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Lenalidomide before and after ASCT for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial.
No full textThe optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n = 2042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib and dexamethasone (CVD) was administered before ASCT to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation (ASCT), eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.75-0.96; P = 0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI, 0.63-0.93; P = 0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI, 0.58-0.93; HR for OS, 0.78; 95% CI, 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI, 0.43-0.84; HR for OS, 0.70; 95% CI, 0.42-1.15) and ultra high-risk cytogenetics (HR for PFS, 0.67; 95% CI, 0.41-1.11; HR for OS, 0.65; 95% CI, 0.34-1.25). Among patients randomized to lenalidomide maintenance (n = 451) or observation (n = 377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI, 0.37-0.60; P < 0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance. The trial was registered with the EU Clinical Trials Register (EudraCT 2009-010956-93) and ISRCTN49407852
The Clinical and Inflammatory Relationships between Periodontitis and Chronic Obstructive Pulmonary Disease.
No full textAIM
To investigate associations between Periodontitis, Chronic Obstructive Pulmonary Disease(COPD) with and without Alpha 1 Anti-trypsin Deficiency(AATD), including neutrophil functions implicated in tissue damage.
METHODS
The presence and severity of periodontitis (using two international criteria) and lung disease was assessed in 156 COPD patients with and without AATD accounting for common confounding factors. Saliva and systemic inflammatory markers were measured by ELISA together with neutrophil migration.
RESULTS
COPD and AATD patients exhibited higher prevalence of periodontitis (COPD 95%; AATD 88%) than reported in unselected community dwelling populations even when risk factors (age, smoking history, socioeconomic status, dental habits) were considered. Periodontitis severity associated with lung disease severity (AATD, Periodontitis vs no periodontitis; FEV1 = 56% vs 99% predicted; TLCO = 59% vs. 81% predicted, p<0.0001 for both). Neutrophil migratory accuracy declined in stages II-IV periodontitis patients with COPD or AATD compared to COPD or AATD with no or stage I periodontitis. Improved dental habits appeared to be associated with a reduction in exacerbation frequency in COPD.
CONCLUSION
The results support shared pathophysiology between periodontitis and COPD, especially when associated with AATD. This may reflect an amplification of neutrophilic inflammation and altered neutrophil functions, already described in periodontitis, COPD and AATD
The impact of ethnicity on clinical outcomes in COVID-19: A systematic review.
No full textBackground
The relationship between ethnicity and COVID-19 is uncertain. We performed a systematic review to assess whether ethnicity has been reported in patients with COVID-19 and its relation to clinical outcomes.
Methods
We searched EMBASE, MEDLINE, Cochrane Library and PROSPERO for English-language citations on ethnicity and COVID-19 (1 December 2019-15 May 2020). We also reviewed: COVID-19 articles in , clinical trial protocols, grey literature, surveillance data and preprint articles on COVID-19 in to evaluate if the association between ethnicity and clinical outcomes were reported and what they showed. PROSPERO:180654.
Findings
Of 207 articles in the database search, five reported ethnicity; two reported no association between ethnicity and mortality. Of 690 articles identified from medical journals, 12 reported ethnicity; three reported no association between ethnicity and mortality. Of 209 preprints, 34 reported ethnicity - 13 found Black, Asian and Minority Ethnic (BAME) individuals had an increased risk of infection with SARS-CoV-2 and 12 reported worse clinical outcomes, including ITU admission and mortality, in BAME patients compared to White patients. Of 12 grey literature reports, seven with original data reported poorer clinical outcomes in BAME groups compared to White groups.
Interpretation
Data on ethnicity in patients with COVID-19 in the published medical literature remains limited. However, emerging data from the grey literature and preprint articles suggest BAME individuals are at an increased risk of acquiring SARS-CoV-2 infection compared to White individuals and also worse clinical outcomes from COVID-19. Further work on the role of ethnicity in the current pandemic is of urgent public health importance.
Funding
NIHR
Impact of obesity and metabolic health status in the development of non-alcoholic fatty liver disease (NAFLD): A United Kingdom population-based cohort study using the health improvement network (THIN).
