Citations

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care, and social work selected the final set. Candidate patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures, and 10 were outcome measures that focused on elements not typically measured in routine care. Among the patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local quality improvement initiatives to improve access and quality of care.

Abstract Prostate cancer (CaP) is a heterogeneous disease characterized by features of non-aggressive, slow-growing disorders to fast-growing disease. Men of African ancestry have disproportionately higher incidence and mortality rates for CaP than men of European ancestry. While there is evidence for a higher genetic predisposition for incidence of CaP in men of African ancestry compared to men of European ancestry, there is paucity of molecular biology and transcriptomic studies on the role of Human endogenous retroviruses (HERVs) in relation to CaP-associated genes in CaP pathogenesis and prognosis. In this study, we performed bulk RNA sequencing (RNA-seq) on formalin-fixed paraffin-embeded (FFPE) CaP samples from Nigerian CaP patients to investigate the expression significance of HERV-R in relation to FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4 and BRAF genes. Based on this findings, we used immunohistochemistry (IHC), enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) to confirm the expression pattern of the HERV-R and FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4 and BRAF proteins on 45 FFPE CaP and blood plasma samples, and 5 CaP-free samples from patients in Zaria, Nigeria. Most of these patients were longitudinally followed from 2017 to date. The DESeq2 procedure was used for data processing, analysis, and differential expression analysis of the aforementioned genes. We found a significant expression of HERV-R in relation with FOXA1, TMPRSS2, BAZ1B, KMT2D, ATF4, CCND1 and BRAF in the CaP from rural Africans in Nigeria. HERV-R expression was found to be associated with increased PSA level, higher Gleason grade and poor prognosis of CaP. A CaP sample from an 80-year-old patient that was histologically diagnosed to have no malignancy seen despite high PSA level of >100 and poor disease outcomes shows a significant cytoplasmic expression of HERV-R, indicating that HERV-R may serve as an important biomarker for early detection. Unfortunately, we lost the 80-year-old patient to late detection before revisiting his case for proper histological diagnosis and management. In addition, some histologically diagnosed BPH samples that are apparently reported to be CaP-free show stromal cells expression of HERV-R and in some cases show expression of HERV-R in the prostatic glandular areas. In contrast, stromal cells of the CaP samples show no expression of HERV-R, but strong expression in the glandular areas. This may implicate a gradual transition from benign prostatic lesion to malignant prostatic disease. HERV-R expression in CaP may have a relationship with BRAF, CCND1, FOXA1, TMPRSS2 and ATF4 genes. These findings combined together, underscore the importance of the expanded concept of HERV-R expression and CaP associated genes in early detection of CaP and prognosis. Citation Format: Faruk Mohammed, Konrad Stawiski, Halimatu Sadiya Musa, Sani Kamarudeen Owolabi, Sani Abubakar, Solomon O. Rotimi, Adoke Kasimu Umar, Yawale Iliyasu, Ahmad Bello, Folakemi T. Odedina, Clayton C. Yates, Kevin Petrie, Franklin W. Huang, Sani Ibrahim. Co-expression of HERV-R, CCND1, BRAF, FOXA1, TMPRSS2, ATF4 and low expression of BAZ1B and KMT2D is associated with early detection and poor prognosis of prostate cancer in African Black men from Nigeria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6432.

Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently no specific histopathological features pathognomonic for metabolic dysfunction–associated steatotic liver disease, alcohol-associated liver disease, or metabolic dysfunction–associated steatotic liver disease with increased alcohol intake. Digitizing traditional pathology slides has created an emerging field of digital pathology, allowing for easier access, storage, sharing, and analysis of whole-slide images. Artificial intelligence (AI) algorithms have been developed for whole-slide images to enhance the accuracy and speed of the histological interpretation of steatohepatitis and are currently employed in biomarker development. Spatial biology is a novel field that enables investigators to map gene and protein expression within a specific region of interest on liver histological sections, examine disease heterogeneity within tissues, and understand the relationship between molecular changes and distinct tissue morphology. Here, we review the utility of digital pathology (using linear and nonlinear microscopy) augmented with AI analysis to improve the accuracy of histological interpretation. We will also discuss the spatial omics landscape with special emphasis on the strengths and limitations of established spatial transcriptomics and proteomics technologies and their application in steatohepatitis. We then highlight the power of multimodal integration of digital pathology augmented by machine learning (ML)algorithms with spatial biology. The review concludes with a discussion of the current gaps in knowledge, the limitations and premises of these tools and technologies, and the areas of future research.

