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.

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.

[Severe malnutrition after gastric: the importance of lifelong follow-up]. / Ernstige malnutritie na gastric bypass.

Two cases are described of patients who present with severe malnutrition more than five years after undergoing a Roux-en-Y gastric bypass and who have deficiencies of both micronutrients (vitamins and minerals) and macronutrients (proteins). This problem appears to be caused by both iatrogenic malabsorption after gastric bypass as well as dysphagia due to a local anastomotic complication (stenosis and marginal ulcer). Although both the severity of the deficiencies and the timing are exceptional, we want to emphasize the importance of lifelong supplement use and follow-up after bariatric surgery. Given the important role of general practitioners in this, we argue for implementation of this topic in national guidelines to improve the quality of follow-up.

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.

The glutathione transferase Mu null genotype leads to lower 6-MMPR levels in patients treated with azathioprine but not with mercaptopurine.

The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 108 RBCs; P<0.01). In patients on MP (control group) 6-MMPR levels were comparable (6195 (1551-10712) versus 6544 (1717-11600) pmol/8 × 108 RBCs; P=0.84). The 6-TGN levels were not affected by the GSTM1 genotype. The presence of genetic variants in GSTA1 and GSTA2 was not related to the 6-MMPR and 6-TGN levels.

Risk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a normal TPMT genotype.

BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial. For this analysis, patients without a variant in TPMT (*2, *3A or*3C) were included. Uni- and multivariate Cox-proportional hazard models were used to identify risk factors for leucopenia and infections. Leucopenia was defined as a white blood cell (WBC) count <3.0 × 109 /L and infections were classified according to the Common Terminology Criteria for Adverse Events. RESULTS: Sixty hundred and ninety-five patients (90.6%) included in the TOPIC-trial had no variant in TPMT, of which 45 (6.5%) developed leucopenia. Median time to leucopenia was 56 (29-112) days. Multivariate analysis showed that use of mercaptopurine compared to azathioprine was associated with leucopenia (hazard ratio [HR] 2.61 [95% CIs, 1.39-4.88; P < .01]) and a higher baseline WBC count was protective (HR 0.80 [95% CIs, 0.71-0.89; P < .01]). Risk factors for infections were older age (per 10 year; HR 2.07 [95% CIs, 1.18-3.63; P = .01]) and concomitant use of biologic drugs (HR 2.15 [95% CIs, 1.14-4.07; P = .02]). CONCLUSIONS: Low baseline WBC count and mercaptopurine, due to a relatively higher dose, were risk factors for thiopurine-induced leucopenia in patients without a TPMT variant.

Presentation of a nationwide multicenter registry of intestinal failure and intestinal transplantation.

BACKGROUND & AIMS: Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date prevalence of CIF and characterizing these patients using the specially developed multicenter web-based Dutch Registry of Intestinal Failure and Intestinal Transplantation (DRIFT). METHODS: Cross-sectional study. CIF was defined as type 3 intestinal failure in which >75% of nutritional requirements were given as home parenteral nutrition (HPN) for ≥ 4 weeks in children and >50% for ≥3 months in adults. All patients with CIF receiving HPN care by the three Dutch specialized centers on January 1, 2013 and all ITx patients were registered in DRIFT (https://drift.darmfalen.nl). RESULTS: In total, 195 patients with CIF (158 adults, 37 children) were identified, of whom 184 were registered in DRIFT. The Dutch point prevalence of CIF was 11.62 per million (12.24 for adults, 9.56 for children) on January 1, 2013. Fifty-seven patients (31%) had one or more indications for ITx, while 12 patients actually underwent ITx since its Dutch introduction. Four patients required transplantectomy of their intestinal graft and 3 intestinal transplant patients died. CONCLUSION: The multicenter registry DRIFT revealed an up-to-date prevalence of CIF and provided nationwide insight into the patients with CIF during HPN and after ITx in the Netherlands. DRIFT will facilitate the multicenter monitoring of individual patients, thereby supporting multidisciplinary care and decision-making.

Dysphagia, malnutrition and gastrointestinal problems in patients with mitochondrial disease caused by the m3243A>G mutation.

