Validation of donor fraction cell-free DNA with biopsy-proven cardiac allograft rejection in children and adults

ObjectivesDonor-specific cell-free DNA shows promise as a noninvasive marker for allograft rejection, but as yet has not been validated in both adult and pediatric recipients. The study objective was to validate donor fraction cell-free DNA as a noninvasive test to assess for risk of acute cellular rejection and antibody-mediated rejection after heart transplantation in pediatric and adult recipients.MethodsPediatric and adult heart transplant recipients were enrolled from 7 participating sites and followed for 12 months or more with plasma samples collected immediately before all endomyocardial biopsies. Donor fraction cell-free DNA was extracted, and quantitative genotyping was performed. Blinded donor fraction cell-free DNA and clinical data were analyzed and compared with a previously determined threshold of 0.14%. Sensitivity, specificity, negative predictive value, positive predictive value, and receiver operating characteristic curves were calculated.ResultsA total of 987 samples from 144 subjects were collected. After applying predefined clinical and technical exclusions, 745 samples from 130 subjects produced 54 rejection samples associated with the composite outcome of acute cellular rejection grade 2R or greater and pathologic antibody-mediated rejection 2 or greater and 323 healthy samples. For all participants, donor fraction cell-free DNA at a threshold of 0.14% had a sensitivity of 67%, a specificity of 79%, a positive predictive value of 34%, and a negative predictive value of 94% with an area under the curve of 0.78 for detecting rejection. When analyzed independently, these results held true for both pediatric and adult cohorts at the same threshold of 0.14% (negative predictive value 92% and 95%, respectively).ConclusionsDonor fraction cell-free DNA at a threshold of 0.14% can be used to assess for risk of rejection after heart transplantation in both pediatric and adult patients with excellent negative predictive value.     

Miocardio no compactado: ¿una enfermedad o un rasgo fenotípico?

Left ventricular noncompaction is a poorly defined and controversial entity, with wide phenotypic expression: from a simple anatomical trait to a disease with overt cardiac affection. Current diagnostic criteria rely exclusively on morphologic features of hypertrabeculation, which have low specificity for identifying true cardiomyopathy cases. The management of left ventricular noncompaction is also heterogeneous, and there are no dedicated clinical practice guidelines. The most common cardiovascular complications are heart failure, ventricular arrhythmias, and systemic embolisms. In this review, we discuss the diagnostic limitations of the available criteria, and propose a comprehensive alternative approach (including functional imaging variables, tissue characterization, genetics, and family screening) that may help in the differential diagnosis of hypertrabeculation cases. We also describe the genetic background of the disease and discuss the overlap with other cardiomyopathies. Finally, we focus on controversial issues in clinical management and suggest the use of the previously-mentioned variables for risk stratification and for individualization of patient follow-up.     

Registro español de marcapasos. XIX informe oficial de la Asociación del Ritmo Cardiaco de la Sociedad Española de Cardiología (2021)

Introduction and objectivesThis document includes cardiac pacing activity performed in Spain in 2021: figures for implanted devices, demographic and clinical factors, characteristics of the implanted material, and remote monitoring data.MethodsThe European Pacemaker Patient Card, the CardioDispositivos.es online platform, the centers’ own databases and the data provided by the supplier companies are used as sources of information.Results17.360 procedures were registered from 95 hospitals, which represents 43% of the activity. The implantation rates of conventional and resynchronization pacemakers were 822 and 31 units per million population, respectively. 652 leadless pacemakers were implanted. The mean age of implantation is high (78.8 years), and atrioventricular block is the most frequent electrocardiographic abnormality. Dual-chamber pacing mode predominated, nonetheless single-chamber pacing was performed in 19% of patients in sinus rhythm, mainly in the elderly. 28.5% of implanted conventional pacemakers and 56,2% of low-energy resynchronization pacemakers were included in the remote monitoring program.ConclusionsIn 2021 the number of conventional pacemakers increased by 8.3% and resynchronizers by 18.9%, despite the decrease in low-energy resynchronization, probably attributable to the development of physiological pacing. Leadless pacemakers increased by 25%. The expansion of remote monitoring continued, consolidating as a fundamental follow-up method.     

