was warranted, and we wished to consider both primary and revision TJA. QUESTIONS/PURPOSES: In this study, we sought to investigate the risk factors for surgical site infections (SSIs) at 90 days and periprosthetic joint infections (PJIs) at 2 years after surgery in patients aged 80 years and older undergoing (1) primary and (2) revision lower extremity TJA. METHODS: All patients aged 80 years or older who underwent primary or revision TJA between 2005 and 2014 were identified using the Medicare Analytical Files of the PearlDiver Supercomputer using ICD-9 codes. This database is unique in that it is one of the largest nationwide databases, and so it provides a large enough sample size of patients 80 years or older. Additionally, this database provides comprehensive and longitudinal patient data tracking, and a low error rate. Our final cohort consisted of 503,241 patients (TKA: n = 275,717; THA: n = 162,489; revision TKA: n = 28,779; revision THA: n = 36,256). Multivariate logistic regression models were constructed to evaluate the association of risk factors on the incidences of 90-day SSI and 2-year PJI. Variables such as sex, diabetes, BMI, and congestive heart failure, were included in the multivariate regression models. Several high-risk comorbidities as identified by the Charlson and Elixhauser comorbidity indices were selected to construct the models. We performed a Bonferroni-adjusted correction to account for the fact that multiple statistical comparisons were made, with a p value < 0.002 being considered statistically significant. RESULTS: For primary TKA patients, an increased risk of 90-day SSIs was associated with male sex (OR 1.28 [95% CI 1.25 to 1.52]; p < 0.001), BMI greater than 25 k/m (p < 0.001), and other comorbidities. For primary THA patients, an increased risk of 90-day SSIs was associated with patients with obesity (BMI 30-39 kg/m; OR 1.91 [95% CI 1.60 to 2.26]; p < 0.001) and those with morbid obesity (BMI 40-70 kg/m; OR 2.58 [95% CI 1.95 to 3.36]; p < 0.001). For revision TKA patients, an increased risk of SSI was associated with iron-deficiency anemia (OR 1.82 [95% CI 1.37 to 2.28]; p < 0.001). For revision THA patients, electrolyte imbalance (OR 1.48 [95% CI 1.23 to 1.79]; p < 0.001) and iron-deficiency anemia (OR 1.63 [95% CI 1.35 to 1.99]; p < 0.001) were associated with an increased risk of 90-day SSI. Similar associations were noted for PJI in each cohort. CONCLUSIONS: These findings show that in this population, male sex, obesity, hypertension, iron-deficiency anemia, among other high-risk comorbidities are associated with a higher risk of SSIs and PJIs. Based on these findings, orthopaedic surgeons should actively engage in comanagement strategies with internists and other specialists to address modifiable risk factors through practices such as weight management programs, blood pressure reduction, and electrolyte balancing. Furthermore, this data should encourage healthcare systems and policy makers to recognize that this patient demographic is at increased risks for PJI or SSI, and these risks must be considered when negotiating payment bundles. LEVEL OF EVIDENCE: Level III, therapeutic study.

Two-Stage Treatment for Total Knee Arthroplasty Infection Utilizing an Articulating Prefabricated Antibiotic Spacer.

Periprosthetic joint infection represents a serious complication following total knee arthroplasty. In the setting of chronic or age-indeterminate total knee arthroplasty infection, a 2-staged approach has been traditionally the preferred method of treatment over single-stage debridement and reimplantation debridement or debridement, antibiotics and implant retention. Two-stage is the preferred treatment method in North America and has demonstrated better overall success than the single stage techniques. Additionally, the 2-stage method is the preferred treatment for difficult to treat pathogens as well as in patients who have already undergone a previous revision procedure. An articulating prefabricated antibiotic spacer has entered the armamentarium of 2-stage revision knee surgery, and has demonstrated comparable results to custom and static spacers in terms of the primary goal of infection control. Importantly, the potential for enhanced mobility and function hold promise by safely providing a more "livable" knee during the convalescent period prior to definitive reimplantation.

Robotic-Assisted versus Manually Implanted Total Hip Arthroplasty: A Clinical and Radiographic Comparison.

