bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report of thrombotic thrombocytopenic purpura during pregnancy with a review of the relevant research
Authors: Xu Jia , Tan Li-na , Li Ling-xia , Qiao Gu-Yuan
Published: May 2024

Rationale:

Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more commonly observed in females, particularly during pregnancy. Pregnancy combined with TTP is a critical and rapidly progressing condition that is often misdiagnosed as an obstetric disorder like severe preeclampsia or HELLP syndrome. To deepen the understanding of TTP during pregnancy with the help of a clinical case.

Patient concerns:

A 20-year-old patient, is pregnancy 1 birth 0, 32 weeks dated by her last menstrual period, presented chest tightness, and shortness of breath after physical activity for 3 days.

Diagnoses:

TTP.

Interventions:

At present, there are no preventive measures. Timely diagnosis and treatment are useful. Plasma exchange and treat to the patient hinder autoantibodies, such as gamma globulin, methylprednisolone, rituximab, and cyclosporine were effective.

Outcomes:

The patient exhibited stable vital signs, normal examination results, and experienced no complications. We continued to monitor her progress after she was discharged.

Lessons subsections:

The acute onset of TTP is often associated with pregnancy, as it is a triggering factor. Timely identification, accurate diagnosis, and a comprehensive treatment approach involving plasma exchange, immunosuppressants, and the termination of pregnancy can lead to remission and a favorable outlook for the majority of patients.
Limb salvage and systemic management of gouty tophi: Case series
Authors: Jiang Xiaoyan , Li Anxin , Hao Wei , Yang Cheng , Wang Hongyan , Deng Wuquan
Published: May 2024

Introduction:

Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to ulcerations, cosmetic problems, mechanical obstruction of joint movement, joint damage and musculoskeletal disability. Currently, the treatment of gouty tophi is controversial and challenging. Both surgical and internal medical treatments have limitations and require further exploration in clinical practice.

Patient concerns:

In Case 1, we treated a patient with severe infection of diabetic foot ulcers with concomitant multiple gouty tophi in the same limb. A systematic management strategy was formulated to close the wound and save the limb. The ulcers healed successfully after half a year. In Case 2, a giant gouty tophi located in the first metatarsophalangeal joint of the left foot was removed by surgical treatment and vancomycin-loaded bone cement implantation. In Case 3, we present a case of gouty tophi that was resolved by standardized systemic medical management.

Diagnosis:

Three patients were all diagnosed with gout accompanied by gouty deposition, although there were other different comorbidities.

Interventions:

In case 1, we used debridement to gradually remove gouty tophi. In case 2, the giant gouty tophi was removed by surgical operation. In case 3, the gouty tophi disappeared after standardized treatment with medicine, diet and lifestyle management.

Outcomes:

Three patients underwent different treatment therapies to remove gouty tophi based on their specific conditions.

Lessons:

We explored effective interventions for tophi in gout by surgical or other interventions in combination with pharmacotherapy.
Analysis of short-term ventilation weaning for patients in spontaneous supratentorial intracranial hemorrhage
Authors: Wu Yi-Chieh , Liao Hsiang-Chih , Chou Yu-Ching , Wang Peng-Wei , Chung Ming-Hsuan , Liu Wei-Hsiu
Published: May 2024

Prolonged ventilation is a complication of spontaneous supratentorial hemorrhage patients, but the predictive relationship with successful weaning in this patient cohort is not understood. Here, we evaluate the incidence and factors of ventilation weaning in case of spontaneous supratentorial hemorrhage. We retrospectively studied data from 166 patients in the same hospital from January 2015 to March 2021 and analyzed factors for ventilation weaning. The clinical data recorded included patient age, gender, timing of operation, initial Glasgow Coma Scale (GCS), Intracranial hemorrhage (ICH) score, alcohol drinking, cigarette smoking, medical comorbidity, and the blood data. Predictors of patient outcomes were determined by the Student t test, chi-square test, and logistic regression. We recruited and followed 166 patients who received operation for spontaneous supratentorial hemorrhage with cerebral herniation. The group of successful weaning had 84 patients and the group of weaning failed had 82 patients. The patient’s age, type of operation, GCS on admission to the Intensive care unit (ICU), GCS at discharge from the ICU, medical comorbidity was significantly associated with successful weaning, according to Student t test and the chi-square test. According to our findings, patients with stereotaxic surgery, less history of cardiovascular or prior cerebral infarction, GCS >8 before admission to the hospital for craniotomy, and a blood albumin value >3.5 g/dL have a higher chance of being successfully weaned off the ventilator within 14 days.
Associations between varicose veins and heart failure: A genetic correlation and mendelian randomization study
Authors: Guo Ping , Fang Qin , Wang Yan
Published: May 2024

Varicose veins and heart failure (HF) are increasingly prevalent. Although numbers of observational studies have indicated that varicose veins might contribute to the risk of HF, the causal relationship between them remains unclear due to the uncontrolled confounding factors and reverse causation bias. Therefore, this study aimed to explore the potential causal relationship between varicose veins and HF. Based on publicly released genome-wide association studies (GWAS), gene correlation was assessed using linkage disequilibrium score (LDSC) regression, and we conducted a two-sample Mendelian randomization (TSMR) analysis to infer the causal relationship. We performed the Inverse variance weighted (IVW) method as the primary analysis, and used Weighted median, MR-Egger, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods to detect and correct for horizontal pleiotropy. LDSC revealed there was a positive genetic correlation between varicose veins and HF (rg = 0.1726184, Se = 0.04511803, P = .0001). The results of the IVW method indicated that genetically predicted varicose veins were associated with an increased risk of HF (odds ratio (OR) = 1.03; 95% confidence interval (CI): 1.01–1.06; P = .009). Our findings illustrated the significant causal effect of varicose veins on HF, suggesting that people with varicose veins might have a higher risk of HF. The results provided a novel and important perspective into the development mechanism of HF.
Association between emphysema and other pulmonary computed tomography patterns in primary varicella pneumonia: A retrospective cohort study
Authors: Li Meng , Zhu Guijuan , Guo Yajun , Ye Qing
Published: May 2024

