Laboratory-based testing does not allow for the sufficiently rapid return of data to enable optimal therapeutic monitoring of patients with metabolic diseases such as phenylketonuria (PKU). The typical turn-around time of several days for current laboratory-based testing is too slow to be practically useful for effective monitoring or optimizing therapy. This report describes the development of a rapid, paper-based, point-of-care device for phenylalanine detection using a small volume (40 μL) of whole blood. The quantitative resolution and reproducibility of this device with instrumented readout are described, together with the potential use of this device for point-of-care monitoring by PKU patients.

BackgroundInternational guidelines recommend coeliac serology in iron deficiency anaemia, and duodenal biopsy for those tested positive to detect coeliac disease. However, pre-endoscopy serology is often unavailable, thus committing endoscopists to take routine duodenal biopsies. Some endoscopists consider duodenal biopsy mandatory in anaemia to exclude other pathologies. We hypothesise that using a point of care test at endoscopy could fill this gap, by providing rapid results to target anaemic patients who require biopsies, and save costs by biopsy avoidance. We therefore assessed three key aspects to this hypothesis: 1) the availability of pre-endoscopy serology in anaemia; 2) the sensitivities and cost effectiveness of pre-endoscopy coeliac screening with Simtomax in anaemia; 3) whether other anaemia-related pathologies could be missed by this targeted-biopsy approach.MethodsGroup 1: pre-endoscopy serology availability was retrospectively analysed in a multicentre cohort of 934 anaemic patients at 4 UK hospitals. Group 2: the sensitivities of Simtomax, endomysial and tissue-transglutaminase antibodies were compared in 133 prospectively recruited patients with iron deficiency anaemia attending for a gastroscopy. The sensitivities were measured against duodenal histology as the reference standard in all patients. The cost effectiveness of Simtomax was calculated based on the number of biopsies that could have been avoided compared to an all-biopsy approach. Group 3: the duodenal histology of 153 patients presenting to a separate iron deficiency anaemia clinic were retrospectively reviewed.ResultsIn group 1, serology was available in 361 (33.8 %) patients. In group 2, the sensitivity and negative predictive value (NPV) were 100 % and 100 % for Simtomax, 96.2 % and 98.9 % for IgA-TTG, and 84.6 % and 96.4 % for EMA respectively. In group 3, the duodenal histology found no causes for anaemia other than coeliac disease.ConclusionSimtomax had excellent diagnostic accuracy in iron deficiency anaemia and was comparable to conventional serology. Duodenal biopsy did not identify any causes other than coeliac disease for iron deficiency anaemia, suggesting that biopsy avoidance in Simtomax negative anaemic patients is unlikely to miss other anaemia-related pathologies. Due to its 100 % NPV, Simtomax could reduce unnecessary biopsies by 66 % if only those with a positive Simtomax were biopsied, potentially saving £3690/100 gastroscopies.Trial registrationThe group 2 study was retrospectively registered with clinicaltrials.gov. Trial registration date: 13th July 2016; Trial registration number: NCT02834429.

