Summary
Background
Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid‐sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to ...these regimens.
Aim
To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes.
Methods
Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first‐line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G.
Results
No serious adverse events occurred in patients treated with TG during a median follow‐up of 18 months (range 1‐194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty‐eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non‐response (n = 2). TG was effective in all AIH patients as first‐line maintenance treatment.
Conclusion
In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy.
Background and study aims:
Conventional reporting of polyps is often incomplete. We tested the Polyp Manager (PM), a new software application permitting the endoscopist to document polyps in real ...time during colonoscopy. We studied completeness of polyp descriptions, user-friendliness and the potential time benefit.
Patients and methods:
In two Dutch hospitals colonoscopies were performed with PM (as a touchscreen endoscopist-operated device or nurse-operated desktop application). Completeness of polyp descriptions was compared to a historical group with conventional reporting (CR
H
). Prospectively, we compared user-friendliness (VAS-scores) and time benefit of the endoscopist-operated PM to conventional reporting (CR) in one hospital. Duration of colonoscopy and time needed to report polyps and provide a pathology request were measured. Provided that using PM does not prolong colonoscopy, the sum of the latter two was considered as a potential time-benefit if the PM were fully integrated into a digital reporting system.
Results:
A total of 144 regular colonoscopies were included in the study. Both groups were comparable with regard to patient characteristics, duration of colonoscopy and number of polyps. Using the PM did reduce incomplete documentation of the following items in CR
H
-reports: location (96 % vs 82 %,
P =
0.01), size (95 % vs 89 %,
P =
0.03), aspect (71 % vs 36 %,
P <
0.001) and completeness of removal (61 % vs 37 %,
P <
0.001). In the prospective study 23 PM-colonoscopies where compared to 28 CR-colonoscopies. VAS-scores were significantly higher in the endoscopist-operated PM group. Time to report was 01:27 ± 01:43 minutes (median + interquartile range) in the entire group (PM as CR), reflecting potential time benefit per colonoscopy.
Conclusions:
The PM is a user-friendly tool that seems to improve completeness of polyp reporting. Once integrated with digital reporting systems, it is probably time saving as well.
Liver transplantation in the setting of sickle-cell anaemia poses several new challenges to the transplant team. Hypoxaemia, acidosis and a decrease in body temperature are common occurrences that ...can cause sickling in the peri-operative period, putting the patient at risk of sickle-cell crises or graft dysfunction. We describe a patient with sickle-cell anaemia who successfully underwent transplantation, and we discuss the rationale of various precautions that had to be taken.
Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based ...registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS).
DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time.
On the 1st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged <45 years, females aged 45-64 years (adjusted incidence rate ratio 4.21, 95% CI 3.76-4.71, p <0.001) and males ≥65 years (adjusted incidence rate ratio 14.41, 95% CI 9.62-21.60, p <0.001) were at the highest risk of being diagnosed with PBC. The male-to-female ratio of patients newly diagnosed with PBC during the study period was 1:14 in those <45 years, 1:10 in patients aged 45-64 years, and 1:4 in those ≥65 years. Point prevalence increased from 11.9 in 2008 to 21.5 per 100,000 persons in 2018. Average annual percent change in this time period was 5.94% (95% CI 5.77-6.15, p <0.05), and was the highest among the population aged ≥65 years (5.69%, 95% CI 5.32-6.36, p <0.001).
In this nationwide cohort study, we observed an increase in both the incidence and prevalence of PBC in the Netherlands over the past decade, with marked age and sex differences.
This nationwide Dutch primary biliary cholangitis (PBC) Cohort Study, including all hospitals in the Netherlands, showed that the incidence and prevalence of PBC have increased over the last decade. The age-dependent PBC incidence rate differed for males (highest risk ≥65 years) and females (highest risk between 45 and 65 years), which may be related to a difference in the timing of exposure to environmental triggers of PBC. The largest increase in PBC prevalence over time was observed in the population aged ≥65 years, which may have implications for the use of second-line therapies. These results therefore indicate that further studies are needed to elaborate on the advantages and disadvantages of add-on therapies in the elderly population.
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•The incidence and prevalence of PBC in the Netherlands increased over the past decade.•The age-dependent risk of PBC differed per sex; incidences were highest among females aged 45-64 years and males aged ≥65 years.•PBC prevalence increased mainly in the elderly, in whom further evaluation of second-line treatment outcomes is needed.
