A Complex Interplay between Notch Effectors and ß-Catenin Signaling in Morular Differentiation of Endometrial Carcinoma Cells.

Notch signaling contributes to tissue development and homeostasis, but little is known about its role in morular differentiation of endometrial carcinoma (Em Ca) cells. The current study focused on crosstalk between Notch and ß-catenin signaling in Em Ca with morules. Promoters of hairy and enhancer of split 1 (Hes1) and mastermind-like 2 (MAML2) were activated by Notch intracellular domain 1 but not ß-catenin, and a positive feedback loop between Hes1 and MAML2 was observed. Immunoreactivities for nuclear ß-catenin, Hes1, and MAML2, as well as the interaction between ß-catenin and Hes1 or MAML2, were significantly higher in morular lesions compared with surrounding carcinoma in Em Ca. Inhibition of glycogen synthase kinase-3ß (GSK-3ß) increased expression of total nuclear and cytoplasmic GSK-3ß and its phosphorylated forms, as well as Notch intracellular domain 1, Hes1, and active ß-catenin. GSK-3ß inhibition also decreased proliferation and migration, consistent with the response of cells stably overexpressing Hes1. Finally, the nuclear/cytoplasmic GSK-3ß score was significantly higher in morules compared with surrounding carcinoma in Em Ca, and it was positively correlated with nuclear ß-catenin, Hes1, and MAML2 scores. This complex interplay between Notch effectors and ß-catenin signaling through GSK-3ß inhibition contributes to the establishment and maintenance of ß-catenin-mediated morular differentiation, which is, in turn, associated with reduced proliferation and inhibition of migration in Em Ca.

Nucleobindin-2 Mediates Transforming Growth Factor-ß1-Driven Phenotypes in Zinc Finger E-Box Binding Homeobox 1-High Uterine Carcinosarcoma.

Epithelial-mesenchymal transition is a hallmark of uterine carcinosarcoma (UCS). Here, shotgun proteomics analysis used to identify biomarkers associated with blebbistatin-mediated epithelial-mesenchymal transition in UCS indicated up-regulation of nucleobindin-2 (NUCB2) in endometrial carcinoma (Em Ca) cells. Expression of N-cadherin, Snail, Slug, and ZEB1 was reduced in NUCB2 knockout Em Ca cells, whereas ZEB1, Twist1, and vimentin were up-regulated in NUCB2-overexpressing Em Ca cells. NUCB2 knockout reduced cell proliferation and migration, whereas NUCB2 overexpression had the opposite effect. Treatment of Em Ca cells with transforming growth factor (TGF)-ß1 dramatically altered morphology toward a fibroblastic appearance; concomitantly, expression of NUCB2 and ZEB1 increased. The NUCB2 promoter was also activated by transfection of Smad2. In UCS tissues, NUCB2 expression was significantly higher in sarcomatous compared with carcinomatous components, which was consistent with increased TGF-ß1 mRNA expression in stromal and sarcomatous components compared with carcinomatous components. In addition, NUCB2 score correlated positively with ZEB1 and vimentin scores, whereas ZEB1 score correlated positively with Slug and vimentin scores and inversely with the E-cadherin score. Collectively, these data indicate that TGF-ß-dependent up-regulation of NUCB2 and ZEB1 contributes to the phenotypic characteristics of sarcomatous components in UCS.

Early Postoperative Stiffness After Arthroscopic Rotator Cuff Repair Correlates With Improved Tendon Healing.

