Clinical experience of pulmonary vein isolation via single transseptal puncture in atrial fibrillation patients: Comprehensive characterization and follow-up.

BACKGROUND: Atrial fibrillation is the most commonly observed cardiac rhythm disorder. Pulmonary vein isolation (PVI) is an effective treatment option to maintain sinus rhythm. This study evaluates the safety, efficacy, clinical outcomes and radiation exposures using a standardized single transseptal puncture (STP)-strategy. METHODS: We analyzed data from patients who underwent our STP-ablation technique with transesophageal echocardiography guidance (TEE) at a university hospital and a regional tertiary health center in Switzerland between January 1, 2017, and May 30, 2022. Collected data included demographics, symptoms, echocardiography results, procedural details, complications and outcomes. Mean follow-up time was 21.4 ±â€¯16 months. RESULTS: The study population included 304 patients with a median age of 67 years, who had at least one ablation using our STP-approach. Among these, 248 (82 %) patients underwent de novo PVI with this technique. Ablation was successful in all patients with isolation of all pulmonary veins, with an average procedure duration of 120 min and an average fluoroscopy time of 3 min, resulting in a mean X-ray dose of 252 cGy × cm2. TEE guidance was performed in 235 (95 %) patients. During the first intervention, 17 complications occurred in 13 patients (5 %). After the first PVI, 135 (54 %) patients experienced no recurrence during the follow-up period. The one-year recurrence rate for atrial fibrillation requiring therapy was 30 %. CONCLUSION: Our STP- approach demonstrated comparable success rates to traditional methods, with similar procedural durations, low radiation exposure and a low complication rate. Therefore, this method may offer procedural, economic and safety benefits without compromising efficacy or safety.

Limitations of biopsy-based transcript diagnostics to detect T cell-mediated allograft rejection.

BACKGROUND AND HYPOTHESIS: Isolated Tubulitis, Borderline Changes, and Isolated Arteritis suspicious for histologic T cell-mediated rejection (hTCMR) remain findings of uncertain significance. Although the Molecular Microscope Diagnostics System (MMDx) has not been trained on those lesions, it was suggested that MMDx might reclassify a subgroup to molecular TCMR (mTCMR). METHODS: In this single-center cohort of 326 consecutive, unselected kidney allograft biopsies assessed by histology and MMDx, we analyzed 249 cases with Isolated Tubulitis (i0, t1-3, v0; n=101), Borderline Changes (according to Banff 2022, v0; n=9), Isolated Arteritis (no borderline, v1; n=37), No Inflammation (i0, t0, v0; n=67) and a Positive Control Cohort (hTCMR, n=27; Mixed histologic Rejection, n=8; both according to Banff 2022; total n=35). The first three groups were summarized as TCMR-Suspicion (n=147). Subcategorization included the presence and absence of microvascular inflammation (MVI; g+ptc≥2). Molecular rejection rates and differentiation were investigated. RESULTS: Molecular rejection rates were 37/147 cases (25.2%; 32 with MVI) in TCMR-Suspicion, 6/67 (9%; 4 with MVI) in No Inflammation and 30/35 (85.7%; 19 with MVI) in the Positive Control Cohort. Molecular antibody-mediated rejection (mAMR) was present in 39/73 (53.4%) of cases. The presence of donor-specific antibodies (DSA) at the time of the biopsy was high (127/249, 51%). Only 3 mAMR/TCMR and no pure mTCMR cases were detected in TCMR-Suspicion and No Inflammation, compared to 12 mAMR/TCMR and 10 mTCMR cases in the Positive Control Cohort (p<0.001). Even though the TCMR-specific molecular (Classifier) score differentiated between TCMR-Suspicion and No Inflammation (p=0.005), rejection phenotype scores (R2 and R3) did not (p=0.157 and 0.121). CONCLUSIONS: MMDx did not identify pure mTCMR among Isolated Tubulitis, Borderline Changes, or Isolated Arteritis, likely due to low sensitivity for TCMR-lesions. However, it identified mAMR or mAMR/TCMR, especially in cases with MVI. Subthreshold findings remain to be further studied.

Molecular diagnosis of antibody-mediated rejection: Evaluating biopsy-based transcript diagnostics in the presence of donor-specific antibodies but without microvascular inflammation, a single-center descriptive analysis.

Biopsy-based transcript diagnostics may identify molecular antibody-mediated rejection (AMR) when microvascular inflammation (MVI) is absent. In this single-center cohort, biopsy-based transcript diagnostics were validated in 326 kidney allograft biopsies. A total of 71 histological AMR and 35 T cell-mediated rejection (TCMR) cases were identified as molecular AMR and TCMR in 55% and 63%, respectively. Among 121 cases without MVI (glomerulitis + peritubular capillaritis = 0), 45 (37%) donor-specific antibody (DSA)-positive and 76 (63%) DSA-negative cases were analyzed. Twenty-one out of the 121 (17%) cases showed borderline changes, or TCMR, while BK nephropathy was excluded. None of the 45 DSA-positive patients showed molecular AMR. Among 76 DSA-negative patients, 2 had mixed molecular AMR/TCMR. All-AMR phenotype scores (sum of R4-R6) exhibited median values of 0.13 and 0.12 for DSA-positive and DSA-negative patients, respectively (P = .84). A total of 13% (6/45) DSA-positive and 11% (8/76) DSA-negative patients showed an all-AMR phenotype score > 0.30 (P = .77). Patients with a higher all-AMR phenotype score showed 33% more histologic TCMR (P = .005). The median all-AMR phenotype scores of glomerular basement membrane double contours = 0 and glomerular basement membrane double contours > 0 biopsies were 0.12 and 0.10, respectively (P = .35). Biopsy-based transcript diagnostics did not identify molecular AMR in cases without MVI. Follow-up biopsies and outcome data should evaluate the clinical relevance of subthreshold molecular alterations.

