Comparison of CT Volumetry versus Nuclear Renography for Predicting Remaining Kidney Function After Uninephrectomy in Living Kidney Donors

Computed tomography (CT) and nuclear renography are used to determine kidney procurement in living kidney donors (LKDs). The present study investigated which modality better predicts kidney function after donation. This study included 835 LKDs and they were divided into two subgroups based on whether the left-right dominance of kidney volume was concordant with kidney function (concordant group) or not (discordant group). The predictive value for post-donation kidney function between the two imaging modalities was compared at 1 month, 6 months, and > 1 year in total cohort, concordant, and discordant groups. Split kidney function (SKF) measured by both modalities showed significant correlation with each other at baseline. SKFs of remaining kidney measured using both modalities before donation showed significant correlation with eGFR (estimated glomerular filtration rate) after donation in the total cohort group and two subgroups, respectively. CT volumetry was superior to nuclear renography for predicting post-donation kidney function in the total cohort group and both subgroups. In the discordant subgroup, a higher tendency of kidney function recovery was observed when kidney procurement was determined based on CT volumetry. In conclusion, CT volumetry is preferred when determining procurement strategy especially when discordance is found between the two imaging modalities.

From the other perspective: Behavioural factors associated with UK sheep farmers’ attitudes towards antibiotic use and antibiotic resistance

Research suggests that many sheep farmers continue to carry out traditional antibiotic use practices despite new ’good practice’ recommendations. The aim of this study was to group farmers depending on their attitudes around antibiotic use and antibiotic resistance, and determine the behaviours that are associated with the farmers in these groups. In 2017, a flock health survey was sent to British sheep farmers. K-means cluster analysis was used to identify groups of farmers with similar attitudes towards antibiotic use and resistance. A multivariable logistic regression model was built to determine the associations between farmers’ past behaviours and their antibiotic attitude group. There were 461 responses. Two groups of farmers were identified based on their antibiotic attitudes. Cluster 1 were defined as the "discordant" group who had positive views of using antibiotics prophylactically and negative views of reducing antibiotic use. Cluster 2 were defined as the "concordant" group who were positive about reducing antibiotic use and had negative views about using antibiotics prophylactically. Using antibiotics in all lambs (OR = 2.689, CI = 1.571, 4.603), using antibiotics in all ewes (OR = 3.388, CI = 1.318, 8.706), always trimming diseased feet over the past three years (OR = 2.487, CI = 1.459, 4.238), not using a computer to record information over the past three years (OR = 1.996, CI = 1.179, 3.381), not changing worming practices over the past three years (OR = 1.879, CI = 1.144, 3.087), and farmers’ perceptions that their sheep flock did not make a financial loss in the past three years (OR = 2.088, CI = 1.079, 4.040) were significantly associated with belonging to the discordant group. Talking to their veterinarian about antibiotic use or the frequency of veterinary visits were not associated with antibiotic attitude group. These results suggest that farmers who had attitudes relating to antibiotic use that did not align with current recommendations carried out more traditional practices, which were strengthened by their positive perceptions of profitability.

Real-world concordance between tumor mutational burden (TMB) from blood (circulating tumor DNA) and tissue in lung cancer.

