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Long-term outcomes of kidney transplantation from expanded criteria donors with Chinese novel donation policy: donation after citizens’ death

BMC Nephrol. 2022 Oct 3;23(1):325. doi: 10.1186/s12882-022-02944-y.

ABSTRACT

INTRODUCTION: The Chinese Government initiated the Donation after Citizens’ Death policy in 2010. To now, it has been a major source of organs for transplant. Since it is still a young policy, corresponding clinical evidence is still urgently needed for its improvement. Compared to kidneys donated by SCD (standard criteria donor), increasing the use of ECD (expanded criteria donor) derived kidneys is a way to expand the donor pool but is also a result of the aging demography of China. This study is based on the data of kidney transplantation in our center with the Donation after Citizens’ Death policy, aiming to provide a reference for the clinical use of ECD kidneys.

METHOD: A retrospective study enrolled 415 kidney transplants derived from 211 donors performed between October 2011 and October 2019. A total of 311 (74.9%) organs were donated from 159 (75.4%) SCDs, and the remaining 104 (25.1%) were from 52 (24.6%) ECDs. The log-rank test was used to compare the difference in survival and postoperative complications. The Chi-square test was used to compare the occurrence of postoperative complications and postoperative renal function. The Cox regression analysis was used for risk factor screening.

RESULT: Analysis showed that grafts from ECD were poorer in survival (P = 0.013), while their recipients had comparable (P = 0.16) survival. Moreover, it also was an independent risk factor for graft loss (HR 2.27, P = 0.044). There were significantly more AR occurrences in the ECD group compared with SCD group (25.0% vs. 15.8%, P = 0.004), but no significant difference was found in infection (51.9% vs. 47.6%, P = 0.497) and DGF (26.0% vs. 21.9%, P = 0.419) between them. Similarly, fewer recipients in the ECD group were free from AR within 1 year after transplantation (P = 0.040), with no statistical difference in all-cause infection prevalence in 1 year (P = 0.168). The eGFR in the ECD group was significantly worse than that in the SCD group at 3 months, 6 months, 1 year, 3 years, and the highest value posttransplant (all < 0.05), but no difference at 5 years posttransplant. Besides, results showed cardiac arrest (uncontrolled vs. controlled, HR 2.49, P = 0.049), HLA mismatch (4-6 loci vs. 0-3 loci, HR 3.61, P = 0.039), and AR occurrence (HR 2.91, P = 0.006) were demonstrated to be independent risk factors for graft loss.

CONCLUSION: The ECD-derived kidney was worse than the SCD-derived kidney in terms of graft survival and AR occurrence, and trend to an inferior renal function postoperative. However, the recipient survival, DGF occurrence, and all-cause infection occurrence were similar.

PMID:36184632 | DOI:10.1186/s12882-022-02944-y

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Comprehensive characterization of ubiquitinome of human colorectal cancer and identification of potential survival-related ubiquitination

J Transl Med. 2022 Oct 2;20(1):445. doi: 10.1186/s12967-022-03645-8.

ABSTRACT

BACKGROUND: According to the Global Cancer Statistics in 2020, the incidence and mortality of colorectal cancer (CRC) rank third and second among all tumors. The disturbance of ubiquitination plays an important role in the initiation and development of CRC, but the ubiquitinome of CRC cells and the survival-relevant ubiquitination are poorly understood.

METHODS: The ubiquitinome of CRC patients (n = 6) was characterized using our own data sets of proteomic and ubiquitin-proteomic examinations. Then, the probable survival-relevant ubiquitination was searched based on the analyses of data sets from public databases.

RESULTS: For the ubiquitinomic examination, we identified 1690 quantifiable sites and 870 quantifiable proteins. We found that the highly-ubiquitinated proteins (n ≥ 10) were specifically involved in the biological processes such as G-protein coupling, glycoprotein coupling, and antigen presentation. Also, we depicted five motif sequences frequently recognized by ubiquitin. Subsequently, we revealed that the ubiquitination content of 1172 proteins were up-regulated and 1700 proteins were down-regulated in CRC cells versus normal adjacent cells. We demonstrated that the differentially ubiquitinated proteins were relevant to the pathways including metabolism, immune regulation, and telomere maintenance. Then, integrated with the proteomic datasets from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) (n = 98), we revealed that the increased ubiquitination of FOCAD at Lys583 and Lys587 was potentially associated with patient survival. Finally, we depicted the mutation map of FOCAD and elucidated its potential functions on RNA localization and translation in CRC.

