Reinfection with SARS-CoV-2 and Waning Humoral Immunity: A Case Report.

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a different strain harboring the spike variant D614G. This case of reinfection was one of the first cases of reinfection reported in 2020. With antibody, B cell and T cell analytics, we show correlates of adaptive immunity at reinfection, including a differential response in neutralizing antibodies to a D614G pseudovirus. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report.

Recovery from COVID-19 is associated with production of anti-SARS-CoV-2 antibodies, but it is uncertain whether these confer immunity. We describe viral RNA shedding duration in hospitalized patients and identify patients with recurrent shedding. We sequenced viruses from two distinct episodes of symptomatic COVID-19 separated by 144 days in a single patient, to conclusively describe reinfection with a new strain harboring the spike variant D614G. With antibody and B cell analytics, we show correlates of adaptive immunity, including a differential response to D614G. Finally, we discuss implications for vaccine programs and begin to define benchmarks for protection against reinfection from SARS-CoV-2.

Outcomes of Arthroscopic All-Inside Repair Versus Observation in Older Patients With Meniscus Root Tears.

BACKGROUND: Meniscus root tears lead to de-tensioning of the meniscus, increased contact forces, and cartilage damage. Management of older patients with root tears is controversial and the efficacy of different treatment options is unclear. PURPOSE: To compare the clinical outcomes of patients with moderate knee osteoarthritis who underwent an all-inside meniscus root repair technique versus nonoperative management for either medial or lateral meniscus root tears. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Patients with a diagnosed posterior meniscus root tear who underwent arthroscopic repair (AR: 30 knees) or nonoperative treatment with observation (O: 18 knees) were followed for a minimum of 2 years (mean follow-up, 4.4 years). The arthroscopic repair included all-inside sutures to reduce the root back to its remnant (reduction sutures), thereby re-tensioning the meniscus, and 1 mattress suture to strengthen the repair by reapproximating the construct to the posterior capsule. The data collected included the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm, Tegner, and Veterans RAND 12-Item Health Survey (VR-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores and conversion to total knee arthroplasty (TKA). RESULTS: Medial meniscus root tears comprised 80.0% of the AR group and 77.8% of the O group. The average Kellgren-Lawrence grade was 2 in both groups. The baseline scores for the KOOS Symptoms subscale were lower for AR (50.2 ± 19.3) than for O (66.5 ± 16.1) (P = .003), as were the KOOS Knee-Related Quality of Life scores (AR, 26.7 ± 16.1; O, 39.6 ± 22.1) (P = .046). No differences were found between groups for the absolute values at follow-up except that follow-up Tegner scores were lower in the O group than in the AR group (P = .004). Significant improvements were seen in the AR group from baseline to ultimate follow-up in average KOOS subscale scores (P < .001), Lysholm scores (P < .001), Tegner scores (P = .0002), and VR-12 PCS scores (P < .001), whereas the O group had a significant improvement only in average KOOS Pain (P = .003), KOOS Function in Daily Living (P = .006), and VR-12 PCS (P = .038) scores. Compared with the O group, the AR group had a significantly larger improvement from baseline to follow-up in average KOOS Pain (P = .009), KOOS Symptoms (P = .029), and Lysholm scores (P = .016). During follow-up, 3.3% of the AR group underwent a TKA compared with 33.3% of the O group (P = .008). The hazard ratio of TKA conversion was 93.2% lower for the AR group compared with the O group (P = .013). CONCLUSION: All-inside medial or lateral meniscus root repair showed improved functional outcomes and decreased TKA conversion rates compared with nonoperative treatment and may be considered as a treatment option for the management of meniscus root tears in older patients with moderate osteoarthritis.

A Phase II Clinical Trial of an Aromatase Inhibitor for Postmenopausal Women with Lymphangioleiomyomatosis.

