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Temporal trends in survival following ward-based NIV for acute hypercapnic respiratory failure in patients with COPD.
No full textINTRODUCTION
Non-invasive ventilation (NIV) is recommended for treatment of acute hypercapnic respiratory failure (AHRF) in acute exacerbations of COPD. National UK audit data suggests that mortality rates are rising in COPD patients treated with NIV.
OBJECTIVE
To investigate temporal trends in in-hospital mortality in COPD patients undergoing a first episode of ward-based NIV for AHRF.
METHODS
Retrospective study of hospitalised COPD patients treated with a first episode of ward-based NIV at a large UK teaching hospital between 2004 and 2017. Patients were split into two cohorts based on year of admission, 2004-2010 (Cohort 1) and 2013-2017 (Cohort 2), to facilitate comparison of patient characteristics.
RESULTS
In total, 547 unique patients were studied. There was no difference in in-hospital mortality rate between the time periods studied (17.6% vs 20.5%, P = .378). In Cohort 2 there were more females, a higher rate of co-morbid bronchiectasis and pneumonia on admission and more severe acidosis, hypercapnia and hypoxia. More patients in Cohort 2 had NIV as the ceiling of treatment. Patients in Cohort 2 experienced a longer time from AHRF diagnosis to application of NIV, higher maximum inspiratory positive airway pressure, lower maximum oxygen and shorter duration of NIV. Finally, patients in Cohort 2 experienced a shorter hospital length of stay (LOS), with no differences observed in rate of transfer to critical care or intubation.
CONCLUSION
In-hospital mortality remained stable and LOS decreased over time, despite greater comorbidity and more severe AHRF in COPD patients treated for the first time with ward-based NIV
Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease.
No full textBACKGROUND
The importance of chimerism status in the very early period after hematopoietic stem cell transplantation is unclear. We determined PBMC and T-cell donor chimerism 50 days after transplantation and related this to disease relapse and overall survival.
METHODS
144 sequential patients underwent transplantation of which 90 had AML/MDS and 54 had lymphoma. 'Full donor chimerism' was defined as ≥99% donor cells and three patient groups were defined: 40% with full donor chimerism (FC) in both PBMC and T-cells; 25% with mixed chimerism (MC) within both compartments and 35% with 'split' chimerism (SC) characterised by full donor chimerism within PBMC and mixed chimerism within T-cells.
RESULTS
In patients with myeloid disease a pattern of mixed chimerism (MC) was associated with a one year relapse rate of 45% and a five year overall survival of 40% compared to values of 8% and 75%, and 17% and 60%, for those with SC or FC respectively. The pattern of chimerism had no impact on clinical outcome for lymphoma.
CONCLUSION
The pattern of lineage-specific chimerism at 50 days after transplantation is highly predictive of clinical outcome for patients with myeloid malignancy and may help to guide subsequent clinical management
Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry.
No full textTo define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)HLA-DRA sublining fibroblasts, IL1B pro-inflammatory monocytes, ITGAXTBX21 autoimmune-associated B cells and PDCD1 peripheral helper T (T) cells and follicular helper T (T) cells. We defined distinct subsets of CD8 T cells characterized by GZMK, GZMB, and GNLY phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1HLA-DRA fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis
Measurement of extravascular lung water to diagnose severe reperfusion lung injury following pulmonary endarterectomy: a prospective cohort clinical validation study.
No full textThe measurement of extravascular lung water is a relatively new technology which has not yet been well validated as a clinically useful tool. We studied its utility in patients undergoing pulmonary endarterectomy as they frequently suffer reperfusion lung injury and associated oedematous lungs. Such patients are therefore ideal for evaluating this new monitor. We performed a prospective observational cohort study during which extravascular lung water index measurements were taken before and immediately after surgery and postoperatively in intensive care. Data were analysed for 57 patients; 21 patients (37%) experienced severe reperfusion lung injury. The first extravascular lung water index measurement after cardiopulmonary bypass failed to predict severe reperfusion lung injury, area under the receiver operating characteristic curve 0.59 (95%CI 0.44-0.74). On intensive care, extravascular lung water index correlated most strongly at 36 h, area under the receiver operating characteristic curve 0.90 (95%CI 0.80-1.00). Peri-operative extravascular lung water index is not a useful measure to predict severe reperfusion lung injury after pulmonary endarterectomy, however, it does allow monitoring and measurement during the postoperative period. This study implies that extravascular lung water index can be used to directly assess pulmonary fluid overload and that monitoring patients by measuring extravascular lung water index during their intensive care stay is useful and correlates with their clinical course. This may allow directed, pre-empted therapy to attenuate the effects and improve patient outcomes and should prompt further studies
Vive les Differences!-A case for optimism in the treatment of patients with heart failure and preserved ejection fraction?
No full textAberrant X chromosome skewing and acquired clonal hematopoiesis in adult-onset common variable immunodeficiency.