INTRODUCTION: Component positioning during THA is one of the more critical surgeon-controlled factors as malposition has been associated with higher rates of hip dislocations, poor biomechanics, accelerated wear rates, leg length discrepancies (LLDs), and revision surgeries. In order to reduce the rates of component malposition and improve surgical accuracy, robotic-assisted THA has developed increased interest. The primary objective of this study was to compare patient outcomes following THA using the Mako Stryker robotic system (Stryker Orthopaedics, Mahwah, New Jersey) to outcomes in patients who underwent conventional instrumented THA. MATERIALS AND METHODS: Consecutive patients undergoing THA with a direct-lateral surgical approach from a single surgeon were reviewed. Patients were treated with either a robotic-arm assisted total hip arthroplasty (RTHA) or a conventional-instrumented total hip arthroplasty (CTHA). Minimum follow up was 16 months. RESULTS: Robotic-assisted THA significantly improved patient outcomes compared to conventional THA. No significant differences were observed in postoperative radiographic outcomes between the RTHA and CTHA cohorts. In our analysis, patients in the RTHA cohort compared to the CTHA cohort had significantly higher Western Ontario and McMaster Universities Arthritis Index (WOMAC) (P<0.001) and Harris Hip Scores (P<0.05) at final follow up. There were no significant differences between the RTHA cohort and CTHA cohorts in regard to cup inclination (°) (P=0.10), hip length difference (mm) (P=0.80), hip length discrepancy (mm) (P=0.10), and global offset difference (mm) (P=0.20). CONCLUSION: Further studies, particularly prospective randomized studies, are necessary to investigate the short- and long-term clinical outcomes, possible long-term complications, and cost-effectiveness of robotic-assisted THA in regard to improving outcomes and accuracy.

Bardoxolone methyl and kidney function in CKD with type 2 diabetes.

BACKGROUND: Chronic kidney disease (CKD) associated with type 2 diabetes is the leading cause of kidney failure, with both inflammation and oxidative stress contributing to disease progression. Bardoxolone methyl, an oral antioxidant inflammation modulator, has shown efficacy in patients with CKD and type 2 diabetes in short-term studies, but longer-term effects and dose response have not been determined. METHODS: In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned 227 adults with CKD (defined as an estimated glomerular filtration rate [GFR] of 20 to 45 ml per minute per 1.73 m(2) of body-surface area) in a 1:1:1:1 ratio to receive placebo or bardoxolone methyl at a target dose of 25, 75, or 150 mg once daily. The primary outcome was the change from baseline in the estimated GFR with bardoxolone methyl, as compared with placebo, at 24 weeks; a secondary outcome was the change at 52 weeks. RESULTS: Patients receiving bardoxolone methyl had significant increases in the mean (±SD) estimated GFR, as compared with placebo, at 24 weeks (with between-group differences per minute per 1.73 m(2) of 8.2±1.5 ml in the 25-mg group, 11.4±1.5 ml in the 75-mg group, and 10.4±1.5 ml in the 150-mg group; P<0.001). The increases were maintained through week 52, with significant differences per minute per 1.73 m(2) of 5.8±1.8 ml, 10.5±1.8 ml, and 9.3±1.9 ml, respectively. Muscle spasms, the most frequent adverse event in the bardoxolone methyl groups, were generally mild and dose-related. Hypomagnesemia, mild increases in alanine aminotransferase levels, and gastrointestinal effects were more common among patients receiving bardoxolone methyl. CONCLUSIONS: Bardoxolone methyl was associated with improvement in the estimated GFR in patients with advanced CKD and type 2 diabetes at 24 weeks. The improvement persisted at 52 weeks, suggesting that bardoxolone methyl may have promise for the treatment of CKD. (Funded by Reata Pharmaceuticals; BEAM ClinicalTrials.gov number, NCT00811889.).

Ultrasound-guided interscalene-supraclavicular block for an intramedullary nailing of a pathologic humeral fracture: practical application of ultrasound-guided regional anesthesia.

