ABSTRACT
AIM: To facilitate midline fascial closure in complex abdominal wall surgery, component separation techniques (CST) are usually required. However, CST is associated with an enlarged morbidity. Prehabilitation could increase the compliance of the abdominal wall and thereby decrease the necessity of myofascial release. This can be accomplished by administration of botulinum toxin type A (BTA) in the lateral abdominal wall musculature. The aim of this study was to determine the effect of BTA on the subsequent necessity to perform CST in patients with complex abdominal wall hernias. METHODS: Patients with a complex abdominal wall hernia, planned to undergo CST between July 2020 and November 2022 were included. Outcome of procedures with 300U of BTA 4 (2-6) weeks prior to surgery, were retrospectively analyzed by comparison with propensity matched subjects of an historical group. Hernia width difference was assessed by CT and operative details were included. RESULTS: A total of 13 patients with a median hernia width of 12 cm (IQR 9-14, range 24) were prehabilitated with BTA between July 2020 and November 2022. A CST was planned for all, however not required in 6/13 patients (46%) to accomplish midline fascial closure. A mean elongation of lateral abdominal wall musculature of 4.01 cm was seen in patients not requiring CST. Compared to the propensity score matched control group, a 27% reduction (p = 0.08) in the need for CST was observed. CONCLUSION: There is a tendency for decrease of necessity for CST by preoperatively administered BTA in patients with complex abdominal wall defects. Although small, as this study used propensity matched comparison, further exploration of BTA should be encouraged.
Subject(s)
Abdominal Wall , Botulinum Toxins, Type A , Hernia, Ventral , Propensity Score , Humans , Male , Botulinum Toxins, Type A/administration & dosage , Female , Middle Aged , Retrospective Studies , Aged , Abdominal Wall/surgery , Hernia, Ventral/surgery , Herniorrhaphy/methods , Preoperative Exercise , Abdominal Muscles , Adult , Abdominal Wound Closure TechniquesABSTRACT
BACKGROUND: Patients often need admission at an Intensive Care Unit (ICU), immediately after complex abdominal wall reconstruction (CAWR). Lack of ICU resources requires adequate patient selection for a planned postoperative ICU admission. Risk stratification tools like Fischer score and Hernia Patient Wound (HPW) classification may improve patient selection. This study evaluates the decision-making process in a multidisciplinary team (MDT) on justified ICU admissions for patients after CAWR. METHODS: A pre-Covid-19 pandemic cohort of patients, discussed in a MDT and subsequently underwent CAWR between 2016 and 2019, was analyzed. A justified ICU admission was defined by any intervention within the first 24 h postoperatively, considered not suitable for a nursing ward. The Fischer score predicts postoperative respiratory failure by eight parameters and a high score (> 2) warrants ICU admission. The HPW classification ranks complexity of hernia (size), patient (comorbidities) and wound (infected surgical field) in four stages, with increasing risk for postoperative complications. Stages II-IV point to ICU admission. Accuracy of the MDT decision and (modifications of) risk-stratification tools on justified ICU admissions were analyzed by backward stepwise multivariate logistic regression analysis. RESULTS: Pre-operatively, the MDT decided a planned ICU admission in 38% of all 232 CAWR patients. Intra-operative events changed the MDT decision in 15% of all CAWR patients. MDT overestimated ICU need in 45% of ICU planned patients and underestimated in 10% of nursing ward planned patients. Ultimately, 42% went to the ICU and 27% of all 232 CAWR patients were justified ICU patients. MDT accuracy was higher than the Fischer score, HPW classification or any modification of these risk stratification tools. CONCLUSION: A MDT's decision for a planned ICU admission after complex abdominal wall reconstruction was more accurate than any of the other risk-stratifying tools. Fifteen percent of the patients experienced unexpected operative events that changed the MDT decision. This study demonstrated the added value of a MDT in the care pathway of patients with complex abdominal wall hernias.