Anatomic vs. reverse shoulder arthroplasty for glenohumeral osteoarthritis with intact rotator cuff: a retrospective comparison of patient-reported outcomes using the systems outcomes database with up to 5-year follow-up

BackgroundThe growing enthusiasm for the use of reverse shoulder arthroplasty (RSA) in the treatment of primary glenohumeral osteoarthritis (GHOA) with an intact rotator cuff is based on data derived from single-center studies with limited generalizability and follow-up. This study compared patient-reported outcomes (PROs) between RSA and total shoulder arthroplasty (TSA) for the treatment of primary GHOA with up to 5-year follow-up and examined temporal trends in the treatment of GHOA between 2012 and 2021.MethodsA retrospective review was performed on patients with primary GHOA undergoing primary arthroplasty surgery from the Surgical Outcomes System global registry between 2012 and 2021. PROs including the American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE) score, and visual analog scale (VAS) for pain were compared between RSA and TSA at 1, 2, and 5 years postoperatively.ResultsA total of 4451 patients were included, with 2693 (60.5%) undergoing TSA and 1758 (39.5%) undergoing RSA. Both RSA and TSA provided clinically excellent outcomes at 1 year postoperatively (ASES: 80.8 ± 17.9 vs. 85.9 ± 15.2, respectively; SANE: 74.8 ± 24.7 vs. 79.5 ± 22.9; VAS pain: 1.3 ± 2.0 vs. 1.1 ± 1.7; all P < .05) that were maintained at 2 years (ASES: 81.3 ± 19.3 vs. 87.3 ± 14.9; SANE: 74.8 ± 26.2 vs. 79.7 ± 24.7; VAS pain: 1.3 ± 2.1 vs. 1.0 ± 1.6; all P < .05) and 5 years (ASES: 81.7 ± 16.5 vs. 86.9 ± 15.3; SANE: 71.6 ± 28.5 vs. 78.2 ± 25.9; VAS pain: 1.0 ± 1.7 vs. 1.0 ± 1.7; all P < .05), with statistical significance favoring TSA. After controlling for age and sex, there was an adjusted difference of 4.5 units in the ASES score favoring TSA (P = .005) at 5 years postoperatively but no differences in adjusted SANE (P = .745) and VAS pain (P = .332) scores. The use of RSA for GHOA grew considerably over time, from representing only 17% of all replacements performed for GHOA in 2012 to nearly half (47%) in 2021 (P < .001).ConclusionRSA as a treatment for GHOA with an intact rotator cuff seems to yield PROs that are largely clinically equivalent to TSA extending to 5 years postoperatively. The observed statistical significance favoring TSA appears to be of marginal clinical benefit based on established minimal clinically important differences and may be a result of the large sample size. Further research using more granular clinical data and examining differences in range of motion and complications is warranted as it may change the value analysis.     

基层医生的儿童功能性便秘诊疗能力研究

背景 功能性便秘（FC）是儿童常见健康问题，也是儿童父母在基层医疗卫生机构门诊就诊中咨询频率较高的问题。尽管便秘不是急症，但如果处理不当，可能会引起严重的并发症，进而影响儿童及其家庭的生活质量。 目的 了解基层医生的儿童FC诊疗水平，为针对性提高基层医生的儿童FC诊疗与管理能力提供依据。 方法 于2020年7月，在北京市西城区基层医疗卫生机构中选取在日常诊疗中能接触到儿童患者的医生130例。采用本研究组自行设计的问卷对纳入医生开展调查，内容包括对≥6个月儿童FC诊断中常见症状的认知，以及对儿童FC的推荐治疗方法、推荐治疗药物、药物治疗时机及治疗持续时间等。 结果 108例（83.1%）基层医生的问卷被有效回收，其中全科医生34例（31.5%）、儿科医生30例（27.8%）、中医科医生30例（27.8%），平均每月门诊接触儿童患者（10.1±4.4）例。对于儿童FC的诊断：当≥6个月患儿出现排便次数少、大便坚硬、排便时出血、大便失禁、排便困难、排出稠便前哭泣症状时，分别有40.7%（44/108）、39.8%（43/108）、23.1%（25/108）、9.3%（14/108）、39.8%（43/108）、23.1%（25/108）的基层医生会考虑将其诊断为FC；51.9%（56/108）的基层医生认为同时存在排便次数少、排便困难两种症状时可诊断为FC；25.0%（27/108）的基层医生认为，同时存在排便次数少、大便坚硬、排便时出血、排便困难4种症状时可诊断为FC。对于儿童FC的治疗：37.0%（40/108）的基层医生推荐将药物治疗作为儿童FC的首选治疗方法；63.0%（68/108）的基层医生推荐将非药物治疗作为首选治疗方法，其中88.2%（60/68）推荐腹部按摩，85.3%（58/68）推荐高纤维饮食，82.4%（56/68）推荐如厕训练，72.1%（49/68）推荐增加液体摄入量。75.9%（82/108）的基层医生推荐使用乳果糖治疗；27.8%（30/108）的基层医生推荐联合应用柠檬酸钠、十二烷基磺基乙酸钠、山梨糖醇的微灌肠为直肠治疗方法，64.8%（70/108）的基层医师建议在患儿排便特别困难时进行直肠给药。基层医生认为，患儿开始治疗到有阳性反应的平均时间为（4.1±2.6）d；基层医生对儿童FC的平均治疗时间为（21.2±4.3）d；88.9%（96/108）的基层医生认为，便秘平均平均治疗（46.0±9.3）d可终止；当排便频率和/或稠度恢复正常/患者不再有不适时，88.9%（96/108）的基层医生会考虑停止治疗。 结论 尽管基层医生对儿童FC的诊断和治疗有一定认识，但总体认知水平有待提高。建议进一步提升现有基层医生对儿童FC的认知和综合管理能力，并制定基层医疗卫生机构的儿童FC综合管理模式，以提高对儿童FC的管理水平，从而降低患病率、提升治愈率。     

