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Purpose The purposes of this study were to determine the incidence of anterior shoulder pain in young athletes undergoing arthroscopic posterior labral repair for symptomatic unidirectional posterior shoulder instability and in patients with preoperative anterior shoulder pain treated without biceps tenodesis at the time of arthroscopic posterior labral repair who underwent a revision biceps tenodesis procedure at short-term follow up. Methods A retrospective review was performed at a single institution over a 24-month period. The study included young patients who underwent an arthroscopic posterior labral repair for symptomatic unidirectional posterior shoulder instability. The electronic medical record, magnetic resonance arthrograms, and arthroscopic images were reviewed to exclude patients with posterior labral tears with anterior labral tear or SLAP (superior labrum anterior-to-posterior) tear extension on advanced imaging and arthroscopic examination. Data collected included the presence of preoperative tenderness to palpation of the biceps tendon in the groove, the results of a preoperative Speed test, postoperative Subjective Shoulder Value, the presence of postoperative anterior shoulder pain, and the need for a secondary biceps tenodesis. Results We identified 65 patients who underwent arthroscopic labral repair for posterior shoulder instability. From this cohort, 26 patients with symptomatic unidirectional posterior shoulder instability underwent an arthroscopic posterior labral repair. The incidence of preoperative anterior shoulder pain with Zone 2 biceps groove tenderness and a positive Speed test was identified in 20 of 26 patients (76.9%). Of 26 patients, 5 (19%) had concomitant biceps tenodesis. The median postoperative Subjective Shoulder Value was 80 (interquartile range, 60-90) at median follow-up of 2.1 years. Of the 20 patients with preoperative anterior shoulder pain, 8 of 20 (40%) reported persistent anterior pain. One patient (4.7%) underwent a secondary biceps tenodesis. Conclusions There is a high incidence of anterior shoulder pain and Zone 2 biceps groove tenderness in patients undergoing isolated arthroscopic posterior labral repair for unidirectional posterior shoulder instability. At short-term follow-up, few patients required a secondary biceps tenodesis procedure; however, 30% of patients had persistent anterior shoulder pain. Level of Evidence Level IV, retrospective diagnostic case series.

Purpose To evaluate the frequency of glenohumeral joint extravasation of ultrasound (US)-guided biceps tendon sheath injections. Methods Fifty shoulders with a clinical diagnosis of bicipital tenosynovitis pain received a US-guided biceps sheath injection with anesthetic, steroid, and contrast (5.0 mL mixture) followed immediately by orthogonal radiographs to localize the anatomic distribution of the injection. Radiographic evaluation of contrast localization was determined and interobserver reliability calculated. Results All 50 postinjection radiographs (100%) demonstrated contrast within the biceps tendon sheath. In addition, 30 of 50 (60%) radiographs also revealed contrast in the glenohumeral joint. Interobserver reliability for determination of intraarticular contrast was good (kappa value 0.87). Conclusions US-guided bicipital sheath injections reproducibly result in intrasheath placement of injection fluid. Bicipital sheath injections performed with 5 mL of volume result in partial extravasation into the joint 60% of the time. These data may be useful for surgeons who use the results of diagnostic biceps injections for diagnosis and surgical decision-making. Level of Evidence III, prospective cohort study, diagnosis

BackgroundPregnancy in women with type 1 diabetes mellitus (T1DM) is associated with an increased risk of congenital malformations, obstetric complications and neonatal morbidity. This study aims to investigate maternal, perinatal and neonatal outcomes of pregnancies in women with onset of T1DM less than 18 years of age.MethodsThis retrospective cohort study extracted data regarding prenatal, intrapartum and postnatal outcomes of pregnancies in women with onset of T1DMResultsSeventeen women with onset of T1DM ConclusionThe high prevalence of unplanned pregnancy and poor uptake of prepregnancy care must be improved on in order to improve outcomes for this high-risk group.