PURPOSE: To assess whether early postoperative stiffness predicts long-term stiffness and its relationship with repair integrity in patients who undergo arthroscopic rotator cuff repair (ARCR). METHODS: This was a single-center retrospective study; 427 patients undergoing primary ARCR by a board-certified orthopaedic surgeon over 4 years were considered. Patients with at least 1 year of follow-up were categorized into stiff and non-stiff groups based on their range of motion (ROM) at 3 months' postoperatively. Stiffness was defined as passive forward flexion <120°, external rotation <30°, or internal rotation below L3. We evaluated clinical outcomes using demographics, ROM, Constant Shoulder (CS) score, University of California, Los Angeles (UCLA) score, and visual analog scale (VAS) for pain preoperatively and at 3, 6, and 12 months' postoperatively. Stiffness, retear rates, and tendon integrity were assessed via magnetic resonance imaging at 12 months. RESULTS: Of 155 patients meeting the inclusion criteria, 68 (43.9%) were stiff, and 87 (56.1%) were non-stiff. The stiff group had significantly lower preoperative CS and UCLA scores (P = .013/.014) and greater VAS score (P = .034). At 3 months, this group showed lower ROM and functional scores (P < .001), persisting at 6 and 12 months (except internal rotation) (P < .001). Their 12-month VAS score was greater (P = .024). Postoperative stiffness occurred in 10.3% of the stiff group and 2.3% of the non-stiff group (P = .035). The 12-month retear rate was 5.9% in the stiff group and 17.2% in the non-stiff group (P = .032). Minimal clinically important difference analysis indicated ROM changes but limited functional score changes in the 2 groups. CONCLUSIONS: This study showed that early postoperative shoulder stiffness correlates with lower preoperative functional scores and greater pain levels. Shoulder stiffness at 3 months' post-ARCR predicts 12-month shoulder stiffness but indicates better tendon integrity. While early stiffness is linked to lower functional scores and more pain, its long-term clinical impact seems limited. LEVEL OF EVIDENCE: Level III, retrospective comparison study.

Factors affecting stress shielding and osteolysis after reverse shoulder arthroplasty: A multicenter study in a Japanese population.

BACKGROUND: Stress shielding and osteolysis around the humeral stem after reverse shoulder arthroplasty causes loosening and periprosthetic fractures and reduces bone stock during revision surgery. In Japanese patients, who have relatively small bodies, different characteristics may exist regarding the occurrence of these changes compared with the characteristics of Westerners, who have relatively larger frames. The purpose of this multicenter study was to investigate the incidence and clarify the predictors of stress shielding and osteolysis in Japanese individuals who underwent reverse shoulder arthroplasty. METHODS: The occurrence of stress shielding and osteolysis was investigated in 135 shoulders that had undergone reverse shoulder arthroplasty at least 2 years prior in five Japanese hospitals. During post-surgical follow-up, which was conducted every 3 months, the locations of the stress shielding occurrences, such as cortical thinning and osteopenia (which primarily occurred in zones 1, 2, and 7, where 1 is the greater tuberosity and 7 is the calcar part), spot weld, and condensation lines, were recorded. Cases without any abnormal findings on radiographs obtained up to ≥2 years after surgery were regarded as having no abnormalities. Finally, the predictors of cortical thinning and proximal humeral osteolysis were assessed using univariate and multivariate regression analyses. RESULTS: Cortical thinning and osteopenia occurred in 68 shoulders, a condensation line occurred in 37 shoulders, and spot weld occurred in 23 shoulders. In particular, greater tuberosity and calcar osteolysis occurred in 40 and 47 shoulders, respectively. Long stem, cementless stem, and a larger proximal filling ratio were independent predictors of cortical thinning and osteopenia, whereas a cementless stem, larger metaphysis diameter, and a larger proximal filling ratio were associated with proximal humeral osteolysis. CONCLUSIONS: The predictors of stress shielding and osteolysis included the use of long stems, cementless stems, larger proximal filling ratios, and larger metaphysis diameters. LEVEL OF EVIDENCE: retrospective comparative study (Level III).

Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK-dependent colorectal cancer.

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context-dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP-rich environment based on curation of two publicly available RNA-sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA-approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders to this regimen.

Anti-cancer effect of afatinib, dual inhibitor of HER2 and EGFR, on novel mutation HER2 E401G in models of patient-derived cancer.

