Impact of Transient and Persistent Donor-Specific Antibodies in Lung Transplantation.

Lung transplantation (LuTx) is an established treatment for patients with end-stage lung diseases, however, outcomes are limited by acute and chronic rejection. One aspect that has received increasing attention is the role of the host's humoral alloresponse, particularly the formation of de novo donor-specific antibodies (dnDSAs). The aim of this study was to investigate the clinical significance of transient and persistent dnDSAs and to understand their impact on outcomes after LuTx. A retrospective analysis was conducted using DSA screening data from LuTx recipients obtained at the Medical University of Vienna between February 2016 and March 2021. Of the 405 LuTx recipients analyzed, 205 patients developed dnDSA during the follow-up period. Among these, 167 (81%) had transient dnDSA and 38 (19%) persistent dnDSA. Persistent but not transient dnDSAs were associated with chronic lung allograft dysfunction (CLAD) and antibody-mediated rejection (AMR) (p < 0.001 and p = 0.006, respectively). CLAD-free survival rates for persistent dnDSAs at 1-, 3-, and 5-year post-transplantation were significantly lower than for transient dnDSAs (89%, 59%, 56% vs. 91%, 79%, 77%; p = 0.004). Temporal dynamics of dnDSAs after LuTx have a substantial effect on patient outcomes. This study underlines that the persistence of dnDSAs poses a significant risk to graft and patient survival.

[Experiences with ultrasound-guided port implantations via the lateral subclavian vein: a retrospective analysis of 1532 patients]. / Ergebnisse sonografisch gesteuerter Portkatheterimplantationen über die laterale Vena subclavia: eine retrospektive Analyse bei 1532 Patienten.

PURPOSE: Evaluation of the success and complication rates in ultrasound-guided central venous port implantations through the lateral subclavian vein. MATERIALS AND METHODS: A total of 1537 subcutaneous central venous ports were implanted in 1532 patients. The catheter remained in place for a mean duration of 202 days (overall 309,464 catheter days). A retrospective analysis within the hospital and radiological information system (HIS/RIS) was performed to assess technical success and complication rates. RESULTS: The implantations of the central venous ports were performed by 21 radiologists (19 residents). The technical success rate was 99.0 % (1517/1537) and the overall complication rate was 8.5 % (130/1537; 0.42 per 1000 catheter days). Procedural and acute complications (< 24 h) occurred in 22 of 1532 patients (1.4 %). Follow-up revealed 45 port explantations ahead of time due to complications in the early (< 30 d) or late (> 31 d) post-interventional period (2.9 %; 0.15 per 1000 catheter days). Catheter-associated vein thrombosis was the most common complication (n = 60, 3.9 %, 0.19 per 1000 catheter days). CONCLUSION: Ultrasound-guided insertion of central venous port catheters through the lateral subclavian vein provides safe vascular access. Procedural complication rate is low with special regard to post-graduate training. The most common reasons for early port explantations were catheter-associated infections and vessel occlusions.

[Sonographic patterns of littoral cell angioma: case report and review of the literature]. / Das sonographische Bild des Littoralzellangioms: Fallbericht und Literaturzusammenstellung.

AIM: Littoral cell angioma is a rare benign tumour of vascular proliferation unique to the spleen. Definitive sonographic patterns are yet unknown and are described in this paper. METHOD: We report about 2 patients with histologically confirmed Littoral cell angioma. The sonographic features of these and 5 additional cases in the literature are presented. RESULTS: Littoral cell angioma is characterized by splenomegaly (6 out of 7 cases) with small nodular hyperechoic focal lesions (6 out of 7 cases). A solitary hyperechoic tumour (1 out of 7 cases) is a rare event. CONCLUSION: Littoral cell angioma is a recently discovered tumour and should be included in the differential diagnosis of a hyperechoic splenic tumour.

A screen for mutations in human homologues of mice exencephaly genes Tfap2alpha and Msx2 in patients with neural tube defects.

BACKGROUND: Very little is known about the identity of genetic factors involved in the complex etiology of nonsyndromic neural tube defects (NTD). Potential susceptibility genes have emerged from the vast number of mutant mouse strains displaying NTD. Reasonable candidates are the human homologues of mice exencephaly genes Tfap2alpha and Msx2, which are expressed in the developing neural tube. METHODS: A single-strand conformation analysis (SSCA) mutation screen of the coding sequences of TFAP2alpha and MSX2 was performed for 204 nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA patients was additionally tested for specific mutations in MTHFD, FRalpha, and PAX1 already shown to be related to NTD. RESULTS: Two TFAP2alpha point mutations in individual SBA patients were silent on the amino acid level (C308C, T396T). On nucleic acid level, these mutations change evolutionary conserved codons and thus may influence mRNA processing and translation efficiency. One SBA patient displayed an exonic 9-bp deletion in MSX2 leading to a shortened and possibly less functional protein. None of these mutations was found in 222 controls. Seven polymorphisms detected in TFAP2alpha and MSX2 were equally distributed in patients and controls. Patients with combined heterozygosity of an exonic MSX2 and an intronic TFAP2alpha polymorphism were at a slightly increased risk of NTD (OR 1.71; 95% CI 0.57-5.39). CONCLUSIONS: Although several new genetic variants were found in TFAP2 and MSX2, no statistically significant association was found between NTD cases and the new alleles or their combinations. Further studies are necessary to finally decide if these gene variants may have acted as susceptibility factors in our individual cases.