Fractures of the proximal upper extremity present a challenge to the anesthesia provider when administering a regional anesthetic because the dermatomal distribution of the upper extremity requires more local anesthetic coverage than any single brachial plexus nerve block can provide. A 60-year-old woman underwent intramedullary nailing of a pathologic humeral fracture using a combination of regional and general anesthesia. This case study shows how ultrasound guidance permitted the performance of both an interscalene and supraclavicular nerve block for a single procedure without the increased volume of local anesthetic that would normally be required, while still providing complete coverage of the entire upper extremity.

ACR Appropriateness Criteria® Right Lower Quadrant Pain: 2022 Update.

This document focuses on imaging in the adult and pregnant populations with right lower quadrant (RLQ) abdominal pain, including patients with fever and leukocytosis. Appendicitis remains the most common surgical pathology responsible for RLQ abdominal pain in the United States. Other causes of RLQ pain include right colonic diverticulitis, ureteral stone, and infectious enterocolitis. Appropriate imaging in the diagnosis of appendicitis has resulted in decreased negative appendectomy rate from as high as 25% to approximately 1% to 3%. Contrast-enhanced CT remains the primary and most appropriate imaging modality to evaluate this patient population. MRI is approaching CT in sensitivity and specificity as this technology becomes more widely available and utilization increases. Unenhanced MRI and ultrasound remain the diagnostic procedures of choice in the pregnant patient. MRI and ultrasound continue to perform best in the hands of the experts. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer-reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer-reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Bardoxolone methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes Nrf2, PPARγ, and HO-1.

Ischemic acute kidney injury (AKI) triggers expression of adaptive (protective) and maladaptive genes. Agents that increase expression of protective genes should provide a therapeutic benefit. We now report that bardoxolone methyl (BARD) ameliorates ischemic murine AKI as assessed by both renal function and pathology. BARD may exert its beneficial effect by increasing expression of genes previously shown to protect against ischemic AKI, NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-γ (PPARγ), and heme oxygenase 1 (HO-1). Although we found that BARD alone or ischemia-reperfusion alone increased expression of these genes, the greatest increase occurred after the combination of both ischemia-reperfusion and BARD. BARD had a different mode of action than other agents that regulate PPARγ and Nrf2. Thus we report that BARD regulates PPARγ, not by acting as a ligand but by increasing the amount of PPARγ mRNA and protein. This should increase ligand-independent effects of PPARγ. Similarly, BARD increased Nrf2 mRNA; this increased Nrf2 protein by mechanisms in addition to the prolongation of Nrf2 protein half-life previously reported. Finally, we localized expression of these protective genes after ischemia and BARD treatment. Using double-immunofluorescence staining for CD31 and Nrf2 or PPARγ, we found increased Nrf2 and PPARγ on glomerular endothelia in the cortex; Nrf2 was also present on cortical peritubular capillaries. In contrast, HO-1 was localized to different cells, i.e., tubules and interstitial leukocytes. Although Nrf2-dependent increases in HO-1 have been described, our data suggest that BARD's effects on tubular and leukocyte HO-1 during ischemic AKI may be Nrf2 independent. We also found that BARD ameliorated cisplatin nephrotoxicity.

Long-term changes in kelp forests in an inner basin of the Salish Sea.

Kelp forests form an important biogenic habitat that responds to natural and human drivers. Global concerns exist about threats to kelp forests, yet long-term information is limited and research suggests that trends are geographically distinct. We examined distribution of the bull kelp Nereocystis luetkeana over 145 years in South Puget Sound (SPS), a semi-protected inner basin in a fjord estuary complex in the northeast Pacific Ocean. We synthesized 48 historical and modern Nereocystis surveys and examined presence/absence within 1-km segments along 452 km of shoreline. Compared to the earliest baseline in 1878, Nereocystis extent in 2017 decreased 63%, with individual sub-basins showing up to 96% loss. Losses have persisted for decades, across a range of climate conditions. In recent decades, Nereocystis predominantly occurred along shorelines with intense currents and mixing, where temperature and nutrient concentrations did not reach thresholds for impacts to Nereocystis performance, and high current speeds likely excluded grazers. Losses predominated in areas with elevated temperature, lower nutrient concentrations, and relatively low current velocities. The pattern of long-term losses in SPS contrasts with stability in floating kelp abundance during the last century in an area of the Salish Sea with greater wave exposure and proximity to oceanic conditions. These findings support the hypothesis that kelp beds along wave-sheltered shorelines exhibit greater sensitivity to environmental stressors. Additionally, shorelines with strong currents and deep-water mixing may provide refugia within sheltered systems.