BACKGROUND: Precision medicine with gene panel testing based on next-generation sequencing for patients with cancer is being used increasingly in clinical practice. HER2, which encodes the human epidermal growth factor receptor 2 (HER2), is a potentially important driver gene. However, therapeutic strategies aimed at mutations in the HER2 extracellular domain have not been clarified. We therefore investigated the effect of EGFR co-targeted therapy with HER2 on patient-derived cancer models with the HER2 extracellular domain mutation E401G, based on our previous findings that this mutation has an epidermal growth factor receptor (EGFR)-mediated activation mechanism. METHODS: We generated a xenograft (PDX) and a cancer tissue-originated spheroid (CTOS) from a patient's cancer containing an amplified HER2 E401G mutation. With these platforms, we compared the efficacy of afatinib, a tyrosine kinase inhibitor having anti-HER2 and anti-EGFR activity, with two other therapeutic options: lapatinib, which has similar properties but weaker EGFR inhibition, and trastuzumab plus pertuzumab, for which evidence exists of treatment efficacy against cancers with wild-type HER2 amplification. Similar experiments were also performed with H2170, a cell line with wild-type HER2 amplification, to contrast the characteristics of these drug's efficacies against HER2 E401G. RESULTS: We confirmed that PDX and CTOS retained morphological and immunohistochemical characteristics and HER2 gene profiles of the original tumor. In both PDX and CTOS, afatinib reduced tumor size more than lapatinib or trastuzumab plus pertuzumab. In addition, afatinib treatment resulted in a statistically significant reduction in HER2 copy number at the end of treatment. On the other hand, in H2170 xenografts with wild-type HER2 amplification, trastuzumab plus pertuzumab was most effective. CONCLUSIONS: Afatinib, a dual inhibitor of HER2 and EGFR, showed a promising effect on cancers with amplified HER2 E401G, which have an EGFR-mediated activation mechanism. Analysis of the activation mechanisms of mutations and development of therapeutic strategies based on those mechanisms are critical in precision medicine for cancer patients.

Pregnancy in MuSK-positive myasthenia gravis: A single-center case series.

INTRODUCTION/AIMS: Myasthenia gravis (MG) with muscle-specific tyrosine kinase (MuSK) antibodies (MMG) is predominantly seen in women of childbearing age. Our objective in this study was to describe the course of MMG during pregnancy and within 6 months postpartum, and to document any effect on fetal health. METHODS: A retrospective review was performed of medical records of patients with MMG seen in the Duke Myasthenia Gravis Clinic from 2003 to 2022. MMG patients with onset of MMG symptoms before or during pregnancy as well as within 6 months postpartum were reviewed. RESULTS: A total of 14 pregnancies in 10 patients were included in our study cohort. Initial MG symptoms developed during pregnancy or within 6 months postpartum in six patients. Four patients had two pregnancies, three of whom developed MG during their first pregnancy. In the patients diagnosed before pregnancy, MG symptoms increased in five of eight patients during pregnancy or postpartum. Four patients required rescue therapy with plasma exchange or intravenous immunoglobulin during pregnancy or postpartum. One patient had a cesarean section after prolonged labor due to failure of progression. There were no other complications of pregnancy or delivery, and all infants were healthy at delivery. DISCUSSION: As in non-MuSK MG, women with MMG may also have worsening or may develop initial MG symptoms during pregnancy or within 6 months postpartum. More aggressive medical therapy may be required for pregnant patients with MMG. Further study is needed to identify the mechanism and risk of worsening of MMG during pregnancy or postpartum.

Preemptive middle glenohumeral ligament release in arthroscopic rotator cuff repair does not reduce the postoperative stiffness: a retrospective comparative study.

BACKGROUND: This study aimed to evaluate the efficacy of preemptive middle glenohumeral ligament (MGHL) release in arthroscopic rotator cuff repair (ARCR) to reduce postoperative stiffness. METHODS: Patients who underwent ARCR were enrolled and allocated into two groups retrospectively: the preemptive MGHL release group (n = 44) and the preemptive MGHL non-release group (n = 42). Clinical outcomes were assessed and compared between the two groups, including the range of motion, Japanese Orthopedic Association Shoulder Score, Constant Shoulder Score, and the University of California, Los Angeles Score preoperatively and 3 months, 6 months, and 12 months postoperatively and complications. The integrity of the repaired tendon was assessed at the 12-month follow-up using magnetic resonance imaging. RESULTS: There were no significant differences between the groups in all range of motion and all functional scores at any of the assessed time points. There was also no significant difference in the healing failure rate 2.3% in the preemptive MGHL group and 2.4% in the preemptive MGHL non-release group (p = .97), and postoperative stiffness was 2.3% in the preemptive MGHL group and 7.1% in the preemptive MGHL non-release group (p = .28). There was no postoperative instability in both group. CONCLUSION: ARCR effectively facilitates the recovery of range of motion and function in patients with a rotator cuff tear. However, preemptive MGHL release could not be an effective method to reduce postoperative stiffness.

Return to sports after arthroscopic Bankart repair in teenage athletes: a retrospective cohort study.