This study aims to evaluate chest computed tomography (CT) findings in hospital patients with primary varicella pneumonia (PVP). We retrospectively analyzed CT images of 77 PVP patients using 3D Slicer, an open-source software, to model lesions and lungs. This retrospective cohort study was approved by the Institutional Review Board (Ethical Committee, Renmin Hospital, Hubei University of Medicine, Shiyan, China) and waived the requirement for written informed consent. The left lung was more frequently and severely affected in PVP, with significant differences between the 2 groups in CT involvement percentage of each lung region, except for total lung inflation. Group A showed higher median percentages of lung collapse compared to Group B. The extent of left lung involvement is a critical predictor of emphysema in PVP patients, highlighting the importance of also monitoring the right lung for more severe cases. Lower emphysema levels correspond to more collapsed and infiltrated lung segments, suggesting a more severe clinical presentation.
The management of goal-directed fluid therapy during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Authors: Tuncel Zeliha , Düzgün Özgül
Published: May 2024

Cytoreductive surgery is a surgical treatment approach that has been applied over the last 3 decades in patients with peritoneal metastases originating from intraabdominal organs. Goal-directed fluid therapy (GDFT) is an approach in which a patient fluid therapy during a medical procedure or surgery is carefully managed based on a specific goal. In this study, we aimed to present the results of GDFT in patients who underwent cytoreductive surgery for peritoneal carcinomatosis (PC) during the perioperative period. This retrospective study included 398 patients patient who underwent cytoreductive surgery + hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) due to PC originating from intraabdominal malignancies. Of the cases, 233 (58.6%) were female, and 165 (41.4%) were male patients. The mean age was 58.9. Perioperative findings revealed an average PC score of 12 (3–24), average lactate levels of 3 (2–7) mmol/L, Pao2/fio2 of 3.3 (2.4–4.1) mm Hg, mean arterial pressure (MAP) of 60 (55–70), average surgery duration of 6.5 hours (3–14), and average blood loss of 400 (200–4000) cc. The mean intraoperative fluid rate was 6.4 mL/kg/h (IQR 5.8–7.1). Sixteen (16.3%) patients experienced Clavien-Dindo Grade 3–4 adverse events. Within 30 days, 25 patients (6.3%) died. CRS + HIPEC procedures utilizing perioperative GDFT along with advanced anesthesia monitoring devices have shown successful application, offering an alternative to traditional and restrictive fluid management approaches.
Network pharmacology and molecular docking technology for exploring the effect and mechanism of high-dose vitamin c on ferroptosis of tumor cells: A review
Authors: Qu Jinxiu , Lu Shuai , Wang Bing , Wang Shiwan , Yang Zhenpeng , Tang Huazhen , He Jia , Zhao Yuan , Wang Xin , Liu Xiaozhu , Rao Benqiang
Published: May 2024

To investigate the mechanism by which high-dose vitamin C (HVC) promotes ferroptosis in tumor cells via network pharmacology, vitamin C-related and ferroptosis-related targets were obtained from the PharmMapper and GeneCards databases, respectively, and their common targets were compared using the Venn diagram. Common targets were imported into the STRING database for protein-protein interaction analysis, and core targets were defined. Core targets were enriched for Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways using the R language packages. A map of the core target-based interaction network and a map of the mechanism by which HVC regulates ferroptosis were constructed. A total of 238 vitamin C-related and 721 ferroptosis-related targets were identified, of which 21 targets were common to both. Furthermore, ALDOA, AHCY, LDHB, HSPA8, LGALS3, and GSTP1 were identified as core targets. GO enrichment analysis suggested that the main biological processes included the extrinsic apoptotic signaling pathway and pyruvate metabolic process. KEGG enrichment analysis suggested that HVC regulates ferroptosis mainly through the amino acid and carbohydrate metabolic pathways. The targets were validated by molecular docking. In conclusion, HVC may promote ferroptosis in tumor cells by regulating metabolic pathways, and there is a synergistic effect between HVC and type I ferroptosis inducers. Glycolysis-dependent tumors may be beneficial for HVC therapy. Our study provides a reference for further clinical studies on HVC antitumor therapy.
A comparative study of two phakic posterior chamber implantable lenses
Authors: Yu Na Hyeon , Kang Kyoung Hae , Tchah Hungwon , Koh Kyungmin
Published: May 2024