e20522 Background: Tumor mutational burden (TMB) level is associated with response to immunotherapy in lung cancer. However, tissue TMB can be difficult to obtain, as tissue samples obtained from biopsies may be insufficient. Circulating tumor DNA-based TMB has been developed in order to complement or replace tissue TMB, but there is limited real-world data on their concordance. Here, we investigate the landscape and concordance between blood and tissue TMB, along with clinical traits of the concordant and discordant groups. Methods: Tumor mutational burden (TMB) was calculated using Tempus (tissue) and Guardant Health (blood) next generation sequencing (NGS) platforms from October 2020 to January 2021. There were 33 patients who had both Tempus and Guardant TMB data. Under the assumption that tissue TMB (tTMB) correlates with blood TMB (bTMB) at a ratio of 1:1.6, the patients were divided into concordant and discordant groups. The concordant group patients had bTMB/tTMB ratios between 1.3 and 1.9. The discordant group was divided into two subgroups: over 1.9 (Group B) and less than 1.3 (Group C). Among the 33 patients, 9 patients were excluded due to their non-evaluable bTMB levels. Treatment response was evaluated using RECIST criteria. Results: Of the remaining 24 patients, 7 patients in the concordant group and 21 patients in the discordant group were analyzed according to their clinical manifestations [Blood TMB (n = 24): range [1.46, 44.01], median = 9.57], [Tissue TMB (n = 24), range [1.3, 18.4], median = 4.5]. We compared the clinical presentations (number of metastatic organs and metastatic sites) between the two discordant groups (Groups B and C). Among the 24 patients, 13% (n = 3) had small cell lung cancer, 50% (n = 12) had adenocarcinoma, and 29% (n = 7) had squamous cell lung carcinoma. Patients with higher bTMB than tTMB (Group B) had more squamous cell carcinoma cases (71%, n = 5) compared to remaining groups (Groups A and C) (29%, n = 2). Among the discordant group, 6% of the patients (n = 1) had small cell lung cancer, 47% (n = 8) had adenocarcinoma, and 35% (n = 6) had squamous cell carcinoma. Further, 58% (n = 14) of the patients had higher bTMB than tTMB levels. Among the concordant and discordant groups, tumor burden as reflected by the number of metastatic sites and metastatic lesions and the sum of the largest diameters of tumor lesions using RECIST had no significant difference (p = 0.10, 0.68, 0.54, respectively). The concordant and discordant groups showed no significant difference in objective response (33% vs. 20%, p = 0.60) or clinical benefit rate (100% vs. 60%, p = 0.33). Conclusions: The majority of the patients had higher blood TMB than tissue TMB (Group A), with a concordance rate as low as 28%. Further studies are warranted to understand the biology behind the difference between blood and tissue TMB, including intertumoral heterogeneity.

Correlation of COVID-19 antigen test and CBNAAT results at a single tertiary care hospital in North India: an experience

Background: Nucleic acid amplification test (NAAT) is considered gold standard in the molecular diagnosis of CoV-2 infection but since it is costly, labor intensive and needs technical expertise, rapid chromatographic immunoassay for the qualitative detection of specific antigens to SARS CoV-2 have been devised. Objectives of this study was to compare the results of Antigen test and NAAT for CoV-2 infection carried out during the months of July and August 2020 by single tertiary care hospital in Lucknow, Uttar Pradesh and to determine the utility of rapid antigen test in the SARS CoV-2 diagnosis.Methods: All the patients who came to our hospital seeking admission during July 2020 and August 2020 were included in the study. A total of 1000 patients were included in this study.Results: Out of a total 1000 cases which were included in the study, 769 cases (76.9%) were found to be SARS CoV-2 negative by both antigen and CBNAAT, 100 cases (10.0%) were SARS CoV-2 positive by both antigen and CBNAAT tests. But in 131 cases (13.1%), antigen was not able to pick up the disease. It was also found that the Cycle Threshold (Ct) value for the discordant group was higher (Mean E= 28, Mean N2=33) when compared to the group where antigen was positive.Conclusions: The present study establishes the role of rapid antigen tests in contributing to the quick, point of care diagnosis of SARS CoV-2. These assays are safe, simple, and fast and can be used in local clinics and hospitals. These tests are very important for real-time patient management and infection control decision.

Association of AID and MUM1 by Immunohistochemistry in Diffuse Large B-Cell Lymphoma

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with dysregulation of somatic hypermutation (SHM) and class switch recombination (CSR) have been known to contribute for its lymphomagenesis. Activation-induced cytidine deaminase (AID) enzyme plays a vital role for both processes. Multiple myeloma oncogene 1 (MUM1) is known to upregulate the AID expression in normal and pathological conditions. However, both AID and MUM1 expression association in DLBCL is still unexplored using immunohistochemistry method. We examined DLBCL samples and then retrospectively tested its correlation with clinical findings.METHODS: A retrospective cohort study with 20 cases of DLBCL biopsy tissue with AID and MUM1 antibody was conducted. The samples were then classified into concordant (AID+/MUM1+ or AID-/MUM1-) and discordant group (AID-/MUM1+). The clinicopathological comparison was performed to observe any association between immunohistochemistry expression and clinical findings.RESULTS: Among 20 samples of DLBCL, concordant expression rate of AID and MUM1 was 80% with kappa Cohen’s of 0.578 (p=0.004). A significant association was observed between AID and MUM1 expression with a prevalence ratio of 2.25 (95% CI: 1.08-4.67; p=0.008). Clinical characteristics were not significantly different between each group. Restricted mean survival time was shorter in the concordant group compared with the discordant group but statistically insignificant (21.16 vs. 22.5 months; p=0.531).CONCLUSION: The result of this study showed the association between AID and MUM1 expression in DLBCL. However, whether the association may add further molecular heterogeneity of DLBCL is still to be confirmed by expanding the study.KEYWORDS: AID, CSR, DLBCL, MUM1, SHM