CONCLUSIONS: The findings of this study described the ubiquitinome of CRC cells and identified abnormal ubiquitination(s) potentially affecting the patient survival, thereby offering new probable opportunities for clinical treatment.

PMID:36184622 | DOI:10.1186/s12967-022-03645-8

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The design and evaluation of hybrid controlled trials that leverage external data and randomization

Nat Commun. 2022 Oct 2;13(1):5783. doi: 10.1038/s41467-022-33192-1.

ABSTRACT

Patient-level data from completed clinical studies or electronic health records can be used in the design and analysis of clinical trials. However, these external data can bias the evaluation of the experimental treatment when the statistical design does not appropriately account for potential confounders. In this work, we introduce a hybrid clinical trial design that combines the use of external control datasets and randomization to experimental and control arms, with the aim of producing efficient inference on the experimental treatment effects. Our analysis of the hybrid trial design includes scenarios where the distributions of measured and unmeasured prognostic patient characteristics differ across studies. Using simulations and datasets from clinical studies in extensive-stage small cell lung cancer and glioblastoma, we illustrate the potential advantages of hybrid trial designs compared to externally controlled trials and randomized trial designs.

PMID:36184621 | DOI:10.1038/s41467-022-33192-1

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Detection of Salmonella Typhi nucleic acid by RT-PCR and anti-HlyE, -CdtB, -PilL, and -Vi IgM by ELISA at sites in Ghana, Madagascar and Ethiopia

BMC Infect Dis. 2022 Oct 2;22(1):766. doi: 10.1186/s12879-022-07726-3.

ABSTRACT

BACKGROUND: We aimed to assess the prevalence of Salmonella Typhi through DNA and IgM-antibody detection methods as a prelude to extended surveillance activities at sites in Ghana, Madagascar, and Ethiopia.

METHODS: We performed species-specific real-time polymerase reaction (RT-PCR) to identify bacterial nucleic acid, and enzyme-linked immunosorbent assay (ELISA) for detecting HlyE/STY1498-, CdtB/STY1886-, pilL/STY4539- and Vi-antigens in blood and biopsy specimens of febrile and non-febrile subjects. We generated antigen-specific ELISA proxy cut-offs by change-point analyses, and utilized cumulative sum as detection method coupled with 1000 repetitive bootstrap analyses. We computed prevalence rates in addition to odds ratios to assess correlations between ELISA outcomes and participant characteristics.

RESULTS: Definitive positive RT-PCR results were obtained from samples of febrile subjects originating from Adama Zuria/Ethiopia (1.9%, 2/104), Wolayita Sodo/Ethiopia (1.0%, 1/100), Diego/Madagascar (1.0%, 1/100), and Kintampo/Ghana (1.0%, 1/100), and from samples of non-febrile subjects from Wolayita Sodo/Ethiopia (1%, 2/201). While IgM antibodies against all antigens were identified across all sites, prevalence rates were highest at all Ethiopian sites, albeit in non-febrile populations. Significant correlations in febrile subjects aged < 15 years versus ≥ 15 years were detected for Vi (Odds Ratio (OR): 8.00, p = 0.034) in Adama Zuria/Ethiopia, STY1498 (OR: 3.21, p = 0.008), STY1886 (OR: 2.31, p = 0.054) and STY4539 (OR: 2.82, p = 0.022) in Diego/Madagascar, and STY1498 (OR: 2.45, p = 0.034) in Kintampo/Ghana. We found statistical significance in non-febrile male versus female subjects for STY1498 (OR: 1.96, p = 0.020) in Adama Zuria/Ethiopia, Vi (OR: 2.84, p = 0.048) in Diego/Madagascar, and STY4539 (OR: 0.46, p = 0.009) in Kintampo/Ghana.

CONCLUSIONS: Findings indicate non-discriminatory stages of acute infections, though with site-specific differences. Immune responses among non-febrile, presumably healthy participants may mask recall and/or reporting bias leading to misclassification, or asymptomatic, subclinical infection signs induced by suppression of inflammatory responses. As most Ethiopian participants were ≥ 15 years of age and not at high-risk, the true S. Typhi burden was likely missed. Change-point analyses for generating ELISA proxy cut-offs appeared robust, though misclassification is possible. Our findings provided important information that may be useful to assess sites prior to implementing surveillance for febrile illness including Salmonella disease.