Subject(s)
Abdominal Wall , COVID-19 , Humans , Abdominal Wall/surgery , Pandemics , Retrospective Studies , Herniorrhaphy/adverse effects , Intensive Care Units , Hernia , Patient Care TeamABSTRACT
PURPOSE: Surgical site occurrences after transversus abdominis release in ventral hernia repair are still reported up to 15%. Evidence is rising that preoperative improvement of risk factors might contribute to optimal patient recovery. A reduction of complication rates up to 40% has been reported. The aim of this study was to determine whether prehabilitation has a favorable effect on the risk on wound and medical complications as well as on length of stay. METHODS: A retrospective cohort study was performed in a tertiary referral center for abdominal wall surgery. All patients undergoing ventral hernia repair discussed at multidisciplinary team (MDT) meetings between 2015 and 2019 were included. Patients referred for a preconditioning program by the MDT were compared to patients who were deemed fit for operative repair by the MDT, without such a program. Endpoints were patients, hernia, and procedure characteristics as well as length of hospital stay, wound and general complications. RESULTS: A total of 259 patients were included of which 126 received a preconditioning program. Baseline characteristics between the two groups were statistically significantly different as the prehabilitated group had higher median BMI (28 vs 30, p < 0.001), higher HbA1c (41 vs 48, p = 0.014), more smokers (4% vs 25%, p < 0.001) and higher HPW classes due to more patient factors (14% vs 48%, p < 0.001). There were no significant differences in intra-operative and postoperative outcome measures. CONCLUSIONS: This study showed prehabilitation facilitates patients with relevant comorbidities achieving the same results as patients without those risk factors. The indication of a preconditioning program might be effective at the discretion of an MDT meeting. Further research could focus on the extent of such program to assess its value.
Subject(s)
Abdominal Wall , Hernia, Ventral , Humans , Retrospective Studies , Preoperative Exercise , Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Hernia, Ventral/surgery , Hernia, Ventral/etiology , Abdominal Muscles/surgery , Patient Care Team , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Complications/surgery , Abdominal Wall/surgeryABSTRACT
BACKGROUND: During ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC), rectal dissection can be performed via close rectal dissection (CRD) or in a total mesorectal excision plane (TME). Although CRD should protect autonomic nerve function, this technique may be more challenging than TME. The aim of this study was to compare long-term outcomes of patients undergoing CRD and TME. METHODS: This single-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC between January 2002 and October 2017. Primary outcomes were chronic pouch failure (PF) among patients who underwent CRD and TME and the association between CRD and developing chronic PF. Chronic PF was defined as a pouch-related complication occurring ≥ 3 months after primary IPAA surgery requiring redo pouch surgery, pouch excision or permanent defunctioning ileostomy. Secondary outcomes were risk factors and causes for chronic PF. Pouch function and quality of life were assessed via the Pouch dysfunction score and Cleveland global quality of life score. RESULTS: Out of 289 patients (155 males, median age 37 years [interquartile range 26.5-45.5 years]), 128 underwent CRD. There was a shorter median postoperative follow-up for CRD patients than for TME patients (3.7 vs 10.9 years, p < 0.01). Chronic PF occurred in 6 (4.7%) CRD patients and 20 (12.4%) TME patients. The failure-free pouch survival rate 3 years after IPAA surgery was comparable among CRD and TME patients (96.1% vs. 93.5%, p = 0.5). CRD was a no predictor for developing chronic PF on univariate analyses (HR 0.7 CI-95 0.3-2.0, p = 0.54). A lower proportion of CRD patients developed chronic PF due to a septic cause (1% vs 6%, p = 0.03). CONCLUSIONS: Although differences in chronic PF among CRD and TME patients were not observed, a trend toward TME patients developing chronic pelvic sepsis was detected. Surgeons may consider performing CRD during IPAA surgery for UC.
