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Abstract Background High glomerular filtration rate (GFR) is often used as a surrogate for single-nephron hyperfiltration. Our objective was to determine the definition for high GFR that best reflects clinical and structural characteristics of hyperfiltration. Methods We studied living kidney donors at the Mayo Clinic and Cleveland Clinic. Potential donors underwent evaluations that included measured GFR (mGFR) by iothalamate clearance and estimated GFR (eGFR) by the serum creatinine–based Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI) equation. High GFR was defined by the 95th percentile for each method (mGFR or eGFR) using either overall or age-specific thresholds. High mGFR was defined as both corrected and uncorrected for body surface area. The association of high GFR by each definition with clinical characteristics and radiologic findings (kidney volume) was assessed. In the subset that donated, the association of high GFR with kidney biopsy findings (nephron number and glomerular volume) and single-nephron GFR was assessed. Results We studied 3317 potential donors, including 2125 actual donors. The overall 95th percentile for corrected mGFR was 134 mL/min/1.73 m2 and for eGFR was 118 mL/min/1.73 m2. The age-based threshold for uncorrected mGFR was 198 mL/min − 0.943×Age, for corrected mGFR it was 164 mL/min/1.73 m2 − 0.730×Age and for eGFR it was 146 mL/min/1.73 m2 − 0.813×Age. High age-based uncorrected mGFR had the strongest associations with higher single-nephron GFR, larger glomerular volume, larger kidney volume, male gender, higher body mass index and higher 24-h urine albumin, but also had the strongest association with high nephron number. A high age-height-gender–based uncorrected mGFR definition performed almost as well but had a weaker association with nephron number and did not associate with male gender. Conclusions High age-based uncorrected mGFR showed the most consistent associations reflective of hyperfiltration. However, high age-based uncorrected mGFR has limited clinical utility because it does not distinguish between hyperfiltration and high nephron number.

Objective: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations. Method: The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified. Results: Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge ‘impairment’ (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders. Conclusion: This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.

PurposeAt our institution, all proton patient plans undergo patient‐specific quality assurance (PSQA) prior to treatment delivery. For intensity‐modulated proton beam therapy, quality assurance is complex and time consuming, and it may involve multiple measurements per field. We reviewed our PSQA workflow and identified the steps that could be automated and developed solutions to improve efficiency.MethodsWe used the treatment planning system's (TPS) capability to support C# scripts to develop an Eclipse scripting application programming interface (ESAPI) script and automate the preparation of the verification phantom plan for measurements. A local area network (LAN) connection between our measurement equipment and shared database was established to facilitate equipment control, measurement data transfer, and storage. To improve the analysis of the measurement data, a Python script was developed to automatically perform a 2D–3D γ‐index analysis comparing measurements in the plane of a two‐dimensional detector array with TPS predictions in a water phantom for each acquired measurement.ResultsDevice connection via LAN granted immediate access to the plan and measurement information for downstream analysis using an online software suite. Automated scripts applied to verification plans reduced time from preparation steps by at least 50%; time reduction from automating γ‐index analysis was even more pronounced, dropping by a factor of 10. On average, we observed an overall time savings of 55% in completion of the PSQA per patient plan.ConclusionsThe automation of the routine tasks in the PSQA workflow significantly reduced the time required per patient, reduced user fatigue, and frees up system users from routine and repetitive workflow steps allowing increased focus on evaluating key quality metrics.

Background: There is controversy regarding the effectiveness of brachial plexus reconstruction for elbow function in older patients, as reported outcomes are generally poor. The purpose of this study was to evaluate elbow function outcomes in patients older than 50. Methods: Fifty-eight patients older than 50 years underwent nerve grafting, transfers, or free functioning muscle transfer to improve elbow function after traumatic brachial plexus injury. Patients were evaluated preoperatively and postoperatively for elbow flexion strength and range of motion; Disabilities of the Arm, Shoulder and Hand scores; pain; concomitant trauma; severity of trauma; and type of reconstruction. Results: The average age of the patients was 57.8 years, and the average follow-up was 24.0 months. The average modified British Medical Research Council elbow flexion grade improved significantly from 0.26 to 2.63. Thirty-three patients (60 percent) achieved functional flexion greater than or equal to M3 postoperatively, compared to zero patients preoperatively. There was no correlation between age and modified British Medical Research Council grade. Active elbow range of motion improved significantly postoperatively, with no effect of age on flexion motion. More patients achieved greater than or equal to M3 flexion with nerve transfers (69 percent) compared to free functioning muscle transfer (43 percent). Patients had worse outcomes with high-energy injuries. The mean Disabilities of the Arm, Shoulder and Hand score decreased from 51.5 to 49.6 postoperatively, and the average pain score decreased from 5.0 to 4.3. Conclusion: Brachial plexus reconstruction for elbow function in patients older than 50 can yield useful flexion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