Human transcription factor SLUG: mutation analysis in patients with neural tube defects and identification of a missense mutation (D119E) in the Slug subfamily-defining region.

Studies in mouse, chicken and Xenopus have shown that Slug is selectively expressed in the dorsal part of the developing neural tube. Ablation and antisense experiments in chicken suggest that Slug may be an important factor during neural tube closure. We therefore investigated the role of Slug as a possible candidate contributing to the aetiology of neural tube defects (NTD) in humans. We characterised the genomic structure of human SLUG including determination of the exon-intron boundaries. The coding sequence of SLUG was screened for mutations in 150 patients with NTD using single strand conformation analysis (SSCA). In one patient, we identified a missense mutation 1548C-->A in exon 2 causing an exchange of a conserved amino acid (D119E) in the Slug subfamily-defining region preceding the first zinc finger. This is the first description of a human mutation in the SLUG gene. In accordance with the findings in model organisms, the SLUG mutation may be causally related to the development of NTD in our patient and could be considered as a predisposing factor.

Radiographic characteristics of Cook detachable and Gianturco coils as well as clinical results of transcatheter closure of the patent ductus arteriosus.

PURPOSE: To describe the radiographic appearance of the Gianturco and the Cook detachable coils and present the clinical results in patients who underwent transcatheter closure of patent ductus arteriosus. MATERIALS AND METHODS: Between January 1994 and June 1997, eighty-two patients underwent closure of patent ductus arteriosus (PDA) using either Gianturco or Cook detachable coils. The chest x-ray and echocardiography of all patients were reviewed and the following parameters were evaluated: 1) the size of the heart (cardiothoracic ratio), 2) the position and the type of the coils in the postero-anterior and the lateral projection, 3) the number of coils used, 4) the existence of residual ductal flow, 5) Doppler velocity in the left pulmonary artery. RESULTS: Complete occlusion was achieved in 94%, and cardio-thoracic ratio regressed from 0.57 to 0.53 (p < 0.01), after a mean follow-up of 1.2 years. The identification of the different coils on the chest radiograph was successful in only 47% of cases, difficulties arising especially, when multiple coils were used. In 55 patients (67%) the coil position was judged to be optimal, in 27 patients (33%) suboptimal. The latter correlates with the presence of residual shunt. Multiple coils correlated more with a left pulmonary artery flow velocity exceeding 1.5 m/s. CONCLUSION: Coil-occlusion of patent ductus arteriosus is effective and leads to reduced cardio-thoracic ratio. Radiographic coil identification is possible but may be difficult if multiple coils are deployed. Suboptimal coil position led more often to residual PDA shunt. Multiple coils are more commonly associated with increased LPA velocities, but hemodynamic significant obstruction to flow is rare.

Comparability of a new turbidimetric digoxin test with other immunochemical tests and with HPLC--a multicenter evaluation.

A new turbidimetric inhibition immunoassay for digoxin (Tina-quant [a] Digoxin, Boehringer Mannheim) was evaluated in seven laboratories. It can be performed without sample pretreatment with ready-to-use reagents on nondedicated analyzers in combination with routine clinical chemistry. The studies revealed a good analytical performance: lower limit of detection 0.12 microg/L (3 SD from mean of blank); linearity up to 7.5 microg/L; median between-run CVs 8.1% (0.6 microg/L), 2.8% (1.5 microg/L), 1.9% (3 microg/L); mean analytical recovery in control sera 98-102%; slopes from 0.97 to 1.09 and intercepts from -0.28 to 0.10 microg/L in comparison with four immunoassays; and a high resistance to common interferents. The test was more resistant to digoxin-like immunoreactive factor (DLIF) interference than other methods, showing cross-reactivity only in some intensive care patient samples. Among 192 patients in whom DLIF is expected (e.g., pregnant women, patients with renal failure, newborns), 90% of results were < or =0.26 microg/L digoxin. Cortisol showed no cross-reactivity and digoxigenin had a low reactivity. An interlaboratory survey revealed a good comparability of the Tina-quant [a] test with the median of all methods (slope 0.99, intercept -0.06 microg/L). An HPLC method for digoxin based on isocratic separation of samples on an RP-18 column followed by detection by an immunoassay yielded a reasonable comparability with the immunochemical tests with noncritical samples. Divergent results of immunoassays caused by DLIFs or different cross-reactivities with digoxin metabolites or derivatives can be explained by the use of this HPLC method.