Subject(s)
Colitis, Ulcerative , Colonic Pouches , Proctocolectomy, Restorative , Rectal Neoplasms , Male , Humans , Adult , Middle Aged , Colitis, Ulcerative/surgery , Retrospective Studies , Quality of Life , Proctocolectomy, Restorative/methods , Rectal Neoplasms/surgery , Anastomosis, Surgical/adverse effects , Postoperative Complications/etiology , Colonic Pouches/adverse effects , Treatment OutcomeABSTRACT
PURPOSE: MYC gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in MYC + and MYC- DLBCL patients. METHODS: Interim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81 MYC + and 129 MYC- DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival. RESULTS: MYC + DLBCL patients had significantly more positive EoT-PET scans than MYC- patients (32.5 vs 15.7%, p = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In MYC + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the MYC- patients (p = 0.002). Nine (34.6%) MYC + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%) MYC- patient. A total of 80.8% of EoT-PET positive MYC + patients showed both increased lesional SUV and MTV compared to I-PET. In MYC- patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both MYC subgroups (81.8-94.1%). PPV was highest at EoT-PET for MYC + patients (61.5%). CONCLUSION: MYC + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: HOVON-84: EudraCT: 2006-005,174-42, retrospectively registered 01-08-2008. HOVON-130: EudraCT: 2014-002,654-39, registered 26-01-2015.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Positron Emission Tomography Computed Tomography , Fluorodeoxyglucose F18 , Gene Rearrangement , Humans , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/therapy , Positron Emission Tomography Computed Tomography/methods , Positron-Emission Tomography , Prognosis , Retrospective StudiesABSTRACT
KEY MESSAGE: We identified cryptic early blight resistance introgressions in tomato breeding lines and demonstrated efficient genotypic selection for resistance in the context of a tomato breeding program. Early blight is a widespread and problematic disease affecting tomatoes (Solanum lycopersicum). Caused by the fungal pathogen Alternaria linariae (syn. A. tomatophila), symptoms include lesions on tomato stems, fruit, and foliage, often resulting in yield losses. Breeding tomatoes with genetic resistance would enhance production sustainability. Using cross-market breeding populations, we identified several quantitative trait loci (QTL) associated with early blight resistance. Early blight resistance putatively derived from 'Campbell 1943' was confirmed in modern fresh market tomato breeding lines. This resistance offered substantial protection against early blight stem lesions (collar rot) and moderate protection from defoliation. A distinctive and potentially novel form of early blight foliar resistance was discovered in a processing tomato breeding line and is probably derived from S. pimpinellifolium via 'Hawaii 7998'. Additional field trials validated the three most promising large-effect QTL, EB-1.2, EB-5, and EB-9. Resistance effects for EB-5 and EB-9 were consistent across breeding populations and environments, while EB-1.2's effect was population specific. Using genome-wide marker-assisted backcrossing, we developed fresh market tomato lines that were near-isogenic for early blight QTL. Resistance in these lines was largely mediated by just two QTL, EB-5 and EB-9, that together captured 49.0 and 68.7% of the defoliation and stem lesion variance, respectively. Our work showcases the value of mining cryptic introgressions in tomato lines, and across market classes, for use as additional sources of disease resistance.
Subject(s)
Ascomycota/physiology , Chromosome Mapping/methods , Chromosome Segregation , Chromosomes, Plant/genetics , Disease Resistance/immunology , Plant Diseases/immunology , Solanum lycopersicum/genetics , Disease Resistance/genetics , Solanum lycopersicum/growth & development , Solanum lycopersicum/microbiology , Plant Diseases/genetics , Plant Diseases/microbiology , Quantitative Trait LociABSTRACT
INTRODUCTION: Adalimumab is effective for maintenance of remission in patients with Crohn's disease (CD) at a dose of 40 mg subcutaneously every 2 weeks. However, adalimumab is associated with (long-term) adverse events and is costly. The aim of this study is to demonstrate non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening compared to standard dosing of every other week (EOW). METHODS AND ANALYSIS: The Lengthening Adalimumab Dosing Interval (LADI) study is a pragmatic, multicentre, open label, randomised controlled non-inferiority trial. Non-inferiority is reached if the difference in cumulative incidence of persistent (>8 weeks) flares does not exceed the non-inferiority margin of 15%. 174 CD patients on adalimumab maintenance therapy in long-term (>9 months) clinical and biochemical remission will be included (C-reactive protein (CRP) <10 mg/L, faecal calprotectin (FC) <150 µg/g, Harvey-Bradshaw Index (HBI) <5). Patients will be randomised 2:1 into the intervention (adalimumab interval lengthening) or control group (adalimumab EOW). The intervention group will lengthen the adalimumab administration interval to every 3 weeks, and after 24 weeks to every 4 weeks. Clinical and biochemical disease activity will be monitored every 12 weeks by physician global assessment, HBI, CRP and FC. In case of disease flare, dosing will be increased. A flare is defined as two of three of the following criteria; FC>250 µg/g, CRP≥10 mg/l, HBI≥5. Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness. ETHICS AND DISSEMINATION: The study is approved by the Medical Ethics Committee Arnhem-Nijmegen, the Netherlands (registration number NL58948.091.16). Results will be published in peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBERS: EudraCT registry (2016-003321-42); Clinicaltrials.gov registry (NCT03172377); Dutch trial registry (NTRID6417).
