Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study.

BACKGROUND: Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study. METHODS: Insomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors. FINDINGS: Insomnia was associated with higher risk of endometrioid EOC (OR = 1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR = 0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR = 1.45, 95% CI 1.13-1.87) and HGSOC (OR = 1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR = 2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors. INTERPRETATION: This study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival. FUNDING: National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.

Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells.

Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.

Glioblastoma: a comprehensive approach combining bibliometric analysis, Latent Dirichlet Allocation, and HJ-Biplot : Glioblastoma insights and trends: a 49-year bibliometric analysis.

Glioblastoma is a common and aggressive malignant central nervous system tumor in adults. This study aims to evaluate and analyze the scientific results, collaboration countries, main research topics, and topics over time reported about glioblastoma. A bibliometric analysis of glioblastoma publications was performed mainly using R and Multbiplot software for author, journal, and resume. Associated statistic methods Latent Dirichlet Allocation (LDA) and HJ-Biplot. Inclusion criteria were research articles from the PubMed database published in English between 1973 and December 2022. A total of 64,823 documents with an annual growth rate of 8.27% indicates a consistent increase in research output over time. The results for the number of citations and significant publications showed Cancer Res, J Neuro-Oncol, and Neuro-Oncology are the most influential journals in the field of glioblastoma. The countries that concentrated research were the tumor United States, China, Germany, and Italy. Finally, there has been a marked growth in studies on prognosis and patient survival, therapies, and treatments for glioblastoma. These findings reinforce the need for increased global resources to address glioblastoma, particularly in underdeveloped countries. Glioblastoma research's exponential growth reflects sustained interest in early diagnosis and patient survival.

Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases.

BACKGROUND: Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis. Outcomes of RDEB-cSCC therapies have primarily been described in case reports. Systematic studies are scarce. This systematic review aims to assess the pathophysiology, clinical characteristics, and outcomes of RDEB-cSCCs, with a focus on results and mechanisms of recent immunotherapies and anti-EGFR treatments. RESULTS: A systematic literature search of epidermolysis bullosa and cSCC was performed in February 2024, using PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EudraCT databases. Cases with administration of systematic therapies and unpublished outcomes regarding death were tracked with corresponding authors. Data extraction and risk of bias assessment was performed by two independent reviewers. Of 1132 references in the original search, 163 relevant articles were identified, representing 59 case reports, 7 cohort studies, 49 abstracts, 47 in-vitro/in-vivo experiments, and 1 bioinformatic study. From these, 157 cases of RDEB-cSCCs were included. The majority of RDEB-cSCCs were well-differentiated (64.1%), ulcerated (59.6%), and at least 2 cm in size (77.6%), with a median age at diagnosis of 30 years old (range 6-68.4). Surgery was the primary form of treatment (n = 128), followed by chemotherapy and radiotherapy. Anti-EGFR therapy and immunotherapy was also reported beginning in 2009 and 2019, respectively. Survival time from first cSCC diagnosis to death was available in 50 cases. When stratified by their treatment regimen, median survival time was 1.85 years (surgery + chemotherapy, n = 6), 2 years (surgery only, n = 19), 4.0 years (+ anti-EFGR therapy, n = 10), 4 years (surgery + radiotherapy, n = 9), 4.6 years (+ immunotherapy, n = 4), and 9.5 years (surgery + chemotherapy + radiotherapy; n = 2). Treatment-related adverse events were primarily limited to impaired wound healing for immunotherapies and nausea and fatigue for anti-EGFR therapies. CONCLUSIONS: Despite the challenges of a limited sample size in a rare disease, this systematic review provides an overview of treatment options for cSCCs in RDEB. When surgical treatment options have been exhausted, the addition of immunotherapy and/or anti-EGFR therapies may extend patient survival. However, it is difficult to attribute extended survival to any single treatment, as multiple therapeutic modalities are often used to treat RDEB-cSCCs.

Optimizing pediatric liver transplantation: Evaluating the impact of donor age and graft type on patient survival outcome.

BACKGROUND: We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS: A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS: Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS: Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.

The ERA Registry Annual Report 2021: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Methods: Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. Result: In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.

Impact of age over 70 years in the new allocation system on the outcomes of heart transplantation in the US.