BACKGROUND: Previous research has shown that dysphagia and gastrointestinal problems occur frequently in carriers of the m.3243A>G mutation; however, the exact frequency and severity have not been determined. We hypothesise that adult carriers have an increased risk for malnutrition. METHODS: In this observational study we evaluated the presence of gastrointestinal problems and dysphagia in 92 carriers of the m.3243A>G mutation. The severity of the general disease involvement was classified using the Newcastle Mitochondrial Disease Adult Scale (NMDAS). Gastrointestinal involvement, dysphagia and the risk for malnutrition were scored using the Gastrointestinal Symptoms Questionnaire and the Malnutrition Universal Screening Tool. Gastrointestinal symptoms and anthropometrics were compared with healthy controls. RESULTS: Our results show that the height, weight and body mass index (BMI) of these carriers were lower than the national average (p < 0.05). Seventy-nine carriers (86%) suffered from at least one gastrointestinal symptom, mainly flatulence or hard stools. Both frequency and severity of symptoms were significantly increased compared with reference data of healthy Dutch adults. Of the carriers, 45% reported (mostly mild) dysphagia. Solid foods cause more problems than liquids. A negative correlation between BMI and heteroplasmy levels in urinary epithelial cells (UEC) was present (Spearman correlation coefficient = - 0.319, p = 0.003). CONCLUSION: Dysphagia and gastrointestinal problems, especially constipation, are common symptoms in the total m.3243A>G carriers cohort and are not related to heteroplasmy levels in UEC or disease severity. The severity of gastrointestinal problems as well as overall disease severity is associated with an increased risk for malnutrition.

Microbiocidal effects of various taurolidine containing catheter lock solutions.

BACKGROUND & AIMS: We have recently shown that a catheter lock solution containing taurolidine dramatically decreases catheter-related bloodstream infections (CRBSI) in patients on home parenteral nutrition (HPN) when compared to heparin. Since several taurolidine formulations are commercially available, some of which also contain citrate or heparin, we were interested in the effect of these different locks on growth and biofilm formation of fungal, Gram-negative and Gram-positive pathogens that are known to impede HPN treatment. METHODS: Clinical isolates obtained during CRBSI of HPN patients were grown in the presence of catheter locks (2% taurolidine, 1.34% taurolidine-citrate, 1.34% taurolidine-citrate-heparin, citrate and heparin) or phosphate buffered saline diluted in lysogeny broth medium for bacteria and sabouraud liquid medium for yeasts. Biofilm formation, assessed by crystal violet staining, and growth of clinical isolates were determined by optical density measurements. RESULTS: We found that 12.5× diluted solutions of all taurolidine containing formulations completely prevented growth of Escherichia coli, Staphylococcus aureus and Candida glabrata. Growth of these microbes was detected earlier in 1.34% taurolidine-citrate(-heparin) than in 2% taurolidine, while citrate and heparin did not inhibit growth of clinical isolates compared to PBS. No differences in biofilm formation were found between taurolidine containing solutions. CONCLUSION: Taurolidine containing lock solutions prevent growth of fungal, Gram-negative and Gram-positive pathogens. While 2% taurolidine appears to be the most potent in this respect in this in vitro setting, the relevance of the small differences in growth inhibition between the commercially available taurolidine containing lock solutions for clinical practice remains to be established.

Long-term olive oil-based parenteral nutrition sustains innate immune function in home patients without active underlying disease.

BACKGROUND & AIMS: It remains unclear whether impaired host defenses contribute to the increased risk for infectious complications seen in patients on home parenteral nutrition (HPN). The aim of this study was to compare the innate immune function of patients on olive oil-based HPN with that of healthy controls. METHODS: Innate immune functions and (anti-)oxidant balance were studied in 20 patients on olive oil-based HPN without an active underlying immune-mediated disease (Clinoleic(®), ≥ 6 months; >3 times/week), and 21 age- and sex-matched healthy controls. RESULTS: Neutrophils of patients and controls had a similar capacity to eliminate Streptococcus pneumoniae. Also, levels of activation markers (CD66b, CD11b, CD62L) in granulocytes and monocytes, phorbol ester- and zymosan-induced neutrophil oxygen radical production were not different between patients and controls. No differences in (anti-)oxidant status were found, except for higher concentrations of oxidized glutathione and lower plasma selenium and vitamin C in patients compared to controls. CONCLUSION: Compromised innate immune function does not seem to explain the increased risk for infectious complications in HPN patients using olive oil-based lipid emulsions.

Screening for psychosocial distress in patients with long-term home parenteral nutrition.