Abstract Background The role of serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved during the pandemic as seroprevalence in global populations has increased. The Infectious Diseases Society of America convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct updated best practice guidance related to SARS-CoV-2 serologic testing. This guideline is an update to the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by the Infectious Diseases Society of America. Objective To develop evidence-based recommendations and identify unmet research needs pertaining to the use of anti–SARS-CoV-2 antibody tests for diagnosis, decisions related to vaccination and administration of monoclonal antibodies or convalescent plasma in immunocompromised patients, and identification of a serologic correlate of immunity. Methods A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature reviewed, identified, and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of evidence and make testing recommendations. Results The panel recommends against serologic testing to diagnose SARS-CoV-2 infection in the first 2 weeks after symptom onset (strong recommendations, low certainty of evidence). Serologic testing should not be used to provide evidence of COVID-19 in symptomatic patients with a high clinical suspicion and repeatedly negative nucleic acid amplification test results (strong recommendation, very low certainty of evidence). Serologic testing may assist with the diagnosis of multisystem inflammatory syndrome in children (strong recommendation, very low certainty of evidence). To seek evidence for prior SARS-CoV-2 infection, the panel suggests testing for immunoglobulin G (IgG), IgG/IgM, or total antibodies to nucleocapsid protein 3 to 5 weeks after symptom onset (conditional recommendation, low certainty of evidence). In individuals with previous SARS-CoV-2 infection or vaccination, the panel suggests against routine serologic testing given no demonstrated benefit to improving patient outcomes (conditional recommendation, very low certainty of evidence). The panel acknowledges further that a negative spike antibody test may be a useful metric to identify immunocompromised patients who are candidates for immune therapy. Conclusions The high seroprevalence of antibodies against SARS-CoV-2 worldwide limits the utility of detecting anti-SARS CoV-2 antibody. The certainty of available evidence supporting the use of serology for diagnosis was graded as very low to low. Future studies should use serologic assays calibrated to a common reference standard.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Background: Telehealth use was previously limited by strict regulations and financial constraints. However, the pandemic prompted some countries to ease their telehealth laws. Thus, we conducted a bibliometric analysis and network visualization to gauge changes in tele-neuropsychology (Tele-NP) and tele-mental Health (Tele-MH) trends with the onset of the COVID-19 pandemic. Materials and methods: The authors conducted a literature search on SCOPUS and included relevant articles pertaining to Tele-NP and Tele-MH, which were published before the COVID-19 pandemic (2017–2019) and during the COVID-19 pandemic (2020–2022). The authors presented publication patterns on psychiatric disorders, mode of administration, journals, active countries, authors, affiliations, funding sponsors, keywords, publication, and citation output. Results: Three hundred forty-one articles were included in our study with 80 articles before the pandemic and 261 during the pandemic. Our analysis revealed the greatest increase in publications and citations output was from the year 2020 to 2021. A greater number of journals published tele-NP and tele-MH-related research, with higher frequency, during the COVID-19 pandemic with Telemedicine and E-health leading the way. WHO regional analysis revealed that the Region of the Americas (AMRO) was the leading contributor in terms of publications. Harvard Medical Center remained the number one contributor both before and during the COVID-19- pandemic. Publications by funding sponsors, particularly by those that were US-based, increased twice as much during the pandemic. Conclusion: The increase in research output following the COVID-19 outbreak reflects the growing interest and relevance of telemedicine for the delivery of mental health services.