Background: Preeclampsia, preterm birth and low birth weight represent key contributing factors to perinatal morbidity and mortality. Pregnancies complicated by type 1 and type 2 diabetes are at increased risk of these complications, which are purported to be largely attributed to placental dysfunction. Studies investigating a potential role for aspirin therapy in optimizing perinatal outcome have consistently failed to demonstrate a benefit among women with pre-existing diabetes, and yet widespread aspirin administration has become common practice in many centres. This study seeks to examine the effect of aspirin therapy, administered from the first trimester until 36 weeks gestation, on perinatal outcome in women with established pre-pregnancy diabetes. Our hypothesis is that aspirin therapy will reduce complications mediated by placental dysfunction, and improve perinatal outcomes. Methods: This phase III double-blinded, placebo-controlled randomized clinical trial will be conducted in seven tertiary-level perinatology centres in Ireland. Consenting participants who meet all eligibility criteria will be allocated randomly to either aspirin 150 mg once daily or matching placebo, commenced between 11 + 0 and 13 + 6 weeks. Allocation will take place electronically using software by Clininfo with randomization tables provided by the trial biostatistician. The primary outcome will be a composite clinical measure of placental dysfunction (preeclampsia, preterm birth before 34 weeks, birthweight below the 10th centile or perinatal mortality). This trial has been set up such that it is parallel in design and is a superiority study. No participants have been recruited yet. The trial has been registered with Eudra Clinical Trials - EudraCT Number 2018-000770-29. Funding for this trial was granted by the Health research Board (HRB) 1/9/2017(DIFA-2017-026). Discussion: Aspirin therapy has been investigated for the prevention of preeclampsia owing to its reduction on thromboxane production. Previous studies have failed to demonstrate a beneficial effect of aspirin on perinatal outcome amongst women with type I or type II diabetes. It is plausible that the failure to observe benefit to date, among the limited aspirin studies that have included participants with diabetes, may be a consequence of aspirin initiation too late in pregnancy to exert any effect on placentation. We believe that if aspirin is to be used for the prevention of placental dysfunction, it must be initiated before the second active phase of trophoblast invasion, which takes place from 14 weeks’ gestation onwards. No randomized trials investigating the role of aspirin in prevention of preeclampsia in pregnancies complicated by diabetes have previously initiated treatment in the first trimester, the gestational period at which it is most likely to exert an effect on placentation. Keywords: Aspirin, Pregnancy, Diabetes, Pre-eclampsia

Intra-articular hip injections have proven clinical value for both diagnostic and therapeutic purposes. Historically, these injections have been performed by radiologists using fluoroscopic guidance. This necessitates a radiology referral, delays the injection, and represents lost productivity for the orthopedist. Ultrasound-guided intra-articular hip injections have been described in the radiology literature with excellent accuracy. These injections were performed by radiologists. The purpose of this study was to determine the accuracy of ultrasound-guided hip injections performed in the orthopedic clinic by orthopedic surgeons and orthopedic physician assistants. Fifty ultrasound-guided hip injections were performed using a standard technique. Contrast was included, and an anteroposterior pelvis radiograph was obtained immediately following injection. Diagnosis, body mass index, procedure time, and visual analog scale scores were recorded. Radiographs were reviewed independently by a musculoskeletal radiologist and an orthopedic surgeon to determine intra-articular placement of the injection. A total of 50 hips were injected. There was no identifiable contrast in 2 patients, leaving 48 hips for analysis. Of these, contrast was injected intra-articularly in 46 hips for an accuracy of 96%. Average procedural time was 2.6 minutes, and the average visual analog scale score was 1.9 during the procedure. Revenue value units ranged from 1.72–2.55 for ultrasound-guided hip injections. These findings indicate ultrasound-guided intra-articular hip injections performed in the orthopedic clinic by surgeons or physician assistants are accurate, efficient, and patient-friendly. Additionally, they preserve patient continuity and maintain productivity within the orthopedic clinic. [ Orthopedics. 2017; 40(2):96–100.]

Background Pregnancy in women with type 1 diabetes mellitus is associated with an increased risk of congenital malformations, obstetric complications, and neonatal morbidity. In order to minimise morbidity for both mothers and infants there needs to be good interdisciplinary care between diabetologists, obstetricians, neonatologists and relevant nursing specialists. Aim To investigate maternal, perinatal, and neonatal outcomes of pregnancies in women with type 1 diabetes in the University Maternity Hospital Limerick, Ireland. Methods This retrospective descriptive study was conducted from charts identified from the diabetes in pregnancy register from 1st July 2007 to 1st July 2017 at University Maternity Hospital Limerick. Results 17 women were identified from the register with juvenile onset ( Conclusion Neonates born to mothers with juvenile onset T1DM should be considered a high risk group and clinicians should have a low threshold for admission to the neonatal unit.