BACKGROUND & AIMS: Long-term home parenteral nutrition (HPN) may cause distress and negatively affect quality of life (QoL). The HPN version of the Distress Thermometer and Problem List (DT/PL) was developed to evaluate distress during HPN. This study validates the DT/PL, examines referral wish for additional care, assesses opinions on the DT/PL, and studies risk factors for distress and referral wish. METHODS: Dutch and Scottish patients completed questions on socio-demographic and HPN-related general characteristics, the DT/PL, referral wish, the Hospital Anxiety and Depression Scale, and opinions on the DT. RESULTS: The HPN version of the DT/PL seemed valid and the PL sufficiently reliable. Cut-off score appeared to be 6. Consequently, 45% of patients were diagnosed as clinically distressed. Fifty-three percent had a referral wish. Emotional and physical problems were most strongly associated with distress. Not being able to work related to elevated distress. Female gender and co-morbidity related to referral wish. Opinions on the DT were generally positive. CONCLUSION: The DT/PL appears to be a good instrument to regularly gain insight into distress and referral wish in HPN patients. Use of the DT/PL facilitates support to patients who most need and want it, thus improving quality of care and QoL.

Absence of microbial adaptation to taurolidine in patients on home parenteral nutrition who develop catheter related bloodstream infections and use taurolidine locks.

BACKGROUND & AIMS: Some home parenteral nutrition (HPN) patients develop catheter related bloodstream infections (CRBSI) despite using an anti-microbial catheter lock solution taurolidine. The aim of this study was to assess whether long-term use of taurolidine leads to selective growth of microorganisms with increased taurolidine minimum inhibitory concentrations (MICs). METHODS: Bloodstream infections among 158 HPN patients with long-term taurolidine catheter locking were analyzed retrospectively. CRBSI-diagnosis was based on clinical symptoms, culture results, and absence of other sources of infections. CRBSIs were classified as definitive, probable or possible and exit site/tunnel/port or luminal infections. MICs were determined by broth microdilution. RESULTS: Between January 2009 and April 2011, 14 patients developed at least one luminal CRBSI episode during long-term taurolidine catheter locking (median (range) = 451 (78-1394) days). Coagulase-negative Staphylococcus species or Staphylococcus aureus predominated among CRBSI-causing Gram-positive bacteria. Taurolidine MICs were 512 mg/l or less in 50% of these isolates (MIC50). Taurolidine MIC50 for Klebsiella pneumoniae and Escherichia coli, the most common CRBSI-causing Gram-negative bacteria, were 256 and 512 mg/l, respectively. Taurolidine MIC50 among CRBSI-causing Candida albicans were 2048 mg/l. CONCLUSION: Adaptation of microorganisms to taurolidine has not yet emerged as a factor in the pathogenesis of CRBSI in HPN patients with long-term taurolidine catheter locking.

[Current options for percutaneous endoscopic access to the digestive tract]. / Huidige mogelijkheden voor percutane endoscopische toegang tot de tractus digestivus.

Four patients, aged 67, 52, 56 and 64 years, respectively, undergoing percutaneous colostomy or jejunostomy are presented to illustrate current options for percutaneous endoscopic access to the digestive tract. The first patient had Parkinson's disease and required percutaneous jejunostomy for continuous post-pyloric administration of medication. The second patient had impaired gastric emptying due to gastric graft-versus-host disease following bone marrow transplantation. He was successfully treated with percutaneous jejunostomy, which was removed 2 years later after full recovery. The third patient had severe constipation due to the use ofmorphinomimetic analgesics. She received percutaneous caecostomy for colonic lavage and desufflation. The fourth patient had combined constipation and sphincteric insufficiency. Although the percutaneous endoscopic colostomy was clinically successful, the catheter had to be removed due to local pain and abscess formation.

Complicating infectious foci in patients with Staphylococcus aureus or Streptococcus species bacteraemia.

Complicating infectious foci resulting from haematogenous or local spread of microorganisms are observed frequently in patients with Staphylococcus aureus bacteraemia (SAB) or Streptococcus species bacteraemia (SSB). The aim of this study was to compare the epidemiology of complicating infectious foci during SAB and SSB in a university hospital in The Netherlands. The charts of all adult patients diagnosed with SAB or SSB (except for Streptococcus pneumoniae bacteraemia) from July 2002 until December 2004 were reviewed retrospectively. Overall, 180 immunocompetent patients were identified, 127 with SAB and 53 with SSB. The percentage of patients with complicating infectious foci (39% of SAB patients, 25% of SSB patients) did not differ significantly between the groups. Endocarditis and cerebral involvement, however, were significantly more common in the SSB group. Of all complicating infectious foci, 32% lacked guiding signs or symptoms and 10% were detected only at autopsy. Factors associated with the development of complicating infectious foci were a delay in treatment for more than 48 h after the onset of symptoms, community acquisition, persistently positive blood cultures, congenital heart disease, and the presence of foreign bodies or prosthetic valves. Infection-related mortality was 18% in SAB patients and 11% in SSB patients and was significantly higher in patients with complicating infectious foci (29 vs. 9%). In conclusion, complicating infectious foci develop in approximately one-third of all patients with SAB and SSB. An active approach that entails searching for the complicating infectious foci is warranted in these patients, because only two-thirds of complicated infectious foci have guiding symptoms or signs, and infection-related mortality is significantly increased in patients with complicating infectious foci compared to patients without these infections.