Detection of donor-derived cell-free DNA in the setting of multiple kidney transplantations.

Background: The routine use of donor-derived cell-free DNA (dd-cfDNA) assays to monitor graft damage in patients after kidney transplantation is being implemented in many transplant centers worldwide. The interpretation of the results can be complicated in the setting of multiple sequential kidney transplantations where accurate donor assignment of the detected dd-cfDNA can be methodologically challenging. Methods: We investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations. Results: The assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%-0.6% and showed a fluctuation over time in patients where we analyzed sequential samples. Conclusion: This is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making.

Pre-existing treatment with aspirin or statins influences clinical presentation, infarct size and inflammation in patients with de novo acute coronary syndromes.

BACKGROUND: Influence of pre-existing treatment with aspirin and/or statins prior to a first acute coronary syndrome (ACS) on clinical presentation, infarct size and inflammation markers. We analyzed patients from the Swiss Program University Medicine ACS-cohort (SPUM-ACS; ClinicalTrials.govnumber:NCT01075867). METHODS: 1639 patients were categorized into 4 groups: (1) patients without either drug (n = 1181); (2) patients only on aspirin (n = 157); (3) patients only on statins (n = 133) and (4) patients on both drugs (n = 168). Clinical features, electrocardiogram (ECG), creatinine kinase (CK, U/l), high-sensitivity troponin T (hsTNT, µg/l), N-terminal brain natriuretic peptide (NT-proBNP, ng/l), leucocytes (Lc, G/l), neutrophils (Nc, G/l), C-reactive protein (CRP, mg/l) and angiographic features were documented at baseline. RESULTS: Incidences of ST-elevation myocardial infarction (STEMI) were 64% in group 1, 45% in group 2, 52% in group 3 and 40% in group 4 (p < 0.0001). Those with both drugs had significantly lower CK (median 145 U/l, interquartile range (IQR) 89-297), hsTNT (median 0.13 µg/l, IQR 0.03-0.52) and higher left ventricular ejection fraction values (LVEF) (mean 55 ±â€¯12%) compared to untreated patients (median CK 273 U/l, IQR 128-638; median hsTNT 0.26 µg/l, IQR 0.08-0.85; mean LVEF 51 ±â€¯11%) (p < 0.0001, p = 0.001, p = 0.028, respectively). Co-medicated groups matched for high risk factors presented less frequently as STEMIs (p < 0.0001), had significantly smaller infarcts determined by CK and hsTNT (both p < 0.0001) and lower CRP levels (p = 0.01) compared to patients without pre-existing treatment with either drug. CONCLUSION: Pre-existing treatment with aspirin and/or statins and particularly with their combination changes the clinical presentation, infarct size, inflammation markers and LVEF in patients suffering their first ACS.

Insulin-like growth factor I is expressed in classical and nodular lymphocyte-predominant Hodgkin's lymphoma tumour and microenvironmental cells.

Hodgkin's lymphoma (HL) is among the most frequent nodal lymphomas in the Western world and is classified into two disease entities: nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) and classical Hodgkin's lymphoma (cHL, 95% of all HL). HL lesions are characterised by a minority of clonal neoplastic cells, namely Hodgkin and Reed-Sternberg (HRS) cells and their variants in cHL and lymphocyte-predominant (LP) cells in NLPHL, both occurring within a microenvironment of, for example, reactive T and B cells, macrophages and granulocytes that are assumed to support the proliferation and maintenance of neoplastic cells through cytokines, chemokines and growth factors. Insulin-like growth factor I (IGF-I) is an important growth factor involved in proliferation, differentiation, apoptosis and cell survival of numerous (including immune) tissues and probably has a role in tumour pathogenesis and maintenance. Although HL is characterised by disturbed cell differentiation and apoptosis mechanisms, with the involvement of the IGF-I receptor (IGF-1R), the distinct location of IGF-I in HL has not yet been defined. We localise IGF-I by double-immunofluorescence in frequent neoplastic cells of all cHL and NLPHL cases investigated. Additionally, IGF-I immunoreactivity is detected in high endothelial venules and various immune cells within the surrounding tissue of cHL including neutrophils and macrophages. IGF-1R immunoreactivity of variable intensity is found in HRS cells and high endothelial venules within the microenvironment in cHL. We assume that autocrine and paracrine IGF-I plays an anti-apoptotic role in tumour pathogenesis and in shaping the tumour microenvironment.