BACKGROUND: Anterior shoulder instability is frequent among young athletes. Surgical treatment for this injury aims to facilitate an early return to sports (RTS). However, the rate of recurrent instability after surgery is reportedly high among young patients, and it is unclear whether surgery ensures satisfactory RTS. The purpose of this study was to verify the clinical outcomes and RTS after arthroscopic Bankart repair in competitive teenage athletes without critical bone loss in the glenoid. METHODS: We retrospectively reviewed competitive teenage athletes who underwent arthroscopic Bankart repair. Patients with large bony defects in the glenoid, larger than 20% of the healthy side, were excluded. Clinical outcomes, recurrent instability, the final level of RTS, and the time needed for RTS were analyzed. RESULTS: In total, 50 patients with a mean follow-up period of 44.5 ± 19.6 (range, 24-85 months) months were included. The mean age at surgery was 16.8 ± 1.7 (range, 13-19 years) years. Two patients (4.0%) experienced recurrent instability. All patients returned to sports, 96% of patients participated competitively, and 76% achieved a complete return to the pre-injury level without any complaints. The time for RTS was 6.6 ± 2.7 months (range, 3-18 months), to competitions was 9.3 ± 4.0 (range, 6-24 months) months, and to complete return was 10.6 ± 4.3 (range, 8-24 months) months. The complete return rates varied by sports type, with 82% in contact athletes, 59% in dominant-hand overhead athletes, and 100% in other athletes (P = 0.026). Other preoperative factors or concomitant lesion such as bony Bankart, superior labrum tear, or humeral avulsion of glenohumeral ligament lesion did not affect the complete RTS. CONCLUSION: Arthroscopic Bankart repair is an effective surgical procedure for anterior shoulder instability, even among competitive teenage athletes. Sports type was the only factor associated with complete RTS after surgery.

Clinical outcomes and tendon lengthening after arthroscopic rotator cuff repair.

BACKGROUND: There is a phenomenon in which the tendon appears to increase the length after rotator cuff repair. However, it is unclear in which cases tendon lengthening occurs and how the degree of lengthening affects the surgical outcome. This study aimed to evaluate preoperative and postoperative musculotendinous junction (MTJ) and tendon length on magnetic resonance imaging and assess the postoperative tendon lengthening and its impact on postoperative outcomes. METHODS: We reviewed 109 patients with good repair integrity after arthroscopic rotator cuff repair. Patients whose supraspinatus tendons were simply pulled out laterally without any additional procedures were included. They underwent serial magnetic resonance imaging before surgery and at 3, 6, and 24 months after surgery. The location of the MTJ in relation to the line of the glenoid fossa and the supraspinatus tendon length were measured. Clinical evaluation was conducted 2 years after surgery, including the range of shoulder motion, shoulder strength index (affected/unaffected strength), Constant score, University of California, Los Angeles score, and pain numeric rating scale. The characteristics of the preoperative tendon, change in tendon length over time, amount of the lateral shift of MTJ location and tendon length, and impact of tendon lengthening on postoperative clinical outcomes were analyzed. RESULTS: The preoperative tendon retraction significantly correlated with the MTJ location (r = -0.75; P < .0001) and preoperative tendon length (r = -0.46; P < .0001). The tendon length at 3, 6, and 24 months after surgery was significantly longer than those before surgery (26.7 ± 5.8 mm, 27.9 ± 6.6 mm, 28.5 ± 5.6 mm, and 21.5 ± 5.1 mm, respectively). From before surgery to 24 months after surgery, the MTJ location moved 8.4 ± 8.6 mm laterally and the tendon length increased 7.0 ± 6.1 mm. A significant and weak negative correlation was found between tendon lengthening and the abduction strength index (r = -0.22; P = .03); however, no significant correlation with pain, range of shoulder motion, external rotation strength index, Constant score, and University of California, Los Angeles score was found. Multiple linear regression analysis also showed that tendon lengthening was only associated with the abduction strength index (standardized coefficient = -0.20, P = .03). CONCLUSIONS: Tendon lengthening and lateral shift of MTJ location were observed after arthroscopic rotator cuff repair, and they correlated with preoperative tendon retraction. Although the amount of tendon lengthening had negative weak correlation with abduction strength index, it did not affect other postoperative outcomes.