No full textBACKGROUND
With the obesity epidemic reaching crisis levels, there has been attention around those who may be resilient to the effects of obesity, termed metabolically healthy obesity (MHO), who initially present without associated metabolic abnormalities. Few longitudinal studies have explored the relationship between MHO and non-alcoholic fatty liver disease (NAFLD), which we address using over 4 million primary care patient records.
METHODS
A retrospective population-based longitudinal cohort was conducted using The Health Improvement Network (THIN) database incorporating adults with no history of NAFLD or alcohol excess at baseline. Individuals were classified according to BMI category and metabolic abnormalities (diabetes, hypertension and dyslipidaemia). Diagnosis of NAFLD during follow-up was the primary outcome measure. NAFLD was identified by Read codes.
RESULTS
During a median follow-up period of 4.7 years, 12,867 (0.3%) incident cases of NAFLD were recorded in the cohort of 4,121,049 individuals. Compared to individuals with normal weight and no metabolic abnormalities, equivalent individuals who were overweight, or obese were at significantly greater risk of incident NAFLD (Adjusted HR 3.32 (95%CI 2.98-3.49), and 6.92 (6.40-7.48, respectively). Metabolic risk factors further increased risk, including in those with normal weight and 1 (2.27, 1.97-2.61) or = < 2 (2.39, 1.99-2.87) metabolic abnormalities.
CONCLUSIONS
MHO individuals are at greater risk of developing NAFLD compared to those with normal weight. This finding supports that the MHO phenotype is a temporary state, and weight must be considered a risk factor even before other risk factors develop. Being normal weight with metabolic abnormalities was also associated with risk of NAFLD
Prolonged deployed hospital care in the management of military eye injuries.
No full textBACKGROUND/OBJECTIVES
Prolonged hospital care is described as deployed medical care, applied beyond doctrinal planning timelines and military medical planning envisages that in future conflicts, patients will have to be managed for up to 5 days without evacuation to their home country. We aimed to investigate the effect of prolonged hospital care on visual outcomes in the management of open and closed globe injures.
METHODS
We conducted a retrospective cohort study in the setting of British military operations in Afghanistan. We included consecutive UK military patients with ocular trauma evacuated from Afghanistan between December 2005 and April 2013. We assessed outcome using best-corrected visual acuity (VA) 6-12 months after injury.
RESULTS
All patients were male, with a mean age of 25. Outcomes adjusted for ocular trauma score (OTS) at presentation were similar to previous reports of military ocular trauma. The mean time to arrival at a centre with an ophthalmologist was 1.74 days. Both patients with penetrating open globe injuries and patients with hyphaema and an OTS of 3 or less displayed an association between worsening 6-12 month VA and time between injury and repair or assessment by an ophthalmologist.
CONCLUSION
Time to specialist ophthalmic care contributes to outcome after military open and closed globe injuries, supporting deployment of ophthalmologists on military operations
The Human Immune Response to Cadaveric and Living Donor Liver Allografts.
No full textThe liver is an important contributor to the human immune system and it plays a pivotal role in the creation of both immunoreactive and tolerogenic conditions. Liver transplantation provides the best chance of survival for both children and adults with liver failure or cancer. With current demand exceeding the number of transplantable livers from donors following brain death, improved knowledge, technical advances and the desire to prevent avoidable deaths has led to the transplantation of organs from living, ABO incompatible (ABOi), cardiac death donors and machine based organ preservation with acceptable results. The liver graft is the most well-tolerated, from an immunological perspective, of all solid organ transplants. Evidence suggests successful cessation of immunosuppression is possible in ~20-40% of liver transplant recipients without immune mediated graft injury, a state known as "operational tolerance." An immunosuppression free future following liver transplantation is an ambitious but perhaps not unachievable goal. The initial immune response following transplantation is a sterile inflammatory process mediated by the innate system and the mechanisms relate to the preservation-reperfusion process. The severity of this injury is influenced by graft factors and can have significant consequences. There are minimal experimental studies that delineate the differences in the adaptive immune response to the various forms of liver allograft. Apart from ABOi transplants, antibody mediated hyperacute rejection is rare following liver transplant. T-cell mediated rejection is common following liver transplantation and its incidence does not differ between living or deceased donor grafts. Transplantation in the first year of life results in a higher rate of operational tolerance, possibly due to a bias toward Th2 cytokines (IL4, IL10) during this period. This review further describes the current understanding of the immunological response toward liver allografts and highlight the areas of this topic yet to be fully understood
Frontal fibrosing alopecia: a descriptive cross-sectional study of 711 female cases from the U.K.