Subject(s)
Crohn Disease , Adalimumab/therapeutic use , Antibodies, Monoclonal, Humanized , Crohn Disease/drug therapy , Humans , Multicenter Studies as Topic , Netherlands , Randomized Controlled Trials as Topic , Tumor Necrosis Factor-alphaABSTRACT
Fibrodysplasia ossificans progressiva (FOP) is a very rare devastating heterotopic ossification disorder, classically caused by a heterozygous single point mutation (c.617G>A) in the ACVR1gene, encoding the Bone morphogenetic protein (BMP) type I receptor, also termed activin receptor-like kinase (ALK)2. FOP patients develop heterotopic ossification episodically in response to inflammatory insults, thereby compromising tissue sampling and the development of in vitro surrogate models for FOP. Here we describe the generation and characterization of a control and a classical FOP induced pluripotent stem cell (iPSC) line derived from periodontal ligament fibroblast cells using Sendai virus vectors.
Subject(s)
Cell Culture Techniques/methods , Cell Line/pathology , Fibroblasts/pathology , Induced Pluripotent Stem Cells/pathology , Periodontal Ligament/pathology , Adult , Base Sequence , Female , Humans , Reproducibility of Results , Young AdultABSTRACT
Many marine animals depend upon a larval phase of their life cycle to locate suitable habitat, and larvae use light detection to influence swimming behaviour and dispersal. Light detection is mediated by the opsin genes, which encode light-sensitive transmembrane proteins. Previous studies suggest that r-opsins in the eyes mediate locomotory behaviour in marine protostomes, but few have provided direct evidence through gene mutagenesis. Larvae of the marine annelid Capitella teleta have simple eyespots and are positively phototactic, although the molecular components that mediate this behaviour are unknown. Here, we characterize the spatio-temporal expression of the rhabdomeric opsin genes in C. teleta and show that a single rhabdomeric opsin gene, Ct-r-opsin1, is expressed in the larval photoreceptor cells. To investigate its function, Ct-r-opsin1 was disrupted using CRISPR/CAS9 mutagenesis. Polymerase chain reaction amplification and DNA sequencing demonstrated efficient editing of the Ct-r-opsin1 locus. In addition, the pattern of Ct-r-opsin1 expression in photoreceptor cells was altered. Notably, there was a significant decrease in larval phototaxis, although the eyespot photoreceptor cell and associated pigment cell formed normally and persisted in Ct-r-opsin1-mutant animals. The loss of phototaxis owing to mutations in Ct-r-opsin1 is similar to that observed when the entire photoreceptor and pigment cell are deleted, demonstrating that a single r-opsin gene is sufficient to mediate phototaxis in C. teleta. These results establish the feasibility of gene editing in animals like C. teleta, and extend previous work on the development, evolution and function of the C. teleta visual system . Our study represents one example of disruption of animal behaviour by gene editing through CRISPR/CAS9 mutagenesis, and has broad implications for performing genome editing studies in a wide variety of other understudied animals.
Subject(s)
Annelida/genetics , Aquatic Organisms/genetics , CRISPR-Cas Systems , Opsins/genetics , Phototaxis , Animals , Annelida/physiology , Aquatic Organisms/physiology , Gene Editing , Larva/genetics , Larva/physiology , Mutagenesis, Site-Directed , Photoreceptor Cells, Invertebrate/metabolism , Photoreceptor Cells, Invertebrate/physiologyABSTRACT
Circuit quantum electrodynamics has proven to be a powerful tool to probe mesoscopic effects in hybrid systems and is used in several quantum computing (QC) proposals that require a transmon qubit able to operate in strong magnetic fields. To address this we integrate monolayer graphene Josephson junctions into microwave frequency superconducting circuits to create graphene based transmons. Using dispersive microwave spectroscopy we resolve graphene's characteristic band dispersion and observe coherent electronic interference effects confirming the ballistic nature of our graphene Josephson junctions. We show that the monoatomic thickness of graphene renders the device insensitive to an applied magnetic field, allowing us to perform energy level spectroscopy of the circuit in a parallel magnetic field of 1 T, an order of magnitude higher than previous studies. These results establish graphene based superconducting circuits as a promising platform for QC and the study of mesoscopic quantum effects that appear in strong magnetic fields.
