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Severe blistering eruptions induced by immune checkpoint inhibitors: a multicentre international study of 32 cases.
No full textAmong dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. To better define the clinical and histological features, treatment, and prognosis of ICI-related severe blistering cutaneous eruptions. This retrospective case series was conducted between 2014/05/15 and 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age ≥18 years old, skin eruption with blisters with detachment covering ≥1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD), or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by four experts in EN or LD/UD. Skin biopsies were blindly reviewed. Thirty-two patients were included. Median time to onset was 52 days (3-420 days). Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, and maximal detachment. Most patients were treated with topical with or without systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending
Lipopolysaccharide induces acute lung injury and alveolar hemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathology.
No full textProgress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell- signaling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intra-tracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being sacrificed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (> 2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p 4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and hemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the inter-alveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans
Comparison of colour contrast sensitivity in eyes at high risk of neovascular age-related macular degeneration with and without subsequent choroidal neovascular membrane development.
No full textBACKGROUND
Neovascular age-related macular degeneration (nAMD) is a leading cause of blind registrations in the elderly. Unfortunately, it is difficult to detect the early stage of the disease, when treatment is more likely to be successful. Subjects with very early disease are likely to have abnormal macular function, even in the pre-symptomatic stage. In this study, colour vision was evaluated to establish if subjects at high risk of developing nAMD can be identified, thus allowing earlier diagnosis and possible treatment.
METHODS
Colour contrast sensitivity (CCS) was evaluated over time in the fellow unaffected eye of subjects with unilateral nAMD. Participants were divided into Group 1 (182 participants) or Group 2 (15 participants) according to whether nAMD did not or did develop in the study period respectively and the two groups were compared.
RESULTS
CCS was increased (i.e. worse colour vision) compared with the age-matched reference range in a high proportion of fellow eyes in both Groups 1 and 2. Global mean CCS values did not show statistically significant differences between the two groups. However, there was a statistically significant difference between mean Group 1 CCS values and the last CCS value prior to nAMD diagnosis from Group 2 subjects.
CONCLUSION
This study shows that in patients with unilateral nAMD, colour vision is frequently abnormal in the fellow unaffected eye. Abnormal CCS does not predict the development of nAMD within the 12 month period of the study and therefore it is not a viable screening tool for this pathology
The Impact of Diabetes and Glucose-Lowering Therapies on Hepatocellular Carcinoma Incidence and Overall Survival.
No full textPURPOSE
The incidence of hepatocellular carcinoma (HCC) in the United Kingdom has increased 60% in the past 10 years. The epidemics of obesity and type 2 diabetes are contributing factors. In this article, we examine the impact of diabetes and glucose-lowering treatments on HCC incidence and overall survival (OS).
METHODS
Data from 1064 patients diagnosed with chronic liver disease (CLD) (n = 340) or HCC (n = 724) were collected from 2007 to 2012. Patients with HCC were followed up prospectively. Univariate and multivariate logistic regression determined HCC risk factors. Kaplan-Meier curves were used to examine survival and Cox proportional hazards analysis estimated hazard ratios (HRs) for death according to use of glucose-lowering therapies.
FINDINGS
Diabetes prevalence was 39.6% and 10.6% within the HCC and CLD cohorts, respectively. The odds ratio for having HCC in patients with diabetes was 5.55 (P < 0.001). Univariate analysis found an increased association of HCC with age, sex, cirrhosis, hemochromatosis, alcohol abuse, diabetes, and Child's Pugh score. In multivariate analysis age, sex, cirrhosis, Child's Pugh score, diabetes status, and insulin use retained significance. Diabetes status did not significantly affect OS in HCC; however, in people with diabetes and HCC, metformin treatment was associated with improved OS (mean survival, 31 vs 24 months; P =0.016; HR for death = 0.75; P = 0.032).
IMPLICATIONS
Diabetes is significantly associated with HCC in the United Kingdom. Metformin treatment is associated with improved OS after HCC diagnosis. Treatment of diabetes should be appropriately reviewed in high-risk populations, with specific consideration of the potential hepatoprotective effects of metformin in HCC
Causes and consequences of diagnostic delay in Guillain-Barré syndrome in a U.K. tertiary centre.
No full textINTRODUCTION/AIMS
Understanding the potential causes and consequences of diagnostic delay in Guillain-Barré syndrome (GBS) could improve quality of care and outcomes. We aimed to determine these.
METHODS
We retrospectively reviewed records of subjects with GBS, admitted to our centre at University Hospitals Birmingham, U.K., between January 2005 and December 2020. We evaluated time to diagnosis from presentation, factors associated with diagnostic delay and its potential consequences.