Importance There is a critical need for careful and independent validation of reported symptomatic efficacy and dopaminergic biomarker changes induced by nilotinib in Parkinson disease (PD). Objectives To assess safety and tolerability of nilotinib in participants with moderately advanced PD. Secondary and exploratory objectives were to assess its affect on PD disability, pharmacokinetics, cerebrospinal fluid (CSF) penetration, and biomarkers. Design, Setting, and Participants This was a 6-month, multicenter, randomized parallel-group, double-blind, placebo-controlled trial. Recruitment was from November 20, 2017, to December 28, 2018, and follow-up ended on September 9, 2019. The study was conducted at 25 US sites. The study approached 173 patients, of whom 48 declined, 125 were screened, and 76 who received a stable regimen of PD medications were enrolled (39% screen failure). Interventions Participants were randomized 1:1:1 to placebo, 150-mg nilotinib, or 300-mg nilotinib once daily orally for 6 months, followed by 2-month off-drug evaluation. Main Outcomes and Measures The primary outcomes were safety and tolerability. The tolerability end point was defined as the ability to complete the study while receiving the assigned dose. An active arm was considered tolerable if the percentage of participants meeting the tolerability end point for that group was not significantly lower than the percentage observed in the placebo group. Secondary outcomes included change in PD disability (Movement Disorder Society Unified Parkinson’s Disease Rating Scale [MDS-UPDRS], Part II OFF/ON). Exploratory outcomes included serum and CSF pharmacokinetic profile, and CSF dopaminergic biomarkers. Results At baseline, mean (SD) participants’ age was 64.6 (7.5) years, 52 were male (68%), mean (SD) disease duration was 9.9 years (4.7), MDS-UPDRS Part 1-3 OFF score was 66.4 (19.3), ON score was 48.4 (16.2), and Montreal Cognitive Assessment score was 27.1 (2.2). The number of participants who completed the study receiving the assigned dose were 21 (84%), 19 (76%), and 20 (77%) in the placebo, 150-mg, and 300-mg arms, respectively. Both active doses had acceptable safety profile. The most common reasons for drug suspension were asymptomatic, dose-dependent elevations of amylase, and/or lipase. Nilotinib, 150 mg and 300 mg, exhibited worse MDS-UPDRS-3 ON scores compared with placebo, achieving significance for nilotinib, 300 mg, at month 1 (P Conclusions and Relevance While we demonstrated acceptable safety and tolerability of nilotinib in our cohort, the low CSF exposure and lack of biomarkers effect combined with the efficacy data trending in the negative direction indicate that nilotinib should not be further tested in PD. Trial Registration ClinicalTrials.gov Identifier:NCT03205488

The obstetric management of women with inherited coagulation factor deficiencies may prove challenging. While some haemostatic parameters may increase in pregnancy (Factors VII, VIII, IX, X, XII, V...

Background: Arthroscopic hip surgery has risen 18-fold in the past decade; however, there is a dearth of clinical trials comparing surgery with nonoperative management. Purpose: To determine the comparative effectiveness of surgery and physical therapy for femoroacetabular impingement syndrome. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients were recruited from a large military hospital after referral to the orthopaedic surgery clinic and were eligible for surgery. Of 104 eligible patients, 80 elected to participate, and the majority were active-duty service members (91.3%). No patients withdrew because of adverse events. The authors randomly selected patients to undergo either arthroscopic hip surgery (surgery group) or physical therapy (rehabilitation group). Patients in the rehabilitation group began a 12-session supervised clinic program within 3 weeks, and patients in the surgery group were scheduled for the next available surgery at a mean of 4 months after enrollment. Patient-reported outcomes of pain, disability, and perception of improvement over a 2-year period were collected. The primary outcome was the Hip Outcome Score (HOS; range, 0-100 [lower scores indicating greater disability]; 2 subscales: activities of daily living and sport). Secondary measures included the International Hip Outcome Tool (iHOT-33), Global Rating of Change (GRC), and return to work at 2 years. The primary analysis was on patients within their original randomization group. Results: Statistically significant improvements were seen in both groups on the HOS and iHOT-33, but the mean difference was not significant between the groups at 2 years (HOS activities of daily living, 3.8 [95% CI, –6.0 to 13.6]; HOS sport, 1.8 [95% CI, –11.2 to 14.7]; iHOT-33, 6.3 [95% CI, –6.1 to 18.7]). The median GRC across all patients was that they “felt about the same” (GRC = 0). Two patients assigned to the surgery group did not undergo surgery, and 28 patients in the rehabilitation group ended up undergoing surgery. A sensitivity analysis of “actual surgery” to “no surgery” did not change the outcome. Twenty (33.3%) patients who underwent surgery and 4 (33.3%) who did not undergo surgery were medically separated from military service at 2 years. Conclusion: There was no significant difference between the groups at 2 years. Most patients perceived little to no change in status at 2 years, and one-third of military patients were not medically fit for duty at 2 years. Limitations include a single hospital, a single surgeon, and a high rate of crossover. Registration: NCT01993615 ( ClinicalTrials.gov identifier)