ABSTRACT
BACKGROUND: Small bowel capsule endoscopy (SBCE) is an important diagnostic tool for small-bowel diseases but its quality may be hampered by intraluminal gas. This study evaluated the added value of the anti-foaming agent, simethicone, to a bowel preparation with polyethylene glycol (PEG) on the quality of small bowel visualisation and its use in the Netherlands. METHODS: This was a retrospective, single-blind, cohort study. Patients in the PEG group only received PEG prior to SBCE. Patients in the PEG-S group ingested additional simethicone. Two investigators assessed the quality of small-bowel visualisation using a four-point scale for 'intraluminal gas' and 'faecal contamination'. By means of a survey, the use of anti-foaming agents was assessed in a random sample of 16 Dutch hospitals performing SBCE. RESULTS: The quality of small bowel visualisation in the PEG group (n = 33) was significantly more limited by intraluminal gas when compared with the PEG-S group (n = 31): proximal segment 83.3% in PEG group vs. 18.5% in PEG-S group (p < 0.01), distal segment 66.7% vs. 18.5% respectively (p < 0.01). No difference was observed in the amount of faecal contamination (proximal segment 80.0% PEG vs. 59.3% PEG-S, p = 0.2; distal segment 90.0% PEG vs. 85.2% PEG-S, p = 0.7), mean small bowel transit times (4.0 PEG vs. 3.9 hours PEG-S, p = 0.7) and diagnostic yield (43.3% PEG vs. 22.2% PEG-S, p = 0.16). Frequency of anti-foaming agent use in the Netherlands was low (3/16, 18.8%). CONCLUSION: Simethicone is of added value to a PEG bowel preparation in improving the quality of visualisation of the small bowel by reducing intraluminal gas. At present, the use of anti-foaming agents in SBCE preparation is not standard practice in the Netherlands.
Subject(s)
Antifoaming Agents/administration & dosage , Capsule Endoscopy/methods , Cathartics/administration & dosage , Intestine, Small/diagnostic imaging , Simethicone/administration & dosage , Adult , Female , Humans , Male , Middle Aged , Netherlands , Prospective Studies , Retrospective Studies , Single-Blind MethodABSTRACT
[This corrects the article DOI: 10.1593/neo.08980.].
ABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Azathioprine/therapeutic use , Glutathione Transferase/genetics , Immunosuppressive Agents/therapeutic use , Thioinosine/analogs & derivatives , Thionucleotides/metabolism , Adult , Azathioprine/metabolism , Case-Control Studies , Female , Genotype , Guanine Nucleotides/genetics , Humans , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/metabolism , Isoenzymes/genetics , Male , Mercaptopurine/metabolism , Middle Aged , Thioinosine/metabolism , Thionucleotides/genetics , Young AdultABSTRACT
Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Burkitt Lymphoma/drug therapy , Cost-Benefit Analysis , HIV Infections/drug therapy , Adolescent , Adult , Aged , Burkitt Lymphoma/complications , Burkitt Lymphoma/economics , Burkitt Lymphoma/mortality , Carmustine/economics , Carmustine/therapeutic use , Cyclophosphamide/economics , Cyclophosphamide/therapeutic use , Cytarabine/economics , Cytarabine/therapeutic use , Etoposide/economics , Etoposide/therapeutic use , Female , HIV Infections/complications , HIV Infections/economics , HIV Infections/mortality , Humans , Ifosfamide/economics , Ifosfamide/therapeutic use , Male , Melphalan/economics , Melphalan/therapeutic use , Methotrexate/economics , Methotrexate/therapeutic use , Middle Aged , Neoplasm Staging , Retrospective Studies , Rituximab/economics , Rituximab/therapeutic use , Survival AnalysisSubject(s)
Aging , Inflammatory Bowel Diseases , Azathioprine , Genotype , Humans , Immunosuppressive Agents , Mercaptopurine , Methyltransferases/geneticsABSTRACT