RESULTS
We included 119 consecutive subjects. Diagnostic delay >5 days from first presentation occurred in 27/119 (22.7%) of patients. Diagnostic delay was associated with age >60 years (OR: 3.58; 95% CI: 1.44-8.85), pre-existing cardiac/respiratory disease (OR: 4.10; 95% CI: 1.46-11.54), pre-existing diabetes (OR: 10.38; 95% CI: 2.47-43.69), documented normal initial neurological examination (OR: 2.49; 95% CI: 1.03-6.02), initial assessment by primary care (OR: 3.33; 95% CI: 1.22-9.10) and >1 visit for medical attention (OR: 10.29; 95% CI: 3.81-27.77). Diagnostic delay was not associated with length of in-patient stay, ICU admission, ventilation, ability to walk at discharge, or in-patient mortality. Independent associations with diagnostic delay were observed for >1 visit for medical attention (OR: 10.15; 95% CI: 3.64-28.32) and pre-existing cardiac/respiratory disease (OR: 3.98; 95% CI: 1.19-13.28). An association of diagnostic delay with in-patient mortality was ascertained specifically in subjects with classic GBS (OR: 5.33; 95% CI: 1.1-25.87).
DISCUSSION
Diagnostic delay in GBS results from patient-specific factors and patient pathways. A high index of suspicion is appropriate for certain patient groups. Prospective studies are needed to further investigate this topic. This article is protected by copyright. All rights reserved
Medium-Term Outcomes in Severely to Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.
No full textBACKGROUND
The medium- and long-term effects of severe acute respiratory syndrome coronavirus 2 infection on survivors are unknown. In the current study, we assessed the medium-term effects of coronavirus disease 2019 (COVID-19) on survivors of severe disease.
METHODS
This is a retrospective, case series of 200 patients hospitalized across 3 large Birmingham hospitals with severe-to-critical COVID-19 infection 4-7 months from disease onset. Patients underwent comprehensive clinical, laboratory, imaging, lung function tests (LFTs), and quality of life and cognitive assessments.
RESULTS
At 4-7 months after disease onset, 63.2% of patients reported persistent breathlessness; 53.5%, significant fatigue; 37.5%, reduced mobility; and 36.8% pain. Serum markers of inflammation and organ injuries that persisted at hospital discharge had normalized on follow-up, indicating no sustained immune response causing chronic maladaptive inflammation. Chest radiographs showed complete resolution in 82.8%, and significant improvement or no change in 17.2%. LFTs revealed gas transfer abnormalities in 80.0% and abnormal spirometric values in 37.6% of patients. Compared with patients who did not experience breathlessness, those who did had significantly higher incidences of comorbid conditions and residual chest radiographic and LFT abnormalities (P < .01 to all). For all parameters assessed and persisting symptoms there were no significant differences between patients in hospital wards and those in intensive treatment units. All patients reported a significantly reduced quality of life in all domains of the EQ-5D-5L quality-of-life measures.
CONCLUSIONS
A significant proportion of severely ill patients with COVID-19 still experience symptoms of breathlessness, fatigue, pain, reduced mobility, depression and reduced quality of life 4-7 months after disease onset. Symptomatic patients tend to have more residual chest radiographic and LFT abnormalities
The burden of subclinical cardiovascular disease in children and young adults with chronic kidney disease and on dialysis.
No full textBackground
Cardiovascular disease (CVD) is a common cause of morbidity and mortality even in young people with chronic kidney disease (CKD). We examined structural and functional CV changes in patients ˂30 years of age with CKD Stages 4 and 5 and on dialysis.
Methods
A total of 79 children and 21 young adults underwent cardiac computed tomography for coronary artery calcification (CAC), ultrasound for carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV) and echocardiography. Differences in structural (CAC, cIMT -score, left ventricular mass index) and functional (carotid distensibility -score and cfPWV -score) measures were examined between CKD Stages 4 and 5 and dialysis patients.
Results
Overall, the cIMT -score was elevated [median 2.17 (interquartile range 1.14-2.86)] and 10 (10%) had CAC. A total of 16/23 (69.5%) patients with CKD Stages 4 and 5 and 68/77 (88.3%) on dialysis had at least one structural or functional CV abnormality. There was no difference in the prevalence of structural abnormalities in CKD or dialysis cohorts, but functional abnormalities were more prevalent in patients on dialysis (P 2 standard deviation (SD) or distensibility <-2 SD) had less carotid dilatation (lumen:wall cross-sectional area ratio) compared with those with normal cIMT and distensibility.
Conclusions
There is a high burden of subclinical CVD in young CKD patients, with a greater prevalence of functional abnormalities in dialysis compared with CKD patients. Longitudinal studies are required to test these hypothesis-generating data and define the trajectory of CV changes in CKD
Editorial for "Quantification of Myocardial Deformation in Patients With Takayasu Arteritis by MRI Feature Tracking Imaging".
No full textFracture of pubic rami during hip fracture fixation: a rare case of traction table-related injury.
No full textWe present a case of an elderly and comorbid patient who was scheduled to undergo a hip fracture fixation using an intramedullary nail. Unfortunately, this was delayed by 3 weeks as the patient was unfit to undergo this procedure. She was placed onto the traction table and intraoperatively sustained a superior and inferior pubic rami fracture while attempting reduction on the traction table. Closed-reduction techniques using traction tables and perineal posts are not without morbidity. Risk factors such as osteoporosis and delayed-fixation should be accounted for when managing this complex and often frail group of patients