This study aimed to compare the postimplantation clinical outcomes of 2 types of posterior chamber phakic intraocular lenses (IOLs): Visian™ implantable collamer lenses (ICL; EVO+ V5; Staar Surgical, Monrovia, CA) and an implantable phakic contact lens (IPCL) (IPCL V2.0, Care Group Sight Solution, India) to correct high myopia and myopic astigmatism. This retrospective study included patients who had undergone phakic IOL implantation performed by a single surgeon between March 2021 and March 2022. Preoperative assessments included slit-lamp examination, fundus examination, spherical equivalent, uncorrected distant visual acuity (UDVA), corrected distant visual acuity (CDVA), specular microscope parameters, and optical quality analysis system parameters. Postoperative assessments after 1 year included slit-lamp examination to detect adverse effects and spherical equivalent, UDVA, CDVA, specular microscope, optical quality analysis system, and anterior-segment optical coherence tomography. Eighty eyes from 42 patients (47 eyes from 24 patients in the ICL group and 33 eyes from 18 patients in the IPCL group) were included. No statistically significant differences were observed between the 2 groups regarding preoperative parameters. At 1-year postoperatively, the mean UDVA in the ICL and IPCL groups was 0.019 ± 0.040 logMAR and 0.019 ± 0.041 logMAR, respectively. The mean CDVA was 0.001 ± 0.008 logMAR and 0.001 ± 0.007 logMAR in the ICL and IPCL groups, respectively, showing no statistically significant differences. The postoperative parameters did not differ significantly between the 2 groups. The visual acuity and refractive results of both groups were excellent, and both groups exhibited similar efficacy and safety profiles.
Potential mechanism of Chai Gui Zexie Decoction for NSCLC treatment assessed using network pharmacology, bioinformatics, and molecular docking: An observational study
Authors: Lin Manbian , Zhao Aiping , Chen Bishan
Published: May 2024

To explore the potential mechanism of Chai Gui Zexie Decoction for non-small cell lung cancer (NSCLC) treatment using network pharmacology, bioinformatics, and molecular docking. The active ingredients of Chai Gui Zexie Decoction and the associated predicted targets were screened using the TCMSP database. NSCLC-related targets were obtained from GeneCards and OMIM. Potential action targets, which are intersecting drug-predicted targets and disease targets, were obtained from Venny 2.1. The protein–protein interaction network was constructed by importing potential action targets into the STRING database, and the core action targets and core ingredients were obtained via topological analysis. The core action targets were entered into the Metascape database, and Gene Ontology annotation analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Differentially expressed genes were screened using the Gene Expression Omnibus, and the key targets were obtained by validating the core action targets. The key targets were input into The Tumor IMmune Estimation Resource for immune cell infiltration analysis. Finally, the molecular docking of key targets and core ingredients was performed. We obtained 60 active ingredients, 251 drug prediction targets, and 2133 NSCLC-related targets. Meanwhile, 147 potential action targets were obtained, and 47 core action targets and 40 core ingredients were obtained via topological analysis. We detected 175 pathways related to NSCLC pharmaceutical therapy. In total, 1249 Gene Ontology items were evaluated. Additionally, 3102 differential genes were screened, and tumor protein P53, Jun proto-oncogene, interleukin-6, and mitogen-activated protein kinase 3 were identified as the key targets. The expression of these key targets in NSCLC was correlated with macrophage, CD4+ T, CD8+ T, dendritic cell, and neutrophil infiltration. The molecular docking results revealed that the core ingredients have a potent affinity for the key targets. Chai Gui Zexie Decoction might exert its therapeutic effect on NSCLC through multiple ingredients, targets, and signaling pathways.
Renal disease associated with multiple sclerosis: A narrative review
Authors: Elendu Chukwuka , Amaechi Dependable C. , Elendu Tochi C. , Ozigis Mutalib O. , Adegbola Michael O. , Adebayo Mololuwa A. , Afolabi Oluwatosin G.
Published: May 2024

Multiple sclerosis (MS) is a chronic autoimmune neurological disorder characterized by central nervous system demyelination, leading to various neurological impairments. While the primary focus of research and clinical management has centered on the neurological aspects of MS, emerging evidence suggests a complex interplay between MS and renal disease. This narrative review endeavors to elucidate the intriguing association between MS and renal disease, providing a comprehensive overview of the current knowledge on this topic. Our review begins by outlining the pathophysiology of MS and the diverse mechanisms contributing to its progression. We then delve into renal disease, categorizing the various types and their clinical presentations. This review focuses on exploring the intricate relationship between these seemingly distinct conditions. We analyze existing literature to uncover shared risk factors, potential pathophysiological links, and the impact of MS on renal function. Furthermore, we discuss the clinical presentation and diagnostic challenges in identifying renal disease in MS patients. Importantly, we examine available treatment options and their efficacy in managing renal complications in this unique patient population. The consequences of renal disease on the overall quality of life (QOL) for individuals living with MS are also examined, shedding light on the multifaceted burden of these coexisting conditions.
5G-enabled smart hospitals: Innovations in patient care and facility management
Authors: Elendu Chukwuka , Elendu Tochi C. , Elendu Ijeoma D.
Published: May 2024