Discordance Between Subjective and Objective Cognitive Function in Older Korean Americans

Objectives: To examine predictors of membership in discordant groups identified by subjective and objective measures of cognitive function. Methods: Participants in the Study of Older Korean Americans ( N = 2046) were classified according to their subjective cognitive ratings ( excellent/ very good/ good vs. fair/ poor) and Mini-Mental State Examination scores (normal cognition vs. cognitive impairment), yielding two discordant groups: (1) positive ratings but cognitive impairment and (2) negative ratings but normal cognition. Logistic regression models examined how the discordant group membership was associated with personal resources. Results: Among those with positive cognitive ratings, the odds of belonging to the discordant group were associated with low personal resources (advanced age and lower levels of education, acculturation, and knowledge about Alzheimer’s disease). However, an opposite pattern was observed among those with negative ratings. Discussion: The pattern of discordance suggests ways to promote early detection of cognitive impairment and close the gap in cognitive health care.

Long‐Term Clinical Outcomes of Nonhyperemic Pressure Ratios: Resting Full‐Cycle Ratio, Diastolic Pressure Ratio, and Instantaneous Wave‐Free Ratio

Background Nonhyperemic pressure ratios (NHPRs) such as instantaneous wave‐free ratio, resting full‐cycle ratio, or diastolic pressure ratio have emerged as invasive physiologic indices precluding the need for hyperemic agents. The current study sought to evaluate the long‐term prognostic implications of NHPRs compared with fractional flow reserve (FFR). Methods and Results NHPRs were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The association between NHPRs and the risk of 5‐year vessel‐oriented composite outcomes (VOCO, a composite of cardiac death, vessel‐related myocardial infarction, and ischemia‐driven revascularization) were analyzed among 864 deferred vessels. Lesions with positive NHPRs (instantaneous wave free ratio, resting full‐cycle ratio, and diastolic pressure ratio ≤0.89) or FFR (≤0.80) showed significantly higher risk of VOCO at 5 years than those with negative NHPRs or FFR, respectively. Discriminant ability for 5‐year VOCO was not different among NHPRs and FFR (C‐index: 0.623–0.641, P for comparison=0.215). In comparison of VOCO among the groups with deferred concordant negative (NHPRs−/FFR−), deferred discordant (NHPRs+/FFR− or NHPRs−/FFR+), and revascularized vessels, the cumulative incidence of VOCO were 7.5%, 14.4%, and 14.8% (log‐rank P <0.001), respectively. The deferred discordant group showed similar risk of VOCO with the revascularized vessel group (hazard ratio, 0.981; 95% CI 0.434–2.217, P =0.964). Conclusions Currently available invasive pressure‐derived indices showed similar prognostic implications for vessel‐related events at 5 years. Deferred lesions with discordant results between NHPRs and FFR did not show higher risk of vessel‐related events at 5 years than revascularized vessels. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifiers: NCT01621438, NCT01621438.

Association of CSF Aβ, amyloid PET, and cognition in cognitively unimpaired elderly adults

ObjectiveTo compare CSF β-amyloid (Aβ) and florbetapir PET measurements in cognitively unimpaired (CU) elderly adults in order to detect the earliest abnormalities and compare their predictive effect for cognitive decline.MethodsA total of 259 CU individuals were categorized as abnormal (+) or normal (−) on CSF Aβ1-42/Aβ1-40 analyzed with mass spectrometry and Aβ PET measured with 18F-florbetapir. Simultaneous longitudinal measurements of CSF and PET were compared for 39 individuals who were unambiguously Aβ-negative at baseline (CSF−/PET−). We also examined the relationship between baseline CSF/PET group membership and longitudinal changes in CSF Aβ, Aβ PET, and cognition.ResultsThe proportions of individuals in each discordant group were similar (8.1% CSF+/PET− and 7.7% CSF−/PET+). Among baseline Aβ-negative (CSF−/PET−) individuals with longitudinal CSF and PET measurements, a larger proportion subsequently worsened on CSF Aβ (odds ratio 4 [95% confidence interval (CI) 1.1, 22.1], p = 0.035) than Aβ PET over 3.5 ± 1.0 years. Compared to CSF−/PET− individuals, CSF+/PET− individuals had faster (estimate 0.009 [95% CI 0.005, 0.013], p < 0.001) rates of Aβ PET accumulation over 4.4 ± 1.7 years, while CSF−/PET+ individuals had faster (estimate −0.492 [95% CI −0.861, −0.123], p = 0.01) rates of cognitive decline over 4.5 ± 1.9 years.ConclusionsThe proportions of discordant PET and CSF Aβ-positive individuals were similar cross-sectionally. However, unambiguously Aβ-negative (CSF−/PET−) individuals are more likely to show subsequent worsening on CSF than PET, supporting the idea that CSF detects the earliest Aβ changes. In discordant cases, only PET abnormality predicted cognitive decline, suggesting that abnormal Aβ PET changes are a later phenomenon in cognitively normal individuals.

