Routine MRI Among Patients With a Suspected Scaphoid Fracture Risks Overdiagnosis.

BACKGROUND: In the setting of a suspected scaphoid fracture, MRI may result in overdiagnosis and potential overtreatment. This is in part because of the low prevalence of true fractures among suspected fractures, but also because of potentially misleading variations in signal that may be more common than fracture-related signal changes. To better understand the risk of overdiagnosis, we first need insight into the relative prevalence of useful and potentially distracting signal changes among patients with a suspected scaphoid fracture. QUESTION/PURPOSE: What is the proportion of signal changes representing definite and possible scaphoid fractures relative to other types of signal changes on MRI among patients with a suspected scaphoid fracture? METHODS: In a retrospective study in an orthopaedic trauma clinic associated with a Level I trauma center, we evaluated MR images of patients 16 years and older with a clinically suspected scaphoid fracture. At our institution, patients with symptoms and signs of a possible scaphoid fracture and negative radiographs undergo MRI scanning. Between January 1, 2012, and September 1, 2019, a total of 310 patients 16 years or older had an MRI to evaluate a suspected scaphoid fracture. Exclusion criteria included a scaphoid fracture that was visible on radiographs before MRI as reported by the radiologist (four patients), no available radiographs before MRI (two), MRI more than 3 weeks after injury (28), unknown date of injury (nine), and repeat or bilateral MRI scans (11), leaving 256 MR images for analysis. Sixty percent (153) of patients were women, and the median age was 34 years (IQR 21 to 50 years). The images were taken a median of 8 days (IQR 2 to 12 days) after injury. MR images were screened for the presence of scaphoid signal changes. We identified the following patterns of signal change with a reliability of kappa 0.62: definite scaphoid fracture, possible scaphoid fracture, signal in the waist area other than possible or definite fractures, and other signal changes. A definite scaphoid fracture was defined as a linear, focal, and bicortical signal abnormality, with adjacent edema and a relatively transverse orientation relative to the scaphoid long axis. The transverse linear signal was visible on more than one cut in multiple planes. A possible scaphoid fracture had a transverse linear signal on more than one cut on sagittal or coronal planes, with or without adjacent edema. RESULTS: Six percent (16 of 256) of MR images were categorized as revealing definite (2% [four of 256]) or possible (5% [12 of 256]) scaphoid fractures, whereas 29% (74 of 256) were categorized as revealing nonspecific signal changes at the waist (14% [35 of 256]) and other areas (15% [39 of 256]). Of the 51 patients with scaphoid waist signal changes, 69% (35) were categorized as having distracting and potentially misleading MRI findings. CONCLUSION: The high prevalence of signal changes that are distracting and potentially misleading, the low prevalence of signal changes that clearly represent a scaphoid fracture, and the low pretest odds of a true fracture among patients with a suspected scaphoid fracture illustrate that routine MRI of suspected scaphoid fractures carries a notable risk of overdiagnosis and potential overtreatment. Two alternative strategies are supported by preliminary evidence and merit additional attention: more-selective use of MRI in people deemed at higher risk according to a clinical prediction rule and strategies for involving the patient in decisions regarding how to manage the notably small risk of future symptomatic nonunion. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Discovery of Levesquamide B through Global Natural Product Social Molecular Networking.

Levesquamide A is an isothiazolinone-containing anti-tubercular natural product isolated from Streptomyces sp. RKND-216. Through the use of Global Natural Product Social Molecular Networking (GNPS), additional members of the levesquamide family were identified (B-G). Levesquamide B is a glycosylated analogue, isolated and structurally elucidated via spectroscopical techniques along with the putative structures of levesquamide C and D. For masses relating to the additional three levesquamides (E-G), their complete structures remain ambiguous.

Operative management of fragility fractures of the pelvis - a systematic review.

BACKGROUND: The incidence of osteoporotic pelvic fractures in elderly patient is rising. This brings an increasing burden on health and social care systems as these injuries often lead to prolonged hospital admissions, loss of independence, morbidity and mortality. Some centres now advocate stabilisation of these injuries to reduce pain, facilitate early mobilisation, decrease hospital stay and restore independence. A systematic review of the literature was planned to establish the evidence for this intervention. METHODS: A systematic review was performed according to PRISMA guidelines. A clinical librarian performed a search of the following databases: NHS Evidence, TRIP, the Cochrane Database of Systematic Reviews, MEDLINE and EMBASE. Seventeen eligible studies were identified with 766 patients. RESULTS: The quality of evidence was poor with no good quality randomised trials. The majority of injuries were minimally displaced. Posterior ring injuries were most often stabilised with percutaneous screws which were sometimes augmented with void filler. A number of techniques were described for stabilisation of the anterior ring although fixation of the anterior ring was frequently not performed. There was consistent evidence from the included studies that operative intervention significantly improved pain. Complications were minimal but there were increased failure rates when a single unaugmented sacroiliac joint screw was used. The limited availability of non-operative comparators made it difficult to draw firm conclusions about the efficacy of surgical over non-surgical management in these patients. CONCLUSIONS: Operative management of fragility fractures of the pelvis should be considered for patients failing a brief period of non-operative management, however prospective randomised trials need to be performed to provide improved evidence for this intervention. Surgeons should consider which fixation techniques for fragility fractures of the pelvis are robust enough to allow immediate weightbearing, whilst minimising operative morbidity and post-operative complications. PROSPERO Systematic Review ID: CRD42020171237.

