Which Combination is the Best? A Comparison of the Predictive Potential of Serum Biomarker Combinations to Diagnose Periprosthetic Joint Infection.

BACKGROUND: Without a gold-standard test, recent periprosthetic joint infections (PJI) literature has explored the utility of combining serological results, with promising findings. However, previous studies evaluated fewer than 200 patients and often studied only 1 to 2 test combinations. The purpose of this study was to accumulate a large single-institution cohort of revision total joint arthroplasty (rTJA) patients to determine the diagnostic utility of combination serum biomarkers to identify PJI. METHODS: A single institution longitudinal database was assessed to identify all patients who underwent rTJA from 2017 to 2020. There were 1,363 rTJA patients (715 rTKA patients and 648 rTHA patients) including 273 PJI cases (20%) analyzed. The PJI was diagnosed post-rTJA utilizing 2011 Musculoskeletal Infection Society (MSIS) criteria. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, and interleukin 6 (IL-6) were systematically collected for all patients. RESULTS: The rTKA combination markers of CRP + ESR (sensitivity: 78.3%, specificity: 88.8%, positive predictive value (PPV): 70.0%, negative predictive value (NPV): 92.5%), CRP + D-dimer (sensitivity: 60.5%, specificity: 92.6%, PPV: 63.4%, NPV: 91.7%), and CRP + IL-6 (sensitivity: 38.5%, specificity: 100.0%, PPV: 100.0%, NPV: 92.9%) all yielded higher specificity than CRP alone (sensitivity: 94.4%, specificity: 75.0%, PPV: 55.5%, NPV: 97.6%). Similarly, the rTHA combination markers of CRP + ESR (sensitivity: 70.1%, specificity: 88.8%, PPV: 58.1%, NPV: 93.1%), CRP + D-dimer (sensitivity: 57.1%, specificity: 90.1%, PPV: 43.2%, NPV: 94.1%), and CRP + IL-6 (sensitivity: 21.4%, specificity: 98.4%, PPV: 60.0%, NPV: 91.7%) all yielded higher specificity than CRP alone (sensitivity: 84.7%, specificity: 77.5%, PPV: 45.4%, NPV: 95.8%). CONCLUSION: Overall, in diagnosing PJI for both rTKA and rTHA, 2-marker combinations yielded higher specificity, while 3-marker combinations yielded higher sensitivity compared to CRP alone. However, compared to all 2-marker and 3-marker combinations, CRP demonstrated superior overall diagnostic utility. These findings suggest that routine combination testing of markers for PJI diagnosis may be excessive and an unnecessary use of resources, especially in resource-limited situations.

Taking a Deeper Dive Into Malnutrition and Revision Arthroplasty: When Do Nutritionists Get Involved?

BACKGROUND: Perioperative malnutrition is associated with increased complications and mortality following revision total joint arthroplasty (rTJA). Nutritional consultations are useful in characterizing patient nutritional status but are inconsistently utilized post rTJA. We sought: 1) to describe the prevalence of nutritional consultations post rTJA, 2) to determine if septic rTJA patients needed consultations more often, and 3) if a diagnosis of 'malnutrition' from the nutritionist conferred increased readmission rates. METHODS: A retrospective study of 2,697 rTJAs performed in a single institution over a 4-year period was performed. Patient demographics, reasons for rTJA, occurrences of nutritional consultation (indicated if body mass index < 20, malnutrition screening tool score ≥ 2, or poor oral intake postoperatively), specific nutritional diagnosis (according to 2020 Electronic Nutrition Care Process Terminology and 90-day readmission rates were recorded and analyzed). Rates of consultations and adjusted logistic regressions were calculated. RESULTS: There were 501 patients (18.6%) who required nutritional consultations, with 55 (11.0%) of these patients receiving a 'malnutrition' diagnosis. Septic rTJA patients required significantly more nutritional consultations (P < .01) and were significantly more likely to have 'malnutrition' (P = .49). A diagnosis of malnutrition was associated with the highest odds of all-cause readmission (odds ratio (OR) = 3.89, P = .01), which was even higher than undergoing a septic rTJA. CONCLUSION: Nutritional consultations occur frequently following rTJA. Patients who receive a diagnosis of 'malnutrition' through consultation are at significantly higher risk for readmission and require close follow-up. Future efforts are needed to further characterize these patients in order to identify as well as optimize them preoperatively.