BACKGROUND: United Network for Organ Sharing (UNOS) allocation criteria changed in 2018 to accommodate the increased prevalence of patients on a ventricular assist device as a bridge to heart transplant and prioritize sicker people in anticipation of a heart graft. We aimed to assess the impact of patient age in the new allocation policy on mortality following heart transplantation. Secondary outcomes included the effect of age ≥70 on post-transplant events, including stroke, dialysis, pacemaker, and rejection requiring treatment. METHODS: The UNOS Registry was queried to identify patients who underwent heart transplants alone in the US between 2000 and 2021. Patients were divided into groups according to their age (over 70 and under 70 years old). RESULTS: Patients aged over 70 were more likely to require dialysis during follow-up, but less likely to experience rejection requiring treatment, compared with patients aged <70. Age ≥70 in the new allocation system was a significant predictor of 1-year mortality (adjusted HR: 1.41; 95% CI: 1.05-1.91; p = .024), but its effect on 5-year mortality was not significant after adjusting for potential confounders (adjusted HR: 1.27; 95% CI:.97-1.66; p = .077). Undergoing transplantation under the new allocation policy vs the old allocation policy was not a significant predictor of mortality in patients over 70 years old. CONCLUSIONS: Age ≥70 is a significant predictor of 1-year mortality following heart transplantation, but not at 5 and 10 years; however, the new allocation does not seem to have changed the outcomes for this group of patients.

Artificial intelligence-based, volumetric assessment of the bone marrow metabolic activity in [18F]FDG PET/CT predicts survival in multiple myeloma.

PURPOSE: Multiple myeloma (MM) is a highly heterogeneous disease with wide variations in patient outcome. [18F]FDG PET/CT can provide prognostic information in MM, but it is hampered by issues regarding standardization of scan interpretation. Our group has recently demonstrated the feasibility of automated, volumetric assessment of bone marrow (BM) metabolic activity on PET/CT using a novel artificial intelligence (AI)-based tool. Accordingly, the aim of the current study is to investigate the prognostic role of whole-body calculations of BM metabolism in patients with newly diagnosed MM using this AI tool. MATERIALS AND METHODS: Forty-four, previously untreated MM patients underwent whole-body [18F]FDG PET/CT. Automated PET/CT image segmentation and volumetric quantification of BM metabolism were based on an initial CT-based segmentation of the skeleton, its transfer to the standardized uptake value (SUV) PET images, subsequent application of different SUV thresholds, and refinement of the resulting regions using postprocessing. In the present analysis, ten different uptake thresholds (AI approaches), based on reference organs or absolute SUV values, were applied for definition of pathological tracer uptake and subsequent calculation of the whole-body metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Correlation analysis was performed between the automated PET values and histopathological results of the BM as well as patients' progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) curve analysis was used to investigate the discrimination performance of MTV and TLG for prediction of 2-year PFS. The prognostic performance of the new Italian Myeloma criteria for PET Use (IMPeTUs) was also investigated. RESULTS: Median follow-up [95% CI] of the patient cohort was 110 months [105-123 months]. AI-based BM segmentation and calculation of MTV and TLG were feasible in all patients. A significant, positive, moderate correlation was observed between the automated quantitative whole-body PET/CT parameters, MTV and TLG, and BM plasma cell infiltration for all ten [18F]FDG uptake thresholds. With regard to PFS, univariable analysis for both MTV and TLG predicted patient outcome reasonably well for all AI approaches. Adjusting for cytogenetic abnormalities and BM plasma cell infiltration rate, multivariable analysis also showed prognostic significance for high MTV, which defined pathological [18F]FDG uptake in the BM via the liver. In terms of OS, univariable and multivariable analysis showed that whole-body MTV, again mainly using liver uptake as reference, was significantly associated with shorter survival. In line with these findings, ROC curve analysis showed that MTV and TLG, assessed using liver-based cut-offs, could predict 2-year PFS rates. The application of IMPeTUs showed that the number of focal hypermetabolic BM lesions and extramedullary disease had an adverse effect on PFS. CONCLUSIONS: The AI-based, whole-body calculations of BM metabolism via the parameters MTV and TLG not only correlate with the degree of BM plasma cell infiltration, but also predict patient survival in MM. In particular, the parameter MTV, using the liver uptake as reference for BM segmentation, provides solid prognostic information for disease progression. In addition to highlighting the prognostic significance of automated, global volumetric estimation of metabolic tumor burden, these data open up new perspectives towards solving the complex problem of interpreting PET scans in MM with a simple, fast, and robust method that is not affected by operator-dependent interventions.

