Traumatic dental injuries in adults attending a London-based trauma clinic in the UK: a seven-year survey

Introduction: This survey reports the incidence of traumatic dental injuries in an adult population attending an adult dental trauma clinic in a London teaching hospital. Materials and methods: Retrospective data were collected from patients attending an adult dental trauma clinic between 2012 and 2018. Results: In total, 1,769 patients attended, with more men seen (1,030; 58.2%) compared to women (739; 41.8%) and this was statistically significant (p <0.05). The most common aetiological factor was an accidental fall (728; 41.15%), followed by assaults (413; 23.35%), bicycle accidents (253; 14.3%), sports injuries (132; 7.46%) and road traffic accidents (84; 4.75%). Lateral luxation (833) was the most common traumatic injury and this was followed by avulsions (362; 17%). Enamel-dentine fractures were the most common type of fracture injury (1,273; 64%). Discussion: This retrospective survey attempts to report on the incidence of traumatic dental injuries in a London-based cohort of patients attending a specialised dental trauma clinic. In line with other reports, there were more men than women affected, which is probably attributed to behavioural activities. Conclusion(s): Accidental falls are the most common cause of a traumatic dental injury, lateral luxation was the most common type of displacement injury and enamel-dentine fractures were the most common type of fracture injury

Chance of healthy versus adverse outcome in subsequent pregnancy after previous loss beyond 16 weeks: data from a specialized follow-up clinic

PURPOSE: Women with a previous fetal demise have a 2-20 fold increased risk of another stillbirth in a subsequent pregnancy when compared to those who have had a live birth. Despite this, there is limited research regarding the management and outcomes of subsequent pregnancies. This study was conducted to accurately quantify the chances of a woman having a healthy subsequent pregnancy after a pregnancy loss. METHODS: A retrospective study was conducted at a tertiary-level unit between March 2019 and April 2021. We collected data on all women with a history of previous fetal demise attending a specialized perinatal history clinic and compared the risk of subsequent stillbirth to those with a normal pregnancy outcome. Outcome data included birth outcome, obstetric and medical complications, gestational age and birth weight and mode of delivery. Those who had healthy subsequent pregnancies were compared with those who experienced adverse outcomes. RESULTS: A total of 101 cases were reviewed. Ninety-six women with subsequent pregnancies after a history of fetal demise from 16 weeks were included. Seventy-nine percent of women (n = 76) delivered a baby at term, without complications. Overall, 2.1% had repeat pregnancy losses (n = 2) and 2.1% delivered babies with fetal growth restriction (n = 2). There were no cases of abruption in a subsequent pregnancy. Eighteen neonates were delivered prematurely (18.4%), 15 of these (83.3%) were due to iatrogenic causes and three (16.7%) were spontaneous. In univariable logistic regression analyses, those with adverse outcomes in subsequent pregnancies had greater odds of pre-eclampsia (Odds ratio *(OR) = 3.89, 95% CI = 1.05-14.43, p = .042) and fetal growth restriction (OR = 4.58, 95% CI = 1.41-14.82, p = 0.011) in previous pregnancies compared to those with healthy outcomes. However, in multivariable logistic regression analyses, neither variable had a significant odds ratio (OR = 2.03, 95% CI = 0.44-9.39, p = .366 and OR = 3.42, 95% CI = 0.90 - 13.09, p = .072 for pre-eclampsia and FGR, respectively). CONCLUSION: Four in five women had a healthy subsequent pregnancy. This is a reassuring figure for women when contemplating another pregnancy, particularly if cared for in a specialist clinic

Reproductive outcomes from ten years of elective oocyte cryopreservation

Research question: To assess the relationship between the number of oocytes retrieved during elective oocyte cryopreservation (EOC) cycles with various clinical, biochemical, and radiological markers, including age, body mass index (BMI), baseline anti-Müllerian hormone (AMH), antral follicle count (AFC), Oestradiol level (E2) and total number of follicles ≥ 12 mm on the day of trigger. To also report the reproductive outcomes from women who underwent EOC. Methods: A retrospective cohort of 373 women embarking on EOC and autologous oocyte thaw cycles between 2008 and 2018 from a single London clinic in the United Kingdom. Results: 483 stimulation cycles were undertaken amongst 373 women. The median (range) age at cryopreservation was 38 (26–47) years old. The median numbers of oocytes retrieved per cycle was 8 (0–37) and the median total oocytes cryopreserved per woman was 8 (0–45). BMI, E2 level and number of follicles ≥ 12 mm at trigger were all significant predictors of oocyte yield. Multivariate analysis confirmed there was no significant relationship between AFC or AMH, whilst on univariate analysis statistical significance was proven. Thirty six women returned to use their cryopreserved oocytes, of which there were 41 autologous oocyte thaw cycles undertaken. There were 12 successful livebirths achieved by 11 women. The overall livebirth rate was 26.8% per cycle. No livebirths were achieved in women who underwent EOC ≥ 40 years old, and 82% of all livebirths were achieved in women who had done so between 36 and 39 years old. Conclusion: Clinical, biochemical and radiological markers can predict oocyte yield in EOC cycles. Reproductive outcomes are more favourable when cryopreservation is performed before the age of 36, with lower success rates of livebirth observed in women aged 40 years and above