Small nucleolar RNA host gene 3 functions as a novel biomarker in liver cancer and other tumour progression

Cancer has become the most life-threatening disease in the world. Mutations in and aberrant expression of genes encoding proteins and mutations in noncoding RNAs, especially long noncoding RNAs (lncRNAs), have significant effects in human cancers. LncRNAs have no protein-coding ability but function extensively in numerous physiological and pathological processes. Small nucleolar RNA host gene 3 (SNHG3) is a novel lncRNA and has been reported to be differentially expressed in various tumors, such as liver cancer, gastric cancer, and glioma. However, the interaction mechanisms for the regulation between SNHG3 and tumor progression are poorly understood. In this review, we summarize the results of SNHG3 studies in humans, animal models, and cells to underline the expression and role of SNHG3 in cancer. SNHG3 expression is upregulated in most tumors and is detrimental to patient prognosis. SNHG3 expression in lung adenocarcinoma remains controversial. Concurrently, SNHG3 affects oncogenes and tumor suppressor genes through various mechanisms, including competing endogenous RNA effects. A deeper understanding of the contribution of SNHG3 in clinical applications and tumor development may provide a new target for cancer diagnosis and treatment.     

To what degree could clinical trials in evidence based medicine reflect reality in the treatment of candidemia?

IntroductionEvidenced based medicine (EBM) is necessary to standardize or treatment for infection since EBM is established based on the results of clinical trials. Entry criteria for clinical trials are very strict, and many patients have difficulties in being enrolled in any clinical trials regarding candidemia. It is questionable if the results of clinical trials reflect the real world of general medicine in this case.Patients and methodsFor the purpose of examining how many patients could join any randomized clinical trials for the treatment of candidemia, we reviewed all the candidemia patients in our institute during 2014–2018. The patients were divided into two groups: patients who were eligible for clinical trials (participation possible group), and those who were not (participation impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials.ResultsA total of 70 patients was enrolled in this study. The median age was 73 years (range 36–93 years). Of these, 41 patients (59%) were male. As for site of infections, catheter related blood stream infection was most frequently seen in 37 (53%). Seventeen patients (24%) were classified as participation possible group and 53 patients (76%) were participation impossible group. Comparing the two groups, participation possible group patients have much better performance status, have less comorbidities and have longer overall survival times than participation impossible group patients.ConclusionOnly 24% of candidemia patients were eligible for the clinical trials. Thus, we can see that clinical trials might not correctly reflect the real world among candidemia patients.     

Accounting for Unobservable Preference Heterogeneity and Evaluating Alternative Anchoring Approaches to Estimate Country-Specific EQ-5D-Y Value Sets: A Case Study Using Spanish Preference Data

ObjectivesThe EuroQol Group published the EQ-5D-Y valuation protocol that recommends 2 valuation techniques to elicit preferences: composite time trade-off (C-TTO) and discrete choice experiments (DCEs). The protocol left the decision of what modeling approach to use open for researchers. Our aims were to explore modeling strategies allowing generation of EQ-5D-Y value sets and to produce an EQ-5D-Y Spanish value set.MethodsWe used EQ-5D-Y DCE and C-TTO data collected in Spain following the protocol and adopted a staged approach for our modeling exercise. First, we selected the best performing DCE latent class model and evaluated models from 2 to 10 classes. We selected the preferred model based on best goodness of fit in terms of the Bayesian information criterion. We considered 2 anchoring approaches to estimate utility values: (1) pits state anchoring and (2) hybrid models (using all available C-TTO responses). All analysis were weighted to be representative of the Spanish population.ResultsWe collected 1005 DCE and 200 C-TTO interviews. We selected a DCE model including 4 classes. Hybrid models using all available C-TTO observations produced a narrower range of values than the pits state anchoring approach.ConclusionsIn this article, we have presented an EQ-5D-Y value set that can be used for cost-utility analysis in Spain. The international EQ-5D-Y valuation protocol should be updated to include a different set of health states for the C-TTO experiment if researchers wish to use alternative anchoring approaches to the “pits state.”