Citations

Background: Debridement and implant retention (DAIR) has variable success as a treatment for acute periprosthetic joint infection (PJI), with generally poor outcomes reported in the literature 1 . Because of the unacceptably high failure rate of DAIR, we implemented a 2-stage debridement protocol that includes the use of high-dose antibiotic beads between stages for the treatment of acute PJI. In 2 previous studies, with an average follow-up of 3.5 years in each study, we reported overall infection-control rates of 87% and 90% 2,3 . Description: Following exposure of the joint, cultures are obtained, and all modular components are removed, scrubbed, and soaked in an antiseptic solution. A thorough irrigation and debridement with complete synovectomy is performed, followed by temporary reinsertion of the original modular parts. High-dose antibiotic cement beads are inserted into the joint, and the joint is closed. Approximately 5 to 6 days later, a second debridement is performed, the beads are removed, and the new modular, sterile components are implanted. The patient is placed on a course of intravenous and, later, oral antibiotics, in addition to a standard postoperative rehabilitation protocol. Alternatives: Long-term suppressive antibiotic therapy. One-stage DAIR. One-stage exchange arthroplasty. Two-stage exchange arthroplasty. Resection arthroplasty. Amputation. Rationale: The treatment of acute PJI has historically consisted of a single irrigation and debridement, with exchange of modular parts and retention of the components, followed by intravenous antibiotic therapy. Despite having lower rates of patient morbidity compared with a 2-stage exchange arthroplasty, this more traditional procedure also has a higher rate of failure, with reported rates as high as 60% to 84% 4–12 . The utility of component retention continues to be a topic of debate 13 . Alternatives to component retention include both 1- and 2-stage exchange procedures. Although these modalities offer potentially higher rates of infection control, they are associated with substantial patient morbidity, particularly in patients with well-fixed implants 14–16 . Furthermore, exchange procedures may result in substantial iatrogenic bone loss, which can be problematic in revision total joint arthroplasty procedures, in which bone stock may already be limited. The double-DAIR protocol offers infection-control rates that are comparable with those of component-exchange procedures, but with the lower patient morbidity associated with component-retention procedures. Furthermore, the double-DAIR procedure provides the added benefit of retaining important bone stock. Expected Outcomes: The success rate for the double-DAIR procedure has been reproducible, with infection-control rates of 87% and 90% reported in 2 studies from a single cohort at our institution 2,3 . These rates represent a substantial improvement compared with a single irrigation and debridement 1 , and are on par with those reported for 2-stage exchange arthroplasty procedures 17–21 . The infection-control rates of the double-DAIR procedure did not significantly vary depending on whether infection occurred following a total knee or total hip arthroplasty. However, not surprisingly, patients who underwent debridement following a revision procedure had a lower rate of success (77.1% successful infection control) compared with patients debrided following a primary procedure (93.8% successful infection control). We could not demonstrate an association with organism and success or failure of treatment. Although not significant, there was a trend toward an association between the time from symptom onset to initial treatment and infection control (p = 0.07) 2 . Patients with successful infection control underwent the initial debridement an average of 6.2 days after symptom onset, compared with 10.7 days in patients in whom treatment had failed. Several other studies have demonstrated that successful infection control is associated with earlier initial irrigation and debridement 22–27 . We strongly support that, in the setting of confirmed acute PJI, prompt initiation of treatment optimizes the chances for successful infection control. Important Tips: Thorough debridement is key to successful infection control of infection. Antibiotic-loaded bone cement has repeatedly been demonstrated to be safe, and we recommend its use 28–31 . Extended oral antibiotics following debridement with component retention can increase infection-free survivorship 32 .

ObjectiveThe aim of this systemic review is to compare different treatments for patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) to inform evidence‐based recommendations for the American College of Rheumatology (ACR)/Vasculitis Foundation (VF) Vasculitis Management Guidelines.MethodsA systemic review was conducted by searching articles in English using OVID Medline, PubMed, Embase, and the Cochrane Library. Articles were screened for suitability in addressing PICO questions, with studies presenting the highest level of evidence given preference.ResultsA total of 729 full‐text articles addressing GPA and MPA PICO questions were reviewed. For remission induction, rituximab was shown to be noninferior to cyclophosphamide (CYC) (odds ratio [OR]: 1.55, moderate certainty of evidence). The addition of plasma exchange to induction therapy in severe disease did not improve the composite end point of death or end stage renal disease (hazard ratio [HR]: 0.86 [95% confidence interval CI: 0.65, 1.13], moderate certainty of evidence). In nonsevere disease, methotrexate was noninferior to CYC for induction of remission (remission at 6 months of 90% vs. 94%). For maintenance of remission, methotrexate and azathioprine showed no difference in the risk of relapse over a mean follow‐up of 29 months (HR: 0.92, [95% CI: 0.52, 1.65]low certainty of evidence). As maintenance therapy, rituximab was superior to a tapering azathioprine strategy in major relapse‐free survival at 28 months (HR: 6.61, [95% CI: 1.56, 27.96], moderate certainty of evidence). In two randomized trials, longer‐term azathioprine maintenance therapy (>24 months) is associated with fewer relapses without an increase in adverse events.ConclusionThis comprehensive systematic review synthesizes and evaluates the benefits and toxicities of different treatment options for GPA and MPA.