Smart hospitals represent the pinnacle of healthcare innovation, leveraging cutting-edge technologies to transform patient care and facility management. This article addresses the pressing need for effective implementation of 5G technology in smart hospitals, aiming to enhance connectivity, improve patient outcomes, and drive operational efficiency. The methodology employed involves a comprehensive review of existing literature, case studies, and expert insights to analyze the impact of 5G on various aspects of smart hospital operations. The article highlights the significance of 5G technology in enabling real-time data analytics, remote monitoring, and telemedicine, thus revolutionizing healthcare delivery. By providing high-speed, low-latency connectivity, 5G facilitates seamless communication and collaboration among healthcare providers, leading to more efficient diagnosis, treatment, and patient care. Additionally, the adoption of 5G enables smart hospitals to leverage artificial intelligence (AI)-based solutions for predictive analytics, personalized medicine and enhanced patient engagement. Furthermore, the article explores the potential of 5G-enabled smart hospitals in enhancing disaster preparedness and emergency response efforts. Case studies and examples demonstrate how 5G technology can improve situational awareness, coordinate resources, and deliver timely care during natural disasters and pandemics. Overall, this article underscores the transformative impact of 5G technology on smart hospitals and emphasizes the importance of embracing innovation to meet the evolving needs of patients and communities. By adopting 5G technology, smart hospitals can usher in a new era of healthcare delivery characterized by enhanced connectivity, improved patient outcomes, and unparalleled efficiency.
Comparison of fascia iliaca block with quadratus lumborum block for hip arthroplasty: A meta-analysis of randomized controlled trials
Authors: Guo Yunqing , Xia Xiaojing , Deng Jialin
Published: May 2024

Background:

The efficacy of fascia iliaca block (FIB) versus quadratus lumborum block (QLB) remains controversial for pain management of hip arthroplasty. We conduct a systematic review and meta-analysis to explore the influence of FIB versus QLB on the postoperative pain intensity of hip arthroplasty.

Methods:

We have searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through July 2023 for randomized controlled trials assessing the effect of FIB versus QLB on pain control of hip arthroplasty. This meta-analysis is performed using the random-effect model or fixed-effect model based on the heterogeneity.

Results:

Four randomized controlled trials and 234 patients were included in the meta-analysis. Overall, compared with QLB for hip arthroscopy, FIB was associated with substantially lower pain scores at 2 hours (mean difference [MD] = –0.49; 95% CI = –0.63 to –0.35; P < .00001) and pain scores at 12 hours (MD = –0.81; 95% CI = –1.36 to –0.26; P = .004), but showed no impact on pain scores at 24 hours (MD = –0.21; 95% CI = –0.57 to 0.15; P = .25), time to first rescue analgesia (standard mean difference = 0.70; 95% CI = –0.59 to 1.99; P = .29), analgesic consumption (MD = –4.80; 95% CI = –16.57 to 6.97; P = .42), or nausea and vomiting (odd ratio = 0.66; 95% CI = 0.32–1.35; P = .25).

Conclusions:

FIB may be better than QLB for pain control after hip arthroplasty, as evidenced by the lower pain scores at 2 and 24 hours.
Diagnostic performance of unenhanced electrocardiogram-gated cardiac CT for detecting myocardial edema
Authors: Emoto Takafumi , Kidoh Masafumi , Oda Seitaro , Sakabe Daisuke , Morita Kosuke , Hatemura Masahiro , Nakaura Takeshi , Nagayama Yasunori , Inoue Taihei , Funama Yoshinori , Takashio Seiji , Tsujita Kenichi , Hirai Toshinori
Published: May 2024

To assess the diagnostic performance of unenhanced electrocardiogram (ECG)-gated cardiac computed tomography (CT) for detecting myocardial edema, using MRI T2 mapping as the reference standard. This retrospective study protocol was approved by our institutional review board, which waived the requirement for written informed consent. Between December 2017 to February 2019, consecutive patients who had undergone T2 mapping for myocardial tissue characterization were identified. We excluded patients who did not undergo unenhanced ECG-gated cardiac CT within 3 months from MRI T2 mapping or who had poor CT image quality. All patients underwent unenhanced ECG-gated cardiac CT with an axial scan using a third-generation, 320 × 0.5 mm detector-row CT unit. Two radiologists together drew regions of interest (ROIs) in the interventricular septum on the unenhanced ECG-gated cardiac CT images. Using T2 mapping as the reference standard, the diagnostic performance of unenhanced cardiac CT for detecting myocardial edema was evaluated by using the area under the receiver operating characteristic curve with sensitivity and specificity. Youden index was used to find an optimal sensitivity-specificity cutoff point. A cardiovascular radiologist independently performed the measurements, and interobserver reliability was assessed using intraclass correlation coefficients for CT value measurements. A P value of <.05 was considered statistically significant. We included 257 patients who had undergone MRI T2 mapping. Of the 257 patients, 35 patients underwent unenhanced ECG-gated cardiac CT. One patient was excluded from the study because of poor CT image quality. Finally, 34 patients (23 men; age 64.7 ± 14.6 years) comprised our study group. Using T2 mapping, we identified myocardial edema in 19 patients. Mean CT and T2 values for 34 patients were 46.3 ± 2.7 Hounsfield unit and 49.0 ± 4.9 ms, respectively. Mean CT values moderately correlated with mean T2 values (Rho = –0.41; P < .05). Mean CT values provided a sensitivity of 63.2% and a specificity of 93.3% for detecting myocardial edema, with a cutoff value of ≤45.0 Hounsfield unit (area under the receiver operating characteristic curve = 0.77; P < .01). Inter-observer reproducibility in measuring mean CT values was excellent (intraclass correlation coefficient = 0.93; [95% confidence interval: 0.86, 0.96]). Myocardial edema could be detected by CT value of myocardium in unenhanced ECG-gated cardiac CT.
Four-factor Prothrombin Complex Concentrate During Liver Transplantation: A Retrospective Cohort Study
Authors: Lee Jennifer , Rivero Andrea , Renew J. Ross , Spaulding Aaron , Borkar Shalmali , Mckenzie Ian , Davey Kuki , Ladlie Beth
Published: May 2024

Background.