No full textAdvances in genomic medicine have elucidated an increasing number of genetic etiologies for patients with common variable immunodeficiency (CVID). However, there is heterogeneity in clinical and immunophenotypic presentations and a limited understanding of the underlying pathophysiology of many cases. The primary defects in CVID may extend beyond the adaptive immune system, and the combined defect in both the myeloid and lymphoid compartments suggests the mechanism may involve bone marrow output and earlier progenitors. Using the methylation profile of the human androgen receptor (AR) gene as a surrogate epigenetic marker for bone marrow clonality, we examined the hematopoietic compartments of patients with CVID. Our data show that clonal hematopoiesis is common among patients with adult-onset CVID who do not have associated noninfectious complications. Nonblood tissues did not show a skewed AR methylation status, supporting a model of an acquired clonal hematopoietic event. Attenuation of memory B cell differentiation into long-lived plasma cells (CD20-CD27+CD38+CD138+) was associated with marked changes in the postdifferentiation methylation profile, demonstrating the functional consequence of clonal hematopoiesis on humoral immunity in these patients. This study sheds light on a potential etiology of a subset of patients with CVID, and the findings suggest that it is a stage of an acquired lymphocyte maturation disorder
Properties and use of a honey dressing and gel in wound management.
No full textWound management is a major clinical challenge and puts a significant financial burden on the NHS. Because of the rise in long-term conditions including diabetes, obesity and an ageing population, practitioners regularly encounter a wide variety of wound types. In recent years, there has been a resurgence of interest in the use of medical-grade honey in the management of wounds. Honey is anti-inflammatory in action and has the capability to treat local infection, promote autolytic debridement, deodorise wounds and promote granulation tissue. Revamil is a recent addition to the range of honey dressings available and is intended to manage the majority of problems that may arise during wound care episodes. The attributes of Revamil will be illustrated through four case studies
Myocardial Infarction with non-obstructed coronaries - atypical presentation of pheochromocytoma.
No full textSummary
Although pheochromocytoma classically presents with headaches, palpitations and paroxysmal hypertension, atypical presentations such as cardiomyopathy, stroke and subarachnoid haemorrhage have been infrequently documented. We present in this case report, an uncommon presentation of pheochromocytoma with myocardial infarction with normal coronary arteries (MINOCA). A 79-year-old woman presented with central crushing chest pain radiating to left arm associated with headache, palpitations, sweating and difficulty in breathing. For 2 years, she experienced brief episodes of headache, tinnitus, dizziness, palpitations, and sweating that spontaneously resolved. Clinical examination was unremarkable except for high blood pressure (210/105 mmHg). Her electrocardiogram showed T wave inversions from V1 to V6 and elevated troponins (774 ng/L at baseline and 932 ng/L 3 h from baseline (normal <16 ng/L) in keeping with a diagnosis of non-ST elevated myocardial infarction. Coronary angiography showed normal coronary arteries. Patient was hence treated as myocardial infarction with normal coronaries (MINOCA). Despite appropriate treatment for MINOCA, she continued to experience episodic headaches, palpitations, dizziness and erratic blood pressures (particularly severe hypertension shortly after beta-blocker administration). Further investigations revealed raised urine noradrenaline of 4724 nmol/24 h (<554 nmol/24 h) and urine adrenaline of 92863 nmol/24 h (<77 nmol/24 h). Computerised tomography demonstrated a well-defined rounded mass in right adrenal gland morphological of pheochromocytoma. She underwent laparoscopic right adrenalectomy with histology confirming pheochromocytoma. This case highlights the importance of thorough investigation for the underlying cause for MINOCA. In patients with unexplained erratic blood pressure control, pheochromocytoma should be considered as a differential diagnosis.
Learning points
Pheochromocytoma is rare tumour that often presents with non-specific symptoms. It is important to investigate underlying cause of MINOCA. Thorough history is the key to diagnosis
Critical Appraisal of the Impact of Oesophageal Stents in the Management of Oesophageal Anastomotic Leaks and Benign Oesophageal Perforations: An Updated Systematic Review.
No full textINTRODUCTION
Endoscopic placement of oesophageal stents may be used in benign oesophageal perforation and oesophageal anastomotic leakage to control sepsis and reduce mortality and morbidity by avoiding thoracotomy. This updated systematic review aimed to assess the safety and effectiveness of oesophageal stents in these two scenarios.
METHODS
A systematic literature search of all published studies reporting use of metallic and plastic stents in the management of post-operative anastomotic leaks, spontaneous and iatrogenic oesophageal perforations were identified. Primary outcomes were technical (deploying ≥ 1 stent to occlude site of leakage with no evidence of leakage of contrast within 24-48 h) and clinical success (complete healing of perforation or leakage by placement of single or multiple stents irrespective of whether the stent was left in situ or was removed). Secondary outcomes were stent migration, perforation and erosion, and mortality rates. Subgroup analysis was performed for plastic versus metallic stents and anastomotic leaks versus perforations separately.
RESULTS
A total of 66 studies (n = 1752 patients) were included. Technical and clinical success rates were 96% and 87%, respectively. Plastic stents had significantly higher migration rates (24% vs 16%, p = 0.001) and repositioning (11% vs 3%, p < 0.001) and lower technical success (91% vs 95%, p = 0.032) than metallic stents. In patients with anastomotic leaks, plastic stents were associated with higher stent migration (26% vs 15%, p = 0.034), perforation (2% vs 0%, p = 0.013), repositioning (10% vs 0%, p < 0.001), and lower technical success (95% vs 100%, p = p = 0.002). In patients with perforations only, plastic stents were associated with significantly lower technical success (85% vs 99%, p < 0.001).
CONCLUSIONS
Covered metallic oesophageal stents appear to be more effective than plastic stents in the management of oesophageal perforation and anastomotic leakage. However, quality of evidence of generally poor and high-quality randomised trial is needed to further evaluate best management option for oesophageal perforation and anastomotic leakage