Cardiac sarcoidosis is a component of an often multiorgan granulomatous disease of still uncertain cause. It is being recognized with increasing frequency, mainly as the result of heightened awareness and new diagnostic tests, specifically cardiac magnetic resonance imaging and 18 F-fluorodeoxyglucose positron emission tomography scans. The purpose of this case-based review is to highlight the potentially life-saving importance of making the early diagnosis of cardiac sarcoidosis using these new tools and to provide a framework for the optimal care of patients with this disease. We will review disease mechanisms as currently understood, associated arrhythmias including conduction abnormalities, and atrial and ventricular tachyarrhythmias, guideline-directed diagnostic criteria, screening of patients with extracardiac sarcoidosis, and the use of pacemakers and defibrillators in this setting. Treatment options, including those related to heart failure, and those which may help clarify disease mechanisms are included.

Abstract Purpose: We have previously identified tissue methylated DNA markers (MDMs) associated with pancreatic ductal adenocarcinoma (PDAC). In this case–control study, we aimed to assess the diagnostic performance of plasma MDMs for PDAC. Experimental Design: Thirteen MDMs (GRIN2D, CD1D, ZNF781, FER1L4, RYR2, CLEC11A, AK055957, LRRC4, GH05J042948, HOXA1, PRKCB, SHISA9, and NTRK3) were identified on the basis of selection criteria applied to results of prior tissue experiments and assays were optimized in plasma. Next, 340 plasma samples (170 PDAC cases and 170 controls) were assayed using target enrichment long-probe quantitative amplified signal method. Initially, 120 advanced-stage PDAC cases and 120 healthy controls were used to train a prediction algorithm at 97.5% specificity using random forest modeling. Subsequently, the locked algorithm derived from the training set was applied to an independent blinded test set of 50 early-stage PDAC cases and 50 controls. Finally, data from all 340 patients were combined, and cross-validated. Results: The cross-validated area under the receiver operating characteristic curve (AUC) for the training set was 0.93 (0.89–0.96) for the MDM panel alone, 0.91 (95% confidence interval, 0.87–0.96) for carbohydrate antigen 19-9 (CA19-9) alone, and 0.99 (0.98–1) for the combined MDM-CA19-9 panel. In the test set of early-stage PDAC, the AUC for MDMs alone was 0.84 (0.76–0.92), CA19-9 alone was 0.87 (0.79–0.94), and combined MDM-CA19-9 panel was 0.90 (0.84–0.97) significantly better compared with either MDMs alone or CA19-9 alone (P = 0.0382 and 0.0490, respectively). At a preset specificity of 97.5%, the sensitivity for the combined panel in the test set was 80% (28%–99%) for stage I disease and 82% (68%–92%) for stage II disease. Using the combined datasets, the cross-validated AUC was 0.9 (0.86–0.94) for the MDM panel alone and 0.89 for CA19-9 alone (0.84–0.93) versus 0.97 (0.94–0.99) for the combined MDM-CA19-9 panel (P ≤ 0.0001). Overall, cross-validated sensitivity of MDM-CA19-9 panel was 92% (83%–98%), with an observed specificity of 92% at the preset specificity of 97.5%. Conclusions: Plasma MDMs in combination with CA19-9 detect PDAC with significantly higher accuracy compared with either biomarker individually.

Abstract Context.—The diagnosis and classification of leukemia is becoming increasingly complex. Current classification schemes incorporate morphologic features, immunophenotype, molecular genetics, and clinical data to specifically categorize leukemias into various subtypes. Although sophisticated methodologies are frequently used to detect characteristic features conferring diagnostic, prognostic, or therapeutic implications, a thorough microscopic examination remains essential to the pathologic evaluation. Detailed blast immunophenotyping can be performed with lineage- and maturation-specific markers. Although no one marker is pathognomonic for one malignancy, a well-chosen panel of antibodies can efficiently aid the diagnosis and classification of acute leukemias. Objective.—To review important developments from recent and historical literature. General immunohistochemical staining patterns of the most commonly encountered lymphoid and myeloid leukemias are emphasized. The goal is to discuss the immunostaining of acute leukemias when flow cytometry and genetic studies are not available. Data Sources.—A comprehensive review was performed of the relevant literature indexed in PubMed (National Library of Medicine) and referenced medical texts. Additional references were identified in the reviewed manuscripts. Conclusions.—Immunophenotyping of blasts using an immunohistochemical approach to lymphoid and myeloid malignancies is presented. Initial and subsequent additional antibody panels are suggested to confirm or exclude each possibility in the differential diagnosis and a general strategy for diagnostic evaluation is discussed. Although the use of immunohistochemistry alone is limited and evaluation by flow cytometry and genetic studies is highly recommended, unavoidable situations requiring analysis of formalin-fixed tissue specimens arise. When performed in an optimized laboratory and combined with a careful morphologic examination, the immunohistochemical approach represents a useful laboratory tool for classifying various leukemias.

