Superior vena cava syndrome in chronic intestinal failure patients: When the going gets tough.

BACKGROUND & AIMS: Catheter-related venous thrombosis is a severe complication of home parenteral nutrition (HPN) with potentially devastating consequences such as superior vena cava syndrome (SVCS). Early recognition and awareness of factors leading to its development are of paramount importance. However, studies are lacking in HPN patients focusing on this topic. In this study, we aimed to determine the incidence of SVCS in HPN patients and describe SVCS-related outcomes. METHODS: This retrospective cohort study comprised all adult HPN patients who developed SVCS between 2000 and 2022 at our national HPN referral center. Primary outcome was the incidence of SVCS. Secondary outcomes include SVCS-related symptoms, tip location of central venous access device (CVAD) post-insertion and at time of SVCS, diagnostics and treatment. RESULTS: SVCS was diagnosed in 38 of 616 patients (6%), with an annual cumulative incidence rate ranging between 0 and 4.2%. Most common presenting symptoms were facial edema (82%) and arm edema (50%). Post-insertion, 17% (6/36) of patients had a correct position of the CVAD tip and 11% (4/36) during SVCS diagnosis. Computed tomography was the most used diagnostic imaging technique (66%). Sixty-three percent of patients started, 11% switched, and 21% continued anticoagulant treatment. CONCLUSIONS: The incidence of SVCS is relatively high in our vulnerable HPN population. It is key to recognize whenever such patients present with vascular obstruction-related symptoms and treat them in an early stage by a multidisciplinary team.

Three-dimensional stereophotogrammetrical analysis of peristomal fixation of adhesive base plates during hands-free speech among laryngectomised patients related to tracheostoma volumes.

OBJECTIVES: This study evaluates the relation between stoma volumes by means of objective three-dimensional measurements of laryngectomised individuals and peristomal fixation of adhesive baseplates during hands-free speech. DESIGN: A three-dimensional stereophotogrammetrical image was captured of the tracheostoma and its surrounding tissue for each participant. The placement of a baseplate adhesive was virtually simulated. Individual stoma volumes were calculated and related to the duration of lifetime of adhesive baseplates. SETTING: Prospective trial in a university hospital setting. PARTICIPANTS: Twenty-four laryngectomised patients. MAIN OUTCOME MEASURES: Stoma volume in cm(3) and adhesive baseplate adherence in minutes. RESULTS: For the 24 three-dimensional images captured, the mean volume of the area under the adhesive (stoma volume) was 9.5 cm(3) (range 3.5-22.5). After relating the different volumes of all patients to their individual fixation score, a significant decrease in duration of adhesive lifetime was found with increasing volumes of the stoma (P = 0.001). An increase of 1 cm(3) in tracheostoma volume resulted in a decrease of 21% in median adhesive lifetime (95% confidence interval 10-31%). CONCLUSIONS: Longer lifetime of the adhesive baseplate in patients with smaller volume outcomes suggests that a more accurate fit between baseplate and stoma leads to better fixation. This should be taken into account when shaping a stoma during laryngectomy. On the other hand, a more custom-made patch that has a more accurate fit could increase the lifetime of fixation. We believe that our three-dimensional volumetric data can contribute to the development of such an adhesive.

Taurolidine-related adverse events in patients on home parenteral nutrition frequently indicate catheter-related problems.

BACKGROUND & AIMS: A catheter-related bloodstream infection (CRBSI) is a serious complication of home parenteral nutrition (HPN) treatment. Despite taurolidine's frequent use as catheter lock solution (CLS) to prevent CRBSIs and its presumed favourable safety profile, data on taurolidine-related adverse events (AEs) and the clinical implications thereof remain merely anecdotal. Aim of this study was to explore taurolidine-related AEs in our large cohort of HPN patients and to develop an algorithm on how to deal with these AEs in clinical practice. METHODS: This retrospective cohort study comprised all adult HPN patients who used taurolidine as a CLS between 2006 and 2021 at our national HPN referral centre. Primary outcome was to identify taurolidine-related AEs. Secondary outcomes were median time to a taurolidine-related AEs and development of a clinical algorithm. A taurolidine-related AE was defined as an event that occurred directly after instillation of taurolidine in the CVAD or at start of fluid/PN infusion. RESULTS: In total, 470 patients used taurolidine during 700.232 catheter days. In 89 (19%) patients, 103 mild- to severe AEs related to taurolidine were observed. Six patients developed an allergic reaction. Reported AEs compromised vascular access device-related problems (group A) or taurolidine-related problems (group B) in 53 (51%) and 50 (49%), patients, respectively. In groups A and B, 51 (85%) and 21 (18%) patients presented with taurolidine infusion-related pain. Upon rechallenge, 45 (85%) and 16 (32%) patients, respectively, successfully resumed taurolidine locking without residual symptoms. CONCLUSION: In this study, use of taurolidine as CLS was generally safe. Most reported AEs were vascular access device-related, and the majority of symptoms concerned pain. Upon rechallenge, a substantial number of patients, especially those in whom pain was the main symptom, could resume CLS locking after addressing the underlying catheter-related problem. Based on these results, we present a clinical algorithm for patients with possible taurolidine-related symptoms.