BACKGROUND AND AIMS: The number of patients with inflammatory bowel disease [IBD], of non-Caucasian descent in Western Europe, is increasing. We aimed to explore the impact of ethnicity and country of birth on IBD phenotype. METHODS: IBD patients treated in the eight University Medical Centers in The Netherlands [Dutch IBD Biobank] were divided into two groups according to their ethnicity: 1] Caucasian patients of Western and Central European descent [CEU]; and 2] patients of non-Caucasian descent [non-CEU]. The non-CEU group was subdivided according to country of birth, into: born in The Netherlands or Western Europe [non-CEU European born]; or born outside Western-Europe who migrated to The Netherlands [non-CEU non-European born]. Both comparisons were analysed for phenotype differences [by chi-square test]. RESULTS: The Dutch IBD Biobank included 2921 CEU patients and 233 non-CEU patients. Non-CEU Crohn's disease [CD] patients more often had upper gastro-intestinal disease [16% vs 8%, p = 0.001] and anal stenosis [10% vs 4%, p = 0.002] than CEU CD patients. The use of anti-tumour necrosis factor [TNF] agents and immunomodulators was higher in non-CEU IBD patients than in CEU IBD patients [45% vs 38%, p = 0.042] and [77% vs 66%, p = 0.001], respectively. Non-CEU IBD patients born in Europe [n = 116] were diagnosed at a lower age than non-CEU IBD patients born outside Europe [n = 115] [at 22.7 vs 28.9 years old, p < 0.001]. CONCLUSION: Non-Caucasians had more severe disease behaviour than Caucasians. Non-CEU patients born in Europe were diagnosed at a lower age with IBD than those born outside Europe who migrated to The Netherlands.
Subject(s)
Colitis, Ulcerative/ethnology , Crohn Disease/ethnology , Intestinal Fistula/ethnology , Phenotype , Residence Characteristics , Adult , Age of Onset , Aged , Anal Canal/pathology , Colitis, Ulcerative/genetics , Colitis, Ulcerative/therapy , Constriction, Pathologic/ethnology , Crohn Disease/genetics , Crohn Disease/therapy , Digestive System Surgical Procedures/statistics & numerical data , Europe/ethnology , Female , Humans , Male , Middle Aged , Netherlands/epidemiology , Prospective Studies , White People/statistics & numerical dataABSTRACT
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.
Subject(s)
Azathioprine/adverse effects , Inflammatory Bowel Diseases/drug therapy , Mercaptopurine/adverse effects , Methyltransferases/genetics , Adult , Azathioprine/therapeutic use , Case-Control Studies , Female , Genotype , Humans , Leukopenia/chemically induced , Male , Mercaptopurine/administration & dosage , Middle Aged , Polymorphism, Genetic , Risk FactorsABSTRACT
OBJECTIVE: To evaluate the performance of the FreeStyle Libre Flash continuous glucose monitoring (FSL-CGM) system against established central laboratory methods. RESEARCH DESIGN AND METHODS: 20 subjects (8 type 1 diabetes mellitus, 12 type 2 diabetes mellitus) were analyzed. FSL-CGM sensor measurements (inserted in arm and abdomen) were compared with capillary blood glucose results analyzed with StatStrip as semigold standard. The glucose response after a standardized oral glucose load was measured by FSL-CGM and capillary samples analyzed by perchloric acid hexokinase (PCA-HK) method, StatStrip and FSL test strip (FSLC), and a commonly used CGM system (iPro2). RESULTS: FSL-CGM arm sensor readings showed 85.5% of paired readings falling within Clarke Error Grid (ISO 15197:2013) zone A when compared with StatStrip. For FSL-CGM abdomen and FSLC, these percentages were 64% and 98%, respectively. The overall correlation of FSL-CGM in the arm and the StatStrip indicates a performance with lower results with the FSL-CGM in the arm than expected based on the StatStrip in the lower glucose ranges, and higher results than expected in the higher ranges. Following a standardized glucose load, a slower rise in glucose level was observed for FSL-CGM arm as compared with PCA-HK, StatStrip, FSLC, and iPro2 during the first 45-60â min after glucose load ingestion. CONCLUSIONS: Certain matters need attention while using the FSL-CGM in daily life including the observed lower values in the lower ranges, and the underestimation of the effect of a meal on glucose response. These effects of such deviations can partly be overcome by optimizing the available user instructions. TRIAL REGISTRATION NUMBER: TC5348; results.