Background As the prevalence of hip pathology in the younger athletic population rises, the medical community continues to investigate effective intervention options. Femoracetabular impingement is the morphologically abnormal articulation of the femoral head against the acetabulum, and often implicated in pre-arthritic hip conditions of musculoskeletal nature. Arthroscopic surgical decompression and non-surgical rehabilitation programs focused on strengthening and stability are common interventions. However, they have never been directly compared in clinical trials. The primary purpose of this study will be to assess the difference in outcomes between these 2 commonly utilized interventions for femoracetabular impingement. Methods The study will be a single site, non-inferiority, randomized controlled trial comparing two different treatment approaches (surgical and nonsurgical) for FAI. The enrollment goal is for a total of 80 subjects with a diagnosis of Femoracetabular impingement that are surgical candidates and have failed 6 weeks of conservative treatment. This will be a convenience sample of consecutive patients that are Tricare beneficiaries and seeking care at Madigan Army Medical Center. Patients that meet the criteria will be screened, provide written consent before enrollment, and then randomized into one of two arms (Group I = hip arthroscopy, Group II = physical therapy). Group I will undergo hip arthroscopy with or without labral repair. Group II will follow an impairment based physical therapy program consisting of 2 sessions per week for 6 weeks. The primary outcome will be the Hip Outcome Score and secondary measures will include the International Hip Outcome Tool and the Global Rating of Change. Measures will be taken at baseline, 6 months, 1 and 2 years. Hip-related healthcare utilization between both groups will also be assessed at the end of 2 years. Discussion The current evidence to support both surgical and conservative interventions for femoroacetabular impingement is based on low-level research. To date, none of these interventions have been directly compared in a randomized clinical trial. Clinical trials are needed to help establish the value of these interventions in the management of femoracetabular impingement and to help define appropriate clinical pathways. Trial registration NCT01993615 30 October 2013. Electronic supplementary material The online version of this article (doi:10.1186/s12891-016-0914-1) contains supplementary material, which is available to authorized users.

Traumatic intrasubstance ruptures of the biceps brachii are rare and historically specific to military static line parachute jumps; however, these injuries have recently been reported in the civilian literature. Diagnosis is made by history, clinical weakness in supination and elbow flexion, extensive ecchymosis and edema, and a palpable defect. Ultrasound and magnetic resonance imaging are useful to confirm the diagnosis and injury severity. Nonoperative treatment involves splinting in acute flexion. Percutaneous hematoma aspiration has been described. Early surgical intervention with primary repair has been shown to be more successful than late reconstruction. Studies comparing operative and nonoperative treatment are lacking.

