Citations

ABSTRACT. The clinical epidemiology of adults admitted with reduced level of consciousness (LOC) in sub-Saharan Africa (SSA) and the impact of HIV infection on the risk of mortality in this population is unknown. We secondarily analyzed data from a cohort study that enrolled 359 consecutive adults with reduced LOC presenting to Mbarara Regional Hospital in Uganda with the aim of comparing the prognostic utility of the Full Outline of Unresponsiveness (FOUR) score to the Glasgow Coma Scale (GCS) Score. For this analysis, we included 336 individuals with known HIV serostatus, obtaining clinical, laboratory, and follow-up data. We recorded investigations and treatments deemed critical by clinicians for patient care but were unavailable. We computed mortality rates and used logistic regression to determine predictors of 30-day mortality. The median GCS was 10. Persons living with HIV infection (PLWH) accounted for 97 of 336 (29%) of the cohort. The 30-day mortality rate in the total cohort was 148 of 329 (45%), and this was significantly higher in PLWH (57% versus 40%, adjusted odds ratio [aOR] 2.39: 95% confidence interval [CI]: 1.31–4.35, P = 0.0046). Other predictors of mortality were presence of any unmet clinical need (aOR 1.72; 95% CIL 1.04–2.84, P = 0.0346), anemia (aOR 1.68; 95% CI: 1.01–2.81, P = 0.047), and admission FOUR score < 12 [aOR 4.26; 95% CI: 2.36–7.7, P < 0.0001). Presentation with reduced LOC in Uganda is associated with high mortality rates, with worse outcomes in PLWH. Improvement of existing acute care services is likely to improve outcomes.

AbstractBackgroundAlthough parkinsonism is a core feature of Parkinson’s Disease Dementia (PDD) and Dementia with Lewy bodies (DLB), its evolution is less delineated. We aimed to assess differences in severity and progression of parkinsonian motor symptoms and signs in a community autopsy cohort with clinicopathologic diagnosis of DLB, PDD or Alzheimer’s Disease (AD).MethodData included were from 194 participants in the Arizona study of Aging and Neurodegenerative Disorders with clinicopathologic diagnosis of DLB (n=48), PDD (n=98) (±AD co‐pathology) or pure AD (n=48), and at least two movement exams performed by movement disorders subspecialists who classified PD and parkinsonism according to MDS‐UPDRS criteria. DLB was subgrouped by presence or absence of parkinsonism at final exam (DLB+Park and DLB–Park). Between group trajectory of UPDRS‐II and UPDRS‐III scores were explored using piecewise‐linear and non‐linear MMRM multivariate analysis.ResultOver 1435 participant‐years of longitudinal data were included in the analyses (Figure 1). Mean±SD age at baseline movement exam and death were 76.0±7.5 and 83.4±6.8 years, respectively. At baseline, most participants did not have dementia or substantial motor abnormalities (except motor abnormalities in PDD). DLB (73.9%) and PDD (69.2%) groups had more males than AD (33.3%). Parkinsonism was present in 65.6% of DLB at last exam. Piecewise‐linear MMRM analysis showed baseline UPDRS‐II and UPDRS‐III scores were highest (p<0.001) for PDD (mean±SE: 14.3±0.78 and 27.4±1.64), followed by DLB+Park (5.0±1.05 and 17.4±3.10), DLB‐Park (3.7±2.54 and 3.8±1.35) and AD (3.2±0.88 and 8.0±1.94). Annual rate of increase in UPDRS‐II was greatest for DLB+Park (1.44±0.20) and PDD (1.04±0.08), followed by DLB‐Park (0.89±0.18) and AD (0.30±0.11). Annual rate of increase in UPDRS‐III was highest for PDD and DLB+Park (2.12±0.20 vs 2.64±0.42), followed by DLB‐Park and AD (1.31 ± 0.38 and 0.64 ± 0.22). Preliminary non‐linear MMRM models (Figure 2) further supported substantial between group/subgroup differences in motor trajectories, and progression in DLB‐Park.ConclusionThese preliminary results in a large, well‐characterized clinicopathological community‐based autopsy cohort support that DLB+Park experience comparable, or greater, parkinsonian motor progression to PDD. Future modeling/sensitivity analyses will better delineate expected trajectories of motor progression to add prognostication value in clinic and design of DLB clinical trials.