Background Below-the-knee amputation (BKA) is relatively common among patients with vascular disease, infection, trauma, or neoplastic disease. Many BKAs are performed in patients with incompletely treated medical comorbidities, and some are performed in patients with acute high-energy trauma or crush injuries, malignant neoplasm undergoing time-sensitive limb removal, and diabetes with active infection or sepsis. Consequently, revision is common. Prior studies of outcomes after BKA, including several based on the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database, have follow-up periods that do not cover the entire at-risk period. Questions/purposes (1) What is the survivorship free from unplanned reoperation within 1 year of BKA? (2) What patient characteristics are associated with reoperation within 1 year of BKA? Methods We retrospectively studied all BKAs performed by the orthopaedic surgery service at a Level 1 trauma center from 2008 to 2018, as identified by Current Procedural Terminology (CPT) codes. Twenty-eight percent (38 of 138) underwent amputation as treatment for traumatic injury, 57% (79 of 138) for infection, and 15% (21 of 138) for malignancy. A total of 17% (23 of 138) had a final follow-up encounter before the 1-year study minimum, without differential loss to follow-up by surgical indication (p = 0.43) or hemoglobin A1c (p = 0.71). Median (range) follow-up was 570 days (6 to 3375). The primary outcome was survivorship from unplanned reoperation within 1 year of BKA index surgery or last planned reoperation, as determined by Kaplan-Meier estimation. Secondarily, we identified patient characteristics independently associated with reoperation within 1 year of BKA. Collected data included age, indication, BMI, diabetes, hemoglobin A1c level, closure method, and substance use. Unplanned reoperation was defined as irrigation and débridement, stump revision, or revision to a higher-level amputation; this did not include planned reoperations for BKAs closed in a staged manner. Factors associated with reoperation were determined using multivariate logistic regression analyses. All endpoints and variables related to patients and their surgical procedures were extracted from electronic medical records by someone other than the operating surgeon. Results Using Kaplan-Meier estimation, 38% of patients (95% confidence interval 29 to 46) who underwent BKA had an unplanned reoperation within 1 year of their index surgery. Twelve percent of patients (95% CI 7 to 17) who underwent BKA did not reach 30 days with the limb survivorship free from unplanned reoperation. The median (range) time between the initial surgery and reoperation was 54 days (6 to 315). After controlling for potential confounding variables like age, gender, platelet count, albumin, and the reason for undergoing amputation, a hemoglobin A1c level greater than 8.1% (relative to A1c ≤ 8.1%) was the only variable independently associated with increased odds of reoperation (odds ratio 4.6 [95% CI 1.3 to 18.1]; p = 0.02). Conclusion BKA carries a higher risk for reoperation than currently reported in studies that use 30-day postoperative follow-up periods. Clinicians should critically assess whether BKA is necessary, especially in patients with uncontrolled diabetes assessed by hyperglycemia. Before planned BKA, patients should have documented glycemic control to minimize the odds of reoperation. Because many of this study’s limitations were due to its retrospective single center design, we recommend that future work cover a clinically appropriate surveillance period using a larger cohort such as a national database and/or employ a prospective design. Level of Evidence Level III, therapeutic study.

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Background A crucial component to improving patient care is better clinician understanding of patients’ health-related quality of life (HRQoL). In orthopaedic surgery, HRQoL assessment instruments such as the NIH developed Patient Reported Outcomes Measurement Information System (PROMIS), provide surgeons with a framework to assess how a treatment or medical condition is affecting each patient’s HRQoL. PROMIS has been demonstrated as a valuable instrument in many diseases; however, the extent to which orthopaedic surgery subspecialties have used and validated PROMIS measures in peer-reviewed research is unclear. Methods Systematic scoping methodology was used to investigate the characteristics of studies using PROMIS to assess HRQoL measures as orthopaedic surgical outcomes as well as studies validating computerized adaptive test (CAT) PROMIS physical health (PH) domains including: Physical Function (PF), Upper Extremity (UE), Lower Extremity (LE). Results A systematic search of PubMed identified 391 publications utilizing PROMIS in orthopaedics; 153 (39%) were PROMIS PH CAT validation publications. One-hundred publications were in Hand and Upper Extremity, 69 in Spine, 44 in Adult Reconstruction, 43 in Foot and Ankle, 43 in Sports, 37 in Trauma, 31 in General orthopaedics, and 24 in Tumor. From 2011 through 2020 there was an upward trend in orthopaedic PROMIS publications each year (range, 1–153) and an increase in studies investigating or utilizing PROMIS PH CAT domains (range, 1–105). Eighty-five percent (n = 130) of orthopaedic surgery PROMIS PH CAT validation publications (n = 153) analyzed PF; 30% (n = 46) analyzed UE; 3% (n = 4) analyzed LE. Conclusions PROMIS utilization within orthopaedics as a whole has significantly increased within the past decade, particularly within PROMIS CAT domains. The existing literature reviewed in this scoping study demonstrates that PROMIS PH CAT domains (PF, UE, and LE) are reliable, responsive, and interpretable in most contexts of patient care throughout all orthopaedic surgery subspecialties. The expanded use of PROMIS CATs in orthopaedic surgery highlights the potential for improved quality of patient care. While challenges of integrating PROMIS into electronic medical records exist, expanded use of PROMIS CAT measurement instruments throughout orthopaedic surgery should be performed. Plain english summary In orthopaedic surgery, health-related quality of life tools such as the NIH developed Patient Reported Outcomes Measurement Information System (PROMIS), offer patients an opportunity to better understand their medical condition and be involved in their own care. Additionally, PROMIS provides surgeons with a framework to assess how a treatment or medical condition is affecting each patient’s functional status and quality of life. The efficacy of PROMIS has been demonstrated in many diseases; however, its application throughout orthopaedic care has yet to be depicted. This study sought to identify the extent to which all orthopaedic surgery subspecialties have used and validated PROMIS measures in peer-reviewed research in order to identify its potential as an applicable and valuable tool across specialties. We determined that PROMIS utilization has significantly increased within the past decade. The existing literature reviewed in this scoping study demonstrates that the PROMIS computerized adaptive test domains evaluating physical function status are reliable, responsive, and interpretable in most contexts of patient care throughout all orthopaedic surgery subspecialties. Based on these results, this study recommends the expanded and more uniform use of PROMIS computerized adaptive test measurement instruments in the clinical care of orthopaedic patients.