BACKGROUND AND OBJECTIVES: Enhanced recovery after surgery (ERAS) protocols aim to optimize patient outcomes by reducing the surgical stress response, expediting recovery, and reducing care costs. We aimed to evaluate the impact of implementing ERAS protocols on the perioperative surgical outcomes and financial implications associated with spine surgeries. METHODS: A systematic review and meta-analysis of peer-reviewed studies directly comparing outcome differences between spine surgeries performed with and without utilization of ERAS pathways was conducted along Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of 676 unique articles identified, 59 with 15 198 aggregate patients (7748 ERAS; 7450 non-ERAS) were included. ERAS-treated patients had shorter operative times (mean difference [MD]: 10.2 mins; P < .01), shorter hospitalizations (MD: 1.41 days, P < .01), fewer perioperative complications (relative risk [RR] = 0.64, P < .01), lower postoperative opioid use (MD of morphine equivalent dose: 164.36 mg; P < .01), and more rapid mobilization/time to first out-of-bed ambulation (MD: 0.92 days; P < .01). Spine surgeries employing ERAS were also associated with lower total costs (MD: $1140.26/patient; P < .01), especially in the United States (MD: $2869.11/patient, P < .01) and lower postoperative visual analog pain scores (MD = 0.56, P < .01), without any change in odds of 30-day readmission (RR: 0.80, P = .13) or reoperation (RR: 0.88, P = .60). Subanalyses based on the region of spine showed significantly lower length of stay in both cervical and lumbar surgeries implementing ERAS. Type of procedure showed a significantly lesser time-to-initiate mobilization in fusion surgeries using ERAS protocols compared with decompression. CONCLUSION: The present meta-analysis indicates that current literature supports ERAS implementation as a means of reducing care costs and safely accelerating hospital discharge for patients undergoing spine surgery.

Background: Lipoprotein glomerulopathy is an infrequent glomerular disorder that culminates in nephrotic syndrome and often progresses to kidney failure. Whereas most patients have been reported in Japan and China, limited reports have been documented outside these regions. This patient represents the first report of lipoprotein glomerulopathy in Pakistan. Case Presentation: A 25-year-old male patient, hypertensive for 2 years, presented with progressive body edema, frothy urine, and fatigue. Examination revealed elevated blood pressure, bilateral pedal edema, and positive shifting dullness. Laboratory results showed significant proteinuria and elevated cholesterol and triglyceride levels. Renal biopsy revealed enlarged glomeruli with a dilated capillary lumen filled with pale-staining mesh-like material “lipoprotein thrombi.” Mild tubular atrophy and interstitial inflammation were observed. No interstitial fibrosis was evident. Electron microscopy detailed the lipoprotein thrombi with lipid granules and vacuoles of various sizes. A diagnosis of lipoprotein glomerulopathy was rendered. Treatment with fenofibrate, rosuvastatin, and captopril led to notable improvements in symptoms, blood pressure, and lipid levels during a 6-month follow-up. Subsequent biopsy showed complete resolution of the lipoprotein thrombi and a significant reduction in subendothelial granular densities. However, the flocculent subendothelial material persisted to some extent despite the complete resolution of lipoprotein thrombi. Conclusion: This report underscores the rarity of lipoprotein glomerulopathy in Pakistan and contributes valuable insights into its histopathologic features and global epidemiology. This unique instance aims to raise awareness among healthcare professionals, aiding in improved recognition of this rare entity. The favorable response to fenofibrate treatment underscores its effectiveness in managing lipoprotein glomerulopathy.

With increasing number of people living with dementia, the problem of late diagnosis significantly impacts a person’s quality of life while early signs of dementia may provide useful insights to facilitate better treatment plans. With time, this progressive neurodegenerative syndrome could progress from mild cognitive impairment to dementia. A pattern of health conditions can be characterized in unsupervised manner to help predict this progress. As a significant extension to our previous work with streaming clustering model, we consider additional information for predicting dementia onset. With empirical observations, we discover the importance of examining sex and age to predict dementia onset. To this end, we propose a sex-specific model with age-constraint for predicting dementia onset and validate the effectiveness of our models using data from Mayo Clinic Study of Aging (MCSA). The proposed sex-specific models for older adult populations (>=65 years of age) outperformed the previous models with F-score of 77% and 78% for male-specific and female-specific models, respectively. Our experiments of sex-specific temporal clustering of features in older adults demonstrate the potential of more personalized models for early alerts of dementia.

AbstractBackgroundThe impact of chronic kidney disease (CKD) on atrial fibrillation outcomes (AF) is not well understood.MethodsWe conducted analyses of comorbid AF and CKD related death in the United States from 1999 to 2020 using descriptive epidemiology.ResultsAge‐adjusted mortality rates (AAMR) per 100,000 increased from 0.39 in 1999 to 1.65 in 2020. Non‐Hispanic populations (1.01) and nonmetropolitan areas (1.08) had higher AAMRs compared to Hispanic (0.62) and metropolitan (0.97) areas. Midwestern (1.11) and Western (1.13) US regions recorded the highest AAMRs.ConclusionsThese findings highlight the need for interventions to address AF death disparities in patients with CKD.