PMID:36184614 | DOI:10.1186/s12879-022-07726-3

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Feasibility, acceptability, and preliminary efficacy of a single-arm, remotely-delivered health coaching intervention to increase physical activity and reduce sedentary behavior during pregnancy

BMC Pregnancy Childbirth. 2022 Oct 2;22(1):740. doi: 10.1186/s12884-022-05073-4.

ABSTRACT

BACKGROUND: Interventions targeting physical activity and sedentary behavior concurrently in pregnancy may be an ideal strategy to reduce the risk of pregnancy complications. We assessed the feasibility, acceptability, and preliminary efficacy of a single-arm, remotely-delivered health coaching intervention to promote physical activity and reduce sedentary behavior in pregnancy.

METHODS: Women (n = 34) between 8 and 12 weeks gestation were recruited to take part in the INcreasing Steps in PREgnancy (INSPiRE) study. Participants were given an activity tracker (Fitbit Inspire) and met virtually with their health coach throughout the second and third trimesters of pregnancy. Feasibility was based on enrollment, retention, and adherence rates. Acceptance was assessed using a process evaluation survey. Intervention efficacy was based on activPAL data obtained at baseline and the end of the second trimester.

RESULTS: Feasibility objectives were met, with greater than 70% enrollment, 97% retention, and 99% adherence. All participants reported high levels of satisfaction with the program. ActivPAL data indicated statistically significant increases in daily steps (+ 1715.8 steps/day, Cohen’s d = 0.97), stepping time (+ 1.9%, d = 0.75), standing time (+ 2.3%, d = 0.29), and decreases in total sedentary time (- 4.2%, d = 0.43) and sedentary bouts of 30 minutes (- 4.1%, d = 0.36) from baseline to the end of the second trimester, all p < 0.05. Decreases were also observed in sedentary bouts of 60 minutes (- 3.9%, d = 0.40), but this was not statistically significant.

CONCLUSIONS: The INSPiRE study demonstrated feasibility, high acceptability, and preliminary efficacy for improving movement behaviors in women during pregnancy, supporting future testing in a randomized controlled trial.

PMID:36184599 | DOI:10.1186/s12884-022-05073-4

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Clinical value of fetal facial profile markers during the first trimester

BMC Pregnancy Childbirth. 2022 Oct 2;22(1):738. doi: 10.1186/s12884-022-05028-9.

ABSTRACT

OBJECTIVES: To study the correlations between facial profile markers and crown-lump length (CRL) in a Chinese population, and to evaluate the clinical value of these markers for abnormal fetuses during the first trimester (11 to 13+6 gestational weeks). METHODS: The facial profile markers were as followings: inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA), frontal space (FS) distance and profile line (PL) distance. These markers were measured in facial mid-sagittal section through ViewPoint 6 software. The diagnostic value of these markers for abnormal fetuses was assessed by receiver operating characteristic (ROC) curves.

RESULTS: According to the first-trimester scanning (FTS) and follow-up, 31 fetuses were enrolled in the abnormal group, including 14 cases of trisomy 21, 7 cases of trisomy 18, 10 cases with cleft lip and palate (CLP), and 1000 normal fetuses were selected. Among the normal fetuses, the IFA, FS distance and PL distance had negative correlations with CRL. The MNM angle and FMA had positive correlations with CRL. The mean IFA values for fetuses with trisomy 21 and trisomy 18 were 74.11° (standard deviation (SD) 7.48) and 69.88° (SD 7.08), respectively, which were significantly smaller than the normal fetuses (p = 0.013; p = 0.003). The mean MNM angle of fetuses with trisomy 18 and CLP were 6.98° (SD 2.61) and 9.41° (SD 2.57), respectively, which were significantly greater than the normal fetuses (p = 0.005; p < 0.001). The mean FMA values of trisomy 18 fetuses were 63.95° (SD 4.77), which was significantly smaller than the normal fetuses (p < 0.001). The mean FS distance of CLP fetuses was -0.22 mm (SD 1.38), which was significantly smaller than the normal fetuses (p < 0.001). The mean PL distance of trisomy 21, trisomy 18 and CLP fetuses were 2.89 mm (SD 0.41), 2.91 mm (SD 0.56) and 2.71 mm (SD 0.37), respectively. The difference with the normal fetuses had no statistical significance (p = 0.56; p = 0.607; p = 0.54).