Adaptive immune responses in patients requiring revision after total knee arthroplasty.

Dissatisfaction occurs in nearly 20% of patients after total knee arthroplasty (TKA); however, there remains only limited understanding of the biologic mechanisms that may contribute to suboptimal postoperative outcomes requiring revision surgery. Expansion of effector T and B cells, could promote an abnormal healing response via local or peripheral immune system mechanisms and contribute to inferior outcomes necessitating revision TKA. In this pilot study, we hypothesized that patients suffering from complications of arthrofibrosis or instability may exhibit differences in adaptive immune function. Patients (n = 31) undergoing revision TKA for an indication of arthrofibrosis or instability were prospectively enrolled. Whole blood and synovial fluid (SF) from the operative knee were collected at time of surgery. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry. Serum and SF were assessed for immunoglobulin levels by Luminex and antiphospholipid antibodies by enzyme-linked immunoassay. No significant differences were observed in peripheral blood T/B cell populations or serum immunoglobulins levels between groups. SF analysis demonstrated significant differences between the two groups, with higher levels of immunoglobulin G1 (IgG1) (p = 0.0184), IgG3 (p = 0.0084) and antiphosphatidyl serine IgG (p = 0.034) in arthrofibrosis relative to instability patients. Increased levels of both IgG subclasses and antiphospholipid antibodies in the SF suggest that intra-articular T-B cell interactions, potentially triggered by exposure to apoptotic components generated during post-op healing, could be functioning as a source of immune complexes that fuel fibrous tissue growth in arthrofibrotic patients.

Breast mass assessment on chest CT: Axial, sagittal, coronal or maximal intensity projection?

OBJECTIVES: The goal of this work is to determine the optimal projection to detect breast masses on Chest CT. METHODS: Institutional Review Board (HIPPA compliant) approval was obtained with a waiver of consent. 10 image pairs of Chest CT images containing breast masses were selected for review by 10 chest radiologists: the pairs consisted of axial, sagittal, coronal and axial MIP images (MIP images) with each projection compared to a MIP and with one another. For each pair, the image where the mass was most conspicuous was recorded. RESULTS: MIPs were preferred to any cross sectional projection 82% of the time; sagittal (63%) or coronal (63%) images were preferred to the axial projection. When sagittal and coronal images were compared there was no preference. CONCLUSIONS: MIP images should be obtained and reviewed for breast pathology; sagittal or coronal projections may provide additional information.

A Review of Quality of Life Measures used in Surgical Outcomes for Stage I Lung Cancers.

This review summarizes the literature on QoL in early stage lung cancer patients who underwent surgery. PubMed and PsycINFO were searched. Twelve articles from 10 distinct studies were identified for a total of 992 patients. Five QoL measures were used. One study reported only on pre-surgical QoL, six only on post-surgical QoL and three studies reported on both pre- and post-surgical QoL. Timing for the administration of post-surgical QoL surveys varied. The literature on QoL in Stage I non-small-cell lung cancer patients is very sparse. Additional research is needed to explore the impact of different surgical approaches on QoL.

Initiative for Early Lung Cancer Research on Treatment: Development of Study Design and Pilot Implementation.

INTRODUCTION: To maximize the benefits of computed tomographic screening for lung cancer, optimal treatment for small, early lung cancers is needed. Limiting the extent of surgery spares lung tissue, preserves pulmonary function, and decreases operative time, complications, and morbidities. It also increases the likelihood of resecting future new primary lung cancers. The goal is to assess alternative treatments in a timely manner. METHODS: The focus sessions with patients and physicians separately highlighted the need to consider their perceptions. Literature reviews and analyses of treatment results using large databases were performed to formulate critical questions about long-term treatment outcomes, recurrence, and quality of life of alternative treatments. Based on these analyses, the investigators developed a prospective multi-institutional cohort study, the Initiative for Early Lung Cancer Research for Treatment, to compare treatments for stage I NSCLC. HIPAA compliant institutional review board approval was obtained and we performed a feasibility study of the first 206 surgical patients. RESULTS: Lobectomy was performed in 89 (43.2%) patients, and sublobar resection was performed in 117 (56.7%) patients. Mediastinal lymph node resection was performed in 173 (84.0%) patients, 8 had N1 and 3 N2 lymph node metastases. Patients stated that both the surgeon's opinion (93%) and the patient's own opinion (93%) were extremely important, followed by the patients' view that the chosen procedure would provide the best quality of life (90%). CONCLUSIONS: It was feasible to obtain pre- and postsurgical information from patients and surgeons. We anticipate statistically meaningful results about treatment alternatives in 3 to 5 years.