Four-factor prothrombin complex concentrate (PCC) is a plasma product that contains factors II, VII, IX, X, protein C, and protein S. PCC can be used off-label to treat coagulopathy during orthotopic liver transplantation (OLT). However, its use comes with safety concerns regarding thrombosis. The purpose of our study is to determine the safety of PCC in OLT.

Methods.

We conducted a retrospective cohort study of patients who received 4-factor PCC during OLT at our institution from January 1, 2018, to May 1, 2022, with a 1:1 match of 83 patients who received PCC and 83 patients who did not. We evaluated 30-d mortality, 1-y mortality, prevalence of thrombotic complications (portal vein thrombosis, deep venous thrombosis, myocardial infarction, and pulmonary embolus), and postoperative intensive care (ICU) length of stay (LOS).

Results.

There was no significant difference in 30-d mortality (odds ratio [OR] 5; 95% confidence interval [CI], 0.58-42.8; P = 0.14), 1-y mortality (OR 3; 95% CI, 0.61-14.86; P = 0.18), or ICU LOS (OR –13.8; 95% CI, –39.2 to 11.6; P = 0.29). There was no increased incidence of thrombotic complications among patients receiving PCC 90 d after surgery, including portal vein thrombosis (OR 1.5; 95% CI, 0.42-5.32; P = 0.53), pulmonary embolus (OR 1; 95% CI, 0.14-7.1; P = 0.99), deep venous thrombosis (OR 0.67; 95% CI, 0.11-3.99; P = 0.66), and myocardial infarction (OR 1.67; 95% CI, 0.4-6.97; P = 0.48).

Conclusions.

Although there was a statistically insignificant increase in mortality after PCC administration during OLT, we did not see a significant increase in perioperative complications, including thrombotic events and increased ICU LOS.
Management and Outcomes of Kidney Transplant Candidates With Severe Pulmonary Hypertension: A Single-center Strategy and Experience
Authors: Kumar Dhiren , Raju Nihar , Prajapati Bhupinder , Moinuddin Irfan , Tripathi Shreyank , Grinnan Daniel , Thomas Deepak , Gupta Gaurav
Published: May 2024

Background.

Severe pulmonary hypertension (PH) is associated with high mortality posttransplant and thus is considered a contraindication to kidney transplantation. In this study, we describe the pretransplant management and posttransplant outcomes in patients with severe PH using a multidisciplinary approach.

Methods.

Between 11 of 2013 and 8 of 2022, we identified all patients with severe PH on initial pretransplant workup who underwent ultrafiltration (UF) or medical therapy for PH before transplant. Posttransplant we evaluated the perioperative course, renal function, graft, and patient survival. We compared survival to those who remained waitlisted or were delisted.

Results.

Three-two patients (mean age = 55.03 ± 10.22 y) diagnosed with severe PH on pretransplant screening echocardiogram. Thirty patients (94%) were subjected to a median of 4 (range, 3–8) UF sessions with an average weight loss of 4.33 ± 2.6 kg. Repeat assessment of PH revealed a decline in mean pulmonary artery systolic pressure from 67 ± 12 mm Hg to 43 ± 13 mm Hg (P < 0.0001). Seventeen patients (53%) received a kidney transplant. The mean estimated Glomerular Filtration Rate at 3, 6, 9, and 12 mo was 72 ± 27, 72 ± 28, 75 ± 29, and 75 ± 29 mL/min/1.73 m2. Among, those who underwent transplantation both graft and patient survival was 100% at 1-y posttransplant. Overall, since the UF intervention, at a median follow-up of 88 ± 12 mo those transplanted had a patient survival of 88% while those who remained on dialysis had a survival of 53% (P = 0.0003).

Conclusion.

In this single-center study, we report postcapillary PH can be a significant contributor to elevations in pulmonary artery systolic pressure. Using a multidisciplinary approach, PH can improve with volume removal and phosphodiesterase 5 inhibitors therapy leading to a successful posttransplant outcome.
The Role of the Urobiome in Kidney Transplantation: A Systematic Review
Authors: Costa Silva Alberto , Pina-Vaz Teresa , Morgado Afonso , Martins-Silva Carlos , Antunes-Lopes Tiago , Alturas Silva João
Published: May 2024

Background.

The urinary microbiome, also known as the urobiome, was traditionally considered sterile. However, emerging evidence suggests its presence in the urinary tract. Urobiome dysbiosis has been associated with various urologic conditions, making it a topic of interest also in kidney transplantation. This systematic review examines the evidence of urobiome changes in kidney transplant recipients (KTRs).

Methods.

Systematic literature searches in the PubMed and SCOPUS databases.

Results.

Of the 770 articles identified, 8 met the inclusion criteria. The urobiome showed reduced diversity in KTRs compared with healthy controls and patients on dialysis. Proteobacteria enrichment was associated with graft stability or spontaneous tolerance in KTRs without immunological events. Kidney interstitial fibrosis and tubular atrophy were associated with changes in resident urinary microbes and increased pathogenic bacteria. Additionally, KTRs with chronic allograft dysfunction had a higher prevalence of Corynebacterium.

Conclusions.