Clinical performance of the iPREDICTLIVING tool for the prediction of the post-transplant recipient and living donor outcomes in a European cohort.

A living donor kidney transplant (LDKT) is the best treatment for ESRD. A prediction tool based on clinical and demographic data available pre-KT was developed in a Norwegian cohort with three different models to predict graft loss, recipient death, and donor candidate's risk of death, the iPREDICTLIVING tool. No external validations are yet available. We sought to evaluate its predictive performance in our cohort of 352 pairs LKDT submitted to KT from 1998 to 2019. The model for censored graft failure (CGF) showed the worse discriminative performance with Harrell's C of .665 and a time-dependent AUC of .566, with a calibration slope of .998. For recipient death, at 10 years, the model had a Harrell's C of .776, a time-dependent AUC of .773, and a calibration slope of 1.003. The models for donor death were reasonably discriminative, although with a poor calibration, particularly for 20 years of death, with a Harrell's C of .712 and AUC of .694 with a calibration slope of .955. These models have moderate discriminative and calibration performance in our population. The tool was validated in this Northern Portuguese cohort, Caucasian, with a low incidence of diabetes and other comorbidities. It can improve the informed decision-making process at the living donor consultation joining clinical and other relevant information.

[Outcome of ABO-incompatible living-donor kidney transplants : A plea for crossover living-donor kidney transplantation]. / Outcome von ABO-inkompatiblen Lebendnierenspenden : Ein Plädoyer für Crossover-Lebendnierenspenden.

BACKGROUND: The lack of postmortem donated organs is the background to varyingly high rates of living-donor kidney transplants worldwide. ABO blood group-incompatible living-donor kidney transplants have also been established for at least 20 years. The equivalence of the results of ABO-incompatible and ABO-compatible transplants has recently been questioned. OBJECTIVE: In the sense of a critical reflection of our own kidney transplant program, we were interested in comparing ABO-incompatible with ABO-compatible living-donor kidney transplants. MATERIALS AND METHODS: A retrospective analysis of the long-term outcomes of all living-donor kidney transplants performed at our center since the first ABO-incompatible transplants were performed in 2005 up to and including 2022 was performed. RESULTS: Between 2005 and 2022, 1099 living kidney transplants were performed at the authors' center. Among them were 241 ABO-incompatible transplants. Transplant survival was significantly lower after ABO-incompatible donation than after ABO-compatible donation. This effect consisted of an increased mortality of the recipients, especially in the early phase, and a reduced longevity of the grafts. CONCLUSION: Including ABO-incompatible pairs for living-donor kidney transplants in crossover programs can improve medical outcomes and reduce costs.

MAL expression downregulation through suppressive H3K27me3 marks at the promoter in HPV16-related cervical cancers is prognostically relevant and manifested by the interplay of novel MAL antisense long noncoding RNA AC103563.8, E7 oncoprotein and EZH2.

