Citations

Linked ContentThis article is linked to Mahadev et al and Braude, Newnham papers. To view these articles visit https://doi.org/10.1111/apt.13988 and https://doi.org/10.1111/apt.14055.

ABSTRACT Background : PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective : We aimed to provide an evidence‐ and consensus‐based revision of the clinical diagnostic criteria for PSP. Methods : We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy‐confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2‐day meeting, and refined in three further Delphi rounds. Results : Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context‐dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions : Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence. © 2017 International Parkinson and Movement Disorder Society

Abstract The meniscal roots are critical in maintaining the normal shock absorbing function of the meniscus. If a meniscal root tear is left untreated, meniscal extrusion can occur rendering the meniscus nonfunctional resulting in degenerative arthritis. Two main repair techniques are described: (1) suture anchors (direct fixation) and (2) sutures pulled through a tibial tunnel (indirect fixation). Meniscal root repair using a suture anchor technique is technically challenging requiring a posterior portal and a curved suture passing device that can be difficult to manipulate within the knee. We present a technique for posterior medial meniscus root repair using 3 sutures (1 leader, 2 cinch), standard arthroscopy portals, and transtibial fixation. Overall, this technique simplifies a challenging procedure and allows for familiarity and efficiency. Technique Video video See video under supplementary data.

The detection and quantification of monoclonal‐proteins (M‐proteins) are necessary for the diagnosis and evaluation of response in plasma cell dyscrasias. Immunoglobulin enrichment‐coupled with matrix‐assisted laser desorption ionization time‐of‐flight mass‐spectrometry (MASS‐FIX) is a simple and inexpensive method to identify M‐proteins, but its clinical generalizability has not yet been elucidated. We compared MASS‐FIX to protein electrophoresis (PEL), serum/urine immunofixation‐electrophoresis (IFE), and quantitative serum free‐light chain (FLC) for the identification of M‐proteins in different clinical diagnoses. Paired serum and urine samples from 257 patients were tested. There were six patients for whom s‐IFE and FLC ratio were positive and serum MASS‐FIX was negative, but when serum and urine MASS‐FIX results were combined, only one patient with light chain‐MGUS was missed. Serum/urine‐MASS‐FIX detected M‐proteins in 18 patients with negative serum/urine‐PEL/IFE and serum‐FLC, 10 of whom had multiple myeloma or AL amyloidosis, who were mistakenly thought to have complete hematologic response by serum/urine‐PEL/IFE and serum‐FLC. Nearly half of the AL amyloidosis patients had atypical spectra, which may prove to be a clue to the diagnosis and pathogenesis of the disease. In conclusion, MASS‐FIX has a comparable sensitivity with PEL/IFE/FLC methods and can help inform the clinical diagnosis.

Background Patients with celiac disease (CD) are at increased risk of certain infections, but it is unknown if mucosal healing influences this risk. Methods We collected data on 29,096 individuals with CD (equal to villous atrophy) through Sweden’s 28 pathology departments undergoing biopsy 1969–2008. Through the Swedish Patient Register we obtained information on any infection and specifically sepsis, streptococcal infection, influenza, Clostridium difficile, herpes zoster and pneumococcal infection up until December 2009. We used Cox regression to calculate hazard ratios (HRs) for the risk of future diagnosis of infection according to mucosal healing on follow-up biopsy (persistent villous atrophy vs mucosal healing). Results Of 5598 CD individuals with no record of any infections before follow-up biopsy, 45% had persistent villous atrophy, 619 (24%) of them had a later infection, compared to 579 (19%) in those with mucosal healing ( p < 0.01); the yearly incidence was 2.1% in both groups. Adjusting for age, sex, calendar period, time between biopsies and education, persistent villous atrophy was however not associated with later infection overall (HR = 0.99; 95% CI = 0.88–1.11) or with any of the specific infections. Conclusions In CD, mucosal healing does not influence the risk of serious infection requiring hospital-based medical attention.

Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics for treating C9ORF72 -associated amyotrophic lateral sclerosis.

AbstractImmunoglobulin light chain (AL) amyloidosis is a fatal complication of B‐cell proliferation secondary to deposition of amyloid fibrils in various organs. Urinary exosomes (UEX) are the smallest of the microvesicles excreted in the urine. Previously, we found UEX of patients with AL amyloidosis contained immunoglobulin light chain (LC) oligomers that patients with multiple myeloma did not have. To further explore the role of the LC oligomers, UEX was isolated from an AL amyloidosis patient with progressive renal disease despite achieving a complete response. LC oligomers were identified. Mass spectrometry (MS) of the UEX and serum identified two monoclonal lambda LCs. Proteomics of the trypsin digested amyloid fragments in the kidney by laser microdissection and MS analysis identified a λ6 LC. The cDNA from plasma cell clone was from the IGLV‐ 6‐57 family and it matched the amino acid sequences of the amyloid peptides. The predicted mass of the peptide product of the cDNA matched the mass of one of the two LCs identified in the UEX and serum. UEX combined with MS were able to identify 2 monoclonal lambda LCs that current clinical methods could not. It also identified the amyloidogenic LC which holds potential for response assessment in the future.