Does Increasing Patient Complexity Have an Effect on Medical Outcomes and Lengths-of-Stay after Total Knee Arthroplasty?

A greater number of medically complex patients with multiple comorbidities are now more readily considered for total knee arthroplasty (TKA). Therefore, the purpose of this study was to determine whether comorbidity burden, measured with the Elixhauser Comorbidity Index (ECI), correlated with 90-day medical complications and longer in-hospital lengths-of-stay (LOS) in TKA patients. The PearlDiver supercomputer was queried for all primary TKA patients in the Medicare Standard Analytic Files from 2005 to 2014 using International Classification of Disease, 9th edition codes. Patients were included based on ECI scores, ranging from 1 to 5. ECI 1 patients served as the control cohort, while ECI 2, 3, 4, and 5 patients were considered study cohorts. Each study cohort was matched based on age and gender to the control cohort, resulting in a total of 715,398 patients included for analysis (ECI 1, n = 144,072; ECI 2, n = 144,072; ECI 3, n = 144,072; ECI 4, n = 144,072; ECI 5, n = 139,110). Logistic regression analyses were performed to compare 90-day medical complications and Welch's t-tests were performed to compare LOS between the cohorts. Patients with higher ECI scores were more likely to develop medical complications and have longer LOS compared with matched patients in the control cohort. Compared with matched ECI 1 patients, patients with ECI scores of 2 (odds ratio [OR]: 1.19, 95% confidence interval [CI]: 1.14-1.24), 3 (OR: 1.27, 95% CI: 1.21-1.32), 4 (OR: 1.32, 95% CI: 1.27-1.38), and 5 (OR: 1.33, 95% CI: 1.27-1.39) were significantly more likely to develop 90-day medical complications. Additionally, the mean LOS of patients in the ECI 2 (2.59 ± 1.49 vs. 2.73 ± 1.52 days), ECI 3 (2.59 ± 1.49 vs. 2.88 ± 1.51 days; p < 0.001), ECI 4 (2.59 ± 1.49 vs. 3.01 ± 1.56 days; p < 0.001), and ECI 5 (2.61 ± 1.49 vs. 3.14 ± 1.61 days; p < 0.001) groups were significantly longer than the mean LOS in the control ECI 1 group. In an increasingly complex patient population, associations between comorbidities and outcomes after TKA procedures can guide providers on how to modify their pre- and postoperative care. These results demonstrate that higher ECI scores are associated with a greater likelihood of 90-day medical complications and longer in-hospital LOS.

Liver transplantation for non-hepatocellular carcinoma malignancy: Indications, limitations, and analysis of the current literature.

Orthotopic liver transplantation (OLT) is currently incorporated into the treatment regimens for specific nonhepatocellular malignancies. For patients suffering from early-stage, unresectable hilar cholangiocarcinoma (CCA), OLT preceded by neoadjuvant radiotherapy has the potential to readily achieve a tumor-free margin, accomplish a radical resection, and treat underlying primary sclerosing cholangitis when present. In highly selected stage I and II patients with CCA, the 5-year survival rate is 80%. As additional data are accrued, OLT with neoadjuvant chemoradiation may become a viable alternative to resection for patients with localized, node-negative hilar CCA. Hepatic involvement from neuroendocrine tumors can be treated with OLT when metastases are unresectable or for palliation of medically uncontrollable symptoms. Five-year survival rates as high as 90% have been reported, and the Ki67 labeling index can be used to predict outcomes after OLT. Hepatic epithelioid hemangioendothelioma is a rare tumor of vascular origin. The data from single-institution series are limited, but compiled reviews have reported 1- and 10-year survival rates of 96% and 72%, respectively. Hepatoblastoma is the most common primary hepatic malignancy in children. There exist subtle differences in the timing of chemotherapy between US and European centers; however, the long-term survival rate after transplantation ranges from 66% to 77%. Fibrolamellar hepatocellular carcinoma is a distinct liver malignancy best treated by surgical resection. However, there is an increasing amount of data supporting OLT when resection is contraindicated. In the treatment of either primary or metastatic hepatic sarcomas, unacceptable survival and recurrence rates currently prohibit the use of OLT.

