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Introduction: We compared the efficacy of the ALBI (albumin–bilirubin) score to the established Child–Pugh (CP) grade in hepatocellular carcinoma (HCC) patients treated with yttrium-90 radioembolization (Y90). We further assessed the individual contributions of albumin and bilirubin to survival prediction. Methods: 1000 consecutive HCC patients treated with Y90 were included. Overall survival (OS) was assessed using Kaplan Meier analysis. Sub-stratification analyses were performed using CP and ALBI and in subgroups determined by United Network for Organ Sharing (UNOS) or Barcelona Clinic Liver Cancer (BCLC) staging. The independent impact (hazard ratio (HR)) of ALBI, CP, albumin, and bilirubin on survival was assessed using Cox proportional hazards analysis. Results: Median OS for ALBI 1, 2, and 3 grades was 46.7, 19.1, and 8.8 months, respectively. The HR for death for ALBI 2 vs. ALBI 1 was 3.39 (1.75–6.57); ALBI 3 vs. ALBI 1 was 7.58 (3.89–14.79); and the c-index was 0.623. Median OS for CP A, B, and C was 21.7, 11.3, and 6.0 months, respectively. The HR for death for CP B vs. CP A was 2.04 (1.71–2.43); CP C vs. CP A was 3.27 (2.08–5.14); and the c-index was 0.616. Stratified OS showed unique prognostic groups identified by ALBI within CP-B and CP-C. Median OS for albumin grades 1, 2, and 3 was 46.0, 17.1, and 9.1 months, respectively. Median OS for bilirubin grades 1, 2, and 3 was 15.6, 21.0, and 5.8 months, respectively. The HR for death for albumin 2 vs. 1 was 2.48 (1.81–3.41); albumin 3 vs. 1 was 4.74 (3.44–6.54); and the c-index was 0.640. The HR for death for bilirubin 2 vs. 1 was 1.09 (0.82–1.44); bilirubin 3 vs. 1 was 2.37 (1.66–3.40); and the c-index was 0.533. Conclusions: ALBI outperforms CP in survival prognosis in Y90 treated patients. On sub-analyses, serum albumin (not bilirubin) appears to be the main driver of survival prediction. Our study supports the prognostic ability of ALBI and may suggest a role of albumin alone as a biomarker for patients with HCC.

Cancer and its treatments can affect fertility in a variety of ways, and recent advances in cancer detection and treatment have led to an increasing number of cancer survivors for whom future fertility is a primary concern. Oncofertility is the study of interactions between cancer, anti-cancer therapy, fertility, and reproductive health. Fertility preservation aims to optimize fertility potential before initiation of gonadotoxic therapies. Sperm cryopreservation from an ejaculated sample is the gold standard for adults and post-pubertal adolescents, though added maneuvers such as medical therapy, penile vibratory stimulation, and electroejaculation can be employed when appropriate. When all these approaches fail, testicular sperm extraction can be used to obtain and cryopreserve testicular sperm from the azoospermic patient. Fertility preservation in the pre-pubertal pediatric patient is still experimental, but recent scientific breakthroughs with use of spermatogonial stem cells and testicular tissue transplantation offer great promise for the future.While there may be several practical, cultural, religious, and other barriers to fertility preservation, the establishment of a dedicated fertility preservation team can help to overcome these obstacles and optimize the utilization of fertility preservation in cancer patients of all ages.

Amyloid β oligomers (AβOs) accumulate early in Alzheimer's disease (AD) and experimentally cause memory dysfunction and the major pathologies associated with AD, for example, tau abnormalities, synapse loss, oxidative damage, and cognitive dysfunction. In order to develop the most effective AβO‐targeting diagnostics and therapeutics, the AβO structures contributing to AD‐associated toxicity must be elucidated. Here, we investigate the structural properties and pathogenic relevance of AβOs stabilized by the bifunctional crosslinker 1,5‐difluoro‐2,4‐dinitrobenzene (DFDNB). We find that DFDNB stabilizes synthetic Aβ in a soluble oligomeric conformation. With DFDNB, solutions of Aβ that would otherwise convert to large aggregates instead yield solutions of stable AβOs, predominantly in the 50–300 kDa range, that are maintained for at least 12 days at 37°C. Structures were determined by biochemical and native top–down mass spectrometry analyses. Assayed in neuronal cultures and i.c.v.‐injected mice, the DFDNB‐stabilized AβOs were found to induce tau hyperphosphorylation, inhibit choline acetyltransferase, and provoke neuroinflammation. Most interestingly, DFDNB crosslinking was found to stabilize an AβO conformation particularly potent in inducing memory dysfunction in mice. Taken together, these data support the utility of DFDNB crosslinking as a tool for stabilizing pathogenic AβOs in structure‐function studies.

