Citations

The tyrosine kinase inhibitor sorafenib improves hepatopulmonary syndrome (HPS) in an experimental model. However, the efficacy and adverse effect profile in patients with HPS are unknown. We aimed to determine the effect of sorafenib on the alveolar‐arterial oxygen gradient (AaPO2) at 3 months in patients with HPS. We performed a randomized, double‐blind, placebo‐controlled parallel trial of sorafenib in patients with HPS at 7 centers. A total of 28 patients with HPS were randomized to sorafenib 400 mg by mouth daily or a matching placebo in a 1:1 ratio. We found no statistically significant difference in the median change in AaPO2 from baseline to 12 weeks between the patients allocated to sorafenib (4.5 mm Hg; IQR, –3.8 to 7.0 mm Hg) and those allocated to placebo (–2.4 mm Hg; IQR, –4.8 to 8.2 mm Hg; P = 0.70). There was also no difference between the groups in terms of degree of intrapulmonary shunting by contrast echocardiography. Sorafenib significantly reduced circulating levels of angiogenic markers, including vascular endothelial growth factor receptors (P < 0.01) and TIE2‐expressing M2 monocytes (P = 0.03), but it reduced the mental component scores of the Short Form 36 (P = 0.04), indicating a worse quality of life. In conclusion, sorafenib did not change the AaPO2 or other disease markers at 3 months in patients with HPS. Alternative antiangiogenic therapies or treatments targeting other pathways should be investigated.

Many hospitalists incorporate point‐of‐care ultrasound (POCUS) into their daily practice to answer specific diagnostic questions or to guide performance of invasive bedside procedures. However, standards for hospitalists in POCUS training and assessment are not yet established. Most internal medicine residency training programs, the major pipeline for incoming hospitalists, have only recently begun to incorporate POCUS in their curricula. The purpose of this document is to inform a broad audience on what POCUS is and how hospitalists are using it. This document is intended to provide guidance for the hospitalists who use POCUS and administrators who oversee its use. We discuss POCUS 1) applications, 2) training, 3) assessments, and 4) program management. Practicing hospitalists must continue to collaborate with their local credentialing bodies to outline requirements for POCUS use. Hospitalists should be integrally involved in decision‐making processes surrounding POCUS program management.

Study Design: This is a retrospective study. Objective: To report the safety profile of S2-alar-iliac (S2AI) in patients over 60, comparing S2AI screws with iliac screws (ISs). Summary of Background Data: The surgical management involving the lumbosacropelvic spine remains a challenge due to high mechanical demand and risk of pseudarthrosis. Previous articles showed lower rates of complications in patients receiving S2AI screws than ISs; however, none of them have focused on patients aged over 60 who may harbor significant comorbidities and thus require more meticulous perioperative management, given these invasive and lengthy procedures. Materials and Methods: Retrospective review of clinical records from 2010 to 2015 identified 60 patients undergoing lumbosacropelvic fixation (17 patients with ISs and 43 patients with S2AI screws) who satisfied the following criteria: (1) patients aged over 60 years old and (2) patients with >1-year follow-up periods. Rates of complications such as unplanned reoperation and cardiorespiratory complications were collected and statistically analyzed. Results: Baseline characteristics such as age, sex, and comorbidities were similar in both groups. The S2AI group had lower rates of reoperation (18.6% vs. 47.4%; P=0.02), surgical site infection (2.3% vs. 29.4%; P=0.006), wound dehiscence (2.3% vs. 29.4%; P=0.006), and postoperative anemia (7.0% vs. 29.4%; P=0.03) and had lower total volume of estimated blood loss (EBL) (mL) (1846.4 vs. 2721.2; P=0.02) and transfused red blood cell units (7.2 vs. 4.7; P=0.04) than the IS group, while rates of L5–S1 pseudarthrosis and other cardiorespiratory complications were similar in both groups. In multivariate analysis, operative time, body mass index, and use of S2AI screws over ISs were independent predictors of EBL. Conclusions: Use of S2AI screws over ISs in patients aged over 60 was associated with lower rates of reoperation, surgical site infection, wound dehiscence, and lower volume of EBL and red blood cell transfusion and is a viable surgical option.

