We describe the first published case of malakoplakia in a dual stem cell and cardiac transplant recipient. In the 2 months following cardiac transplantation, our patient developed persistent diarrhea ...and recurrent E coli bacteremia. Biopsies obtained from areas of colonic thickening revealed malakoplakia. Despite improvement in symptoms with prolonged antimicrobial therapy and reduction of his immunosuppression, he eventually died from sepsis. Our case highlights not only the importance of the timely diagnosis of this rare disorder, but also the difficulty in determining optimal treatment duration, particularly where excision of involved areas is not possible, as data on this disease are lacking. Here we describe our case and review the available literature published on malakoplakia in the cardiac transplant population.
Despite the growing evidence base supporting intensive lifestyle and medical treatments for severe obesity, patient engagement in specialist obesity services is difficult to achieve and poorly ...understood. To address this knowledge gap, we aimed to develop a model for predicting non-completion of a specialist multidisciplinary service for clinically severe obesity, termed the Metabolic Rehabilitation Programme (MRP).
Using a case-control study design in a public hospital setting, we extracted data from medical records for all eligible patients with a body mass index (BMI) of ≥35 kg/m
with either type 2 diabetes or fatty liver disease referred to the MRP from 2010 through 2015. Non-completion status (case definition) was coded for patients whom started but dropped-out of the MRP within 12 months. Using multivariable logistic regression, we tested the following baseline predictors hypothesised in previous research: age, gender, BMI, waist circumference, residential distance from the clinic, blood pressure, obstructive sleep apnoea (OSA), current continuous positive airway pressure (CPAP) therapy, current depression/anxiety, diabetes status, and medications. We used receiver operating characteristics and area under the curve to test the performance of models.
Out of the 219 eligible patient records, 78 (35.6%) non-completion cases were identified. Significant differences between non-completers versus completers were: age (47.1 versus 54.5 years, p < 0.001); residential distance from the clinic (21.8 versus 17.1 km, p = 0.018); obstructive sleep apnoea (OSA) (42.9% versus 56.7%, p = 0.050) and CPAP therapy (11.7% versus 28.4%, p = 0.005). The probability of non-completion could be independently associated with age, residential distance, and either OSA or CPAP. There was no statistically significant difference in performance between the alternate models (69.5% versus 66.4%, p = 0.57).
Non-completion of intensive specialist obesity management services is most common among younger patients, with fewer complex care needs, and those living further away from the clinic. Clinicians should be aware of these potential risk factors for dropping out early when managing outpatients with severe obesity, whereas policy makers might consider strategies for increasing access to specialist obesity management services.
Perianal fistulizing Crohn’s Disease (pCD) affects about 25% of patients with Crohn’s Disease (CD). It remains a difficult entity to manage with a therapeutic ceiling of treatment success despite ...improving medical and surgical management. The refractory nature of the disease calls for an imminent need to better understand its immunopathogenesis and classification to better streamline our treatment options. In this article, we overview the current state of pCD management and discuss where the future of its management may lie.
The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 ...vaccine-induced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs.
In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 Oxford-AstraZeneca, BNT162b2 Pfizer-BioNTech, or mRNA1273 Moderna) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing.
Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156·8 U/mL geometric SD 5·7; p<0·0001), infliximab plus thiopurine (111·1 U/mL 5·7; p<0·0001), or tofacitinib (429·5 U/mL 3·1; p=0·0012) compared with controls (1578·3 U/mL 3·7). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019·8 U/mL 4·3; p=0·74), ustekinumab (582·4 U/mL 4·6; p=0·11), or vedolizumab (954·0 U/mL 4·1; p=0·50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0·12, 95% CI 0·08-0·17; p<0·0001) and tofacitinib (0·43, 0·23-0·81; p=0·0095), but not with ustekinumab (0·69, 0·41-1·19; p=0·18), thiopurines (0·89, 0·64-1·24; p=0·50), or vedolizumab (1·16, 0·74-1·83; p=0·51). mRNA vaccines (3·68, 2·80-4·84; p<0·0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0·79, 0·72-0·87; p<0·0001) with lower antibody concentrations.
For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipients of infliximab, infliximab plus thiopurines, and tofacitinib. Scheduling of third primary, or booster, doses could be personalised on the basis of an individual's treatment, and patients taking anti-tumour necrosis factor and tofacitinib should be prioritised.
Pfizer.
Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal ...fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.
We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with inflammatory bowel ...disease IBD.
We conducted a prospective study including 213 IBD patients and 53 healthy controls: 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab, or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination, and interval between vaccination and sampling.
Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (geometric mean ratio 0.35 95% confidence interval 0.20-0.60, p = 0.0002), combination of infliximab and thiopurine therapy (0.46 0.27-0.79, p = 0.0050), and tofacitinib (0.28 0.14-0.57, p = 0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 0.15-0.56, p = 0.0003), combination of infliximab and thiopurine therapy (0.34 0.17-0.66, p = 0.0016), thiopurine monotherapy (0.46 0.24-0.87, p = 0.017), and tofacitinib (0.23 0.10-0.56, p = 0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 r = 0.27; p = 0.0004 and H1N1 r = 0.33; p < 0.0001.
Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to influenza/A, similar to COVID-19 vaccine-induced antibody responses.
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