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Lessons from a multicentre retrospective study of peptide receptor radionuclide therapy combined with lanreotide for neuroendocrine tumours: a need for standardised practice.
No full textPURPOSE
PRELUDE aimed to assess use and effectiveness/safety of lanreotide autogel/depot (LAN) combined with Lu-DOTATOC or Lu-DOTATATE (LAN-peptide receptor radionuclide therapy [PRRT]) in patients with progressive neuroendocrine tumours (NETs).
METHODS
International, non-interventional, retrospective, non-comparative analysis of medical records from patients with progressive metastatic or locally advanced grade 1 or 2 gastroenteropancreatic (GEP)- or lung-NETs. The primary endpoint was progression-free survival (PFS) at end of last LAN-PRRT cycle. Secondary endpoints included PFS at last available follow-up, best overall response, objective response rate (ORR), presence and severity of diarrhoea and flushing, and safety. Post-hoc analyses were conducted to determine pre-treatment tumour growth rate (TGR) cutoffs that best predicted the ORR during treatment.
RESULTS
Forty patients were enrolled (GEP-NETs, n = 39; lung-NETs, n = 1). PFS rates were 91.7% at end of last LAN-PRRT cycle and 95.0% at last available follow-up. In the full analysis set, best overall response among patients with GEP-NETs (n = 23) was stable disease (n = 14, 60.9%), partial response (n = 8, 34.8%) and progressive disease (n = 1, 4.3%). The ORR was 27.3% at end of last LAN-PRRT cycle and 36.8% at last available follow-up. Optimal baseline TGR cutoffs for predicting ORR at these time points were 1.18% and 0.33%, respectively. At baseline, 81.0% of patients had diarrhoea or flushing; both remained stable or improved in most cases. No increased adverse drug reactions were reported.
CONCLUSION
Despite the major recruitment shortfall for the PRELUDE study, effectiveness data were encouraging in this selected population, highlighting the potential usefulness and feasibility of LAN combined with and after PRRT in patients with GEP-NETs. The study also identified challenges associated with evaluating clinical practice in a rare-disease setting and highlighted the need for standardisation of PRRT procedures.
TRIAL REGISTRATION
Trial number: NCT02788578; URL: https://clinicaltrials.gov/ct2/show/NCT02788578
Presence of donor-encoded centromeric KIR B content increases the risk of infectious mortality in recipients of myeloablative, T-cell deplete, HLA-matched HCT to treat AML.
No full textThe reported influence of donor Killer-cell Immunoglobulin-like Receptor (KIR) genes on the outcomes of haematopoietic cell transplantation (HCT) are contradictory, in part due to diversity of disease, donor sources, era and conditioning regimens within and between different studies. Here, we describe the results of a retrospective clinical analysis establishing the effect of donor KIR motifs on the outcomes of 119 HLA-matched, unrelated donor HCT for adult acute myeloid leukaemia (AML) using myeloablative conditioning (MAC) in a predominantly T-cell deplete (TCD) cohort. We observed that HCT involving donors with at least one KIR B haplotype were more likely to result in non-relapse mortality (NRM) than HCT involving donors with two KIR A haplotypes (p = 0.019). Upon separation of KIR haplotypes into their centromeric (Cen) and telomeric (Tel) motif structures, we demonstrated that the Cen-B motif was largely responsible for this effect (p = 0.001). When the cause of NRM was investigated further, infection was the dominant cause of death (p = 0.006). No evidence correlating donor KIR B haplotype with relapse risk was observed. The results from this analysis confirm previous findings in the unrelated, TCD, MAC transplant setting and imply a protective role for donor-encoded Cen-A motifs against infection in allogeneic HCT recipients
A service evaluation comparing home-based testing to clinic-based testing for HIV, syphilis and hepatitis B in Birmingham and Solihull.
No full textThe sexual health services in the Birmingham and Solihull area of the United Kingdom, called Umbrella, has been offering home-based testing for sexually transmitted infections to patients since August 2015. The aim of this service evaluation was to evaluate the uptake, return rate and new diagnosis rates of home-based testing in comparison with clinic-based testing for human immunodeficiency virus (HIV), syphilis (STS) and hepatitis B. Home-based testing, although popular, had low uptake amongst high-risk groups such as men who have sex with men (MSM), compared to the clinic-based group (1% versus 11%, p < 0.001). This resulted in low positivity rates for HIV (0.02%) and STS (0.17%) and no new cases of hepatitis B in the home-based group. Therefore, our results show that home-based testing is not a cost-effective method of testing for HIV and likely this is also the case for hepatitis B and STS. Our recommendation would be to encourage uptake of home-based testing in high-risk groups such as MSM and Black Africans to improve the diagnosis rates of HIV, STS and hepatitis B. Alternatively, the continuation of home-based blood testing in the Birmingham and Solihull area will need to be reviewed by Umbrella as a cost-saving strategy for the service in the future
Vitamin D deficiency is not associated with graft versus host disease after hematopoietic stem cell transplantation: A meta-analysis.
No full textOBJECTIVE
Vitamin D status plays an important role in immunoregulation, and a deficiency is believed to be related to Graft Versus Host Disease (GVHD) in patients after hematopoietic stem cell transplantation (HSCT). We aim to study the association between vitamin D deficiency and GVHD after HSCT.