Background & Aims: Antidepressants could be effective in the treatment of functional gastrointestinal disorders through their anticholinergic and pain-modulating effects. Previous studies with these ...drugs lacked sufficient power and were predominantly conducted in patients with irritable bowel syndrome. This study aimed to assess the effectiveness of the serotonin and norepinephrine reuptake inhibitor venlafaxine in patients with functional dyspepsia. Methods: This was a multi-center, randomized, double-blind, placebo-controlled trial. Participants had persistent dyspeptic symptoms and underwent upper gastrointestinal endoscopy in a secondary care hospital to exclude organic abnormalities. They were randomly assigned to receive 8 weeks of treatment with either venlafaxine XR (2 weeks 75 mg once daily, 4 weeks 150 mg once daily, and 2 weeks 75 mg once daily) or placebo. Symptoms, health-related quality of life, anxiety, and depression were assessed before and at 4, 8, 12, and 20 weeks after inclusion. Results: One hundred sixty patients were randomized; 56% and 73% of participants completed treatment with venlafaxine or placebo, respectively, according to protocol. There was no difference in proportions of symptom-free patients after 8 weeks of treatment or at 20 weeks after inclusion, with venlafaxine in comparison to placebo (37% and 39%, respectively; odds ratio OR, 0.8; 95% confidence interval CI, 0.3–2.1; and 42% and 41%, respectively; OR, 3.1; 95% CI, 0.9–12.6). Per-protocol analysis did not reveal any differences between venlafaxine and placebo either (38% and 39% symptom-free, respectively; OR, 1.0; 95% CI, 0.4–2.4 at 8 weeks). Conclusions: Treatment with the selective serotonin and norepinephrine reuptake inhibitor venlafaxine is not more effective than placebo in patients with functional dyspepsia.
Cholangitis is usually the consequence of a combination of factors: impairment of the flow of bile and bacterial colonization of the biliary tract. Although reestablishing biliary drainage is the ...mainstay of treatment, antibiotics play an important role in the management of cholangitis. In this review, the use of antibiotics for treatment, prophylaxis, and maintenance therapy is discussed. Antibiotics for the treatment of acute cholangitis should be given for 7–10 days in therapeutic dosages and may allow a more selective timing of further interventions. Antibiotic prophylaxis for cholangitis ought to be given as a single (high) dose shortly before surgical or nonsurgical manipulations of the biliary system. Patients with a compromised biliary system (e.g., on account of an endoprosthesis in situ or hepaticojejunostomy) who are prone to develop recurrent bouts of cholangitis may benefit from antibiotic maintenance therapy, given daily in lower-than-therapeutic dosages.
Plant parasitic nematodes are unusual Metazoans as they are equipped with genes that allow for symbiont-independent degradation of plant cell walls. Among the cell wall-degrading enzymes, glycoside ...hydrolase family 5 (GHF5) cellulases are relatively well characterized, especially for high impact parasites such as root-knot and cyst nematodes. Interestingly, ancestors of extant nematodes most likely acquired these GHF5 cellulases from a prokaryote donor by one or multiple lateral gene transfer events. To obtain insight into the origin of GHF5 cellulases among evolutionary advanced members of the order Tylenchida, cellulase biodiversity data from less distal family members were collected and analyzed.
Single nematodes were used to obtain (partial) genomic sequences of cellulases from representatives of the genera Meloidogyne, Pratylenchus, Hirschmanniella and Globodera. Combined Bayesian analysis of ≈ 100 cellulase sequences revealed three types of catalytic domains (A, B, and C). Represented by 84 sequences, type B is numerically dominant, and the overall topology of the catalytic domain type shows remarkable resemblance with trees based on neutral (= pathogenicity-unrelated) small subunit ribosomal DNA sequences. Bayesian analysis further suggested a sister relationship between the lesion nematode Pratylenchus thornei and all type B cellulases from root-knot nematodes. Yet, the relationship between the three catalytic domain types remained unclear. Superposition of intron data onto the cellulase tree suggests that types B and C are related, and together distinct from type A that is characterized by two unique introns.
All Tylenchida members investigated here harbored one or multiple GHF5 cellulases. Three types of catalytic domains are distinguished, and the presence of at least two types is relatively common among plant parasitic Tylenchida. Analysis of coding sequences of cellulases suggests that root-knot and cyst nematodes did not acquire this gene directly by lateral genes transfer. More likely, these genes were passed on by ancestors of a family nowadays known as the Pratylenchidae.
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