Reduced Physical Activity Alters the Leucine-Stimulated Translatome in Aged Skeletal Muscle.

Periods of inactivity experienced by older adults induce nutrient anabolic resistance creating a cascade of skeletal muscle transcriptional and translational aberrations contributing to muscle dysfunction. The purpose of this study was to identify how inactivity alters leucine-stimulated translation of molecules and pathways within the skeletal muscle of older adults. We performed ribosomal profiling alongside RNA sequencing from skeletal muscle biopsies taken from older adults (n = 8; ~72 years; 6 F/2 M) in response to a leucine bolus before (Active) and after (Reduced Activity) 2 weeks of reduced physical activity. At both visits, muscle biopsies were taken at baseline, 60 minutes (early response), and 180 minutes (late response) after leucine ingestion. Previously identified inactivity-related gene transcription changes (PFKFB3, GADD45A, NMRK2) were heightened by leucine with corresponding changes in translation. In contrast, leucine also stimulated translational efficiency of several transcripts in a manner not explained by corresponding changes in mRNA abundance ("uncoupled translation"). Inactivity eliminated this uncoupled translational response for several transcripts, and reduced the translation of most mRNAs encoding for ribosomal proteins. Ingenuity Pathway Analysis identified discordant circadian translation and transcription as a result of inactivity such as translation changes to PER2 and PER3 despite unchanged transcription. We demonstrate inactivity alters leucine-stimulated "uncoupled translation" of ribosomal proteins and circadian regulators otherwise not detectable by traditional RNA sequencing. Innovative techniques such as ribosomal profiling continues to further our understanding of how physical activity mediates translational regulation, and will set a path toward therapies that can restore optimal protein synthesis on the transcript-specific level to combat negative consequences of inactivity on aging muscle.

A Generalized Equation for Prediction of VO2peak from a Step Test.

This study aimed to develop an equation to reduce variability of VO2peak prediction from a step test and compare VO2peak prediction from the new equation to the Queen's College Step Test (QCST). The development group (n=86; 21.7±2 years) was utilized to develop the SDState step test equation to predict relative VO2peak. The cross-validation group (n=99; 21.6±2 years) was used to determine the validity of the SDState step test VO2peak prediction equation. A regression analysis was used to identify the best model to predict VO2peak. Analysis of variance (ANOVA) was further used to determine differences among predicted and measured VO2peak values. Forward stepwise multiple regression identified age, sex, abdominal circumference, and active heart rate at the 3-min mark of the step test to be significant predictors of VO2peak (mL·kg-1·min-1). No differences among measured VO2peak (47.3±7.1 mL·kg-1·min-1) and predicted VO2peak (QCST, 46.9±9.3 mL·kg-1·min-1; SDState 48.3±5.7 mL·kg-1·min-1) were found. Pearson correlations, ICC, SEE, TEE, Bland-Altman plots, and Mountain plots indicate the SDState step test equation provides less variation in the prediction of VO2peak compared to the QCST. The SDState step test equation is effective for predicting VO2peak from the YMCA step test in young, healthy adults.

Sequence Dependence of Viral RNA Encapsidation.

We develop a Flory mean-field theory for viral RNA (vRNA) molecules that extends the current RNA folding algorithms to include interactions between different sections of the secondary structure. The theory is applied to sequence-selective vRNA encapsidation. The dependence on sequence enters through a single parameter: the largest eigenvalue of the Kramers matrix of the branched polymer obtained by coarse graining the secondary structure. Differences between the work of encapsidation of vRNA molecules and of randomized isomers are found to be in the range of 20 kBT, more than sufficient to provide a strong bias in favor of vRNA encapsidation. The method is applied to a packaging competition experiment where large vRNA molecules compete for encapsidation with two smaller RNA species that together have the same nucleotide sequence as the large molecule. We encounter a substantial, generic free energy bias, that also is of the order of 20 kBT, in favor of encapsidating the single large RNA molecule. The bias is mainly the consequence of the fact that dividing up a large vRNA molecule involves the release of stored elastic energy. This provides an important, nonspecific mechanism for preferential encapsidation of single larger vRNA molecules over multiple smaller mRNA molecules with the same total number of nucleotides. The result is also consistent with recent RNA packaging competition experiments by Comas-Garcia et al.1 Finally, the Flory method leads to the result that when two RNA molecules are copackaged, they are expected to remain segregated inside the capsid.