The review highlights the importance of studying the urobiome in KTRs and its potential impact on transplant outcomes. The field remains largely unexplored, and further research is needed to establish consistent study designs and objectives. Future studies could lead to biomarker discovery, personalized therapies, and improved outcomes and graft survival in KTRs.
Long-term Safety in Epstein–Barr Virus–Seropositive Kidney-only Transplant Recipients Treated With Belatacept in Clinical Practice: Final Study Results From the ENLiST Registry
Authors: Larsen Christian P. , Vincenti Flavio , D. Kou Tzuyung , Shadur Craig A. , Bresnahan Barbara , Jordan Stanley C. , Woodle E. Steve , Goes Nelson , Vella John , Wojciechowski David , Polinsky Martin S. , Gomez-Caminero Andres
Published: May 2024

Background.

Belatacept, a selective T-cell costimulation blocker, was associated with improved survival and renal function but also with a risk of posttransplant lymphoproliferative disorder (PTLD) in adult kidney transplant recipients in phase 3 trials. This registry examined long-term safety in Epstein–Barr virus (EBV)–seropositive kidney transplant recipients treated with belatacept.

Methods.

This US-based, prospective, voluntary, multicenter registry (Evaluating Nulojix Long-Term Safety in Transplant [ENLiST]) included adult EBV-seropositive kidney-only transplant recipients treated de novo (within 14 d of transplantation) with belatacept. Primary objectives were to estimate incidence rates of confirmed PTLD, central nervous system (CNS) PTLD, and progressive multifocal encephalopathy (PML). The minimum follow-up was 2 y.

Results.

Of 985 enrolled transplant recipients, 933 EBV-seropositive patients received belatacept, with 523 (56.1%) receiving concomitant tacrolimus at transplant (for up to 12 mo). By study end, 3 cases of non-CNS PTLD (incidence rate, 0.08/100 person-years), 1 case of CNS PTLD (0.03/100 person-years), and no cases of PML had been reported. Two patients with non-CNS PTLD received concomitant belatacept and tacrolimus and 1 received belatacept and lymphocyte-depleting therapy. Incidence rates were comparable between patients who received concomitant belatacept and tacrolimus and those who did not receive tacrolimus (0.09/100 person-years and 0.07/100 person-years, respectively; P = 0.96). Two of 4 patients with PTLD died, and 2 were alive at the end of the study. Cumulatively, 131 graft losses or deaths were reported by study end.

Conclusions.

Our results from the ENLiST registry, a large, prospective real-world study, showed that the incidence rates of PTLD and CNS PTLD in belatacept-treated EBV-seropositive transplant recipients were consistent with findings from previous phase 3 trials.
Left Ventricular Hypertrophy After Renal Transplantation: Systematic Review and Meta-analysis
Authors: Tian Zhejia , Bergmann Kai , Kaufeld Jessica , Schmidt-Ott Kai , Melk Anette , Schmidt Bernhard M.W.
Published: May 2024

Background.

Left ventricular hypertrophy (LVH) in patients with end stage renal disease undergoing renal replacement is linked to an increased risk for cardiovascular diseases. Dialysis does not completely prevent or correct this abnormality, and the evidence for kidney transplantation (KT) varies. This analysis aims to explore the relationship between KT and LVH.

Methods.

MEDLINE and Scopus were systematically searched in October 2023. All cross-sectional and longitudinal studies that fulfilled our inclusion criteria were included. Outcome was left ventricular mass index (LVMI) changes. We conducted a meta-analysis using a random effects model. Meta-regression was applied to examine the LVMI changes dependent on various covariates. Sensitivity analysis was used to handle outlying or influential studies and address publication bias.

Results.

From 7416 records, 46 studies met the inclusion criteria with 4122 included participants in total. Longitudinal studies demonstrated an improvement of LVMI after KT −0.44 g/m2 (−0.60 to −0.28). Blood pressure was identified as a predictor of LVMI change. A younger age at the time of KT and well-controlled anemia were also associated with regression of LVH. In studies longitudinally comparing patients on dialysis and renal transplant recipients, no difference was detected −0.09 g/m2 (−0.33 to 0.16). Meta-regression using changes of systolic blood pressure as a covariate showed an association between higher blood pressure and an increase in LVMI, regardless of the modality of renal replacement treatment.

Conclusions.

In conclusion, our results indicated a potential cardiovascular benefit, defined as the regression of LVH, after KT. This benefit was primarily attributed to improved blood pressure control rather than the transplantation itself.
Clinical Characterization of Veterans With Alzheimer Disease by Disease Severity in the United States
Authors: Morin Peter , Aguilar Byron J. , Berlowitz Dan , Zhang Raymond , Tahami Monfared Amir Abbas , Zhang Quanwu , Xia Weiming
Published: May 2024

Purpose:

We aimed to examine the clinical characteristics of US veterans who underwent neurocognitive test score-based assessments of Alzheimer disease (AD) stage in the Veterans Affairs Healthcare System (VAHS).

Methods:

Test dates for specific stages of AD were referenced as index dates to study behavioral and psychological symptoms of dementia (BPSD) and other patient characteristics related to utilization/work-up and time to death.

Patients:

We identified veterans with AD and neurocognitive evaluations using the VAHS Electronic Health Record (EHR).

Results:

Anxiety and sleep disorders/disturbances were the most documented BPSDs across all AD severity stages. Magnetic resonance imaging, neurology and psychiatry consultations, and neuropsychiatric evaluations were slightly higher in veterans with mild AD than in those at later stages. The overall average time to death from the first AD severity record was 5 years for mild and 4 years for moderate/severe AD.