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Background: Complications such as nonunion and infection following ankle arthrodesis can lead to increased patient morbidity and financial burden from repeat operations. Improved knowledge of risk factors can improve patient selection and inform post–ankle arthrodesis surveillance protocols. Methods: This is a large retrospective, database study with structured query of a national insurance claims database (PearlDiver Technologies) for patients treated with ankle arthrodesis from 2015 to 2019 as identified by International Classification of Diseases, Tenth Revision ( ICD-10), codes. Patients with any operation 1 year prior to or following ankle arthrodesis were excluded from analysis to prevent attributing complications to another operation. Likelihoods of nonunion and infection within 1 year and 3 years following ankle arthrodesis were analyzed using Kaplan-Meier estimations. Patient characteristics associated with the identified complications following ankle arthrodesis were analyzed using multivariable logistic regression analyses. Results: Our query yielded 2463 patients in the 5-year period who underwent ankle arthrodesis. Nonunion occurred in 11% (95% CI 10-12) of patients within 1 year of ankle arthrodesis and 16% (95% CI 14-17) of patients within 3 years. Infection occurred in 3.9% (95% CI 3.1-4.7) of patients within 1 year of ankle arthrodesis and in 6.2% (95% CI 5.1-7.2) of patients within 3 years. Obese patients increased odds of nonunion on multivariable analysis (OR 1.6, 95% CI 1.3-2.0; P < .001). On multivariable analysis, diabetes (OR 1.7, 95% CI 1.2-2.6; P = .010) and each 1-unit increase in Elixhauser Comorbidity Index scores (OR 1.1, 95% CI 1.1-1.2; P < .001) contributed to increased odds of infection after ankle arthrodesis. Conclusion: Nonunion and infection following ankle arthrodesis have a 3-year probability of 16% and 6%, respectively. More than one-quarter of patients with nonunion following ankle arthrodesis experience a delay in diagnosis beyond 1 year. The risk of post–ankle arthrodesis nonunion is highest in patients with obesity; the risk of post–ankle arthrodesis infection is highest in patients with diabetes or an elevated Elixhauser Comorbidity Index score. Level of Evidence: Level III, prognostic study.

Background: Lisfranc injuries are among the most debilitating injuries to the foot. Characterization of first tarsometatarsal (TMT) joint involvement in Lisfranc injuries is limited. Multiple studies have indicated that this joint is damaged in a variety of Lisfranc injury patterns, but there is sparse information regarding how often and in what form. Methods: A retrospective review was performed of operative Lisfranc fractures from 2010 to 2020 with patients identified by Combined Procedural Terminology codes. Hardcastle and Myerson Lisfranc injury classifications and computed tomography and radiograph characterizations of the first TMT joint were evaluated by 3 foot and ankle fellowship–trained orthopaedic surgeons. Radiographic characteristics were collected. Light’s kappa coefficient evaluated interrater reliability for injury classification. Injury mechanism and Lisfranc classification effects on the first TMT joint were further assessed using inferential statistics. Results: Of 71 patients with a Lisfranc injury of which 37 (52%) were high energy, 61 (86%) showed radiographic evidence of first TMT joint injury. A fragment was present in the TMT articular surface in 33 (47%) with median size = 8.7 mm and medial capsular avulsion in n = 25 (35%). Forty-eight patients (68%) had medial/lateral TMT joint incongruence ≥2 mm (median overhang = 4 mm), 21 (30%) had dorsal/plantar incongruence (median overhang = 6 mm). Angulation of TMT articular surfaces ≥5 degrees on the transverse/anteroposterior plane occurred in n = 32 (45%) and in n = 12 (17%) on the sagittal/lateral plane, which significantly differed between classifications ( P = .020). Conclusion: The overwhelming majority of Lisfranc midfoot injuries seen at our tertiary referral center had imaging evidence of damage to the first TMT joint (86%), and the incidence may be higher. The most common patterns of first TMT joint involvement we found were joint incongruity, articular surface fractures, angulation of the articular surfaces, and medial capsular ligament avulsion fractures. A better understanding of injuries to the first TMT joint can help orthopaedic surgeons with diagnosis.