Citations

8009 Background: Measuring response among patients with multiple myeloma is essential for the care of patients. Deeper responses have been associated with better progression free survival (PFS) and overall survival (OS). Serum (SIFE) and urine immunofixation are the currently used markers for biochemical documentation of CR after which marrow is tested for plasma cell clearance. Next generation flow cytometry and sequencing are used to document the presence of minimal residual disease (MRD). Mass spectrometry of blood by MALDI (Mass-Fix) is a new simple, inexpensive, sensitive, and specific means of detecting monoclonal immunoglobulins. To better test the hypothesis that Mass-Fix is superior to existing methodologies to predict for survival outcomes—especially SIFE-- samples from the STAMINA trial (NCT01109004), a trial comparing 3 transplant approaches among patients who have already received induction, were employed. Methods: Five-hundred and seventy-five patients were included. Samples from enrollment post-induction (post-I) and 1-year post enrollment (1YR) were tested when available. Four response parameters were assessed univariately: Mass-Fix, SIFE, complete response, and MRD by next generation flow cytometry. Mass spectrometry spectra were evaluated in a blinded fashion. Complete response was according to the 2006 International Myeloma Working Group criteria. Multivariate Cox proportional hazard models using stepwise regression were developed to explore the independent effect of the different response parameters on PFS and OS and interactions with other risk factors. Results: Of the 4 response measures, only MRD and Mass-Fix predicted for PFS and OS at multiple testing points on multivariate analyses (Table). Of the 4 post-I measurements, only MRD predicted for PFS; however, Mass-Fix was the only post-I measurement to predict for OS. Of all the 1-year measures, both 1YR Mass-Fix and 1YR MRD positivity predicted for inferior PFS and OS. In models including MRD and Mass-Fix, SIFE and CR were not prognostic for PFS or OS. Conclusions: Mass-Fix is a powerful means to track monoclonal proteins. The full utility of Mass-Fix was not exploited given the absence of a diagnostic sample and the fact that only serum (and not urine) was tested. Despite these limitations, it performed well at pre-induction and at 1 year. Mass-Fix provides a convenient and non-invasive means of predicting for myeloma outcomes. Clinical trial information: NCT01109004. [Table: see text]

AbstractPatients with early‐onset Alzheimer's disease (EOAD) are commonly excluded from large‐scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial‐ready network. LEADS will follow 400 amyloid beta (Aβ)‐positive EOAD, 200 Aβ‐negative EOnonAD that meet National Institute on Aging–Alzheimer's Association (NIA‐AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age‐matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18F]Florbetaben and [18F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post‐mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.

H. pylori is the most common infection in the world and is associated with gastrointestinal and extra-gastrointestinal manifestations, including peptic ulcer disease, gastrointestinal bleeding, and lymphoproliferative disorders. Despite being discovered less than half a century ago, antibiotic resistance, exacerbated by medication non-adherence and inefficacy of proton pump inhibitors, has grown substantially, explaining the rising incidence of refractory H. pylori infection. In this review, we discuss risk factors, treatment options, surveillance and follow-up, as well as emerging therapies for refractory H. pylori.

Abstract Patients with immunoglobulin M (IgM) light chain (AL) amyloidosis have a distinct clinical presentation compared with those with non-IgM amyloidosis. We hypothesized that differential immunoglobulin light-chain variable region (IGVL) gene usage may explain the differences in organ involvement, because IGVL usage correlates with organ tropism. IGVL usage was evaluated by mass spectrometry of amyloid deposits (IgM, n = 45; non-IgM, n = 391) and differed across the 2 groups. In the λ family, LV2-08 (13% vs 2%; P < .001) and LV2-14 (36% vs 10%; P < .001) usage was more common in IgM vs non-IgM amyloidosis, whereas LV1-44 (0% vs 10%; P = .02) and LV6-57 (2% vs 18%; P = .004) usage was less common. In the κ family, there was a trend toward higher KV4-01 (11% vs 4%; P = .06) usage in IgM amyloidosis. IGVL usage correlated with disease characteristics/organ tropism. LV2-14 (more common in IgM amyloidosis) has historically been associated with peripheral nerve involvement and lower light chain burden, which were more frequent in IgM amyloidosis. LV1-44 (less common in IgM), associated with cardiac involvement, was less frequent in IgM patients. LV6-57 (less common in IgM) is associated with t(11;14), which was less frequent in IgM patients. In conclusion, IGVL gene usage differs in patients with IgM vs non-IgM amyloidosis and may explain the distinct clinical presentation.