Patients with locally advanced and metastatic urothelial carcinoma have a low survival rate (median 15.7 months, 13.1-17.8), with only a 23% response rate to monotherapy treatment with anti-PDL1 checkpoint immunotherapy. To identify new therapeutic targets, we profiled the immune regulatory signatures during murine cancer development using the BBN carcinogen and identified an increase in the expression of the T cell inhibitory protein B7-H4 (VTCN1, B7S1, B7X). B7-H4 expression temporally correlated with decreased lymphocyte infiltration. While the increase in B7-H4 expression within the bladder by CD11b + monocytes is shared with human cancers, B7-H4 expression has not been previously identified in other murine cancer models. Higher expression of B7-H4 was associated with worse survival in muscle-invasive bladder cancer in humans, and increased B7-H4 expression was identified in luminal and luminal-papillary subtypes of bladder cancer. Evaluation of B7-H4 by single-cell RNA-Seq and immune mass cytometry of human bladder tumors found that B7-H4 is expressed in both the epithelium of urothelial carcinoma and CD68+ macrophages within the tumor. To investigate the function of B7-H4, treatment of human monocyte and T cell co-cultures with a B7-H4 blocking antibody resulted in enhanced IFN-γ secretion by CD4 + and CD8 + T cells. Additionally, anti-B7-H4 antibody treatment of BBNcarcinogen bladder cancers resulted in decreased tumor size, increased CD8 + T cell infiltration within the bladder, and a complimentary decrease in tumor-infiltrating T regulatory cells (Tregs). Furthermore, treatment with a combination of anti-PD-1 and anti-B7-H4 antibodies resulted in a significant reduction in tumor stage, a reduction in tumor size, and an increased level of tumor necrosis. These findings suggest that antibodies targeting B7-H4 may be a viable strategy for bladder cancers unresponsive to PD-1 checkpoint inhibitors.

Even mild renal disease at the time of LT is a risk factor for posttransplant all-cause and CV mortality. More rapid declines in eGFR soon after LT correlate with risk of adverse CV outcomes, highlighting the need to study whether early renal preservation interventions also reduce CV complications.

Objectives Respiratory syncytial virus (RSV) is an important cause of morbidity and mortality in adults. Existing studies are limited by the number of seasons studied and most have focused on the immunocompromised. Methods A retrospective cohort study was conducted on all adults (≥18 years) with a positive RSV molecular test admitted from 2009 to 2015 to one hospital in Chicago, IL. Epidemiologic and outcomes data were collected after IRB approval. Results Of the 489 eligible patients, 227 had RSV A and 262 had RSV B. Patients had a median age of 61 years and comorbidity (eg, chronic lung disease [40.6%], obesity [37.8%], and cardiac disease [34.3%]). On presentation, most had cough (86.5%), fever (42.4%), and shortness of breath (38.2%). Severe disease was present in 27.6% of patients. Antibiotic was used in 76.3% inpatients and 45.8% at discharged despite few patients (4.7%) having documented bacterial infections. Supplemental oxygen and mechanical ventilation were utilized in 44.6% and 12.3%, respectively, while ICU level care was required in 26.9%. Most patients were discharged home (82.7%). Most deaths (68.4%, 13/19) were attributed to pneumonia or hypoxemia likely from RSV. Most fatal cases were seen in those with recent cancer treatment and older adults. Conclusions Respiratory syncytial virus in hospitalized adults is associated with significant morbidity and mortality with 26.9% requiring ICU level care. Antibiotics are commonly prescribed to patients with documented RSV, and antibiotics are frequently continued after diagnosis. Novel antiviral therapies are needed for RSV to improve outcomes and potentially improve antibiotic stewardship in patients without a bacterial infection.

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