C-reactive protein is essential for innate resistance to pneumococcal infection

Summary: No deficiency of human C-reactive protein (CRP), or even structural polymorphism of the protein, has yet been reported so its physiological role is not known. Here we show for the first time that CRP-deficient mice are remarkably susceptible to Streptococcus pneumoniae infection and are protected by reconstitution with isolated pure human CRP, or by anti-pneumococcal antibodies. Autologous mouse CRP is evidently essential for innate resistance to pneumococcal infection before antibodies are produced. Our findings are consistent with the significant association between clinical pneumococcal infection and non-coding human CRP gene polymorphisms which affect CRP expression. Deficiency or loss of function variation in CRP may therefore be lethal at the first early-life encounter with this ubiquitous virulent pathogen, explaining the invariant presence and structure of CRP in human adults

Prognostic importance of the 6 min walk test in light chain (AL) amyloidosis

OBJECTIVES: In AL amyloidosis, organ response assessment is based on surrogates (eg, cardiac biomarkers). An objective functional test, such as the 6 min walk test (6MWT), capturing overall clinical improvement, is required. We aimed to evaluate the prognostic impact of the 6MWT at baseline and change following chemotherapy. METHODS: This study evaluated the outcomes of patients who enrolled in a prospective observational study at the UK National Amyloidosis Centre (2012-2017). Patients underwent comprehensive assessments inclusive of blood testing, echocardiogram and 6MWT at baseline and annually thereafter. RESULTS: In total, 799 patients were included within the study. Median baseline 6 min walk distance (6MWD) was 362 m (IQR: 231 m). 6MWD progressively decreased with worsening cardiac disease stage (458 m, 404 m, 331 m and 168 m for cardiac Mayo stages I, II, IIIa and IIIb, respectively (p<0.0001)). In patients with a baseline 6MWT of ≥350 m, the median overall survival was not reached (vs 30.0 (95% CI 23.2 to 36.8) months if <350 m and 5.0 (95% CI 2.8 to 7.2) months if unable to attempt 6MWT (p<0.0001). Following chemotherapy, only patients in a complete haematological response improved their 6MWD by 12 months (p=0.001). Improvement in 6MWD prolonged survival in patients with cardiac amyloidosis (p=0.005). CONCLUSION: The 6MWT is prognostic in AL amyloidosis. A baseline distance of ≥350 m independently predicts better survival. These data suggest that 6MWT has utility in AL amyloidosis for baseline prognosis and assessing response

Expansion of the National Amyloidosis Centre staging system to detect early mortality in transthyretin cardiac amyloidosis

Aims: Transthyretin cardiac amyloidosis (ATTR-CA) is stratified into prognostic categories using the National Amyloidosis Centre (NAC) staging system. The aims of this study were to further expand the existing NAC staging system to incorporate an additional disease stage that would identify patients at high risk of early mortality. Methods and results: The traditional NAC staging system (stage 1: N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≤3000 ng/L and estimated glomerular filtration rate [eGFR] ≥45 ml/min; stage 3: NT-proBNP &gt;3000 ng/L and eGFR &lt;45 ml/min; stage 2: remainder) was expanded by the introduction of a new stage 4 (defined as NT-proBNP ≥10 000 ng/L irrespective of eGFR) and studied in 2042 patients. The optimal NT-proBNP cut-point was established using time-dependent receiver operating characteristic curves in the subgroup of patients with NAC stage 3 disease. Mortality at 1 year according to NAC stage was 2.3% (n = 20/886) for stage 1, 8.8% (n = 62/706) for stage 2, 10.4% (n = 28/270) for stage 3, and 30.6% (n = 55/180) for stage 4 (log-rank p &lt; 0.001). After adjustment for age, mortality hazard for stage 4 was &gt;15-fold higher than that of stage 1 (hazard ratio [HR] 15.5; 95% confidence interval [CI] 9.3-26.1) and &gt;3-fold higher than that of stage 3 (HR 3.4; 95% CI 2.2-5.4). The increased risk of early mortality was consistent across the different genotypes and subclasses of patients based on the severity of heart failure symptoms and echocardiographic parameters. Conclusions: The proposed modification of the NAC staging system identifies patients with ATTR-CA at a high risk of early mortality, who may benefit from a more intensive treatment strategy, and who are most likely to experience an event early in the course of a clinical trial

Prognostic Value of a 6-Minute Walk Test in Patients With Transthyretin Cardiac Amyloidosis