Abstract: The COVID-19 crisis has challenged the U.S. health-care system in a variety of ways, including how we teach and train orthopaedic surgery residents and fellows. During the spring of 2020, the cessation of all elective surgical procedures and the diminished number of outpatient visits challenged graduate medical education. While residency programs in less affected areas may not have had to make many dramatic adjustments, some of those located in pandemic hotspots had to redirect trainees from orthopaedic rotations to COVID-19 units. No matter the region, the time that trainees have spent in rotations has been altered, and absences have occurred due to quarantines. This symposium summarizes the impact of restrictions related to the COVID-19 pandemic on residency and fellowship programs from the perspectives of the Accreditation Council for Graduate Medical Education (ACGME), a program director, and a graduating resident. Although new opportunities for virtual curricula, virtual surgical simulation, and virtual interviews have been innovated, residency programs and residents report primarily a negative effect from the pandemic due to decreased surgical volumes and the limitation of patient-care experiences. Ultimately, program directors have an obligation to the program, the trainee, and the general public to graduate only those residents and fellows who are truly prepared to practice independently; they have the responsibility of making the final decision regarding graduation. The COVID-19 pandemic has continued to underscore the need for competency-based medical education. Assessing competency includes evaluation of the knowledge, the operative skills, the nonoperative patient-care skills, and the professional behavior of each and every individual graduating from orthopaedic residency and fellowship training programs. A hybrid model for time and competency-based training, with established national standards not only for accreditation for our training programs but also for board certification of our graduating residents, was enhanced by the COVID-19 pandemic and is highlighted in this symposium.

Objective: To report the injury characteristics, radiographic findings, and long-term outcomes of nonoperative management for posterior shoulder instability (PSI). Design: A retrospective review of 143 patients with PSI using a large geographic database. Setting: Single county between January 1994 and July 2012. Patients: A clinical history and diagnosis of PSI, one confirmatory imaging study to support the diagnosis, and a minimum of 5 years follow-up were required for inclusion. Patients with seizure disorders, anterior-only instability, multidirectional instability, and superior labrum from anterior to posterior diagnosis were excluded. Interventions: Patients with PSI were managed nonoperatively or operatively. Main Outcome Measures: Pain, recurrent instability, and progression into glenohumeral osteoarthritis at long-term follow-up. Results: One hundred fifteen patients were identified. Thirty-seven (32%) underwent nonoperative management. Twenty (54%) patients were diagnosed with posterior subluxation, 3 (8%) with a single dislocation, and 7 (19%) with multiple dislocations. Symptomatic progression of glenohumeral arthritis was observed in 8% (3) of patients. Pain improved in 46% (17) of patients and worsened in 19% (7). Recurrent instability and progression to osteoarthritis occurred in 15% (3/20) of patients with a traumatic instability event compared with 0% of atraumatic patients after nonoperative management ( P = 0.234). Pain at follow-up was more common in nonoperative than operative patients ( P = 0.017). Conclusions: Nonoperative management is a viable option for many patients with posterior shoulder instability; however, many may continue to have posterior shoulder pain.

AbstractNeurofibrillary tangles, one of the neuropathologic hallmarks of Alzheimer's disease, have a dynamic lifespan of maturity that associates with progressive neuronal dysfunction and cognitive deficits. As neurofibrillary tangles mature, the biology of the neuron undergoes extensive changes that may impact biomarker recognition and therapeutic targeting. Neurofibrillary tangle maturity encompasses three levels: pretangles, mature tangles, and ghost tangles. In this review, we detail distinct and overlapping characteristics observed in the human brain regarding morphologic changes the neuron undergoes, conversion from intracellular to extracellular space, tau immunostaining patterns, and tau isoform expression changes across the lifespan of the neurofibrillary tangle. Post‐translational modifications of tau such as phosphorylation, ubiquitination, conformational events, and truncations are discussed to contextualize tau immunostaining patterns. We summarize accumulated and emerging knowledge of neurofibrillary tangle maturity, discuss the current tools used to interpret the dynamic nature in the postmortem brain, and consider implications for cognitive dysfunction and tau biomarkers.