RATIONALE: Lymphangioleiomyomatosis (LAM) is a progressive cystic lung disease that predominantly affects women and can worsen with pregnancy, estrogen treatment, and the menstrual cycle, suggesting an important role for estrogen in disease pathogenesis. OBJECTIVES: To assess the efficacy and safety of the aromatase inhibitor letrozole in the treatment of LAM. METHODS: Seventeen postmenopausal women with LAM were enrolled in this phase II trial and randomized to receive letrozole 2.5 mg daily (n = 9) or placebo (n = 8) for a period of 12 months. Five patients in each group were also taking sirolimus at baseline and remained on the drug throughout the treatment period. Lung function, exercise capacity, quality of life, and serum vascular endothelial growth factor D (VEGF-D) were measured at baseline and at 3-month intervals. RESULTS: Fifteen patients completed the study. Two patients withdrew. There were no differences in adverse events in the letrozole and placebo groups. The target enrollment of 25 patients per arm was not met, so the efficacy of letrozole could not be assessed as planned. After adjusting for sirolimus use, we found that the rate of change in FEV1 for all subjects was -3 ± 3 ml/mo (P = 0.4), and for serum VEGF-D, the rate of change was -0.024 ± 0.009 pg/ml/mo (P = 0.015), showing a steeper decline in the letrozole group (-0.029 ± 0.013; P = 0.025). All patients who were taking sirolimus had a reduction in VEGF-D levels from baseline to the last visit, compared with only half of the patients who were not taking sirolimus. In a post hoc analysis, eight matched letrozole-treated-placebo-treated pairs were constructed, six of which demonstrated better FEV1 improvement for the letrozole-treated patients. CONCLUSIONS: Letrozole treatment appears to be safe and well tolerated in postmenopausal patients with LAM, including those taking sirolimus. Enrollment in this trial was compromised by the publication of an effective treatment (sirolimus) in the same month as the study opened, resulting in limited power to detect treatment effects. Post hoc matched pairs exploration studies provide tentative support for additional studies of letrozole in LAM. Considering the reduced rate of lung function decline in postmenopausal patients, future studies will likely require enhanced study designs, such as selective enrollment of those with prognostic biomarkers predictive of decline. Clinical trial registered with www.clinicaltrials.gov (NCT01353209).

Magnetic Resonance Imaging of Asymptomatic Knees in Collegiate Basketball Players: The Effect of One Season of Play.

OBJECTIVE: To determine the prevalence of abnormal structural findings using 3.0-T magnetic resonance imaging (MRI) in the asymptomatic knees of male and female collegiate basketball players before and after a season of high-intensity basketball. DESIGN: Institutional review board-approved prospective case series. PARTICIPANTS: Asymptomatic knees of 24 NCAA Division I collegiate basketball players (12 male, 12 female) were imaged using a 3.0-T MRI scanner before and after the end of the competitive season. Three subjects did not undergo scanning after the season. MAIN OUTCOME MEASURES: Images were evaluated for prepatellar bursitis, fat pad edema, patellar and quadriceps tendinopathy, bone marrow edema, and articular cartilage and meniscal injury. RESULTS: Every knee imaged had at least 1 structural abnormality both preseason and postseason. A high preseason and postseason prevalence of fat pad edema (75% and 81%), patellar tendinopathy (83% and 90%), and quadriceps tendinopathy (75% and 90%) was seen. Intrameniscal signal change was observed in 50% preseason knees and 62% of postseason knees, but no discrete tears were found. Bone marrow edema was seen in 75% and 86% of knees in the preseason and postseason, respectively. Cartilage findings were observed in 71% and 81% of knees in the preseason and postseason, respectively. The cartilage injury score increased significantly in the postseason compared with the preseason (P = 0.0009). CONCLUSIONS: A high prevalence of abnormal knee MRI findings was observed in a population of asymptomatic young elite athletes. These preliminary data suggest that high-intensity basketball may have potentially deleterious effects on articular cartilage.

Abduction and external rotation in shoulder impingement: an open MR study on healthy volunteers initial experience.

PURPOSE: To prospectively evaluate rotator cuff contact with the glenoid in healthy volunteers placed in the unloaded and loaded abduction and external rotation (ABER) positions in an open magnetic resonance (MR) imager. MATERIALS AND METHODS: The study was institutional review board approved and HIPAA compliant, and informed consent was received. Eight male volunteers with no history of shoulder pain or pathology were imaged in a 0.5-T open MR imager. Volunteers were imaged in an unloaded ABER position with the arm at 90 degrees abduction and in a loaded ABER position, with a 1-kg load that produced an average external rotation of 111 degrees+/-6 (standard deviation). Two radiologists graded rotator cuff contact on a three-point scale. Three-dimensional anatomic models generated from the MR images were used to measure distances. Minimum distances were computed between the tendon insertion sites and the glenoid, acromion, and coracoid for the loaded ABER position. Minimum distances were compared by using a paired Student t test. RESULTS: In the unloaded ABER position, contact was seen between the infraspinatus and supraspinatus tendons and the glenoid in all eight volunteers. In the loaded ABER position, contact was also observed between the infraspinatus and supraspinatus and the posterior and posterosuperior glenoid, respectively. Deformation of the infraspinatus on the glenoid was seen in four volunteers, whereas supraspinatus deformation was only seen in one volunteer. The minimum distance between the supraspinatus insertion and acromion in the loaded ABER position decreased significantly (P<.01). Supraspinatus tendon to glenoid and infraspinatus tendon to glenoid minimum distances also decreased significantly (P<.01). CONCLUSION: The unloaded and loaded ABER positions resulted in contact of the supraspinatus and infraspinatus with the glenoid in all volunteers. Distances between the rotator cuff insertion sites and the glenoid decreased in the loaded ABER position.