No full textFrontal fibrosing alopecia (FFA) is an inflammatory primary scarring alopecia of uncertain aetiology that represents a variant of lichen planopilaris. It predominantly, although not exclusively, affects post-menopausal women. Its pathogenesis is characterised by immune-mediated follicular destruction at the level of the hair bulge, which leads to a clinical phenotype of progressive fronto-temporal hair and eyebrow loss that is often preceded by widespread body hair loss
Cilostazol for Secondary Prevention of Stroke and Cognitive Decline: Systematic Review and Meta-Analysis.
No full textBACKGROUND AND PURPOSE
Cilostazol, a phosphodiesterase 3' inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression.
METHODS
A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742).
RESULTS
We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57-0.81]; 6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance.
CONCLUSIONS
Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease
Severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP syndrome and acute kidney injury following SARS-CoV-2 infection.
No full textThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented many diagnostic challenges and uncertainties. Little is known about common pathologies complicating pregnancy and how their behaviour is modified by the presence of SARS-CoV-2. Pregnancy itself can alter the body's response to viral infection, which can cause more severe symptoms. We report the first case of a patient affected with sudden-onset severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP (haemolysis, elevated liver enzymes and low platelet) syndrome and acute kidney injury following SARS-CoV-2 infection. Although an initial diagnostic dilemma, a multidisciplinary team approach was required to ensure a favourable outcome for both the mother and the baby. Our case report highlights the need for health professionals caring for pregnant women to be aware of the complex interplay between SARS-CoV-2 infection and hypertensive disorders of pregnancy
Simulation via instant messaging-Birmingham advance (SIMBA) model helped improve clinicians' confidence to manage cases in diabetes and endocrinology.
No full textBACKGROUND
Simulation-based learning (SBL) has been increasingly used in both undergraduate and postgraduate medical training curricula. The aim of Simulation via Instant Messaging-Birmingham Advance (SIMBA) is to create a simple virtual learning environment to improve trainees' self-reported confidence in diabetes and Endocrinology.
METHODS
This study was done as part of the continuous professional development for Health Education England West Midlands speciality trainees in diabetes and Endocrinology. Standardized transcripts of anonymized real-life endocrinology (endocrine session) and diabetes cases (diabetes session) were used in the simulation model. Trainees interacted with moderators through WhatsApp® in this model. All cases were then discussed in detail by a consultant endocrinologist with reference to local, national and international guidelines. Trainee acceptance rate and improvement in their self-reported confidence levels post-simulation were assessed.
RESULTS
70.8% (n = 17/24) and 75% (n = 18/24) strongly agreed the simulation session accommodated their personal learning style and the session was engaging. 66.7% (n = 16/24) strongly felt that the simulation was worth their time. In the endocrine session, there was a significant improvement in trainees' confidence in the management of craniopharyngioma (p = 0.0179) and acromegaly (p = 0.0025). There was a trend towards improved confidence levels to manage Cushing's disease and macroprolactinoma. In diabetes session, there was a significant improvement in trainees' confidence to interpret continuous glucose monitor readings (p = 0.01). There was a trend towards improvement for managing monogenic diabetes, hypoglycaemic unawareness and interpreting Libre readings. Overall, there was a significant improvement in trainees' confidence in managing cases that were discussed post-simulation.
CONCLUSION
SIMBA is an effective learning model to improve trainees' confidence to manage various diabetes and endocrine case scenarios. More sessions with a variety of other speciality case scenarios are needed to further assess SIMBA's effectiveness and application in other areas of medical training