Purpose: To investigate the musculus uvulae morphology in vivo in adults with normal velopharyngeal anatomy and to examine sex and race effects on the muscle morphology. We also sought to provide a preliminary comparison of musculus uvulae morphology in adults with normal velopharyngeal anatomy to adults with repaired cleft palate. Methods: Three-dimensional magnetic resonance imaging data and Amira 5.5 Visualization Modeling software were used to evaluate the musculus uvulae in 70 participants without cleft palate and 6 participants with cleft palate. Muscle length, thickness, width, and volume were compared among participant groups. Results: Analysis of covariance analysis did not yield statistically significant differences in musculus uvulae length, thickness, width, or volume by race or sex among participants without cleft palate when the effect of body size was accounted for. Two-sample t test revealed that the musculus uvulae in participants with repaired cleft palate is significantly shorter ( P = .008, 13.65 mm vs 16.07 mm) and has less volume ( P = .002, 51.08 mm 3 vs 97.62 mm 3 ) than participants without cleft palate. Conclusion: In adults with normal velopharyngeal anatomy, the musculus uvulae is a cylindrical oblong-shaped muscle lying on the nasal surface of the soft palate, with its greatest bulk located just nasal to the levator veli palatini muscle sling. In participants with repaired cleft palate, the musculus uvulae is substantially reduced in volume. This diminished muscle bulk located just at the point where the palate contacts the posterior pharyngeal wall may contribute to velopharyngeal insufficiency in children with repaired cleft palate.

Background: The purpose of this study was to compare the Vickers physiolysis procedure with osteotomy for correction of digital clinodactyly and determine which method provides better correction at final follow-up or whether the patient’s age, preoperative angulation, or presence of syndactyly affects final outcomes. Methods: All patients of skeletal immaturity who underwent surgical correction of clinodactyly were evaluated with clinical examination and radiographs to determine the percentage and absolute change in the degree of clinodactyly pre- versus postoperatively, in addition to stratification based on the degree of deformity, age, and presence of syndactyly. Results: Vickers’ physiolysis and osteotomy were undertaken in 30 and 11 digits, respectively. The angulation significantly improved from 43.0° to 23.9°, with a 46.2% correction of deformity in the Vickers group at 46.3 months. The angulation decreased from 39.2° to 22.4° in the osteotomy group, with a 55.3% correction of deformity at 55.3 months. There was better correction in those with isolated clinodactyly compared with those with concomitant syndactyly and better percentage of correction in patients with lesser deformity in the Vickers group. There were more reoperations in the osteotomy group. Conclusions: The use of osteotomy may lead to more revision cases, whereas the Vickers procedure has minimal complications and need for revision. The Vickers physiolysis procedure is more effective in those with angulation <55°.

Objective: Athletes who return to sport after anterior cruciate ligament reconstruction (ACLR) demonstrate persistent biomechanical and neuromuscular deficits of the knee. There is limited evidence on what effect a neuromuscular training (NMT) program has on knee biomechanics in a cohort of athletes with ACLR. Therefore, the primary aim of this study was to quantify the effect of an NMT program on knee biomechanics in a cohort of ACLR athletes. Second, the post-training knee biomechanics were compared between the cohort of ACLR and control athletes. Design: Cohort study. Setting: Controlled laboratory setting. Participants: Eighteen athletes with ACLR and 10 control athletes. Interventions: Neuromuscular training. Main Outcome Measures: Knee kinematics and kinetics during a double-limb jump-landing task. Results: There were no significant interactions (P > 0.05) observed for the athletes with ACLR. However, there was a significant main effect of biomechanics testing session (P < 0.05) for knee flexion angle and moments; athletes with ACLR demonstrated greater knee flexion angle and lower knee flexion moment during the post-training biomechanics testing session. Post-training comparison between the ACLR and control athletes demonstrated no significant interactions (P > 0.05) between the groups. There was a significant main effect of group (P < 0.05) for knee frontal angle, as athletes with ACLR landed with greater knee adduction than the control athletes. Conclusions: Significant improvements in knee sagittal plane biomechanical measures were observed after the NMT program by the athletes with ACLR. In addition, post-training comparison of the ACLR and control groups demonstrates comparable knee biomechanics.