Abstract Background To determine if proton radiotherapy (PT), compared to intensity-modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma (GBM). Methods Eligible patients were randomized unblinded to PT vs IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes (PROs). Results A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45-1.75; P = .74). PT was associated with a lower rate of fatigue (24% vs 58%, P = .05), but otherwise, there were no significant differences in PROs at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44-1.23; P = .24) or OS (HR, 0.86; 95% CI, 0.49-1.50; P = .60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P = .02). Conclusions In this signal-seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient-reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for GBM and cognitive preservation in patients with lower-grade gliomas with a longer survival time.

Introduction: Serum folate (SF), vitamin B12 (B12), and iron deficiency (def) are common causes of nutritional anemias (NA). These deficiencies are usually multifactorial, with nutritional and non-nutritional causes playing a role. SF, B12, and iron levels are usually ordered in the setting of anemia, and malnutrition with or without neurologic symptoms. Clinical evidence suggests that these def have a strong dietary component and socioeconomic status (SES). The relationship of NA and area-based SES in the US has not been studied. We aimed to determine the relationship of SES with the prevalence of NA. Methods: We performed a cross-sectional analysis of adult patients with SF, B12 and iron levels at Mayo Clinic Arizona and Florida between 2010 and 2018. Race was classified using the NIH criteria. Normal laboratory values were determined according to our lab reference and the US NHANES III. SF levels (mcg/Lt) were defined as deficient <4, normal ≥4.0, and excess ≥20. B12 levels (ng/L) as deficient <150, borderline 150-400, normal >400-900, and excess ≥900. Iron def was determined by ferritin levels (mcg/L) as low <24, normal 24-336, elevated >336 for men, low <11, normal 11-307, elevated >307 for women. Area-Level SES indicators: Median Household income (MHI), unemployment rate (UR), median gross rent month (MGRM), % uninsured, median house value (MHV), % high school; were geocoded by zip code using the 2014 American Community Survey. Demographics and clinical variables were compared between groups by chi-square test for frequency data or Kruskal Wallis rank-sum test for continuous variables. Results: 202,046 samples from 128,084 patients were analyzed. In the sample-level analysis, there were statistically significant associations between SES and SF def; all SES indicators except UR for B12 def; and no differences for iron def, except % uninsured (Table 1). There was no statistically significant interaction between race and SES for SF def and iron def. Race was a statistically significant modifier between B12 def and MHI (p<0.001), % uninsured (p=0.002), and MHV (p=0.007). Asian and Other race had an increase in odds of B12 def with increasing MHI (Asian OR=1.11 , Other OR=1.18); white race had a decrease in odds of B12 def with increasing MHI (OR=0.95 for a $10,000 increase in MHI). Conclusions: We show significant relationships between SES and NA in the US. Differences were observed between SF def and all the SES indicators without race interactions. There were significant interactions between B12 def, race and SES for pts of White, Asian and Other race. There were no differences between SES and race for iron def. These relationships confirm that NA are related to area-level SES and other social determinants of health. Research regarding the causes of these disparities on a population level are needed. Disclosures No relevant conflicts of interest to declare.

Background: Cleft lip and cleft palate (CLP) are among the world’s most common congenital malformation and has a higher prevalence in developing nations due to environmental and genetic factors. Global efforts have been developed in order to prevent and treat the malformation. Telemedicine has been implemented in various humanitarian global missions with success and is currently the primary means of care due to COVID-19. Objective: To assess the benefits and barriers of telehealth in the care of patients with CLP through a global approach. Methods: Systematic review of the PubMed and Cochrane Review databases with relevant terms related to telemedicine in cleft lip and palate surgery. Results: Eight articles fit the inclusion criteria and suggested benefits with the use of telemedicine in regard to education, preoperative, and postoperative care as well as increased access to underserved populations. Barriers included connectivity and accessibility concerns. Conclusion: Telehealth is a beneficial way to evaluate patients with CLP in developing countries with proper care and follow-up to reduce complications and to improve health outcomes.

ObjectiveTakayasu’s arteritis (TAK) is a granulomatous large‐vessel vasculitis primarily affecting the aorta and its proximal branches. TAK can be a difficult disease to diagnose and manage given the rarity of the disease as well as current limitations in biomarkers, imperfect imaging modalities, and few randomized controlled trials.MethodsIn developing the American College of Rheumatology/Vasculitis Foundation guideline for the management of TAK, we performed an extensive systematic literature review to guide our recommendations. We included RCTs first. When RCTs were not available, we included observational studies that reported on patient‐important outcomes for the intervention and comparison. When studies with comparative data were not available, we included case series that present patient‐important outcomes for either the intervention or the comparison.ResultsThree hundred forty‐seven articles were included for full review to answer 27 population, intervention, comparison, and outcome questions related to TAK. Ten studies were evaluated that addressed the use of glucocorticoids (GCs), non‐GC nonbiologic therapies, as well as biologics in treating TAK. A total of 33 studies, including 8 comparative studies, were included to determine the test accuracy of commonly available diagnostic tests for TAK.ConclusionThis comprehensive systematic review synthesizes and evaluates the benefits and harms of different treatment options and the accuracy of commonly used tests for the management of TAK.