BACKGROUND: MAL (T-lymphocyte maturation-associated protein) is highly downregulated in most cancers, including cervical cancer (CaCx), attributable to promoter hypermethylation. Long noncoding RNA genes (lncGs) play pivotal roles in CaCx pathogenesis, by interacting with human papillomavirus (HPV)-encoded oncoproteins, and epigenetically regulating coding gene expression. Hence, we attempted to decipher the impact and underlying mechanisms of MAL downregulation in HPV16-related CaCx pathogenesis, by interrogating the interactive roles of MAL antisense lncRNA AC103563.8, E7 oncoprotein and PRC2 complex protein, EZH2. RESULTS: Employing strand-specific RNA-sequencing, we confirmed the downregulated expression of MAL in association with poor overall survival of CaCx patients bearing HPV16, along with its antisense long noncoding RNA (lncRNA) AC103563.8. The strength of positive correlation between MAL and AC103563.8 was significantly high among patients compared to normal individuals. While downregulated expression of MAL was significantly associated with poor overall survival of CaCx patients bearing HPV16, AC103563.8 did not reveal any such association. We confirmed the enrichment of chromatin suppressive mark, H3K27me3 at MAL promoter, using ChIP-qPCR in HPV16-positive SiHa cells. Subsequent E7 knockdown in such cells significantly increased MAL expression, concomitant with decreased EZH2 expression and H3K27me3 marks at MAL promoter. In silico analysis revealed that both E7 and EZH2 bear the potential of interacting with AC103563.8, at the same binding domain. RNA immunoprecipitation with anti-EZH2 and anti-E7 antibodies, respectively, and subsequent quantitative PCR analysis in E7-silenced and unperturbed SiHa cells confirmed the interaction of AC103563.8 with EZH2 and E7, respectively. Apparently, AC103563.8 seems to preclude EZH2 and bind with E7, failing to block EZH2 function in patients. Thereby, enhanced EZH2 expression in the presence of E7 could potentially inactivate the MAL promoter through H3K27me3 marks, corroborating our previous results of MAL expression downregulation in patients. CONCLUSION: AC103563.8-E7-EZH2 axis, therefore, appears to crucially regulate the expression of MAL, through chromatin inactivation in HPV16-CaCx pathogenesis, warranting therapeutic strategy development.

Elevated hemoglobin levels in renal transplant recipients with polycystic kidney disease versus other etiologies: exploring mechanisms and implications for outcomes.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD)-related end-stage kidney disease (ESKD) often necessitates transplantation. However, the impact of ADPKD on post-transplant outcomes, specifically hemoglobin levels, remains unknown. METHODS: We retrospectively analyzed 513 Kidney Transplant Recipients (KTRs), of whom 81 had ESKD due to ADPKD (20 with pre-transplant native nephrectomy and 61 without). Hemoglobin levels were evaluated at multiple time intervals post-transplant. RESULTS: Kidney transplant recipients with ADPKD vs. KTRs with ESKD due to other causes exhibited significantly higher hemoglobin levels in repeated measurement analysis. Multivariable analyses confirmed ADPKD as an independent predictor for elevated hemoglobin levels. In a multivariable logistic regression analysis, the odds for maximum hemoglobin > 15 mg/dL at 3-12 months post-transplant were more than twice as high in ADPKD patients vs. all the other KTRs (Odds Ratio [OR] 2.31, 95% Confidence Interval [CI] 1.3-4.13, p < 0.001). Pre-transplant native nephrectomy revealed a trend toward lower hemoglobin levels. Elevated hemoglobin levels were linked to improved estimated glomerular filtration rate (eGFR) at one year post-transplant. Patient survival was enhanced among KTRs with ADPKD compared to other ESKD causes. CONCLUSIONS: Kidney transplant recipients with ADPKD exhibited elevated hemoglobin levels post-transplant, possibly due to prolonged native kidney erythropoietin production. These elevated hemoglobin levels were linked to improved outcomes, including allograft function and patient survival. Future research should further investigate the underlying mechanisms driving favorable ADPKD KTR outcomes.

Immediate-start peritoneal dialysis without break-in-period: an 18-year retrospective cohort study on patient survival.

Background: Immediate-start peritoneal dialysis (ISPD) is an effective renal replacement therapy that can prevent central venous catheterization due to its immediate initiation of peritoneal dialysis (PD) after catheter insertion without a break-in period. This study aimed to investigate the effect of ISPD on long-term patient survival. Methods: In this retrospective single-center cohort study, 178 consecutive patients who started PD from August 2005 to March 2023 were enrolled, from whom 144 patients with ISPD were analyzed. PD was initiated without a break-in period within 24 hours of catheter insertion using percutaneous needle-guidewire technique. The primary outcome was patient survival, estimated using the Kaplan-Meier method. A Cox proportional hazard regression model was used to identify factors independently associated with patient survival. Results: The median follow-up period was 4.00 years (interquartile range, 1.23‒5.75 years). The mean age of patients was 61.6 ± 13.6 years; 58 patients (40.3%) were male and 93 patients (64.6%) were diabetic. Overall patient survival rates at 1, 3, 5, and 10 years were 98.5%, 93.5%, 92.1%, and 65.6%, respectively. The technique survival rates at 1, 3, 5, and 10 years were 88.1%, 74.9%, 63.2%, and 40.2%, respectively. The peritonitis-free survival rates at 1, 3, 5, and 10 years were 92.3%, 76.0%, 59.4%, and 28.0%, respectively. In the multivariate analysis, diabetes was the only factor associated with patient survival and technique survival. Conclusion: Our study demonstrated that patient survival and technique survival rates were relatively high in ISPD patients who were catheterized using percutaneous needle-guidewire technique.