Background: The medial ulnar collateral ligament (UCL) insertion of the elbow has been shown to extend distally beyond the sublime tubercle. The contribution to valgus stability of the distal aspect of the footprint is unknown. Purpose/Hypothesis: The purpose of this study was to determine the contribution of each part of the UCL footprint to the elbow valgus stability provided by the UCL. It was hypothesized that the distal two-thirds of the ulnar UCL footprint would not contribute significantly to valgus stability provided by the UCL. Study Design: Descriptive laboratory study. Methods: Fifteen cadaveric arms were dissected to the capsuloligamentous elbow structures and potted. A servohydraulic load frame was used to place 5 N·m of valgus stress on the intact elbow at 30°, 60°, 90°, and 120° of flexion. The UCL insertional footprint was measured and divided into thirds (proximal, middle, and distal). One-third of the UCL footprint was elevated off the bone (leaving the ligament in continuity), and the elbow was retested at the same degrees of flexion. This was repeated until the entire UCL footprint on the ulna was sectioned. Each elbow was randomized for how the UCL would be sectioned (sectioning the proximal, then middle, and then distal third or sectioning the distal, then middle, and then proximal third). Ulnohumeral joint gapping (millimeters) was recorded with a 3-dimensional motion capture system using physical and virtual markers. Two-group comparisons were made between each sectioned status versus the intact condition for each flexion angle. Results: When the UCL was sectioned from distal to proximal, none of the ligaments failed prior to complete sectioning. When the UCL was sectioned from proximal to distal, 3 of the 6 ligaments failed after sectioning of the proximal third, while 2 more failed after the proximal and middle thirds were sectioned. Of the specimens with the distal third of the ligament sectioned first, no significant differences were found between intact, distal third cut, and distal plus middle thirds cut at all flexion angles. Conclusion: The middle and distal thirds of the insertional footprint of the UCL on the ulna did not significantly contribute to gap resistance at 5 N·m of valgus load. The proximal third of the footprint is the primary resistor of valgus load. Clinical Relevance: This cadaveric biomechanical study demonstrated that the middle and distal thirds of the native UCL insertion onto the ulna did not significantly contribute to valgus resistance at the elbow. When a UCL reconstruction is performed, the proximal third of the UCL insertion may be the most clinically important portion of the ligament to reconstruct.

Background: Studies examining the evolution of shoulder and elbow range of motion (ROM) in baseball pitchers over a single season have yielded inconsistent results. Purpose: To evaluate shoulder and elbow ROM in Major League Baseball (MLB) pitchers over a single season and to assess for correlations between these changes and measures of a pitcher’s workload. Study Design: Case-control study; Level of evidence, 3. Methods: Bilateral shoulder ROM (internal rotation [IR], external rotation [ER], and total range of motion [TROM]) was assessed in 92 MLB pitchers pre- and postseason. Shoulder forward flexion (FF) was measured in 64 pitchers, horizontal adduction (HA) was measured in 87 pitchers, and elbow ROM was measured in 86 pitchers. Data collected included demographics (age, height, weight, and body mass index) and measures of workload for pitchers (pitches thrown, innings pitched, and mean fastball velocity). Pitchers were not specifically excluded if they had an injury during the season but had recovered and were actively pitching at the time of postseason measurements. The change in motion from pre- to postseason was measured and the associations with player demographics and workload were calculated by use of the Pearson correlation coefficient. Results: On average, pitchers demonstrated an increase in dominant shoulder ER from 118.8° to 125.4° ( P < .001) and TROM from 173.1° to 181.7° ( P < .001). HA was increased by an average of 15.7° ( P < .001). The average shoulder IR ( P = .189), FF ( P = .432), and elbow ROM (flexion, P = .549; extension, P = .185) remained similar over the span of the season. Average glenohumeral IR deficit did not increase. Pitcher demographics and measures of throwing workload (total pitches thrown, innings pitched, mean fastball velocity) were not significantly correlated with changes in shoulder or elbow ROM. Conclusion: Significant increases in dominant shoulder ER, TROM, and HA were identified in MLB pitchers over the course of a single baseball season. These ROM changes were not correlated with measures of pitching workload.

Abstract The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states contributes to their metastatic potential. Therefore, driving tumor cells into a stable mesenchymal state, as opposed to complete tumor cell eradication, presents an opportunity to pharmacologically limit disease progression by promoting an asymptomatic state of dormancy. Here, we compare a reversible model of epithelial–mesenchymal transition (EMT) induced by TGFβ to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor lapatinib. Only cells capable of returning to an epithelial phenotype resulted in skeletal metastasis. Gene expression analyses of the two mesenchymal states indicated similar transition expression profiles. A potently downregulated gene in both datasets was spleen tyrosine kinase (SYK). In contrast to this similar diminution in mRNA, kinome analyses using a peptide array and DNA-conjugated peptide substrates showed a robust increase in SYK activity upon TGFβ-induced EMT only. SYK was present in cytoplasmic RNA processing depots known as P-bodies formed during the onset of EMT, and SYK activity was required for autophagy-mediated clearance of P-bodies during mesenchymal–epithelial transition (MET). Genetic knockout of autophagy-related 7 (ATG7) or pharmacologic inhibition of SYK activity with fostamatinib, a clinically approved inhibitor of SYK, prevented P-body clearance and MET, inhibiting metastatic tumor outgrowth. Overall, this study suggests assessment of SYK activity as a biomarker for metastatic disease and the use of fostamatinib as a means to stabilize the latency of disseminated tumor cells. Significance: These findings present inhibition of spleen tyrosine kinase as a therapeutic option to limit breast cancer metastasis by promoting systemic tumor dormancy. See related commentary by Farrington and Narla, p. 1756