Mobile-bearing total knee arthroplasty: better than a fixed-bearing?

The purported advantages of mobile-bearing knee include increased survivorship and restoration of more natural knee kinematics compared to a standard fixed-bearing design. To evaluate these claims, an extensive review of the available literature was undertaken. We compared survivorship and clinical function, including patient preference. We found no difference in survivorship at 12 to 23 years. Kinematic profiles of both designs did not differ significantly: rotation, flexion, and extension were comparable. Studies evaluating both designs in the same patient showed no difference in range of motion, knee preference, knee scores, and survivorship at midterm follow-up. Both designs were capable of producing excellent long-term results and clinical outcomes if properly implanted. The available evidence does not point to the superiority of one design over another in survivorship and clinical function.

The Effect of the COVID-19 Pandemic on Orthopedic Practices in New York.

The SARS-CoV-2 (COVID-19) crisis has strained hospitals and health systems across the world. In the United States, New York City has faced a surge of cases as the epicenter of the North American outbreak. Northwell Health, as the largest regional health system in New York City, has implemented various practices and policies to adapt to the evolving situation and prepare for future global events. [Orthopedics. 2020;43(4):245-249.].

Utilization, outcomes, and retransplantation of liver allografts from donation after cardiac death: implications for further expansion of the deceased-donor pool.

OBJECTIVE: Utilization, outcomes, and retransplantation (ReTx) of liver allografts obtained by donation after cardiac death (DCD) are examined to identify mechanisms to optimize donation. SUMMARY AND BACKGROUND DATA: DCD for liver transplantation (LTX) has immediate potential to expand the donor pool but application is limited. METHODS: Retrospective analysis of the Scientific Registry of Transplant Recipients (SRTR) from January 2002 to April 2007 identified 855 DCD and 21,089 donation after brain death (DBD) adult, initial, whole-organ, liver-only LTX. Donor, recipient, and transplant characteristics were compared. Outcome measures were listing for ReTx within 1 year and graft survival determined as death or ReTx. RESULTS: DCD donors were younger (P < 0.001), with fewer African American and non-white race (P < 0.001), and fewer deaths secondary to stroke (P < 0.001). DCD recipients were older (P < 0.001), with lower Model for End-Stage Liver Disease (MELD) scores (P < 0.001), and less likely in intensive care (P = 0.02) or high-urgency status (P < 0.001). DCD allografts were more frequently imported from another allocation region (12% vs. 7%; P < 0.001). Cox regression analysis of time to DCD graft failure demonstrates higher DCD graft failure within the first 180 days (20.5% DCD vs. 11.5% DBD; P < 0.001) with convergence thereafter. DCD listing for ReTx and graft failure progressed continuously over 180 days versus 20 days in DBD. At ReTx, DCD recipients waited longer and received higher risk allografts (P = 0.039) more often from another region. More DCD recipients remain waiting for ReTx with fewer removed for death, clinical deterioration, or improvement. CONCLUSIONS: DCD utilization is impeded by early outcomes and a temporally different failure pattern that limits access to ReTx. Allocation policy that recognizes these limitations and increases access to ReTx is necessary for expansion of this donor population.

Correction: The effect of isohydric hemodialysis on the binding and removal of uremic retention solutes.

[This corrects the article DOI: 10.1371/journal.pone.0192770.].

The effect of isohydric hemodialysis on the binding and removal of uremic retention solutes.