Quality of Life in Patients with Acromegaly before and after Transsphenoidal Surgical Resection

Objective. We aimed to determine the perioperative changes in the quality of life (QoL) in patients with acromegaly and to reveal the relationship between biochemical indicators and quality of life change after tumor resection. Methods. Patients with acromegaly were enrolled from a tertiary pituitary center. SF-36 scale and AcroQoL scale were used to determine the QoL before and after surgery. We analyzed changes in QoL using a generalized linear model for repeated measurements. We compared the changes in QoL among three groups (remission, active, and discordant group) based on postoperative growth hormone (GH) and insulin-like growth factor-1. Results. 151 patients (75 males and 76 females) diagnosed with acromegaly were included. The average age was 43.9 ± 12.3 years. The median total SF-36 scale was 65.3% (IQR: 63.2%–69.2%). Overall AcroQoL score at baseline was 59.1% (IQR: 51.8%–71.8%). Nadir GH levels (coefficient −0.08, p=0.047), T3 levels (coefficient 2.8, p=0.001), and testosterone levels (coefficient −0.20, p=0.033) in males were independent predictive factors of the total SF-36 score. During the follow-up, the median overall SF-36 score increased to 66.1% at 3 months and 75.3% at 6 months (p<0.001) after surgery. The median overall AcroQoL score increased to 74.5% at 3 months and 77.3% at 6 months (p<0.001) after surgery. At 6-month follow-up, median scores were still less than 70% in appearance, vitality, and mental health dimensions. The QoL after surgery were similar among the three groups, although higher GH and more preoperative somatostatin analogs usage were observed in the active group. Conclusion. In conclusion, acromegalic patients were associated with low QoL, which could be reversed partially by surgery. The improvement was independent of the endocrine remission. Appearance, vitality, and mental health were three major aspects that warrant further attention from physicians and caregivers after surgery.

Discordant Alzheimer's neurodegenerative biomarkers and their clinical outcomes in older adults without dementia

Background: In 2018 ATN framework, Alzheimer's neurodegenerative biomarkers comprised cerebrospinal fluid (CSF) total tau, 18 F-fluorodeoxyglucose-positron emission tomography, and brain atrophy. Although these biomarkers could be used interchangeably, some cases had discordant neurodegenerative biomarkers. Our aim was to assess the clinical outcomes of having discordant Alzheimer's neurodegenerative biomarkers. Methods: A total of 721 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative database were included and then further categorized into concordant negative, discordant, and concordant positive groups. Demographic distributions of the groups were compared. Longitudinal changes in clinical outcomes and risk of conversion were assessed using linear mixed-effects models and multivariate Cox proportional hazard models, respectively. Results: Discordant group was intermediate to concordant-negative and concordant-positive groups in terms of APOE ε4 positivity, CSF amyloid-beta and phosphorylated tau. Compared with concordant-negative group, discordant group deteriorated faster in cognitive scores (Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Functional Activities Questionnaire) and demonstrated greater rates of atrophy in brain structures (hippocampus, entorhinal cortex and whole brain), and concordant-positive group performed worse over time than discordant group. Moreover, the risk of cognitive progression increased from concordant-negative to discordant to concordant-positive. The longitudinal results were validated in A+T+, cognitively normal and mild cognitive impairment individuals, and were also validated by applying different cut-offs for neurodegenerative biomarkers. Conclusions: Discordant neurodegenerative status denotes a stage of cognitive function which is intermediate between concordant-negative and concordant-positive. Identification of discordant cases would provide insights into intervention and new therapy approaches, particularly in A+T+ individuals. Moreover, this work may be a complement to the ATN scheme.