CONCLUSIONS: Fetal facial profile markers had excellent correlations with CRL during the first trimester. IFA had certain clinical significance in detecting trisomy 21. FMA, IFA and MNM angle were reliable indicators for screening trisomy 18. The abnormal MNM angle and FS distance could be used as sensitive indicators for CLP. However, PL distance was not the best markers for trisomy 21, trisomy 18 and CLP.

PMID:36184592 | DOI:10.1186/s12884-022-05028-9

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Estimating vaccine effectiveness against SARS-CoV-2 infection, hospitalization and death from ecologic data in Costa Rica

BMC Infect Dis. 2022 Oct 2;22(1):767. doi: 10.1186/s12879-022-07740-5.

ABSTRACT

BACKGROUND: Clinical trials and individual-level observational data in Israel demonstrated approximately 95% effectiveness of mRNA-based vaccines against symptomatic SARS-CoV-2 infection. Individual-level data are not available in many countries, particularly low- and middle- income countries. Using a novel Poisson regression model, we analyzed ecologic data in Costa Rica to estimate vaccine effectiveness and assess the usefulness of this approach.

METHODS: We used national data from December 1, 2020 to May 13, 2021 to ascertain incidence, hospitalizations and deaths within ecologic units defined by 14 age groups, gender, 105 geographic areas, and day of the epidemic. Within each unit we used the proportions of the population with one and with two vaccinations, primarily tozinameran. Using a non-standard Poisson regression model that included an ecologic-unit-specific rate factor to describe rates without vaccination and a factor that depended on vaccine effectiveness parameters and proportions vaccinated, we estimated vaccine effectiveness.

RESULTS: In 3.621 million persons aged 20 or older, there were 125,031 incident cases, 7716 hospitalizations, and 1929 deaths following SARS-CoV-2 diagnosis; 73% of those aged ≥ 75 years received two doses. For one dose, estimated effectiveness was 59% (95% confidence interval 53% to 64%) for SARS-CoV-2 incidence, 76% (68% to 85%) for hospitalizations, and 63% (47% to 80%) for deaths. For two doses, the respective estimates of effectiveness were 93% (90% to 96%), 100% (97% to 100%), and 100% (97% to 100%).

CONCLUSIONS: These effectiveness estimates agree well with findings from clinical trials and individual-level observational studies and indicate high effectiveness in the general population of Costa Rica. This novel statistical approach is promising for countries where ecologic, but not individual-level, data are available. The method could also be adapted to monitor vaccine effectiveness over calendar time.

PMID:36184587 | DOI:10.1186/s12879-022-07740-5

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Impaired Left Atrial Function in Patients with Atrial Septal Defect and History of Atrial Fibrillation

Int Heart J. 2022;63(5):864-873. doi: 10.1536/ihj.22-265.

ABSTRACT

In patients with atrial septal defect (ASD), atrial left-to-right shunting causes left atrial (LA) remodeling and dysfunction, leading to atrial fibrillation (AF). In adults with ASD and concomitant AF, LA function should be evaluated after ASD closure plus AF radiofrequency catheter ablation (RFCA).This multicenter retrospective cohort study included patients who underwent transcatheter ASD closure at one of the four leading hospitals. Patients with a history of AF also underwent preceding RFCA. The association between AF history and LA ejection fraction (EF) (indicating LA global function) at 6-12 months following ASD closure was evaluated. To account for differences in baseline characteristics between patients with and without a history of AF, we conducted the following statistical methods: (1) multivariate regression analysis in the prepropensity score (PS)-matched cohort and (2) univariate comparisons in the PS-matched cohort.Overall, this study included 231 patients (30 with AF history, 201 without). Multiple regression analysis showed that AF history was independently associated with impaired LAEF (β = -10.425, P < 0.001, model created prior to propensity matching). A one-to-one PS matching (25 pairs) showed that the LAEF at 6-12 months following ASD closure was significantly impaired in patients with ASD and AF history compared to that in patients without history of AF (median LAEF, 37.5% (interquartile range [IQR] 29.4%-48.5%) versus 52.3 [IQR 50.0%-56.6%]; P < 0.001).LA function was impaired in patients with ASD and a history of AF at 6-12 months after successful transcatheter ASD closure and on maintenance of sinus rhythm by RFCA.

PMID:36184548 | DOI:10.1536/ihj.22-265

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Scale of psychological pain: Spanish adaptation of the Psychache Scale in young adults

Rev Psiquiatr Salud Ment (Engl Ed). 2022 Sep 29:S2173-5050(22)00044-9. doi: 10.1016/j.rpsmen.2022.09.006. Online ahead of print.