Tranexamic acid administration for arthroscopic rotator cuff repair: A prospective, double-blind, randomized controlled trial.

BACKGROUND: The purpose of this study was to compare the efficacy of tranexamic acid versus placebo after arthroscopic rotator cuff repair. METHODS: This prospective, double-blind, and randomized study involved 66 patients who consecutively underwent arthroscopic rotator cuff repair from 2020 to 2021 at our hospital. Thirty-three shoulders each were randomly assigned to the tranexamic acid and control groups. In the former group, 1000 mg of tranexamic acid (20 mL) was administered intravenously 10 min before surgery and the same volume of normal saline (20 mL) was administered intravenously in the control group. We evaluated visual clarity; visual analog scale pain scores at rest, during activity, and at night; the circumference and diameter of the shoulder joint in the groups before and after the surgery at 1, 2, and 3 days, and 1 week; estimated perioperative blood loss; and operative time. Visual clarity was rated using a numeric rating scale from grade 1 (poor) to grade 3 (clear) every 15 min throughout the surgery. We compared and analyzed the results between the groups. Statistical significance was set at a p-value of <0.05. RESULTS: Visual clarity was found to be significantly better in the tranexamic acid group, with a greater percentage of grade 3 visual clarity (75.6 ± 11.2% vs 68.1 ± 13.4%, p = 0.045). The visual analog scale scores at rest and at night in the control group were significantly lower than those in the tranexamic acid group for 1 week postoperatively (13.8 ± 14.8 vs 5 ± 9.3, p = 0.008, 36.1 ± 23.3 vs 19.3 ± 24, p = 0.012). The circumference and diameter of the shoulder joint, estimated perioperative blood loss, and operative time were not significantly different between the two groups. CONCLUSION: Intravenous administration of tranexamic acid is an alternative way to improve visual clarity in arthroscopic rotator cuff repair; however, there are no other significant differences compared to the administration of placebo.

Clinical outcome and repair integrity after arthroscopic full-thickness rotator cuff repair: Triple-row versus suture-bridge techniques.

BACKGROUND: This study aimed to compare the clinical outcomes and cuff integrity of the triple-row technique and suture-bridge technique in arthroscopic rotator cuff repair. METHODS: Among patients with more than two years of follow-up (mean 27.4 ± 7.2 months), 71 shoulders that underwent the triple-row technique (46 male and 25 female; mean age, 62.7 ± 10.1 years; small-to-medium tears, 42 shoulders; large-to-massive tears, 29 shoulders) and 64 shoulders that underwent the suture-bridge technique (43 male and 21 female; mean age, 65.5 ± 8.4 years; small-to-medium tears, 46 shoulders; large-to-massive tears, 18 shoulders) were examined. The patient background, operation time, number of anchors used during the operation, Japanese Orthopedic Association (JOA) score, Active range of motion, and retear rate were evaluated and compared between the two techniques. RESULTS: There was no significant difference in the patient background between the two techniques. The JOA score and Active range of motion were significantly improved compared to preoperative scores; however, there were no difference between the two techniques. The number of anchors used during the operation was 5.4 ± 1.6 for the triple-row technique and 4.1 ± 1.9 for the suture-bridge technique. Although significantly more anchors were used for the triple-row technique, there was no significant difference in the operation time between the two techniques. The retear rate was 7.1% for small-to-medium tears and 3.4% for large-to-massive tears using the triple-row technique, and 10.9% for small-to-medium tears and 33.3% for large-to-massive tears using the suture-bridge technique. The retear rate was significantly lower in large-to-massive tears when using the triple-row technique. CONCLUSION: The triple-row technique was an effective method compared to the suture-bridge technique in cases with large-to-massive tears.

Comparison of clinical outcome and repair integrity after arthroscopic suture-bridge and triple-row rotator cuff repairs of Fosbury flop tears.