Recurrent pancreatitis after trimethoprim-sulfamethoxazole rechallenge.

We report a female patient who repeatedly developed pancreatitis after trimethoprim-sulfamethoxazole (TMP/SMX) use. During childhood she had undergone an ureterosigmoidostomy after which she had been on TMP/SMX 480 mg daily as prophylaxis for pyelonephritis for many years. The patient presented with abdominal pain caused by acute pancreatitis. No other cause, except for TMP/SMX use, could be identified. A causal relationship was confirmed by relapse of the pancreatitis after rechallenge. Our case is unique in demonstrating that acute pancreatitis related to the use of TMP/SMX may occur even after long-term treatment. We advise that the medication is discontinued immediately if a causal relationship with pancreatitis is suspected.

[Diagnostic image (190). A man with melaena. Enteral varices due to portal hypertension]. / Diagnose in beeld (190). Een man met melaena. Enterale varicose door portale hypertensie.

A 58-year-old man was seen because of anaemia and melaena, due to bleeding from colonic varices resulting from thrombosis of the V. portae hepatis and the V. lienalis.

Saturated triglycerides and fatty acids activate neutrophils depending on carbon chain-length.

BACKGROUND: Unsaturated fatty acids are known as neutrophil activators. In the present study we investigated whether saturated triglycerides and fatty acids may also contribute to the previously observed activation of neutrophils by nutritional lipid emulsions. Furthermore we tested the hypothesis that carbon-chain length is of importance in this respect. MATERIALS AND METHODS: Neutrophils (1 x 10(6) mL(-1)) were isolated from the blood of nine volunteers. Chemiluminescence was used to evaluate neutrophil activation, characterized by the production of oxygen radicals by neutrophils during incubation with 1 mmol L(-1) saturated fatty acid (6-20 carbon) or triglycerides (6-12 carbon fatty acid), dissolved in aqueous medium by preparing micelles with dipalmitoyl phosphatidylcholine (DPPC). Results were expressed as means +/- SEMs of the overall luminescence signal relative to the signal of cells incubated in medium. RESULTS: Similar to a positive control, the polyunsaturated fatty acid arachidonic acid (C20 : 4), the triglycerides tricaproin (TC6 : 0), tricaprylin (TC8 : 0) and trilaurin (TC12 : 0) as well as the fatty acids lauric acid (C12 : 0), palmitic acid (C16 : 0), stearic acid (C18 : 0) and arachidic acid (C20 : 0) all induced oxygen radical production in neutrophils, while the medium-chain triglyceride tricaprin (TC10 : 0) and fatty acids caproic acid (C6 : 0), caprylic acid (C8 : 0) and capric acid (C10 : 0) exerted no clear effects, similar to negative controls (DPPC and glycerol). CONCLUSIONS: Besides their (poly)-unsaturated counterparts, saturated triglycerides and fatty acids also activate neutrophils. Carbon chain-length is pivotal in the interaction of fatty acids and triglycerides and cells of the immune system.

Human neutrophil membrane fluidity after exposure to structurally different lipid emulsions.

BACKGROUND: We have previously reported that medium-chain triglyceride (MCT)-containing lipid emulsions, contrary to long-chain triglyceride (LCT) emulsions, activate human neutrophils. This activation might result from functional alterations in cellular membranes induced by MCT. Membrane fluidity is such a feature with known clinical implications and can be assessed by fluorescence polarization measurements. This study was performed to investigate whether exposure to various emulsions distinctively influences neutrophil membrane fluidity. METHODS: Neutrophils from 8 volunteers were incubated in medium or physiologic 2.5 mmol/L emulsions containing LCT, mixed LCT/MCT, or structured lipids (SL). Subsequently, the cells were washed and anisotropy, ie, the reciprocal of fluidity, was measured using the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethyl-ammonium (TMA)-DPH. RESULTS: Compared with nonlipid-exposed neutrophils, LCT/MCT and, to a lesser degree, SL decreased fluorescence anisotropy and thus increased membrane fluidity, which was measured by DPH anisotropy, whereas LCT had no effect. Similar results were obtained with the more polar probe TMA-DPH. CONCLUSIONS: These data suggest that the neutrophil-activating effect of MCT-containing emulsions may, at least in part, be mediated by an effect on cellular membrane fluidity.