Controversies on lung cancers manifesting as part-solid nodules.

PURPOSE: Summarise survival of patients with resected lung cancers manifesting as part-solid nodules (PSNs). METHODS: PubMed/MEDLINE and EMBASE databases were searched for all studies/clinical trials on CT-detected lung cancer in English before 21 December 2015 to identify surgically resected lung cancers manifesting as PSNs. Outcome measures were lung cancer-specific survival (LCS), overall survival (OS), or disease-free survival (DFS). All PSNs were classified by the percentage of solid component to the entire nodule diameter into category PSNs <80% or category PSNs ≥80%. RESULTS: Twenty studies reported on PSNs <80%: 7 reported DFS and 2 OS of 100%, 6 DFS 96.3-98.7%, and 11 OS 94.7-98.9% (median DFS 100% and OS 97.5%). Twenty-seven studies reported on PSNs ≥80%: 1 DFS and 2 OS of 100%, 19 DFS 48.0%-98.0% (median 82.6%), and 16 reported OS 43.0%-98.0% (median DFS 82.6%, OS 85.5%). Both DFS and OS were always higher for PSNs <80%. CONCLUSION: A clear definition of the upper limit of solid component of a PSN is needed to avoid misclassification because cell-types and outcomes are different for PSN and solid nodules. The workup should be based on the size of the solid component. KEY POINTS: • Lung cancers manifesting as PSNs are slow growing with high cure rates. • Upper limits of the solid component are important for correct interpretation. • Consensus definition is important for the management of PSNs. • Median disease-free-survival (DFS) increased with decreasing size of the nodule.

The chest radiologist's role in invasive breast cancer detection.

PURPOSE: To assess the ability of chest CT to identify patients needing further evaluation of the breasts. METHODS: IRB approval was obtained with a waiver of consent. Women with chest CT and mammogram within 12months formed the cohort. A breast assessment and recommendation CT score (BARCS) analogous to mammographic BI-RADS was created and compared to the mammogram BI-RADS. RESULTS: BARCS and mammographic BI-RADS management recommendations were concordant for 77.1%. 11 invasive cancers were detected; all by mammogram while CT missed 2. CONCLUSION: BARCS score should be studied in prospective trials. Chest CT might be the earliest opportunity to detect breast cancer.

Outcomes of lung cancers manifesting as nonsolid nodules.

This is a comprehensive review and re-analysis of available literature to assess the outcome of lung cancer presenting as nonsolid nodules (NSNs), a more indolent form of cancer. PubMed and EMBASE were searched for articles reporting on CT-detected lung cancers manifesting as NSNs published in English on or before July 17, 2015. Only studies including clinicopathologic data, lung cancer-specific survival, or overall survival were included. Data extraction was performed by three independent reviewers using prespecified criteria. Twenty-four articles from 5 countries met criteria and they included 704 subjects with 712 lung cancers manifesting as NSNs. Each article reported from 2 to 100 lung cancer cases with a median follow up of 18-51 months. All NSNs were Stage I adenocarcinoma without pathologic nodal involvement upon resection, except for one case in which the NSN progressed to become part-solid nodule after 6 years of follow-up. The five-year lung cancer-specific survival rate was 100%. These findings suggest an indolent course for lung cancers manifesting as NSNs.

Danio rerio in K-12 classrooms: sparking interest in the new generation of scientists.

Zebrafish are ideal for experimental studies in the classroom because, in contrast to chicks or mammals, fish embryos are relatively easy and inexpensive to maintain, and embryonic development can be observed with common classroom equipment. The eight student-developed laboratory exercises described here have been used by students in Neuroscience Research at Sidwell Friends School. This course uses zebrafish as a vertebrate model to study genetics, development, behavior, neurobiology, regeneration, learning, and memory. The students develop protocols through collaboration with the teacher and scientists in specific fields. Through individual research, students develop and perform their own experiments, formulate and test hypotheses, learn basic laboratory and microscopy techniques, collect and analyze data, read original scientific literature, and collaborate with prominent zebrafish researchers.