BACKGROUND: The Fosbury flop tear (FFT) has recently been described as a rotator cuff tear that has flipped upon itself and adhered medially. FFT is known to have a high retear rate after arthroscopic rotator cuff repair. The cause of the high postoperative retear rate after arthroscopic rotator cuff repair is believed to be due to the inability to achieve anatomical reduction because of difficulties in reducing the torn tendon stump. Arthroscopic rotator cuff repairs using the triple-row technique may allow better anatomical reduction of the cuff tear when compared with the suture-bridge technique. We compared the clinical outcomes and cuff integrity of the triple-row and suture-bridge techniques in arthroscopic rotator cuff repair for FFT. METHODS: Patients with small-to-medium sized cuff tears of the supraspinatus tendon alone who were diagnosed with FFT, underwent arthroscopic rotator cuff repair, and had 2 or more years of follow-up were included. A total of 34 shoulders underwent the triple-row technique and 22 shoulders underwent the suture-bridge technique. The following were compared between the two techniques: patient background, operation time, number of anchors used during the operation, Japanese Orthopedic Association (JOA) score, active range of motion, and retear rate. RESULTS: No significant difference in patient background was found between the two techniques. Although active range of motion was significantly improved compared with preoperative scores, no significant difference was observed between techniques. The triple-row technique demonstrated a significantly higher 24-month postoperative JOA score, significantly shorter surgery time, significantly lower retear rate, and significantly larger number of anchors used during the operation. CONCLUSIONS: The triple-row technique was an effective method compared with the suture-bridge technique in cases with FFT.

Bone marrow edema in the acromioclavicular joint after arthroscopic rotator cuff repair.

BACKGROUND: Bone marrow edema (BME) in the acromioclavicular joint (ACj) may occur after arthroscopic rotator cuff repair (ARCR), resulting in persistent postoperative ACj pain. We investigated the incidence and clinical characteristics of BME in ACj after ARCR. METHODS: Patients exhibiting ACj-related symptoms prior to ARCR surgery, no BME in the ACj on MRI, and an ability to undergo 2-year postoperative physical and MRI examinations of the ACj were included. Patients who underwent distal clavicle resection or osteophyte resection below the ACj and those unable to achieve primary repair of the rotator cuff were excluded. MRI evaluation was performed preoperatively and at 3, 6, 12, and 24 months postoperatively. Patients who showed BME in ACj on fat-suppressed T2 MRI at 24 months postoperatively were classified into the BME + group, and those with no BME were classified into the BME- group. Patient background, operation time, Japanese Orthopedic Association (JOA) score, re-tear rate, ACj tenderness, and cross-body adduction test were compared between groups. In addition, we examined the time of occurrence of BME. RESULTS: A total of 345 ARCRs were performed during the study period. After the exclusion of 114 shoulders, the remaining 231 shoulders were included in this study. There were 208 cases in the BME- group and 23 cases in the BME + group. The incidence of BME was 9.96 %. Although the JOA scores of both groups showed a significant improvement postoperatively compared to preoperatively, there was no significant difference between the two groups. In terms of re-tear, there was 1 case in the BME + group and 7 in the BME- group. Positive ACj tenderness and cross-body adduction test were significantly higher in the BME + group (P < 0.001). BME occurred in 6 cases at 3 months, 9 cases at 6 months, and 8 cases at 1 year postoperatively. None of the patients developed BME at more than 1 year postoperatively. BME was observed on MRI in all cases at 2 years postoperatively. CONCLUSIONS: The rate of occurrence of BME in the ACj after ARCR was 9.96 %. Patients with BME were significantly more likely to have ACj tenderness and positive cross-body adduction test. BME in the ACj often occurs within 6 months to 1 year after ARCR of small-to-medium rotator cuff tears, suggesting a relationship with postoperative functional improvement of the shoulder joint. The ACj should be considered as a potential site of persistent pain after ARCR for small-to-medium rotator cuff tears.

A prospective randomized study to compare standard versus intensive training strategies on long-term improvement in critical care ultrasonography proficiency.

BACKGROUND: Critical care ultrasonography (CCUS) has become a daily diagnostic tool for intensivists. While the effective training measures for ultrasound novices are discussed widely, the best curriculum for the novices to retain a long-term proficiency is yet to be determined. METHODS: Critical care medicine fellows who underwent an introductory CCUS workshop were randomly allocated into the standard training (ST) or the intensive training (IT) group. The IT group received an 8-h training besides the standardized fellowship education that the ST group received. Participant improvement in CCUS proficiency tests (maximum score, 200) after a 6-month training intervention was compared between the groups. CCUS examinations performed in patient care were observed over 2 years. RESULTS: Twenty-one fellows were allocated into the ST (n = 10) or the IT (n = 11) group. No statistically significant difference was observed in the median (interquartile range [IQR]) improvement in CCUS proficiency tests between the ST group and the IT group: 18 (3.8-38) versus 31 (21-46) (P = .09). Median (IQR) test scores were significantly higher in postintervention than preintervention for both groups: ST, 103 (87-116) versus 124 (111-143) (P = .02), and IT, 100 (87-113) versus 143 (121-149) (P < .01). Participating fellows performed 226 examinations over the 2 years of observation. CONCLUSIONS: Fellows improved their CCUS proficiency significantly after 6-month training intervention. However, an additional 8-h training did not provide further benefits.