Conclusion:

We found differences in clinical symptoms, healthcare utilization, and survival among the mild, moderate, and severe stages of AD. These differences are limited by the low documentation of BPSDs among veterans with test score-based AD stages. These data support the hypothesis that our cohorts represent coherent subgroups of patients with AD based on disease severity.
Highlights from the 2023 International Meeting on the Molecular Biology of Hepatitis B virus
Authors:   HBV2023, Allweiss Lena , Cohen Chari , Dias Joao , Fumagalli Valeria , Guo Haitao , Harris James M. , Hu Jianming , Iannacone Matteo , Isogawa Masanori , Jeng Wen-Juei , Kim Kyun-Hwan , Kramvis Anna , Li Wenhui , Lucifora Julie , Muramatsu Masamichi , Neuveut Christine , Ploss Alexander , Pollicino Teresa , Protzer Ulrike , Tan Anthony , Tanaka Yasuhito , Tu Thomas , Tsukuda Senko , Thimme Robert , Urban Stephan , Watashi Koichi , Yuan Zhenghong , Yeh Shiou-Hwei , McKeating Jane A. , Revill Peter A.
Published: May 2024

Since its discovery in 1965, our understanding of the hepatitis B virus (HBV) replication cycle and host immune responses has increased markedly. In contrast, our knowledge of the molecular biology of hepatitis delta virus (HDV), which is associated with more severe liver disease, is less well understood. Despite the progress made, critical gaps remain in our knowledge of HBV and HDV replication and the mechanisms underlying viral persistence and evasion of host immunity. The International HBV Meeting is the leading annual scientific meeting for presenting the latest advances in HBV and HDV molecular virology, immunology, and epidemiology. In 2023, the annual scientific meeting was held in Kobe, Japan and this review summarises some of the advances presented at the Meeting and lists gaps in our knowledge that may facilitate the development of new therapies.
The emergence and circulation of human immunodeficiency virus (HIV)-1 subtype C
Authors: Li Xingguang , Tamim Sana , Trovão Nídia S.
Published: May 2024

Introduction. Human immunodeficiency virus (HIV)-1 subtype C is the most prevalent globally and is thought to have originated in non-human primates in the Democratic Republic of Congo.

Hypothesis/Gap Statement. Although the global dominance of HIV-1 subtype C is well established, a thorough understanding of its evolutionary history and transmission dynamics across various risk populations remains elusive. The current knowledge is insufficient to fully capture the global diversification and dissemination of this subtype.

Aim. We for the first time sought to investigate the global evolutionary history and spatiotemporal dynamics of HIV-1 subtype C using a selection of maximum-likelihood-based phylodynamic approaches on a total of 1210 near full-length genomic sequences sampled from 32 countries, collected in 4 continents, with sampling dates between 1986–2019 among various risk groups were analysed.

Methodology. We subsampled the HIV-1 subtype C genomic datasets based on continent and risk group traits, and performed nucleotide substitution model selection analysis, maximum likelihood (ML) phylogenetic reconstruction, phylogenetic tree topology similarity analysis, temporal signal analysis and traced the timings of viral spread both geographically and by risk group.

Results. Based on the phylodynamic analyses of four datasets (full1210, locrisk626, loc562 and risk393), we inferred the time to the most recent common ancestor (TMRCA) in the 1930s and an evolutionary rate of 0.0023 substitutions per site per year. The total number of introduction events of HIV-1 subtype C between continents and between risk groups is estimated to be 71 and 115, respectively. The largest number of introductions occurred from Africa to Europe (n=32), from not-recorded to heterosexual (n=40) and from heterosexual to not-recorded (n=51) risk groups.

Conclusion. Our results emphasize that HIV subtype C has mainly spread from Africa to Europe, likely through heterosexual transmission.
Integrated combinatorial functional genomics and spatial transcriptomics of tumors decodes genotype to phenotype relationships
Authors: Breinig Marco , Lomakin Artem , Heidari Elyas , Ritter Michael , Rukhovich Gleb , Böse Lio , Butthof Luise , Wendler-Link Lena , Wiethoff Hendrik , Poth Tanja , Sahm Felix , Schirmacher Peter , Stegle Oliver , Gerstung Moritz , Tschaharganeh Darjus F.
Published: May 2024

Linking the complex genetic changes underlying cancer to relevant disease-phenotypes poses a challenge. Therefore, we present CHOCOLAT-G2P, a scalable approach that integrates multiplex in vivo functional genomics with spatial transcriptomics. By redeploying RNA-templated ligation probes of commercial spatial transcriptomics technology, we streamline mapping composite genetic alterations and transcriptome-wide phenotyping on the same tissue section on a single readout platform. Using this framework, we studied combinatorial effects of 8 perturbations that induce autochthonous mosaic liver tumors sampled from 256 genotypes. Interrogating 324 tumors across six ∼6×6 mm2sections, we charted phenotypic landscapes of genotypically-defined tumor ecosystems, revealing zonation-associated hepatocellular carcinoma subclasses and associations between tumor subtypes and stromal-as well as immune-cell signatures. Further, we decoded epistasis within compound genotypes uncovering opposing roles ofVegfaand mutantCtnnb1to cholangiocarcinoma development. Thus, CHOCOLAT-G2P lays a foundation to decipher how combinations of alterations interact to reprogram tumor cells and their microenvironment within the holistic context of tissue and whole organisms. (https://chocolat-g2p.dkfz.de/).
Transient evolutionary epidemiology of viral adaptation and lethal mutagenesis
Authors: Guillemet Martin , Hardy Erwan , Roze Denis , Gandon Sylvain
Published: May 2024