Identification and in vivo characterization of a brain-penetrating nanobody.

BACKGROUND: Preclinical models to determine blood to brain transport ability of therapeutics are often ambiguous. In this study a method is developed that relies on CNS target-engagement and is able to rank brain-penetrating capacities. This method led to the discovery of an anti-transferrin receptor nanobody that is able to deliver a biologically active peptide to the brain via receptor-mediated transcytosis. METHODS: Various nanobodies against the mouse transferrin receptor were fused to neurotensin and injected peripherally in mice. Neurotensin is a neuropeptide that causes hypothermia when present in the brain but is unable to reach the brain from the periphery. Continuous body temperature measurements were used as a readout for brain penetration of nanobody-neurotensin fusions after its peripheral administration. Full temperature curves were analyzed using two-way ANOVA with Dunnett multiple comparisons tests. RESULTS: One anti-transferrin receptor nanobody coupled to neurotensin elicited a drop in body temperature following intravenous injection. Epitope binning indicated that this nanobody bound a distinct transferrin receptor epitope compared to the non-crossing nanobodies. This brain-penetrating nanobody was used to characterize the in vivo hypothermia model. The hypothermic effect caused by neurotensin is dose-dependent and could be used to directly compare peripheral administration routes and various nanobodies in terms of brain exposure. CONCLUSION: This method led to the discovery of an anti-transferrin receptor nanobody that can reach the brain via receptor-mediated transcytosis after peripheral administration. This method could be used to assess novel proteins for brain-penetrating capabilities using a target-engaging readout.

Randomised clinical trial: 2% taurolidine versus 0.9% saline locking in patients on home parenteral nutrition.

BACKGROUND: The catheter lock solutions 2% taurolidine and 0.9% saline are both used to prevent catheter-related bloodstream infections (CRBSIs) in home parenteral nutrition patients. AIMS: To compare the effectiveness and safety of taurolidine and saline. METHODS: This multicentre double-blinded trial randomly assigned home parenteral nutrition patients to use either 2% taurolidine or 0.9% saline for 1 year. Patients were stratified in a new catheter group and a pre-existing catheter group. Primary outcome was the rate of CRBSIs/1000 catheter days in the new catheter group and pre-existing catheter group, separately. RESULTS: We randomised 105 patients, of which 102 were analysed as modified intention-to-treat population. In the new catheter group, rates of CRBSIs/1000 catheter days were 0.29 and 1.49 in the taurolidine and saline arm respectively (relative risk, 0.20; 95% CI, 0.04-0.71; P = 0.009). In the pre-existing catheter group, rates of CRBSIs/1000 catheter days were 0.39 and 1.32 in the taurolidine and saline arm respectively (relative risk, 0.30; 95% CI, 0.03-1.82; P = 0.25). Excluding one outlier patient in the taurolidine arm, mean costs per patient were $1865 for taurolidine and $4454 for saline (P = 0.03). Drug-related adverse events were rare and generally mild. CONCLUSIONS: In the new catheter group, taurolidine showed a clear decrease in CRBSI rate. In the pre-existing catheter group, no superiority of taurolidine could be demonstrated, most likely due to underpowering. Overall, taurolidine reduced the risk for CRBSIs by more than four times. Given its favourable safety and cost profile, taurolidine locking should be considered as an additional strategy to prevent CRBSIs. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT01826526.