ABSTRACT

INTRODUCTION: Psychological pain is understood as an intolerable and disturbing mental state characterized by an internal experience of negative emotions. This study was aimed at making a Spanish adaptation of the Psychache Scale by Holden and colleagues in a sample of young adults.

MATERIAL AND METHODS: The scale evaluates psychological pain as a subjective experience. It is composed of 13 items with a Likert-type response format. Following the guidelines of the International Tests Commission for the adaptation of the test, we obtained a version conceptually and linguistically equivalent to the original scale. Through an online questionnaire, participants completed the psychological pain scale along with other scales to measure depression (BDI-II), hopelessness (Beck’s scale of hopelessness) and suicide risk (Plutchik suicide risk scale). The participants were 234 people (94 men, 137 women and three people who identified as a different sex) from 18 to 35 years old.

RESULTS: The EFA showed a one-factor solution, and the FCA revealed adequate indexes of adjustment to the unifactorial model. It also showed good reliability of the test scores. The evidence of validity of the scale in relation to the other variables showed high, positive and statistically significant correlations with depression, hopelessness, suicidal ideation and suicidal risk.

CONCLUSION: In summary, this Spanish adaptation of the Psychache Scale could contribute to improving the evaluation of both the patient with suicide risk and the effectiveness of psychological therapy, as well as suicidal behaviour prevention and intervention.

PMID:36184539 | DOI:10.1016/j.rpsmen.2022.09.006

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Targeted Multiparametric Magnetic Resonance Imaging/Ultrasound Fusion Biopsy for Quantitative Gleason 4 Grading Prediction in Radical Prostatectomy Specimens: Implications for Active Surveillance Candidate Selection

Eur Urol Focus. 2022 Sep 29:S2405-4569(22)00217-6. doi: 10.1016/j.euf.2022.09.010. Online ahead of print.

ABSTRACT

BACKGROUND: Quantitative Gleason grading appears to be a reliable prognostic parameter and provides broader risk stratification then the traditional Gleason grading in patients with prostate cancer (PCa) treated with radical prostatectomy (RP).

OBJECTIVE: To determine if quantification of Gleason pattern (GP) 4 for targeted and systematic biopsy (TBx + SBx) cores together with further clinical variables can identify the lowest quantitative GP 4 fraction on RP.

DESIGN, SETTING, AND PARTICIPANTS: A total of 548 patients underwent TBx + SBx of the prostate and then RP, with pathology revealing Gleason score 3 + 4, 4 + 3, or 4 + 4 disease.

INTERVENTION: TBx + SBx of the prostate followed by RP.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: GP 4 fraction thresholds of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% were compared between the TBx + SBx and RP specimens. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy for predicting the GP 4 fraction in the RP specimen were determined. Logistic regression models were used to establish a probabilistic relationship between various combinations of clinical and biopsy variables and the GP 4 fraction in the RP specimen.

RESULTS AND LIMITATIONS: GP 4 fractions of ≤5%, ≤10%, ≤15%, ≤20%, and ≤25% was observed in 33%, 49%, 58%, 65%, and 70% of patients on TBx, and 18%, 41%, 53%, 63%, and 70% of patients on RP, respectively. The sensitivity, specificity, NPV, PPV, and accuracy were 75%, 67%, 91%, 39%, and 74% for a TBx GP 4 fraction of ≤5%, and 65%, 85%, 65%, 85%, and 79% for a TBx GP 4 fraction of ≤25%, respectively. A model combining quantified TBx + SBx GP 4 with clinical parameters demonstrated the highest diagnostic accuracy. Limitations include the retrospective study design.

CONCLUSIONS: Our results demonstrate that the combination of MRI-TBx + SBx and GP 4 quantification allowed precise detection of a low fraction of GP 4 when using RP specimens as the reference standard. Moreover, we found that clinical variables including Prostate Imaging-Reporting and Data System score without biopsy are limited in detection of low GP 4 fractions.

PATIENT SUMMARY: Combination of targeted biopsy alone as well as combined with systematic biopsy and quantitative Gleason grading of biopsy specimen showed high agreement with pathology findings after surgical removal of the prostate. This could help in identifying patients who are suitable for active surveillance.

PMID:36184537 | DOI:10.1016/j.euf.2022.09.010