Mechanical ventilation management during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a retrospective international multicenter study.

OBJECTIVE: To describe mechanical ventilation settings in adult patients treated for an acute respiratory distress syndrome with extracorporeal membrane oxygenation and assess the potential impact of mechanical ventilation settings on ICU mortality. DESIGN: Retrospective observational study. SETTING: Three international high-volume extracorporeal membrane oxygenation centers. PATIENTS: A total of 168 patients treated with extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from January 2007 to January 2013. INTERVENTIONS: We analyzed the association between mechanical ventilation settings (i.e. plateau pressure, tidal volume, and positive end-expiratory pressure) on ICU mortality using multivariable logistic regression model and Cox-proportional hazards model. MEASUREMENT AND MAIN RESULTS: We obtained detailed demographic, clinical, daily mechanical ventilation settings and ICU outcome data. One hundred sixty-eight patients (41 ± 14 years old; PaO2/FIO2 67 ± 19 mm Hg) fulfilled our inclusion criteria. Median duration of extracorporeal membrane oxygenation and ICU stay were 10 days (6-18 d) and 28 days (16-42 d), respectively. Lower positive end-expiratory pressure levels and significantly lower plateau pressures during extracorporeal membrane oxygenation were used in the French center than in both Australian centers (23.9 ± 1.4 vs 27.6 ± 3.7 and 27.8 ± 3.6; p < 0.0001). Overall ICU mortality was 29%. Lower positive end-expiratory pressure levels (until day 7) and lower delivered tidal volume after 3 days on extracorporeal membrane oxygenation were associated with significantly higher mortality (p < 0.05). In multivariate analysis, higher positive end-expiratory pressure levels during the first 3 days of extracorporeal membrane oxygenation support were associated with lower mortality (odds ratio, 0.75; 95% CI, 0.64-0.88; p = 0.0006). Other independent predictors of ICU mortality included time between ICU admission and extracorporeal membrane oxygenation initiation, plateau pressure greater than 30 cm H2O before extracorporeal membrane oxygenation initiation, and lactate level on day 3 of extracorporeal membrane oxygenation support. CONCLUSIONS: Protective mechanical ventilation strategies were routinely used in high-volume extracorporeal membrane oxygenation centers. However, higher positive end-expiratory pressure levels during the first 3 days on extracorporeal membrane oxygenation support were independently associated with improved survival. Further prospective trials on the optimal mechanical ventilation strategy during extracorporeal membrane oxygenation support are warranted.

Impact of fluid balance on outcome of adult patients treated with extracorporeal membrane oxygenation.

PURPOSE: To assess the relationship between early daily fluid balance (FB) and 90-day outcome in adult patients treated with extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective observational study. SETTING: Tertiary referral centre for ECMO. PATIENTS: 115 patients treated with ECMO for refractory heart failure and 57 patients treated with ECMO for refractory respiratory failure. METHODS: We analysed the association between early daily FB versus hospital and 90-day mortality using multivariable logistic regression model, Cox proportional-hazards model and propensity score. RESULTS: We obtained detailed demographic, clinical, and biochemical data, daily FB, and continuous renal replacement days. Fifty-seven per cent of patients had acute kidney injury (AKI) at ECMO initiation, and 60 % (n = 103) of patients received continuous renal replacement therapy (CRRT) during ECMO course, beginning at a median of 1 (0-3.5) days after ECMO initiation. Overall 90-day mortality was 24 %. Survivors exhibited lower daily FB from day 3 to day 5. After adjustments, Acute Physiology and Chronic Health Evaluation (APACHE) III, CRRT during the first 3 days, major bleeding event at day 1 and positive FB on day 3 were independent predictors of 90-day mortality. Positive FB at ECMO day 3 remained an independent predictor of hospital and 90-day mortality, regardless of the statistical model used or the inclusion of a propensity score to have positive FB. CONCLUSIONS: Positive FB at ECMO day 3 is an independent predictor of 90-day mortality. Further interventional studies aimed at testing the value of strategy of tight control of FB during the early ECMO period are now warranted.