Does the timing of shoulder manipulation under ultrasound-guided cervical nerve root block for frozen shoulder affect the clinical outcome?

BACKGROUND: Although the clinical outcomes of manipulation under ultrasound-guided fifth and sixth cervical nerve root block for frozen shoulder have been reported, few studies have focused on the timing of manipulation. This study aimed to determine whether the timing of manipulation impacts the clinical outcomes. METHODS: We retrospectively reviewed the outcomes of 103 frozen shoulder patients (mean age 51.5 years) who underwent manipulation in one shoulder (n = 103 shoulders) between January 2012 and April 2019. Stiff shoulder was defined as limited range of motion in at least three directions, i.e., passive forward flexion of ≤100°, passive external rotation at the side of ≤10°, and internal rotation of ≤L5. The patients were categorized into two groups: those mobilized within 6 months after symptom onset (early group, 44 shoulders) and those mobilized >6 months after symptom onset (late group, 59 shoulders). The range of motion (forward flexion, external rotation, and internal rotation), Japanese Orthopaedic Association shoulder scores, Constant Shoulder Score, and University of California, Los Angeles scores before and 3, 6, and 12 months after manipulation were compared between groups. RESULTS: The late group exhibited significant improvement in forward flexion, external rotation, internal rotation, Japanese Orthopaedic Association scores, Constant Shoulder Score, and University of California, Los Angeles scores at 3 months; forward flexion at 6 months; and forward flexion and University of California, Los Angeles scores at 12 months after manipulation compared to the early group. CONCLUSIONS: Our results indicate that timing has a significant influence on the outcome of manipulation for frozen shoulders. The optimal time for manipulation may be >6 months after symptom onset. These findings can be applied in counselling for frozen shoulder patients and for improved outcomes after manipulation.

Return to sports after arthroscopic bankart repair on the dominant shoulder in overhead athletes.

BACKGROUND: Arthroscopic Bankart repair (ABR) yields good results in young athletes with anterior shoulder instability. However, the treatment for overhead athletes is challenging because recovery of range of motion is necessary for return to play and repeated shoulder motion may lead to recurrent instability. The aim of this study was to investigate the clinical outcomes and return to sports after ABR on the dominant shoulder in overhead athletes. METHODS: This study included 24 competitive level overhead athletes who underwent ABR on their dominant shoulders. The mean age at surgery was 17.6 years, and the mean follow-up was 39.7 months. The range of bilateral shoulder motion, the Rowe score, the Japanese Shoulder Society Shoulder Instability Score (JSS-SIS), and the Japanese Shoulder Society Shoulder Sports Score (JSS-SSS) were evaluated before the surgery and at the final visit. Recurrent instability, the final level of return to sports, and the duration before returning to sports were confirmed, as well as the pre-, intra- and postoperative factors, which prohibited complete return to play. RESULTS: There were no cases of recurrent instability. The Rowe score, JSS-SIS, JSS-SSS, and the range of flexion, abduction, internal rotation significantly improved postoperatively. Fifteen athletes (62.5%) returned to the same or superior levels without any complaint in their shoulders. The mean duration needed for a complete return was 13.3 months. The postoperative external rotation deficit in abduction was larger in the athletes who returned incompletely than those who returned completely, 7.8° and 2.3°, respectively. CONCLUSIONS: ABR is a reliable surgery for preventing recurrent instability in overhead athletes, however the rate of a complete return to preinjury level was low and a long duration was needed for complete return to play. The postoperative external rotation may be necessary for a complete return to overhead sports. LEVEL OF EVIDENCE: Level IV: Retrospective Case Series.

Prevalence of Rotator Cuff Tears Among Older Tennis Players and Its Impact on Clinical Findings and Shoulder Function.

