Citations

Background: The syndrome of thyrotoxicosis typically relies on radioactive iodine scans for establishing its etiology. Alternatively, the determination of thyrotropin (TSH) receptor antibodies (TRAbs) helps to distinguish Graves' disease (GD) from thyrotoxic thyroiditis. Current assays are impacted by limitations in sensitivity and/or turnaround time. Therefore, we decided to test a new assay for the detection of TSH receptor stimulating antibodies (TSAbs) and compare it with the clinically available assays. Methods: We enrolled 110 individuals in 5 cohorts: patients with incident or recurrent GD (cohort 1); patients with thyroiditis, painless or subacute (cohort 2); patients with Graves' orbitopathy/thyroid eye disease (TED) in cohort 3; patients with Hashimoto's thyroiditis (cohort 4), and a control group of normal volunteers (cohort 5). The patients were tested with the two clinically available assays: Roche Elecsys anti-TSHR assay (ROC-TBII) from Roche Diagnostics and Thyretain™ TSI Reporter BioAssay Kit (QUI-TSI) from Quidel. In addition, the samples were tested with the aequorin TSAb assay (OTS-TSI) provided by Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). The data were collected in a cross-sectional manner before initiation of therapy. Results: We had 36 cases of GD, 17 cases of thyroiditis, 27 cases of TED, 10 cases of Hashimoto's thyroiditis, and 20 normal volunteers. OTS-TSI had 100% sensitivity and specificity in distinguishing GD from thyroiditis, identical with QUI-TSI but superior to ROC-TBII (sensitivity 86% and specificity 94.1%). OTS-TSI had 93% sensitivity and 100% specificity for the diagnosis of TED, compared with normal controls. QUI-TSI and ROC-TBII performed similarly in this analysis, demonstrating 82% sensitivity and 100% specificity. The range of detectable values for OTS-TSI was 20–29,000 mIU/L and the turnaround time was ≤6 hours, without the need for cell culture equipment. Conclusions: OTS-TSI performed excellently, though similarly to QUI-TSI, for the differential diagnosis of GD vs. thyroiditis, while being superior in that respect to ROC-TBII. Furthermore, OTS-TSI has superior sensitivity to QUI-TSI and ROC-TBII for TED diagnosis, while retaining high specificity. It has a short turnaround time and avoids the need for cell culture and sterility. Larger studies in U.S. populations are needed for its validation.

OBJECTIVE Neurolymphomatosis (NL) is a rare manifestation of lymphoma confined to the peripheral nervous system that is poorly understood. It can be found in the cauda equina, but extraspinal disease can be underappreciated. The authors describe how extraspinal NL progresses to the cauda equina by perineural spread and the implications of this on timely and safe diagnostic options. METHODS The authors used the Mayo Clinic medical records database to find cases of cauda equina NL with sufficient imaging to characterize the lumbosacral plexus diagnosed from tissue biopsy. Demographics (sex, age), clinical data (initial symptoms, cerebrospinal fluid, evidence of CNS involvement, biopsy location, primary or secondary disease), and imaging findings were reviewed. RESULTS Ten patients met inclusion and exclusion criteria, and only 2 of 10 patients presented with cauda equina symptoms at the time of biopsy, with 1 patient undergoing a cauda equina biopsy. Eight patients were diagnosed with diffuse large B-cell lymphoma, 1 with low-grade B-cell lymphoma, and 1 with mantle cell lymphoma. Isolated spinal nerve involvement was identified in 5 of 10 cases, providing compelling evidence regarding the pathophysiology of NL. The conus medullaris was not radiologically involved in any case. Lumbosacral plexus MRI was able to identify extraspinal disease and offered diagnostically useful biopsy targets. FDG PET/CT was relatively insensitive for detecting disease in the cauda equina but was helpful in identifying extraspinal NL. CONCLUSIONS The authors propose that perineural spread of extraspinal NL to infiltrate the cauda equina occurs in two phases. 1) There is proximal and distal spread along a peripheral nerve, with eventual spread to anatomically connected nerves via junction and branch points. 2) The tumor cells enter the spinal canal through corresponding neural foramina and propagate along the spinal nerves composing the cauda equina. To diffusely infiltrate the cauda equina, a third phase occurs in which tumor cells can spread circumdurally to the opposite side of the spinal canal and enter contralateral nerve roots extending proximally and distally. This spread of disease can lead to diffuse bilateral spinal nerve disease without diffuse leptomeningeal spread. Recognition of this phasic mechanism can lead to identification of safer extraspinal biopsy targets that could allow for greater functional recovery after appropriate treatment.

SummaryWe report a comparative analysis of patients with therapy‐related acute lymphoblastic leukaemia (tr‐ALL) vs de novo ALL. We identified 331 patients with B‐ALL; 69 (21%) were classified as tr‐ALL. The most common prior malignancies were breast (23·2%) and plasma cell disorders (20·3%). Patients with tr‐ALL were older (median 63·2 vs. 46·2 years, P < 0.001), more often female (66·7% vs. 43·5%, P < 0·001), and more likely to have hypodiploid cytogenetics (18·8% vs. 5·0%, P < 0·001). In multivariable analysis, patients with tr‐ALL were less likely to achieve complete remission [odds ratio (OR) = 0·16, P < 0·001] and more likely to be minimal residual disease‐positive (OR = 4·86, P = 0·01) but had similar OS after diagnosis and allo‐haematopoietic cell transplantation.

Abstract The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P &lt; .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P &lt; .001) and grade 3 to 4 aGVHD (HR, 1.97; P &lt; .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

Background: Individuals with spinal cord injury (SCI) who use manual wheelchairs (MWCs) have a higher rate of rotator cuff pathology progression than able-bodied individuals. Objectives: This study aimed to test the ability of risk and recovery metrics of arm use to differentiate between (1) MWC users with SCI and matched able-bodied participants (cross-sectional matched-sample study) and (2) MWC users with rotator cuff pathology progression over 1 year from those without pathology progression (longitudinal study). Methods: Thirty-four MWC users and 34 age- and sex-matched able-bodied individuals were recruited. Upper arm risk (humeral elevation >60°) and recovery (static ≥5 seconds and humeral elevation <40°) metrics were calculated from wireless inertial measurement units (IMUs) worn on the upper arms and torso in the free-living environment. Two separate magnetic resonance imaging studies were completed and assessed for a subset of 16 MWC users approximately 1 year apart. Results: The frequency of risk events ( p = .019), summated duration of recovery events ( p = .025), and duration of each recovery event ( p = .003) were higher for MWC users than able-bodied participants. The summated duration of risk events ( p = .047), frequency of risk events ( p = .027), and risk to recovery ratio ( p = .02) were higher and the summated duration of recovery events ( p = .036) and frequency of recovery events ( p = .047) were lower for MWC users with rotator cuff pathology progression ( n = 5) compared to those without progression ( n = 11). Conclusion: IMU-derived metrics quantifying arm use at postures >60° and risk to recovery ratios may provide insights of potential risk factors for rotator cuff pathology progression.