Abstract Background Treating COVID-19 infection in SOT is challenging due to long-term use of immunosuppressive agents. REM is the only FDA-approved anti-viral for SARS-COV-2 infection. DEX showed decrease in mortality in the Recovery Trial. COVID-19 treatment guidelines for SOT patients are the same as NTP despite limited literature on those outcomes. Our primary objective was to determine if 30-day mortality was different between SOT and NTP matched cohorts using these 2 drugs. The secondary objectives included comparisons of length of stay (LOS), days on mechanical ventilation (DMV), and the use of other treatment modalities. Methods We retrospectively collected data for hospitalized SOT and NTP, 18 years and older, with pcr-confirmed SARS-CoV-2 infection receiving REM and DEX from May 1, 2020, to October 10, 2020, at Mayo Clinic Florida. IRB approval was obtained. Descriptive statistics were used to analyze the data. Continuous variables were summarized as mean (standard deviation) or median (range) where appropriate, while categorical variables were reported as frequency (percentage). Results Of 80 patients who met the inclusion criteria, 28 were SOT, and 52 were NTP. The SOT cohort was subcategorized below: SOT patients were significantly younger than NTP (p &lt; .001). Further, SOT patients had significantly longer LOS (p = 0.043) and more COVID-19 modalities (75% vs. 36.5%, p = 0.002) compared to NTP. Among the 28 SOT patients, 2 of them died within 30 days of admission, and among the 52 NTP patients, 7 of them died within 30 days. The 30-d survival estimate for SOT group is 92.9% (95% CI: 83.8% - 100.0%) and for NTP group is 86.5% (95% CI: 77.7% - 96.3%). The log-rank test was not significant between the groups (p=0.37), but the NTP has a worse survival curve from the figure below. SOT-NTP Survival Curve Conclusion SOT group was younger, had longer LOS, and more COVID-related modalities. The 30-d survival estimate for SOT group is 92.9% and for NTP group is 86.5%, but the survival curve for NTP was worse likely secondary to age. Use of REM & DEX in SOT recipients is a valid recommendation. Disclosures Claudia R. Libertin, MD, Gilead (Grant/Research Support)

ABSTRACT Background Nephrolithiasis in allograft kidneys is rare, but this diagnosis may lead to allograft complications and patient morbidity. Previous studies that have evaluated nephrolithiasis posttransplant have focused on surgical stone management, with limited data on urine metabolic risk factors and the presence of stones after follow-up. Methods We retrospectively evaluated kidney transplant recipients who were diagnosed with transplant nephrolithiasis between 2009 and 2019. Computed tomography and ultrasound imaging were used to confirm stone presence. Results The incidence of allograft kidney stone formation was 0.86% of 6548 kidney transplant recipients. Of the 56 cases identified, 17 (30%) had a pretransplant history of nephrolithiasis. Only four (7%) patients received a known kidney stone at the time of allograft implantation. Of the 56 cases, 34 had a 24-h supersaturation study. The urine supersaturation study showed 32 patients (94%) had a urine citrate of &lt;450 mg excreted in 24 h (median 124.5 mg/24 h, reference range &gt;500 mg/24 h), along with 22 patients (61%) having a urine oxalate excretion of ≥30 mg in 24 h (median 34.4 mg/24 h, reference range &lt;30 mg/24 h). Calcium oxalate composition was most common (91% with &gt;1 supersaturation for calcium oxalate crystals), with normal median urine calcium levels (median urine calcium 103.5 mg/24 h, reference range &lt;200 mg/24 h). After a 4-year follow-up, 50% (n = 28) required surgical intervention and 43 (77%) patients continued to have evidence of transplant nephrolithiasis on imaging. Conclusions This is the largest study of transplant nephrolithiasis confirming that hypocitraturia and hyperoxaluria were the most significant urine metabolic risk factors associated with allograft nephrolithiasis and that hyperoxaluria was the most prevalent driver for calcium oxalate stone composition. Our study is first to show low stone-free rates at the last follow-up and a significant proportion requiring surgical intervention.