In vivo anatomy of the Neer and Hawkins sign positions for shoulder impingement.

The Neer and Hawkins impingement signs are commonly used to diagnose subacromial pathology, but the anatomy of these maneuvers has not been well elucidated in vivo. This 3-dimensional open magnetic resonance imaging study characterized shoulder anatomy and rotator cuff impingement in 8 normal volunteers placed in the Neer and Hawkins positions. Subacromial and intraarticular contact of the rotator cuff was graded, and minimum distances were computed between the tendon insertion sites and the glenoid, acromion, and coracoid. Both the Neer and Hawkins maneuvers significantly decreased the distance from the supraspinatus insertion to the acromion and posterior glenoid and from the subscapularis insertion to the anterior glenoid. However, the Hawkins position resulted in significantly greater subacromial space narrowing and subacromial rotator cuff contact than the Neer position. In the Hawkins position, subacromial contact of the supraspinatus and infraspinatus was observed in 7 of 8 and 5 of 8 subjects, respectively. In contrast, rotator cuff contact with the acromion did not occur in any subject in the Neer position. Intraarticular contact of the supraspinatus with the posterosuperior glenoid was observed in all subjects in both positions. Subscapularis contact with the anterior glenoid was also seen in 7 of 8 subjects in the Neer position and in all subjects in the Hawkins position. This extensive intraarticular contact suggests that internal impingement may play a role in the Neer and Hawkins signs.

Cine phase-contrast magnetic resonance imaging as a tool for quantification of skeletal muscle motion.

In recent years, biomechanics researchers have increasingly used dynamic magnetic resonance imaging techniques, such as cine phase contrast (cine PC), to study muscle and bone motion in vivo. Magnetic resonance imaging provides a non-invasive tool to visualize the anatomy and measure musculoskeletal tissue velocities during joint motion. Current application of cine PC magnetic resonance imaging in biomechanics includes study of knee joint kinematics, tendon strain, and skeletal muscle displacement and shortening. This paper article reviews the use of cine PC magnetic resonance imaging for quantification of skeletal muscle motion. The imaging studies presented examine the relative motion of the knee flexor and extensor muscles after orthopedic surgery and examine the uniformity of shortening within the biceps brachii muscle. The current challenges and limitations of using cine PC magnetic resonance imaging in biomechanics research are addressed as well as opportunities for future studies of skeletal muscle motion using dynamic magnetic resonance imaging.

Nonuniform shortening in the biceps brachii during elbow flexion.

This study tested the common assumption that skeletal muscle shortens uniformly in the direction of its fascicles during low-load contraction. Cine phase contrast magnetic resonance imaging was used to characterize shortening of the biceps brachii muscle in 12 subjects during repeated elbow flexion against 5 and 15% maximum voluntary contraction (MVC) loads. Mean shortening was relatively constant along the anterior boundary of the muscle and averaged 21% for both loading conditions. In contrast, mean shortening was nonuniform along the centerline of the muscle during active elbow flexion. Centerline shortening in the distal region of the biceps brachii (7.3% for 5% MVC and 3.7% for 15% MVC) was significantly less (P < 0.001) than shortening in the muscle midportion (26.3% for 5% MVC and 28.2% for 15% MVC). Nonuniform shortening along the centerline was likely due to the presence of an internal aponeurosis that spanned the distal third of the longitudinal axis of the biceps brachii. However, muscle shortening was also nonuniform proximal to the centerline aponeurosis. Because muscle fascicles follow the anterior contour and centerline of the biceps brachii, our results suggest that shortening is uniform along anterior muscle fascicles and nonuniform along centerline fascicles.