ABSTRACT Developing novel approaches to treat skeletal disorders requires an understanding of how critical molecular factors regulate osteoblast differentiation and bone remodeling. We have reported that (1) retinoic acid receptor-related orphan receptor beta (Rorβ) is upregulated in bone samples isolated from aged mice and humans in vivo; (2) Rorβ expression is inhibited during osteoblastic differentiation in vitro; and (3) genetic deletion of Rorβ in mice results in preservation of bone mass during aging. These data establish that Rorβ inhibits osteogenesis and that strict control of Rorβ expression is essential for bone homeostasis. Because microRNAs (miRNAs) are known to play important roles in the regulation of gene expression in bone, we explored whether a predicted subset of nine miRNAs regulates Rorβ expression during both osteoblast differentiation and aging. Mouse osteoblastic cells were differentiated in vitro and assayed for Rorβ and miRNA expression. As Rorβ levels declined with differentiation, the expression of many of these miRNAs, including miR-219a-5p, was increased. We further demonstrated that miR-219a-5p was decreased in bone samples from old (24-month) mice, as compared with young (6-month) mice, concomitant with increased Rorβ expression. Importantly, we also found that miR-219a-5p expression was decreased in aged human bone biopsies compared with young controls, demonstrating that this phenomenon also occurs in aging bone in humans. Inhibition of miR-219a-5p in mouse calvarial osteoblasts led to increased Rorβ expression and decreased alkaline phosphatase expression and activity, whereas a miR-219a-5p mimic decreased Rorβ expression and increased osteogenic activity. Finally, we demonstrated that miR-219a-5p physically interacts with Rorβ mRNA in osteoblasts, defining Rorβ as a true molecular target of miR-219a-5p. Overall, our findings demonstrate that miR-219a-5p is involved in the regulation of Rorβ in both mouse and human bone. © 2018 American Society for Bone and Mineral Research.

Background: Establishing continuity of the cutaneous roll is critical to cleft lip repair. Unfortunately, this landmark can be difficult to appreciate depending on the patient’s skin tone, surgical lighting, or preexisting scar. Solution: When applied to the lip, dilute povidone-iodine solution beads off the cutaneous roll and dry vermilion, clearly defining these structures. What We Do: We use dilute povidone-iodine solution not only to prep the lip but to delineate landmarks critical to cleft lip repair.

New Findings What is the central question of this study? The goal of this study was to investigate the effect of alterations in tidal volume and alveolar volume on the elevated physiological dead space and the contribution of ventilatory constraints thereof in heart failure patients during submaximal exercise. What is the main finding and its importance? We found that physiological dead space was elevated in heart failure via reduced tidal volume and alveolar volume. Furthermore, the degree of ventilatory constraints was associated with physiological dead space and alveolar volume. AbstractPatients who have heart failure with reduced ejection fraction (HFrEF) exhibit impaired ventilatory efficiency [i.e. greater ventilatory equivalent for carbon dioxide () slope] and elevated physiological dead space (VD/VT). However, the impact of breathing strategy on VD/VT during submaximal exercise in HFrEF is unclear. The HFrEF (n = 9) and control (CTL, n = 9) participants performed constant‐load cycling exercise at similar ventilation (). Inspiratory capacity, operating lung volumes and arterial blood gases were measured during submaximal exercise. Arterial blood gases were used to derive VD/VT, alveolar volume, dead space volume, alveolar ventilation and dead space ventilation. During submaximal exercise, HFrEF patients had greater slope and VD/VT than CTL subjects (P = 0.01). At similar , HFrEF patients had smaller tidal volumes and alveolar volumes (HFrEF 1.11 ± 0.33 litres versus CTL 1.66 ± 0.37 litres; both P ≤ 0.01), whereas dead space volume was not different (P = 0.47). The augmented breathing frequency in HFrEF patients resulted in greater dead space ventilation compared with CTL subjects (HFrEF 15 ± 4 l min−1 versus CTL 10 ± 5 l min−1; P = 0.048). The HFrEF patients exhibited greater increases in expiratory reserve volume and lower inspiratory capacity (as a percentage of predicted) than CTL subjects (both P < 0.05), which were significantly related to VD/VT and alveolar volume in HFrEF patients (all P < 0.03). In HFrEF, the reduced tidal volume and alveolar volume elevate physiological dead space during submaximal exercise, which is worsened in those with the greatest ventilatory constraints. These findings highlight the negative consequences of ventilatory constraints on physiological dead space during submaximal exercise in HFrEF.

Objectives The objective was to assess the impact of procedural characteristics on risk of stroke or transient ischaemic attack (TIA) after transcatheter aortic valve replacement (TAVR). Methods We included 370 consecutive patients who underwent balloon-expandable TAVR from 1 November 2008 to 30 June 2014. Procedural characteristics that may be associated with stroke/TIA were assessed. The primary outcome was stroke/TIA at 30 days. A propensity score was constructed using a logistic regression model with 29 parameters. Cox proportional hazards models were used with a propensity score covariate. Results Mean age was 80.9±7.9 years and mean Society of Thoracic Surgeons score was 8.3±5.0. The total number of balloon dilations ranged from 2 to 7. Out of 370 patients, 13 patients (3.5%) suffered stroke/TIA in the first 30 days after TAVR. In univariate analysis, postdeployment balloon dilation (PD) (HR 3.8, 95% CI 1.24 to 11.61; p=0.02) and emergent cardiopulmonary bypass (CPB) (HR 9.66, 95% CI 2.66 to 35.15; p<0.001) were significantly associated with 30-day stroke/TIA. In the multivariable Cox-proportional hazards model, PD (HR 4.95, 95% CI 1.02 to 24.03; p=0.04) and emergent CPB (HR 7.15, 95% CI 1.39 to 36.89; p=0.02) were independently associated with increased risk of 30-day stroke/TIA after adjusting for propensity score, total number of balloon dilations and periprosthetic regurgitation. Conclusion Postdilation as compared with total number of dilations, and emergent CPB were independently associated with increased risk of clinical neurological events in the first 30 days after TAVR. Reduction in balloon postdilation with appropriate valve sizing may reduce the risk of stroke or TIA after TAVR.