Beneficial mutations drive the within-host adaptation of viral populations and can prolong the duration of host infection. Yet, most mutations are not adaptive and the increase of the mean fitness of viral populations is hampered by deleterious and lethal mutations. Because of this ambivalent role of mutations, it is unclear if a higher mutation rate boosts or slows down viral adaptation. Here we study the interplay between selection, mutation, genetic drift and within-host dynamics of viral populations. We obtain good approximations for the transient evolutionary epidemiology of viral adaptation under the assumption that the mutation rate is high and the effects of non-lethal mutations remain small. We use this theoretical framework to discuss the feasibility of lethal mutagenesis to treat viral infections in the light of quantitative predictions we obtained for the critical mutation rates of a range of different viruses.
Pre-existing stem cell heterogeneity dictates clonal responses to acquisition of cancer driver mutations
Authors: Singh Indranil , Fernandez-Perez Daniel , Sanchez-Sanchez Pedro , Rodriguez-Fraticelli Alejo E
Published: May 2024

Cancer cells display wide phenotypic variation even across patients with the same mutations. Differences in the cell of origin provide a potential explanation, but these assays have traditionally relied on surface markers, lacking the clonal resolution to distinguish heterogeneous subsets of stem and progenitor cells. To address this challenge, we developed STRACK, an unbiased framework to longitudinally trace clonal gene expression and expansion dynamics before and after acquisition of cancer mutations. We studied two different leukemia driver mutations, Dnmt3a-R882H and Npm1cA, and found that the response to both mutations was highly variable across different stem cell states. Specifically, a subset of differentiation-biased stem cells, which normally become outcompeted with time, can efficiently expand with both mutations. Npm1c mutations surprisingly reversed the intrinsic bias of the clone-of-origin, with stem-biased clones giving rise to more mature malignant states. We propose a clonal reaction norm, in which pre-existing clonal states show different cancer phenotypic potential.
Suppression of miRs-497/195 axis possibly confers endocrine therapy resistance via elevated expression of FLT4 and the noncoding RNA MIR503HG
Authors: Pramanik Saheli , Das Partha , Mukherjee Monalisa , Desai Kartiki V.
Published: May 2024

Background

Endocrine therapy resistance (ETR) in breast cancer is achieved via multiple pathways including a decrease in ER, dysregulation of cell cycle genes, and/or mutations in ER/co-activators/co-repressors. We have reported earlier that high expression of Jumonji domaining containing protein 6 (JMJD6) induced ETR by depleting ER expression. In this study, 3 cellular models representing distinct ETR pathways; Tamoxifen resistant (TAMR), Long-term Estrogen deprived (LTEDI), JMJD6 overexpressing (JOE) cells, and parental MCF7 were subjected to RNA-sequencing, CNC, and ceRNA network analysis. We hypothesised that post-comparison RNA regulations that are common to all cell lines, will reveal actionable markers and targets. These will be shared by all patients with ET-resistant disease, independent of the initiating event.

Results

170 differentially expressed genes were found, of these, 73 maintained the same directionality in expression (ETR cassette genes). These genes segregated TCGA ER+ tumors into two groups, one intermixing with ER-tumors. Pathway-based curation of ETR genes identified 21 genes (7 up- and 14 down-regulated) that participated in multiple cancer hallmark pathways. Genes upregulated in ETR cells were less expressed in ER+ tumors at diagnosis when compared to normal breast samples but their higher expression indicated adverse survival outcomes. Next, these genes were used for CNC and ceRNA network construction and a triad FLT4:MIR503HG:miR-497/195/424 was discovered. The expression levels of miRNAs were predicted via network analysis and quantitative RT-PCR was used to validate the down regulation of miR-497/195/424 and upregulation of their targets, FLT4 and MIR503HG in ETR cells.

Conclusions

We show that total RNA-seq data can be successfully used to predict actionable miRNAs that achieve drug resistance. Re-expression of ETR genes such as FLT4 in tumor cells, that are less expressed at diagnosis, may be indicative of ETR onset. Finally, ETR may arise due to suppression of miR-424/497/195 leading to higher expression of FLT4 and MIR503HG. We posit that FLT4 may be a suitable target and RT-PCR analysis of this RNA triad could be developed as a detection strategy for ETR in ER+ breast cancer.
Clinical considerations on antimicrobial resistance potential of complex microbiological samples
Authors: Solymosi Norbert , Tóth Adrienn Gréta , Nagy Sára Ágnes , Csabai István , Feczkó Csongor , Reibling Tamás , Németh Tibor
Published: May 2024

Antimicrobial resistance (AMR) is one of our greatest public health challenges. Targeted use of antibiotics (AB) can reduce the occurrence and spread of AMR and boost the effectiveness of treatment. This requires knowledge of the antibiotic susceptibility (AS) of the pathogens involved in the disease. Therapeutic recommendations based on classical antibiotic susceptibility testing (AST) are based on the analysis of only a fraction of the bacteria present in the disease process. Next and third generation sequencing technologies allow the identification of antimicrobial resistance genes (ARGs) present in a bacterial community. Using this genomic approach, we can map the antimicrobial resistance potential (AMRP) of a complex, multi-bacterial microbial sample. The same approach can be used to identify antibiotics without any ARGs in the sample that interfere with their activity. Our paper summarises the clinical interpretation opportunities of genomic analysis results from 574Escherichia colistrains and a complex microbiological sample from canine external otitis. In clinical metagenomics, AMRP may be an important approach to make AB therapy more targeted and effective.

Graphical abstract