The People's Hospital of Guangxi Zhuang Autonomous Region

Calcineurin inhibitors (CNIs) are effective immunosuppressive agents for idiopathic membranous nephropathy (iMN). Focal segmental glomerular sclerosis (FSGS) lesions, frequently observed in MN, have been identified as indicators of poor prognosis. This retrospective study enrolled 71 patients with biopsy-proven iMN accompanied by FSGS lesions, all of whom were initially treated with CNIs. This study identified independent risk factors for renal function progression and assessed the predictive significance of CD44. The primary outcome was defined as a 50% decline in the eGFR. Fifty-eight patients (81.7%) had CD44+ visceral epithelial cells (VECs), with 36 (36/71, 50.7%) demonstrating a linear positive pattern, of whom 19 patients showed a strong positive (3+) linear distribution in VECs. The patients with a strong linear distribution of CD44+ VECs had a higher rate of progression to the primary outcome (13/19 vs. 6/52, p < 0.001). The model based on age (OR, 1.134; p = 0.004), failure to achieve CR with CNIs treatment (non-CR) (OR, 6.924; p = 0.042), and strong linear CD44+ VECs (OR, 37.139; p < 0.001) showed good discrimination in predicting renal function decline, with a receiver operating characteristic AUC of 0.929 (0.871-0.986) (p < 0.001). Therefore, patients with strong linear CD44+ VECs showed a lower remission rate and a higher rate of progression to the primary outcome. The model, which incorporated age, non-CR status, and strongly linear CD44+ VECs, demonstrated effective discrimination in predicting renal function deterioration.

Zeta (ζ)-thalassemia is a rare form of thalassemia. In clinical practice, ζ-thalassemia is frequently a missed diagnosis due to its normal hematological phenotype. Here, we report a novel HBZ-HBZP1 deletion within the α-globin gene cluster.

The proband was first tested for six common deletional α-thalassemia using Gap-PCR and for three point mutations using PCR-based reverse dot blot (PCR-RDB). Multiplex ligation-dependent probe amplification (MLPA) was subsequently employed to detect copy number variations in the α-globin gene cluster. Third-generation sequencing (TGS) was performed to characterize potential deletion locations. Finally, based on the breakpoints suggested by TGS, Gap-PCR with specific primers followed by Sanger sequencing confirmed the precise breakpoints.

The proband's hematological parameters were normal, except for a decreased Hb A₂ level (2.3%). Gap-PCR showed an internal control band but no normal control band. MLPA indicated a copy number of zero for probes 292 and 391 and a copy number of two for probe 190, suggesting concomitant deletion and duplication events. TGS identified a 10.7 kb deletion (Chr16:154,355 - 165,114del; NG_000006.1:g.15218_25972del) and a homozygous point mutation (Chr16:169,854T > C; NG_000006.1:g.30717T > C; rs2258435). Subsequent Sanger sequencing of the Gap-PCR product amplified with specific primers validated both the deletion breakpoints (NG_000006.1:g.15218_25972del) and the point mutation (NG_000006.1:g.30717T > C), which was consistent with the TGS findings.

This study describes the identification of a novel 10.7 kb deletion (Nanning deletion, -ζ^{10.7 kb}) causing ζ-thalassemia. Our findings confirm that this deletion is associated with a silent carrier phenotype.

Evidence for atrial shunt devices in heart failure with reduced ejection fraction (HFrEF) is limited. This study aimed to evaluate the 1-year clinical and haemodynamic outcomes associated with an atrial shunt device in this population.

In this prospective, multicentre, single-arm cohort study of an interatrial shunt in heart failure with reduced ejection fraction (SUSTAIN-HF), 120 symptomatic HFrEF patients (left ventricular ejection fraction; LVEF ≤40%) on guideline-directed medical therapy were enrolled across 16 centres in China. The intervention was implantation of the D-Shant atrial shunt device. Prespecified primary outcomes were the changes from baseline to 1 year in 6 min walk distance (6MWD) and New York Heart Association (NYHA) functional class. Secondary outcomes included quality of life (Kansas City Cardiomyopathy Questionnaire; KCCQ), echocardiographic parameters and adjudicated adverse events.

Between October 2017 and December 2021, 120 patients were enrolled. At 1-year follow-up, implantation of the shunt device was associated with significant improvements in clinical outcomes. The mean 6MWD increased by 54.1 m (95% CI 45.9 to 62.3; p<0.0001), and the KCCQ overall score was improved by 16.5 points (95% CI 13.9 to 19.1; p<0.0001). The proportion of patients in NYHA class III/IV decreased from 95.0% to 22.9% (p<0.0001). The annualised rate of heart failure hospitalisation was reduced from 3.3 to 0.3 events per patient-year (p<0.0001). LVEF increased by 9.0% (95% CI 6.9% to 11.1%; p<0.0001). The primary safety endpoint, a composite of major adverse cardiac and device-related events at 1 year, occurred in 15.0% of patients, driven primarily by cardiovascular death.

In this prospective cohort study of symptomatic HFrEF patients, treatment with the D-Shant atrial shunt device was associated with significant improvements in functional capacity, quality of life and rates of heart failure hospitalisation at 1 year. The single-arm design precludes definitive conclusions on treatment efficacy, underscoring the need for randomised, sham-controlled trials.