METHODS
A literature search was conducted utilizing MEDLINE, EMBASE, and The Cochrane Library Database from inception to July 2019. Eligible studies were required to be clinical trials or observational studies (cohort, case-control, or cross-sectional studies); provide data to calculate the odds ratios (OR) of GVHD in HSCT patients with vitamin D deficiency. Two reviewers independently extracted the data and assessed the risk of bias. Pooled odds ratios (OR) with 95% confidence interval (CI) were estimated using random-effects meta-analysis through the Comprehensive Meta-Analysis 3.3 software.
RESULTS
In total, 8 observational studies consisting of 1335 HSCT patients were enrolled in this systematic review. Overall, there was no significant association between vitamin D deficiency and acute GVHD (OR = 1.06, 95% CI 0.74-1.53, P > 0.05). There was no significant association between vitamin D deficiency and chronic GVHD (OR = 1.75, 95% CI 0.72-4.26, P > 0.05). Funnel plots and Egger regression asymmetry test were performed and showed no publication bias.
CONCLUSION
There is not a statistically significant association between vitamin D deficiency and neither acute nor chronic GVHD
Longitudinal development of PHOMS suggest a novel pathological pathway in MS.
No full textOBJECTIVE
Peripapillary Hyperreflective Ovoid Mass-like Structures (PHOMS) are a new spectral domain Optical Coherence Tomography (OCT) finding.
METHODS
Prospective, longitudinal study. Patients (n=212) with MS (n=418 eyes), 59 healthy controls (HC, n=117 eyes) and 267 non-MS disease controls (534 eyes). OCT and Diffusion Tensor Imaging.
RESULTS
There were no PHOMS in HC eyes (0/117, 0%). The prevalence of PHOMS was significantly higher in patients with MS (34/212, p=0.001) and MS eyes (45/418, p=0.0002) if compared to HC (0/59, 0/117). The inter-rater agreement for PHOMS was 97.9%, kappa 0.951. PHOMS were present in 16% of patients with relapsing remitting, 16% of patients with progressive and 12% of patients with secondary progressive disease course (2% of eyes). There was no relationship of PHOMS with age, disease duration, disease course, disability or disease modifying treatments. The fractional anisotropy of the optic radiations was lower in patients without PHOMS (0.814) if compared to patients with PHOMS (0.845, p=0.03). The majority of PHOMS remained stable, but increase in size and de novo development of PHOMS were also observed. In non-MS disease controls, PHOMS were observed in intracranial hypertension (62%), ODD (47%), anomalous optic discs (44%), isolated optic neuritis (19%) and optic atrophy (12%).
INTERPRETATION
These data suggest that PHOMS are a novel finding in MS pathology. Future research is needed to determine if development of PHOMS in MS is due to intermittently raised intracranial pressure or an otherwise impaired "glymphatic" outflow from eye to brain. This article is protected by copyright. All rights reserved
Added value of three-dimensional transesophageal echocardiography in management of mitral paravalvular leaks.
No full textProsthetic paravalvular leak (PVL) is a well-known serious complication following surgically as well as percutaneously implanted prosthetic valves. It usually happens due to incomplete sealing of the prosthetic ring to the native cardiac tissue whether immediately postoperative or considerably later as a complication of infective endocarditis, etc Surgery has been always the treatment of choice for clinically significant PVLs. However, percutaneous transcatheter closure therapy has become a successful alternative in carefully selected group of patients. Echocardiography is a cornerstone in the initial diagnosis, assessment of the severity and location of the PVL. Furthermore, it plays a crucial role in the assessment of the feasibility for percutaneous closure and during intra-procedural guidance. Transesophageal echocardiography (TEE) has the advantage over transthoracic echocardiography (TTE) of not being affected by the acoustic shadow of the mitral prosthesis that usually hides the regurgitation jets and makes TTE evaluation difficult. Three-dimensional (3D) TEE has been shown to provide better diagnostic accuracy compared to two-dimensional (2D) TEE as regard to evaluation of PVLs especially in patients with more than one PVL. This is due to better delineation of the location, shape, and size of the PVL and equally important during guiding the transcatheter percutaneous closure
Management of endocrine conditions at the end of life.
No full textAn important facet to end-of-life care is deprescribing. This can be challenging when reviewing life-sustaining endocrine medications but, unlike for diabetes, there is no national guidance to support patients and clinicians faced with care planning. This article reviews the limited current evidence to highlight areas for further discussion and research with the aim of moving towards consensus opinion. Discontinuation of certain endocrine medications, including corticosteroids, desmopressin and levothyroxine, is likely to precipitate an 'endocrine-driven mechanism of death', while it may be reasonable to discontinue other endocrine medications without the risk of hastening death or causing unnecessary symptoms. However, the over-arching theme should be that early discussion with patients regarding conversion or discontinuation of endocrine medications or monitoring is central to care planning
Glue ear management & deprivation - a retrospective study of 89 patients.
No full textIn accordance with National Guidelines, intervention for otitis media with effusion (OME) is considered when there is evidence of persistence over a 3-month period and hearing loss is judged to have a significant impact on the child's development. Deprivation is officially measured by the UK government and can be used to compare neighbourhoods and relative changes over time. There is a delay in the diagnosis of persistent OME with the majority of patients being seen well beyond the recommended 3-month active observation period. A higher deprivation score was associated with a significantly longer waiting time for diagnosis of persistent bilateral OME (p= 0.037) Universal healthcare does not guarantee fair and equal access to services for all. It is not always clear why such differences exist; however, clinicians must remain vigilant to the inequalities that may affect patient care