Citations

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Objective The radiologically isolated syndrome (RIS) represents the earliest detectable pre‐clinical phase of multiple sclerosis (MS). This study evaluated the impact of therapeutic intervention in preventing first symptom manifestation at this stage in the disease spectrum. Methods We conducted a multi‐center, randomized, double‐blinded, placebo‐controlled study involving people with RIS. Individuals without clinical symptoms typical of MS but with incidental brain MRI anomalies consistent with central nervous system (CNS) demyelination were included. Within 12 MS centers in the United States, participants were randomly assigned 1:1 to oral dimethyl fumarate (DMF) 240 mg twice daily or placebo. The primary endpoint was the time to onset of clinical symptoms attributable to a CNS demyelinating event within a follow‐up period of 96 weeks. An intention‐to‐treat analysis was applied to all participating individuals in the primary and safety investigations. The study is registered at ClinicalTrials.gov , NCT02739542 (ARISE). Results Participants from 12 centers were recruited from March 9, 2016, to October 31, 2019, with 44 people randomized to dimethyl fumarate and 43 to placebo. Following DMF treatment, the risk of a first clinical demyelinating event during the 96‐week study period was highly reduced in the unadjusted Cox proportional‐hazards regression model (hazard ratio [HR] = 0.18, 95% confidence interval [CI] = 0.05–0.63, p = 0.007). More moderate adverse reactions were present in the DMF (34 [32%]) than placebo groups (19 [21%]) but severe events were similar (DMF, 3 [5%]; placebo, 4 [9%]). Interpretation This is the first randomized clinical trial demonstrating the benefit of a disease‐modifying therapy in preventing a first acute clinical event in people with RIS. ANN NEUROL 2023;93:604–614

Abstract Context Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. Objective (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. Methods (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. Results (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody–positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from –10.8% to –21.8% for TSH and –1.2% to –13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. Conclusion We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

Background: Iron-overload cardiomyopathy initially manifests with diastolic dysfunction and can progress to dilated cardiomyopathy if untreated. Previous studies have shown that patients with primary and secondary hemochromatosis can have subclinical left ventricle dysfunction with abnormalities on strain imaging. This study aimed to evaluate the relationship between cardiac T2* values and myocardial-wall strain in patients with hereditary hemochromatosis (HH) at the time of diagnosis and after a course of venesection treatment. Materials and Methods: Baseline cardiac magnetic resonance (CMR) at 3 T was performed in 19 patients with newly diagnosed HH with elevated serum ferritin levels and repeated after a course of treatment with venesection. Quantitative T2* mapping and strain analysis were performed offline using dedicated relaxometry fitting and feature-tracking software. Results: The majority (84%) of patients had normal baseline myocardial T2* values (mean 19.3 ms, range 8.9 to 31.2 ms), which improved significantly after venesection (mean 24.1 ms, range 11 to 38.1 ms) (P=0.021). Mean global radial strain significantly improved from 25.0 (range: 15.6 to 32.9) to 28.3 (range: 19.8 to 35.8) (P=0.001) and mean global circumferential strain improved, decreasing from −15.7 (range: −11.1 to −19.2) to −17.1 (range: −13.0 to −20.1) (P=0.001). Conclusion: Patients with HH may have normal T2* values in the presence of subclinical left ventricle dysfunction, which can be detected by abnormal radial and circumferential strain. As strain imaging improves following venesection in HH, it may serve as a useful biomarker to guide treatment.

Abstract Transtendinous abductor tendon repair is a technique the authors described previously to diagnose and treat undersurface tears of the abductor tendons. In this surgical technique article, the authors describe a technique for knotless repair of undersurface tears of the abductor tendons that does not require a transtendinous split or suture passage through the abductor tendon. Because there is no suture passage through the abductor tendon or knot tying, the potential advantages include expeditious technique, compression of tendon against bony footprint, anatomic repair, and avoidance of knots facing the undersurface of the iliotibial band, which may lead to bursal irritation. Technique Video video See video under supplementary data.

Objectives: To report the minimum two-year outcomes of trans-tendinous repairs of Partial Thickness Undersurface Tears of the Abductor (PUSTA) tendon using patient reported outcomes (PROs), visual analog scale (VAS), and patient satisfaction scores. Methods: All patients who underwent endoscopic trans-tendinous gluteus medius repair between October 2009 and May 2013 at one institution were prospectively evaluated. Exclusion criteria consisted of less than two-year follow-up, previous hip surgery, inflammatory arthritis, open surgery, full thickness abductor tear, and worker’s compensation patients. All patients had a documented pre-operative physical exam with strength testing (0-5) and observation of their gait. Patient satisfaction and PRO scores were recorded preoperatively, at 3 months postoperatively, and annually thereafter. The PRO scores collected were mHHS, HOS-ADL, HOS-SSS, NAHS, and VAS. Preoperative strength and gait were compared to latest follow-up. Results: There were 25 patients that fit our criteria. Significant improvement in PRO scores were demonstrated for mHHS, HOS-ADL, HOS-SSS, NAHS, and VAS from 54.9-76.2, 50.2-80.6, 30.1-67.3, 51.9-82.4, and 7.1-2.7 respectively (p<0.001). There were 11 patients with objective weakness prior to surgery; seven of these patients moved up at least one strength grade by final follow-up. There were 14 patients who had a Trendelenbrug gait pre-operatively, 12 of them had a normal gait at latest follow-up (p-<0.001). Average patient satisfaction was 7.5. There were no revision surgeries, and no complications noted. Conclusion: PUSTA lesions can be treated successfully with endoscopic trans-tendinous repair preserving the intact attachment of superficial fibers of the gluteus medius. We recommend this treatment for partial undersurface tears recalcitrant to non-operative treatment, as patients demonstrated clinical benefit at greater than 2 years follow up that exceeds substantial clinical benefit and minimally clinical important difference.