CONTEXT: Tennis is a noncontact sport playable at an individual's own pace. Thus, it is popular among the older adults. It is known that older adults often suffer from rotator cuff tears (RCTs), which may affect tennis activity. However, the prevalence and influence of RCTs on tennis play among older players are not well-known. This study aimed to evaluate the prevalence of RCTs in older tennis players and its impact on physical findings and shoulder function. DESIGN: A cross-sectional study. METHODS: Fifty-three tennis players (mean age: 70.7 y; range: 60-83 y) participating in a recreational-level tennis tournament were examined in this study. An ultrasonographic examination of both shoulders was performed to detect RCTs. Relationships between RCTs of the dominant shoulder and clinical findings, shoulder pain, and shoulder function including range of motion, shoulder strength, and Single Assessment Numeric Evaluation score, and Disability of the Arm, Shoulder and Hand-Sports Module score were assessed. RESULTS: RCTs were detected in 19 (36%) dominant shoulders and 6 (11%) nondominant shoulders. Asymptomatic RCTs were detected in 11 (58%) dominant shoulders and 5 (83%) nondominant shoulders. Increased crepitus and more positive results in the empty can test, and infraspinatus test were observed in the dominant shoulders with RCTs than in those without; however, there was no difference in shoulder pain, range of motion; strength; Single Assessment Numeric Evaluation score; and Disability of the Arm, Shoulder and Hand-Sports Module score between the players with and without RCTs. CONCLUSIONS: One-third of the older tennis players in this study had RCTs in the dominant shoulder with some positive physical sign of an RCT. However, shoulder pain and shoulder function did not differ between the players with and without RCTs, suggesting that RCTs had a minor impact on the tennis performance in the participants of this study.

A neuromuscular-based analysis of the open payments program.

INTRODUCTION: In August 2013, the Centers for Medicare and Medicaid Services (CMS) Open Payments Program (OPP) made eligible payment information publicly available. Data about industry payments to neuromuscular neurologists are lacking. METHOD: Financial relationships were investigated between industry and US neuromuscular neurologists from January 2014 through December 2018 using the CMS OPP database. RESULTS: The total annual payments increased more than 6-fold during the study period. The top 10% of physician-beneficiaries collected 80% to 90% of total industry payments except in 2014. In 2018, the most common drugs associated with payments to neuromuscular neurologists were nusinersen, vortioxetine, eteplirsen, alglucosidase alpha, edaravone, and intravenous immunoglobulin. DISCUSSION: A substantial increase in the annual payments to neuromuscular physicians during the study period is likely due to the development of new treatments, including gene therapy.

Factors affecting the outcome of septic arthritis of the shoulder joint with arthroscopic management.

BACKGROUND: Good results have been reported with arthroscopic therapy of septic arthritis of the shoulder; however, few studies have focused on the risk factors for failure of arthroscopic surgery. The purpose of this study was to identify the risk factors affecting the recurrence or death post-surgery in cases of septic arthritis of the shoulder. METHODS: We retrospectively assessed the records of patients who underwent surgical treatment for septic arthritis of the shoulder between 2009 and 2019. Patients were divided into 2 groups based on complete recovery, recurrence, or death after a single arthroscopic surgery: the eradicated group and the recurred/death group. To identify risk factors for the failure of arthroscopic surgery for septic arthritis of the shoulder, the following parameters were considered: age, sex, presentation of a rotator cuff tear, the arthroscopic staging of the infection, diabetes mellitus, the causative organism, preoperative white blood cell count, and C-reactive protein level in blood. We compared two groups with respect to the presence of potential risk factors. RESULTS: This study included 22 patients with a mean age of 67.9 years. Septic arthritis of the shoulder was eradicated completely with a single arthroscopic surgery in 17 patients (77.3%). However, failure of the surgery resulting in recurrence or death was observed in 5 patients (22.7%). No significant differences were observed in other parameters between the two groups except for the causative organism. Methicillin-resistant Staphylococcus aureus was found in 1 patient (5.9%) in the eradicated group. On the other hand, Methicillin-resistant S. aureus was found in 3 patients (60%) in the recurred/death group (p = 0.024). CONCLUSION: Most patients with septic arthritis of the shoulder are effectively treated with a single arthroscopic surgery. This study suggests that Methicillin-resistant S. aureus as the causative organism may be the most important prognostic factor in these cases.