Abstract Introduction: A test that detects cancer signal across multiple cancer types and predicts signal (tissue) origin (SO) could aid in more efficient diagnostic workup and shorten time to cancer diagnosis in individuals with signs and symptoms.Methods: The Circulating Cell-free Genome Atlas (CCGA; NCT02889978) study is a prospective, longitudinal, multicenter, case-control study to develop and validate a multi-cancer detection test. The 2nd CCGA substudy utilized a targeted methylation-based cell-free DNA assay and machine learning algorithm and included assessment of test performance (sensitivity and SO prediction accuracy) in a subgroup of participants with clinically presenting cancers (CPCs) that were undiagnosed prior to blood draw. Specificity was assessed in the noncancer group and subgroups with confounding (nonmalignant) conditions (CCs; eg, cirrhosis) and noncancer participants enrolled in hematology clinics (HCs).Results: Specificity was 99.5% (95% confidence interval: 98.2-99.9%; 396/398), 93.8% (71.7-99.7%; 15/16), and 99.3% (96.0-100.0%; 136/137) for the noncancer group, CCs subgroup, and HCs subgroup, respectively. Overall sensitivity among those with CPCs was 66.4% (62.2-70.3%; 344/518). Sensitivity of cancer signal detection increased with increasing clinical stage (Table). SO prediction accuracy was 91.7% (88.3-94.3%; 300/327) among CPC participants with cancers detected, excluding those with multiple or unknown primaries. The test demonstrated prognostic value as detected cancer participants had worse survival probability than those not detected. Conclusions: This multi-cancer detection test detected cancer signals and predicted SO in individuals with CPCs with high specificity. These findings support further clinical development of this multi-cancer detection test that could accelerate the diagnostic resolution of symptomatic cancers. Table. Sensitivity by Clinical Stage Across Cancer Type in Clinically Presenting CancersClinical StagePositive Test/Total Cancer; Sensitivity (95% CI)All*344/518; 66.4% (62.2-70.3%)I33/122; 27.0% (20.0-35.5%)II60/102; 58.8% (49.1-67.9%)III103/121; 85.1% (77.7-90.4%)IV136/147; 92.5% (87.1-95.8%)Not expected to be staged9/21; 42.9% (24.5-63.5%)Non-informative2/4; 50.0% (15.0-85.0%)CI, confidence interval.*One participant who had a positive test result had multiple primaries with clinical stage I and not-expected-to-be-staged. Citation Format: Alan H. Bryce, Minetta C. Liu, Michael V. Seiden, David D. Thiel, Donald Richards, Carlos Becerra, Kathryn N. Kurtzman, Xiaoji Chen, Tony Wu, Quan Zhang, Jingjing Gao, Nan Zhang, Earl Hubbell, Arash Jamshidi, Eric T. Fung, Eric A. Klein. Performance of a cell-free DNA-based multi-cancer detection test as a tool for diagnostic resolution of symptomatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB058.

Abstract Introduction Several independent studies report an alarming increase in patients younger than 40 being diagnosed with squamous cell carcinoma. There is currently a lack of available data clearly tracking changes in the age distribution of head and neck cancer (HNC) within the United States. This study attempts to elucidate any trends in oral cavity, oropharynx, larynx and hypopharynx cancer age distribution in the United States population from 1975 to 2016. Unlike previous studies, this paper does not track incidence but rather reports proportional changes of prevalence within age cohorts over time. Methods This is a retrospective chart review centred on data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Each decade interval from 1975 to 2016 displays the proportion of HNC patients, classified by primary tumour subsite, within each age cohort. Results Mean age at diagnosis increased for all subsites except oropharynx. Oropharyngeal cancer was the only subsite to show a decrease in the mean age at diagnosis. In addition, oropharyngeal cancer was the only subsite to demonstrate an overall increase in proportional prevalence, largely due to increased incidence in middle‐age (40–59 years) patients. Cancers of the oral cavity were the only subset to show a true increase in the proportion of young (0–39 years) patients, but its mean age at diagnosis still increased. When stratifying by gender, the proportion of young patients in female HNC cases is higher than the young male proportion. Conclusion Overall, this study demonstrates an increased proportion of older HNC patients that is consistent with the ageing population. Oral cavity cancer demonstrated a true increase in the proportion of young patients, likely due to the increased incidence of young women diagnosed with this cancer. Oropharyngeal cancer was the only subsite to show a decrease in the mean age at diagnosis. The increased proportion of middle‐age patients with oropharyngeal cancer likely reflects the increase in HPV‐related cancers.

AbstractBackgroundHyposmia is characteristic of idiopathic Parkinson's disease (PD) and dementia with Lewy bodies (DLBs), whereas progressive supranuclear palsy (PSP) typically has normal sense of smell. However, there is a lack of pathologically confirmed data.ObjectiveThe objective is to study hyposmia in pathologically confirmed PSP patients and compare to PD patients and nondegenerative controls.MethodsWe studied autopsied subjects in the Arizona Study of Aging and Neurodegenerative Disorders who had antemortem olfactory testing and a neuropathological diagnosis of either PD, PSP, or control.Results: This study included 281 cases. Those with neuropathologically confirmed PSP (N = 24) and controls (N = 174) had significantly better sense of smell than those with PD (N = 76). Although most PSP patients had normal olfaction, there were some with hyposmia, resulting in an overall reduced sense of smell in PSP compared to controls. The sensitivity of having PSP pathologically in those presenting with parkinsonism and normosmia was 93.4% with a specificity of 64.7%. Cases with both PSP and PD pathologically had reduced sense of smell similar to PD alone (N = 7). Hyposmic PSP patients had significantly higher Lewy body burden not meeting criteria for additional PD/DLB diagnosis.ConclusionsPathologically confirmed PD had reduced olfaction compared with PSP or controls. In the setting of parkinsonism in this sample, the presence of normosmia had high sensitivity for PSP. Hyposmia in PSP suggests the presence of additional Lewy body pathology. © 2021 International Parkinson and Movement Disorder Society