Background Non-invasive micro-ultrasound was evaluated as a method to quantify intrauterine growth phenotypes in mice. Improved methods are required to accelerate research using genetically-altered mice to investigate the interactive roles of genes and environments on embryonic and placental growth. We determined (1) feasible age ranges for measuring specific variables, (2) normative growth curves, (3) accuracy of ultrasound measurements in comparison with light microscopy, and (4) weight prediction equations using regression analysis for CD-1 mice and evaluated their accuracy when applied to other mouse strains. Methods We used 30–40 MHz ultrasound to quantify embryonic and placental morphometry in isoflurane-anesthetized pregnant CD-1 mice from embryonic day 7.5 (E7.5) to E18.5 (full-term), and for C57Bl/6J, B6CBAF1, and hIGFBP1 pregnant transgenic mice at E17.5. Results Gestational sac dimension provided the earliest measure of conceptus size. Sac dimension derived using regression analysis increased from 0.84 mm at E7.5 to 6.44 mm at E11.5 when it was discontinued. The earliest measurement of embryo size was crown-rump length (CRL) which increased from 1.88 mm at E8.5 to 16.22 mm at E16.5 after which it exceeded the field of view. From E10.5 to E18.5 (full term), progressive increases were observed in embryonic biparietal diameter (BPD) (0.79 mm to 7.55 mm at E18.5), abdominal circumference (AC) (4.91 mm to 26.56 mm), and eye lens diameter (0.20 mm to 0.93 mm). Ossified femur length was measureable from E15.5 (1.06 mm) and increased linearly to 2.23 mm at E18.5. In contrast, placental diameter (PD) and placental thickness (PT) increased from E10.5 to E14.5 then remained constant to term in accord with placental weight. Ultrasound and light microscopy measurements agreed with no significant bias and a discrepancy of less than 25%. Regression equations predicting gestational age from individual variables, and embryonic weight (BW) from CRL, BPD, and AC were obtained. The prediction equation BW = -0.757 + 0.0453 (CRL) + 0.0334 (AC) derived from CD-1 data predicted embryonic weights at E17.5 in three other strains of mice with a mean discrepancy of less than 16%. Conclusion Micro-ultrasound provides a feasible tool for in vivo morphometric quantification of embryonic and placental growth parameters in mice and for estimation of embryonic gestational age and/or body weight in utero.

Primitive mammalian neural stem cells (NSCs), arising during the earliest stages of embryogenesis, possess pluripotency in embryo chimera assays in contrast to definitive NSCs found in the adult. We hypothesized that adhesive differences determine the association of stem cells with embryonic cells in chimera assays and hence their ability to contribute to later tissues. We show that primitive NSCs and definitive NSCs possess adhesive differences, resulting from differential cadherin expression, that lead to a double dissociation in outcomes after introduction into the early- versus midgestation embryo. Primitive NSCs are able to sort with the cells of the inner cell mass and thus contribute to early embryogenesis, in contrast to definitive NSCs, which cannot. Conversely, primitive NSCs sort away from cells of the embryonic day 9.5 telencephalon and are unable to contribute to neural tissues at midembryogenesis, in contrast to definitive NSCs, which can. Overcoming these adhesive differences by E-cadherin overexpression allows some definitive NSCs to integrate into the inner cell mass but is insufficient to allow them to contribute to later development. These adhesive differences suggest an evolving compartmentalization in multipotent NSCs during development and serve to illustrate the importance of cell–cell association for revealing cellular contribution.

Background In utero microinjection has proven valuable for exploring the developmental consequences of altering gene expression, and for studying cell lineage or migration during the latter half of embryonic mouse development (from embryonic day 9.5 of gestation (E9.5)). In the current study, we use ultrasound guidance to accurately target microinjections in the conceptus at E6.5–E7.5, which is prior to cardiovascular or placental dependence. This method may be useful for determining the developmental effects of targeted genetic or cellular interventions at critical stages of placentation, gastrulation, axis formation, and neural tube closure. Results In 40 MHz ultrasound images at E6.5, the ectoplacental cone region and proamniotic cavity could be visualized. The ectoplacental cone region was successfully targeted with 13.8 nL of a fluorescent bead suspension with few or no beads off-target in 51% of concepti microinjected at E6.5 (28/55 injected). Seventy eight percent of the embryos survived 2 to 12 days post injection (93/119), 73% (41/56) survived to term of which 68% (38/56) survived and appeared normal one week after birth. At E7.5, the amniotic and exocoelomic cavities, and ectoplacental cone region were discernable. Our success at targeting with few or no beads off-target was 90% (36/40) for the ectoplacental cone region and 81% (35/43) for the exocoelomic cavity but tended to be less, 68% (34/50), for the smaller amniotic cavity. At E11.5, beads microinjected at E7.5 into the ectoplacental cone region were found in the placental spongiotrophoblast layer, those injected into the exocoelomic cavity were found on the surface or within the placental labyrinth, and those injected into the amniotic cavity were found on the surface or within the embryo. Following microinjection at E7.5, survival one week after birth was 60% (26/43) when the amniotic cavity was the target and 66% (19/29) when the target was the ectoplacental cone region. The survival rate was similar in sham experiments, 54% (33/61), for which procedures were identical but no microinjection was performed, suggesting that surgery and manipulation of the uterus were the main causes of embryonic death. Conclusion Ultrasound-guided microinjection into the ectoplacental cone region at E6.5 or E7.5 and the amniotic cavity at E7.5 was achieved with a 7 day postnatal survival of ≥60%. Target accuracy of these sites and of the exocoelomic cavity at E7.5 was ≥51%. We suggest that this approach may be useful for exploring gene function during early placental and embryonic development.