The BAR Score Predicts and Stratifies Outcomes Following Liver Retransplantation: Insights From a Retrospective Cohort Study.

Liver retransplantation (reLT) yields poorer outcomes than primary liver transplantation, necessitating careful patient selection to avoid futile reLT. We conducted a retrospective analysis to assess reLT outcomes and identify associated risk factors. All adult patients who underwent a first reLT at the Medical University of Innsbruck from 2000 to 2021 (N = 111) were included. Graft- and patient survival were assessed via Kaplan-Meier plots and log-rank tests. Uni- and multivariate analyses were performed to identify independent predictors of graft loss. Five-year graft- and patient survival rates were 64.9% and 67.6%, respectively. The balance of risk (BAR) score was found to correlate with and be predictive of graft loss and patient death. The BAR score also predicted sepsis (AUC 0.676) and major complications (AUC 0.720). Multivariate Cox regression analysis identified sepsis [HR 5.179 (95% CI 2.575-10.417), p < 0.001] as the most significant independent risk factor for graft loss. At a cutoff of 18 points, the 5 year graft survival rate fell below 50%. The BAR score, a simple and easy to use score available at the time of organ acceptance, predicts and stratifies clinically relevant outcomes following reLT and may aid in clinical decision-making.

Interaction between cold ischemia time and Kidney Donor Profile Index on postrenal transplant outcomes.

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.

Prevention of Delayed Graft Function in Kidney Transplant Recipients through a Continuous Infusion of the Prostaglandin Analogue Iloprost: A Single-Center Prospective Study.

BACKGROUND: Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. METHODS: This prospective, randomized (1:1), placebo-controlled study enrolled all consecutive patients who received a kidney transplant from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin analogue iloprost at 0.27 µg/min through an elastomeric pump (treatment group) or with a placebo (control group). RESULTS: A total of 476 patients were included: DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that the donor's age > 70 years (OR 2.50, 95% confidence interval (CI): 1.40-3.05, p < 0.001), cold ischemia time > 24 h (OR 2.60, 95% CI: 1.50-4.51, p < 0.001), the donor's acute kidney injury (OR 2.71, 95% CI: 1.61-4.52, p = 0.021) and, above all, the recipient's arterial hypotension (OR 5.06, 95% CI: 2.52-10.1, p < 0.0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p < 0.001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.5 ± 8.3 vs. 13.4 ± 6.7, days, p = 0.016). CONCLUSIONS: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased-donor kidneys, allowing a better graft functionality as well as a better graft survival.

Lung transplantation in HIV seropositive recipients: An analysis of the UNOS registry.

BACKGROUND: Experience with lung transplantation (LT) in patients with human immunodeficiency virus (HIV) is limited. Many studies have demonstrated the success of kidney and liver transplantation in HIV-seropositive (HIV+) patients. Our objective was to conduct a national registry analysis comparing LT outcomes in HIV+ to HIV-seronegative (HIV-) recipients. METHODS: The United Network for Organ Sharing database was queried to identify LTs performed in adult HIV+ patients between 2016 and 2023. Patients with unknown HIV status, multiorgan transplants, and redo transplants were excluded. The primary endpoints were mortality and graft rejection. Survival time was analyzed using Kaplan-Meier analysis. RESULTS: The study included 17 487 patients, 67 of whom were HIV+. HIV+ recipients were younger (59 vs. 62 years, p = .02), had higher pulmonary arterial pressure (28 vs. 25 mm Hg, p = .04), and higher lung allocation scores (47 vs. 41, p = .01) relative to HIV- recipients. There were no differences in graft/recipient survival time between groups. HIV+ recipients had higher rates of post-transplant dialysis (18% vs. 8.4%, p = .01), but otherwise had similar post-transplant outcomes to HIV-recipients. CONCLUSIONS: This national registry analysis suggests LT outcomes in HIV+ patients are not inferior to outcomes in HIV- patients and that well-selected HIV+ recipients can achieve comparable patient and graft survival rates relative to HIV- recipients.

