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Early relapse after high-dose melphalan autologous stem cell transplant predicts inferior survival and is associated with high disease burden and genetically high-risk disease in multiple myeloma.
No full textPredicting patient outcome in multiple myeloma remains challenging despite the availability of standard prognostic biomarkers. We investigated outcome for patients relapsing early from intensive therapy on NCRI Myeloma XI. Relapse within 12 months of autologous stem cell transplant was associated with markedly worse median progression-free survival 2 (PFS2) of 18 months and overall survival (OS) of 26 months, compared to median PFS2 of 85 months and OS of 91 months for later relapsing patients despite equal access to and use of subsequent therapies, highlighting the urgent need for improved outcome prediction and early intervention strategies for myeloma patients
First case of near haploid philadelphia negative B-Cell acute lymphoblastic leukaemia relapsing as acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation.
No full textHerein we present a female patient aged 61 with Philadelphia negative acute lymphoblastic leukaemia demonstrating near haploid karyotype and abnormal TP53 expression at diagnosis, who relapsed with lineage switch as Acute Monocytic Leukemia post allogeneic stem cell transplantation. Molecular analysis established that both neoplasms were derived from the same founder clone. The leukemic lineage switch phenomenon has recently re-attracted interest as mechanism of leukemic evasion post treatment with chimeric antigen receptor T-cells but there is paucity of data on its presence post allograft or following novel antibody treatments such as Inotuzumab Ozogamicin or Blinatumomab. Our proposition for cancer research is that near haploidy in ALL could be linked to leukemic stem cell plasticity evading stem cell transplantation and other immunotherapy approaches
Vaginoscopy for office hysteroscopy: A systematic review & meta-analysis.
No full textOBJECTIVE
To investigate the effect of the vaginoscopic approach to office hysteroscopy on patients' experience of pain, when compared with the traditional approach where a vaginal speculum is used.
METHODS
Medline, Embase, CINAHL and the Cochrane library were searched from inception until December 2019, in order to perform a systematic review and meta-analysis of all randomised controlled trials investigating vaginoscopy compared to traditional hysteroscopy on pain experienced by women undergoing diagnostic or operative hysteroscopy in an office setting. Data regarding procedural time, feasibility, incidence of vasovagal reactions and complications, acceptability and satisfaction were also recorded.
RESULTS
The literature search returned 363 results of which seven were selected for systematic review, and six for meta-analysis. The vaginoscopic approach was associated with a statistically significant reduction in pain (4 studies including 2214 patients; SMD -0.27, 95 % CI -0.48 to -0.06), procedural time (6 studies including 2443 patients; SMD -0.25, 95 % CI -0.43 to -0.08) and the incidence of vasovagal episodes (3 studies including 2127 patients; OR 0.35; 95 % CI 0.15 to 0.82). Failure rates between the two techniques were similar (p = .90). No study reported significant differences in complications or patient or clinician acceptability or satisfaction.
CONCLUSION
Clinicians performing office hysteroscopy should use the vaginoscopic technique because it makes office hysteroscopy quicker, less painful and reduces the likelihood of inducing a vasovagal reaction. The traditional approach should only be used when vaginoscopy fails or when the need for cervical dilatation is anticipated
The National Lung Matrix Trial of personalized therapy in lung cancer.
No full textThe majority of targeted therapies for non-small-cell lung cancer (NSCLC) are directed against oncogenic drivers that are more prevalent in patients with light exposure to tobacco smoke. As this group represents around 20% of all patients with lung cancer, the discovery of stratified medicine options for tobacco-associated NSCLC is a high priority. Umbrella trials seek to streamline the investigation of genotype-based treatments by screening tumours for multiple genomic alterations and triaging patients to one of several genotype-matched therapeutic agents. Here we report the current outcomes of 19 drug-biomarker cohorts from the ongoing National Lung Matrix Trial, the largest umbrella trial in NSCLC. We use next-generation sequencing to match patients to appropriate targeted therapies on the basis of their tumour genotype. The Bayesian trial design enables outcome data from open cohorts that are still recruiting to be reported alongside data from closed cohorts. Of the 5,467 patients that were screened, 2,007 were molecularly eligible for entry into the trial, and 302 entered the trial to receive genotype-matched therapy-including 14 that re-registered to the trial for a sequential trial drug. Despite pre-clinical data supporting the drug-biomarker combinations, current evidence shows that a limited number of combinations demonstrate clinically relevant benefits, which remain concentrated in patients with lung cancers that are associated with minimal exposure to tobacco smoke
Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort.
No full textAn amendment to this paper has been published and can be accessed via a link at the top of the paper
Insights into Systemic Disease through Retinal Imaging-Based Oculomics.
No full textAmong the most noteworthy developments in ophthalmology over the last decade has been the emergence of quantifiable high-resolution imaging modalities, which are typically non-invasive, rapid and widely available. Such imaging is of unquestionable utility in the assessment of ocular disease however evidence is also mounting for its role in identifying ocular biomarkers of systemic disease, which we term . In this review, we highlight our current understanding of how retinal morphology evolves in two leading causes of global morbidity and mortality, cardiovascular disease and dementia. Population-based analyses have demonstrated the predictive value of retinal microvascular indices, as measured through fundus photography, in screening for heart attack and stroke. Similarly, the association between the structure of the neurosensory retina and prevalent neurodegenerative disease, in particular Alzheimer's disease, is now well-established. Given the growing size and complexity of emerging multimodal datasets, modern artificial intelligence techniques, such as deep learning, may provide the optimal opportunity to further characterize these associations, enhance our understanding of eye-body relationships and secure novel scalable approaches to the risk stratification of chronic complex disorders of ageing
Combat Facial Fractures Sustained During Operation Resolute Support and Operation Freedom's Sentinel in Afghanistan.
No full textINTRODUCTION
Facial fractures sustained in combat are generally unrepresentative of those commonly experienced in civilian practice. In the US military, acute trauma patient care is guided by the Joint Trauma System Clinical Practice Guidelines but currently none exists for facial trauma.
MATERIALS AND METHODS
All casualties that underwent surgery to facial fractures between January 01, 2016 and September 15, 2019 at a US deployed Military Treatment Facility in Afghanistan were identified using the operating room database. Surgical operative records and outpatient records for local Afghan nationals returning for follow-up were reviewed to determine outcomes.
RESULTS
55 casualties underwent treatment of facial fractures; these were predominantly from explosive devices (27/55, 49%). About 46/55 (84%) were local nationals, of which 32 (70%) were followed up. Length of follow-up ranged between 1 and 25 months. About 36/93 (39%) of all planned procedures developed complications, with the highest being from ORIF mandible (18/23, 78%). About 8/23 (35%) casualties undergoing ORIF mandible developed osteomyelitis, of which 5 developed nonunion. Complications were equally likely to occur in those procedures for "battlefield type" events such as explosive devices and gunshot wounds (31/68, 46%) as those from "civilian type" events such as falls or motor vehicle collisions (5/11, 45%).
CONCLUSIONS
Complications Rates from facial fractures were higher than that reported in civilian trauma. This likely reflects factors such as energy deposition, bacterial load, and time to treatment. Load sharing osteosynthesis should be the default modality for fracture fixation. External fixation should be considered in particular for complex high-energy or infected mandible fractures where follow-up is possible