BACKGROUND: There is growing evidence that the accumulation of protein- bound uremic retention solutes, such as indoxyl sulfate, p-cresyl sulfate and kynurenic acid, play a role in the accelerated cardiovascular disease seen in patients undergoing chronic hemodialysis. Protein-binding, presumably to albumin, renders these solutes poor-dialyzable. We previously observed that the free fraction of indoxyl sulfate was markedly reduced at the end of hemodialysis. We hypothesized that solute binding might be pH-dependent and attributed the changes in free solute concentration to the higher serum pH observed at the end of standard hemodialysis with dialysis buffer bicarbonate concentration greater than 35 mmol/L. We observed that acidification of uremic plasma to pH 6 in vitro greatly increased the proportion of freeIS. METHODS: We tested our hypothesis by reducing the dialysate bicarbonate buffer concentration to 25 mmol/L for the initial half of the hemodialysis treatment ("isohydric dialysis"). Eight stable hemodialysis patients underwent "isohydric dialysis" for 90 minutes and then were switched to standard buffer (bicarbonate = 37mmol/L). A second dialysis, 2 days later, employed standard buffer throughout. RESULTS: We found a clearcut separation of blood pH and bicarbonate concentrations after 90 minutes of "isohydric dialysis" (pH = 7.37, bicarbonate = 22.4 mmol/L) and standard dialysis (pH = 7.49, bicarbonate = 29.0 mmol/L). Binding affinity varied widely among the 10 uremic retention solutes analyzed. Kynurenic acid (0.05 free), p-cresyl sulfate (0.12 free) and indoxyl sulfate (0.13 free) demonstrated the greatest degree of binding. Three solutes (indoxyl glucuronide, p-cresyl glucuronide, and phenyl glucuronide) were virtually unbound. Analysis of free and bound concentrations of uremic retention solutes confirmed our prediction that binding of solute is affected by pH. However, in a mixed models analysis, we found that the reduction in total uremic solute concentration during dialysis accounted for a greater proportion of the variation in free concentration, presumably an effect of saturation binding to albumin, than did the relatively small change in pH produced by isohydric dialysis. The effect of pH on binding appeared to be restricted to those solutes most highly protein-bound. The solutes most tightly bound exhibited the lowest dialyzer clearances. An increase in dialyzer clearance during isohydric and standard dialyses was statistically significant only for kynurenic acid. CONCLUSION: These findings provide evidence that the binding of uremic retention solutes is influenced by pH. The effect of reducing buffer bicarbonate concentration ("isohydric dialysis:"), though significant, was small but may be taken to suggest that further modification of dialysis technique that would expose blood to a greater decrease in pH would lead to a greater increase the free fraction of solute and enhance the efficacy of hemodialysis in the removal of highly protein-bound uremic retention solutes.

Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department.

INTRODUCTION: Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage. METHODS AND ANALYSIS: This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 µg/kg) for analgesia in 80 children aged 4-17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug. ETHICS AND DISSEMINATION: This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial. TRIAL REGISTRATION NUMBER: NCT02521415.

Prune belly syndrome, splenic torsion, and malrotation: a case report.

An 18 year old male with a history of prune belly syndrome (PBS) presented with acute abdominal pain and palpable left upper quadrant mass. Computed tomography (CT) of the abdomen revealed a medialized spleen with a "whirl sign" in the splenic vessels, consistent with splenic torsion. Coincidentally, the small bowel was also noted to be on the right side of the abdomen, while the colon was located on the left, indicative of malrotation. Emergent diagnostic laparoscopy confirmed splenic torsion and intestinal malrotation. Successful laparoscopic reduction of the splenic torsion was achieved, however, conversion to an open procedure by a vertical midline incision was necessary owing to the patient's unique anatomy. Open splenopexy with a mesh sling and Ladd's procedure were subsequently performed. Malrotation and wandering spleen are known, rare associated anomalies in PBS; however, both have not been reported concurrently in a patient with PBS in the literature. In patients with PBS, acute abdominal pain, and an abdominal mass, high clinical suspicion for gastrointestinal malformations and prompt attention can result in spleen preservation and appropriate malrotation management. We present a case of a teenager who presented with a history of PBS, acute abdominal pain, and a palpable abdominal mass. The patient was found to have splenic torsion and intestinal malrotation. The clinical findings, diagnostic imaging, and surgical treatment options of splenic torsion are reviewed.