Concepts in B-cell Acute Lymphoblastic Leukemia Pathogenesis.

B-cell acute lymphoblastic leukemia (B-ALL) arises from genetic alterations impacting B-cell progenitors, ultimately leading to clinically overt disease. Extensive collaborative efforts in basic and clinical research have significantly improved patient prognoses. Nevertheless, a subset of patients demonstrate resistance to conventional chemotherapeutic approaches and emerging immunotherapeutic interventions. This review highlights the mechanistic underpinnings governing B-ALL transformation. Beginning with exploring normative B-cell lymphopoiesis, we delineate the influence of recurrent germline and somatic genetic aberrations on the perturbation of B-cell progenitor differentiation and pro-tumorigenic signaling, thereby facilitating the neoplastic transformation underlying B-ALL progression. Additionally, we highlight recent advances in the multifaceted landscape of B-ALL, encompassing metabolic reprogramming, microbiome influences, inflammation, and the discernible impact of socioeconomic and racial disparities on B-ALL transformation and patient survival.

Clinical phenotypes and prognosis of IgG4-related diseases accompanied by deteriorated kidney function: a retrospective study.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a multiorgan autoimmune disorder that causes irreversible injury. Deteriorated kidney functions are common but easily ignored complications associated with IgG4-RD. Yet the clinical manifestations and prognosis of this specific entity have not been fully illustrated. METHOD: Three hundred fifty patients with IgG4-RD were retrospectively enrolled and divided into 119 IgG4-RD with chronic kidney disease (IgG4-RD CKD+) and 231 IgG4-RD without CKD (IgG4-RD CKD-). Demographic clinical and laboratory characteristics and survival of two cohorts were compared using restricted cubic splines, logistic and Cox regression, and Kaplan-Meier analysis. A nomogram was generated for calculating the probability of CKD in IgG4-RD. RESULTS: The spectrum of organ involvement was different between IgG4-RD CKD+ and CKD- cohorts (p<0.001). Lung (26.89%) and retroperitoneum (18.49%) involvement were more common in the IgG4-RD CKD+ cohort. Increased serum potassium and phosphorus, reduced calcium levels, and hypocomplementemia (all p<0.05) were observed in IgG4-RD CKD+. Restricted cubic splines revealed a U-shaped plot regarding associations between serum potassium and CKD. Kaplan-Meier analysis demonstrated significantly lower long-term survival rates in IgG4-RD patients with kidney function at CKD stages 4-5. Cox regression revealed declined kidney functions (G4 HR 6.537 (95% CI: 1.134-37.675)) associated with increased all-cause mortality in IgG4-RD patients. A nomogram was constructed to predict CKD in IgG4-RD promptly with a discrimination (C-index) of 0.846. CONCLUSIONS: CKD in IgG4-RD was associated with poor outcomes and electrolyte disturbances. Patients with IgG4-RD should be aware of possible deterioration in kidney function. The nomogram proposed would help to identify the subtle possibility of CKD in IgG4-RD. Key points • IgG4-related diseases with deteriorated kidney function have specific clinical and laboratory characteristics. • It is crucial to recognize and address the negative impact of deteriorating kidney function in IgG4-related diseases to prevent further harm. • The nomogram proposed would help to identify subtle kidney involvement by evaluating the possibility of CKD in IgG4-related diseases.

Mutational landscape and predictors of survival in head and neck mucosal melanoma.

KEY POINTS: Head and neck mucosal melanomas have a diverse mutational landscape with low mutational burden. A molecular subset (∼13%) has ROS1 mutations, which is an actionable driver mutation. ROS1-mutated patients have improved overall survival likely due to high mutational burden.