small foramen into left uterine cavity. Patient delivered a healthy baby by elective cesarean section at 34 wks. No constriction band was found in umbilical cord. A thick fibrous band was discovered in uterine cavity attaching from anterior wall to the posterior wall. Conclusions: Complete amniotic sheets may be associated with intrauterine death due to cord accident. Incomplete amniotic sheets with a small foramen can be benign, but close monitoring and appropriate obstetric management is important.

HOWARD BERGER, VANDANA CHADHA, JOHN SLEVIN, CRAIG PENNELL, OLENA BEREZOVSKA, P. SEAWARD, RORY WINDRIM, GREG RYAN, Mount Sinai Hospital, University of Toronto, Obstetrics and Gynecology, Toronto, Ontario, Canada, University of Western Australia, Women’s and Infants’ Health, Perth, Western Australia, Australia OBJECTIVE: Twin-to-twin transfusion syndrome (TTTS) occurs in approximately 15% of all monochorionic diamniotic (MC/DA) pregnancies. Correct diagnosis of chorionicity on early ultrasound scanning greatly facilitates the evaluation of suspected TTTS later in pregnancy. The objective of this study is to determine the accuracy of the referring diagnosis in relation to actual diagnosis at the time of laser treatment of TTTS. STUDY DESIGN: We performed a retrospective study of a cohort of 75 consecutive twin pairs that underwent selective laser ablation of placental anasomoses for treatment of TTTS between 1998-2004 at Mount Sinai Hospital, Toronto. Referring diagnosis and ultrasound assesment were compared to the preoperative ultrasound assesment and findings during laser coagulation. RESULTS: Mean gestational age at diagnosis of TTTS was 18.5 weeks. At the time of referral 73.3% had a correct diagnosis of chorionicity,of these, only 45% were correctly diagnosed in the first trimester. In 14.6% of cases, previous ultrasound examinations had been performed but had not commented on chorionicity. Misdiagnosed chorionicity was found in 12% of cases. In these nine cases, TTTS was misdiagnosed as either monoamniocity or twin discordancy.In one case two separate placentas were seen despite classic TTTS features. An anastomosing vessel noted on ultrasound was the clue to identifying a placental ‘‘bridge’’ whose presence was confirmed after laser therapy. CONCLUSION: Current data from the Eurofetus trial show that endoscopic laser coagulation is the treatment of choice for moderate-severe TTTS diagnosed before 26 weeks of gestation. Early assesment of chorionicity is critical in facilitating the diagnosis and staging of TTTS and will help prevent delays in recognition of a potentially treatable condition.Some pitfalls to making the correct diagnosis have been identified.

To the Editor.— I am not aware of any cases reported in the Englishlanguage literature of carbon monoxide (CO) poisoning producing rhabdomyolysis and myoglobinuria without signs of localized pressure necrosis. Many reports of CO poisoning, pressure necrosis, and subsequent myoglobinuria are, in fact, cases of overexposure to natural gas that contains no CO. The following case is of a man with myoglobinuria, but no pressure necrosis. Report of a Case.— Gas company officials who investigated the apartment of this patient at the time of the incident found several improperly connected appliances and dirty flues. (Incomplete combustion of natural gas commonly produces CO.) Neighbors, detecting a strong odor of natural gas, called the rescue squad, who found the patient unconscious. He was lying beside a second man who had typical cherry-red viscera at the time of autopsy. Therapy with oxygen was begun during the patient's trip to the hospital, but a