Purpose The purpose of this study is to identify radiographic risk factors (RRFs) and radiographic signs of abductor tendon tears. Methods Between April 2008 and October 2015, patients with intraoperative diagnosis of partial‐ or full‐thickness abductor tear noted at the time of open or endoscopic treatment were included in this study. Exclusion criteria included lack of preoperative standard supine pelvic radiograph, lack of preoperative magnetic resonance imaging (MRI), or abductor tear not present at the time of operative intervention. Patients were matched by age ±5 years, gender, and body mass index ±5 with patients with no abductor pathology by clinical exam and MRI. A standardized supine anterior‐posterior pelvis radiograph was performed on all patients. The radiographs were evaluated for RRF (pelvic width, body weight moment arm, abductor moment arm, abductor angle, pelvic height) and signs of abductor tendon pathology (greater trochanteric enthesophyte). Femoral version was measured on MRI when images were available. Statistical analysis was performed and included bivariate and multivariate analyses. Results There were 152 patients with abductor tears identified at the time of surgery out of 2,838 eligible patients matched with 125 patients without abductor tendon pathology. The study institution was unable to perform a 1:1 match because of the advanced age of the abductor tendon group, which led to a greater age in the abductor group ( n = 58) versus the control group ( n = 54; P = .01. In abductor group the average age was 58, and 137 of 152 (90%) patients were female; in the control group the average age was 54, with 111 of 125 (89%) patients being female. Abductor tear patients were treated with surgical repair. The RRFs found with bivariate analysis were an increased pelvic width (14.8 cm for abductor tears vs 14.3 cm for control; P < .001), body weight moment arm (11.1 cm vs 10.9 cm; P < .001), and abductor moment arm (7.8 cm vs 7.6 cm; P < .001); decreased femoral anteversion (7.6° vs 10.6°; P = .045); and enthesophyte presence (41% vs 3%; P < .001). Multivariate regression analysis of all variables showed that teardrop distance and enthesophyte presence were the 2 variables most predictive of abductor tears, and other variables did not significantly increase or decrease the likelihood of tear when these 2 variables were considered. The presence of an enthesophyte on the greater trochanter was notable for an odds ratio of 20.7 of having an abductor tear. Conclusions Patients with abductor tears have a wider pelvis, longer abductor moment arm, and longer body weight moment arm and have greater trochanteric enthesophyte as noted on nearly half of patients with an abductor tear. Presence of an enthesophyte was noted to have an odds ratio of 20.7 and a positive predictive value of 94% for having an abductor tendon tear. The 2 variables predictive of abductor tendon tear when controlling for all variables were enthesophyte presence and teardrop distance, with no other variables significantly increasing or decreasing the likelihood of tear when these 2 variables were considered. Level of Evidence Level III, retrospective comparative study.

Purpose The purpose of this study was to evaluate the greater than 2‐year patient‐reported outcomes (PROs) and patient satisfaction of patients who were treated with hip arthroscopy for snapping iliopsoas tendons that were painful with concomitant acetabular dysplasia and who underwent iliopsoas lengthening for symptomatic iliopsoas tendon snapping with concomitant capsular plication and treatment of hip impingement. Secondary measures included observation of the change in the Tönnis grade at greater than 2 years' follow‐up. Methods Between July 2009 and December 2011, data on patients with a lateral center‐edge angle (LCEA) of less than 25° (range, 19°‐24°) who underwent hip arthroscopy with central‐compartment iliopsoas fractional lengthening and capsular plication were prospectively collected and retrospectively reviewed. Interportal capsular repair was performed using between 2 and 5 simple sutures. Patients also underwent procedures to treat hip impingement pathology. All patients had preoperative and minimum 2‐year postoperative PRO measures: modified Harris Hip Score, Hip Outcome Score–Activities of Daily Living subscale, Hip Outcome Score–Sports‐Specific subscale, and Non‐arthritic Hip Score. The visual analog scale score and patient satisfaction with surgery (from 0 to 10) were also collected. Radiographs were analyzed preoperatively and at latest follow‐up to assess progression of the Tönnis grade. Results We analyzed 32 patients who met the inclusion criteria (30 female and 2 male patients; mean age, 25 years). The mean LCEA and anterior center‐edge angle were 21.6° and 25.5°, respectively. Four patients required revision arthroscopy for labral retears. Among the 28 patients who did not undergo revision surgery, the modified Harris Hip Score, Hip Outcome Score–Activities of Daily Living subscale, Hip Outcome Score–Sports‐Specific subscale, and Non‐arthritic Hip Score improved from 68.7 to 83.5, from 64.9 to 86.6, from 71.6 to 86.7, and from 52.6 to 75.8, respectively ( P < .001). The visual analog scale score improved from 5.6 preoperatively to 1.9 at latest follow‐up ( P < .001). The mean patient satisfaction rating was 8.0. There was no radiographic progression of the Tönnis grade at final follow‐up. Conclusions This study showed that patients with an LCEA of less than 25° and associated painful iliopsoas snapping can be treated by addressing concomitant pathology and performing central‐compartment fractional lengthening of the iliopsoas tendon with concomitant capsular plication and have high satisfaction, improvement in PROs, and improved pain scores, without significant progression of osteoarthritis. Level of Evidence Level IV, case series.