Background The 6-minute walk test (6MWT) represents a comprehensive functional assessment that is commonly used in patients with heart failure; however, data are lacking in patients with transthyretin cardiac amyloidosis (ATTR-CA). Objectives This study aimed to assess the prognostic importance of the 6MWT in patients with ATTR-CA.Methods A retrospective analysis of patients diagnosed with ATTR-CA at the National Amyloidosis Centre who underwent a baseline 6MWT between 2011 and 2023 identified 2,141 patients, of whom 1,118 had follow-up at 1 year.Results The median baseline 6MWT distance was 347 m (Q1-Q3: 250-428 m) and analysis by quartiles demonstrated an increased death rate with each distance reduction (deaths per 100 person-years: 6.3 vs 9.2 vs 13.6 vs 19.0; log-rank P &lt; 0.001). A 6MWT distance of 35 m) and relative worsening (reduction of &gt;5%) of 6MWT at 1 year was associated with an increased risk of mortality (HR: 1.80; 95% CI: 1.51-2.15; P &lt; 0.001 and HR: 1.89; 95% CI: 1.59-2.24; P &lt; 0.001, respectively), which was similar across the aforementioned subgroups. When combined with established measures of disease progression (N-terminal pro–B-type natriuretic peptide progression and outpatient diuretic intensification), each incremental increase in progression markers was associated with an increased death rate (deaths per 100 person-years: 7.6 vs 13.9 vs 22.4 vs 32.9; log-rank P &lt; 0.001). Conclusions The baseline 6MWT distance can refine risk stratification beyond traditional prognosticators. A worsening 6MWT distance can stratify disease progression and, when combined with established markers, identifies patients at the highest risk of mortality

Albuminuria in transthyretin cardiac amyloidosis: Prevalence, progression and prognostic importance

Aims: Transthyretin cardiac amyloidosis (ATTR-CA) is an infiltrative cardiomyopathy that commonly presents with concomitant chronic kidney disease. Albuminuria is common in heart failure and associated with worse outcomes, but its prevalence and relationship to outcome in ATTR-CA remains unclear.Methods and results: A total of 1181 patients with ATTR-CA were studied (mean age 78.1 +/- 7.9 years; 1022 [86.5%] male; median estimated glomerular filtration rate 59 ml/min/1.73m(2) [interquartile range: 47-74]). Albuminuria was present in 563 (47.7%) patients (499 [88.6%] with microalbuminuria and 64 [11.4%] with macroalbuminuria). Patients with albuminuria had a more severe cardiac phenotype evidenced by higher serum cardiac biomarkers (median N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 4027 ng/L [2173-6889] vs. 1851 ng/L [997-3209], p < 0.001; median troponin T: 69 ng/L [46-101] vs. 48 ng/L [34-68], p < 0.001) and worse echocardiographic indices of systolic (longitudinal strain: -10.0 +/- 3.6% vs. -11.6 +/- 3.8%, p < 0.001) and diastolic function (E/e': 17.5 +/- 6.4 vs. 16.4 +/- 6.7, p < 0.001) than those with a normal urinary albumin to creatinine ratio (UACR). Microalbuminuria and macroalbuminuria were independently associated with mortality in the overall population (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.13-1.92, p = 0.005 and HR 1.87, 95% CI 1.15-3.05, p = 0.012, respectively). In a subgroup of patients (n = 349) without concomitant hypertension, diabetes mellitus or chronic kidney disease, albuminuria was also associated with mortality (HR 2.98, 95% CI 1.72-5.17, p < 0.001). At 12 months, 330 patients had a repeat UACR measurement; those in whom UACR increased by 30% or more (n = 148, 44.8%) had an increased risk of mortality (HR 1.84, 95% CI 1.06-3.19, p = 0.030).Conclusions: Albuminuria is common in patients with ATTR-CA, and more prevalent in those with a more severe cardiac phenotype. Albuminuria at diagnosis and a significant increase in UACR during follow-up are associated with mortality

Conventional heart failure therapy in cardiac ATTR amyloidosis

BACKGROUND AND AIMS: The aims of this study were to assess prescription patterns, dosages, discontinuation rates and association with prognosis of conventional heart failure (HF) medications in patients with transthyretin cardiac amyloidosis (ATTR-CA). METHODS: A retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000-2022 identified 2371 patients with ATTR-CA. RESULTS: Prescription of HF medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEi)/angiotensin-II receptor blockers (ARB) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (IQR 10.6-51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARB discontinued. In contrast, only 7.5% had MRAs discontinued. Propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population (HR 0.77 [95% CI 0.66-0.89], P40% (HR 0.75 [95% CI 0.63-0.90], P=0.002); and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% (HR 0.61 [95% CI 0.45-0.83], P=0.002). No convincing differences were found for treatment with ACEi/ARBs. CONCLUSIONS: Conventional HF medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials