A routine invasive strategy is recommended in the management of higher risk patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs). However, patients with previous coronary artery bypass ...graft (CABG) surgery were excluded from key trials that informed these guidelines. Thus, the benefit of a routine invasive strategy is less certain in this specific subgroup.
A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. A comprehensive search was performed of PubMed, EMBASE, Cochrane, and ClinicalTrials.gov. Eligible studies were RCTs of routine invasive vs. a conservative or selective invasive strategy in patients presenting with NSTE-ACS that included patients with previous CABG. Summary data were collected from the authors of each trial if not previously published. Outcomes assessed were all-cause mortality, cardiac mortality, myocardial infarction, and cardiac-related hospitalization. Using a random-effects model, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.
Summary data were obtained from 11 RCTs, including previously unpublished subgroup outcomes of nine trials, comprising 897 patients with previous CABG (477 routine invasive, 420 conservative/selective invasive) followed up for a weighted mean of 2.0 (range 0.5-10) years. A routine invasive strategy did not reduce all-cause mortality (RR 1.12, 95% CI 0.97-1.29), cardiac mortality (RR 1.05, 95% CI 0.70-1.58), myocardial infarction (RR 0.90, 95% CI 0.65-1.23), or cardiac-related hospitalization (RR 1.05, 95% CI 0.78-1.40).
This is the first meta-analysis assessing the effect of a routine invasive strategy in patients with prior CABG who present with NSTE-ACS. The results confirm the under-representation of this patient group in RCTs of invasive management in NSTE-ACS and suggest that there is no benefit to a routine invasive strategy compared to a conservative approach with regard to major adverse cardiac events. These findings should be validated in an adequately powered RCT.
The current risk stratification system defined by clinicopathological features does not identify the risk of recurrence in early-stage (stage I-II) colorectal cancer (CRC) with sufficient accuracy. ...We aimed to investigate whether DNA methylation could serve as a novel biomarker for predicting prognosis in early-stage CRC patients.
We analyzed the genome-wide methylation status of CpG loci using Infinium MethylationEPIC array run on primary tumor tissues and normal mucosa of early-stage CRC patients to identify potential methylation markers for prognosis. The machine-learning approach was applied to construct a DNA methylation-based prognostic classifier for early-stage CRC (MePEC) using the 4 gene methylation markers FAT3, KAZN, TLE4, and DUSP3. The prognostic value of the classifier was evaluated in 2 independent cohorts (n = 438 and 359, respectively).
The comprehensive analysis identified an epigenetic subtype with high risk of recurrence based on a group of CpG loci in the CpG-depleted region. In multivariable analysis, the MePEC classifier was independently and statistically significantly associated with time to recurrence in validation cohort 1 (hazard ratio = 2.35, 95% confidence interval = 1.47 to 3.76, P < .001) and cohort 2 (hazard ratio = 3.20, 95% confidence interval = 1.92 to 5.33, P < .001). All results were further confirmed after each cohort was stratified by clinicopathological variables and molecular subtypes.
We demonstrated the prognostic statistical significance of a DNA methylation profile in the CpG-depleted region, which may serve as a valuable source for tumor biomarkers. MePEC could identify an epigenetic subtype with high risk of recurrence and improve the prognostic accuracy of current clinical variables in early-stage CRC.
IMPORTANCE: Glaucoma represents a major public health challenge in an aging population. The Tanjong Pagar Eye Study reported the prevalence and risk factors of glaucoma in a Singapore Chinese ...population in 1997, which established the higher rates of blindness in this population. OBJECTIVES: To determine the prevalence and associated risk factors for glaucoma among Chinese adults in Singapore and to compare the results with those of the 1997 study. DESIGN, SETTING, AND PARTICIPANTS: In a population-based survey of 4605 eligible individuals, we selected 3353 Chinese adults 40 years or older from the southwestern part of Singapore. Participants underwent examination at a single tertiary care research institute from February 9, 2009, through December 19, 2011. EXPOSURES: All participants underwent slitlamp ophthalmic examination, applanation tonometry, measurement of central corneal thickness, gonioscopy, and a dilated fundus examination. MAIN OUTCOMES AND MEASURES: Glaucoma as defined by the International Society of Geographical and Epidemiological Ophthalmology guidelines and age-standardized prevalence estimates computed as per the 2010 Singapore Chinese census. Blindness was defined as logMAR visual acuity of 1.00 (Snellen equivalent, 20/200 or worse). RESULTS: Of the 3353 respondents, 134 (4.0%) had glaucoma, including primary open-angle glaucoma (POAG) in 57 (1.7%), primary angle-closure glaucoma (PACG) in 49 (1.5%), and secondary glaucoma in 28 (0.8%). The age-standardized prevalence (95% CI) of glaucoma was 3.2% (2.7%-3.9%); POAG, 1.4% (1.1%-1.9%); and PACG, 1.2% (0.9%-1.6%). In a multivariate model, POAG was associated with being older and male and having a higher intraocular pressure. Of the 134 participants with glaucoma, 114 (85.1%; 95% CI, 78.1%-90.1%) were not aware of their diagnosis. Prevalence (95% CI) of blindness caused by secondary glaucoma was 14.3% (5.7%-31.5%), followed by 10.2% (4.4%-21.8%) for PACG and 8.8% (3.8%-18.9%) for POAG. We could not identify a difference in the prevalence of glaucoma compared with the 3.2% reported in 1997 (difference, −0.04%; 95% CI, −1.2 to 1.2; P = .97). CONCLUSIONS AND RELEVANCE: The prevalence of glaucoma among Singapore Chinese likely ranges from 2.7% to 3.9%, with secondary glaucoma being the most visually debilitating type. We could not identify a difference compared with previous studies approximately 12 years earlier. We report a high proportion of previously undiagnosed disease, suggesting the need to increase public awareness of this potentially blinding condition.
Summary
Background
Chronic hepatitis B patients (CHB) treated with adefovir were followed up to evaluate nephrotoxicity and its outcome.
Aim
To assess the incidence of renal dysfunction during ...adefovir therapy in Asian patients and factors associated with it, and evaluate strategies to improve adefovir‐related renal dysfunction and their impact on viral suppression.
Methods
Chronic hepatitis B clinic patients from a tertiary hospital on adefovir treatment, with their clinical and laboratory parameters were extracted from the hospital electronic clinical database in an observational study design. Patients were excluded if they had liver/renal transplant, baseline renal impairment or were on dialysis. Adefovir‐related renal dysfunction was defined as adefovir‐related abnormal serum creatinine (ARASC) > 125 μmol/L (males), >90 μmol/L (females); adefovir‐related abnormal GFR <60 mL/min; and adefovir‐related increased serum creatinine >0.5 mg/dL, without other known causes of nephrotoxicity.
Results
A total of 271/383 adefovir‐treated patients were suitable for analysis and 33(12%) patients developed abnormal serum creatinine. Cumulative increase in proportion of patients with ARASC was 33.8% and GFR ≤60 mL/min was 38.3% by 6 years, while serum creatinine increase ≥0.5 mg/dL was 21.48% by 5 years. Using multivariate analysis, the only independent baseline predictor of ARASC was GFR ≤76.1 mL/min. Patients who had ARASC had similar levels of viral suppression to those who did not have ARASC. Those who had ARASC either continued adefovir (24%), switched therapy (24%) or had adefovir dose reduction (52%). ARASC resolved and GFR normalised in almost all patients after either switching therapy or reducing adefovir dose, with no difference between the two strategies (P = 0.737). Those with adefovir dose reduction had no significant increase in HBV DNA (P = 0.170).
Conclusions
Adefovir‐related renal dysfunction occurred in a significant number of adefovir‐treated patients, but reduction of the dose led to renal improvement without compromising treatment efficacy.
The average age-specific cumulative risk (penetrance) of breast cancer has been studied for
BRCA1
and
BRCA2
mutation carriers living in Western countries, but not for those living in East Asian ...countries where the population breast cancer incidence is lower. From 2007 to 2011, the Korean Hereditary Breast Cancer study identified 151
BRCA1
and 225
BRCA2
mutation-carrying families from family cancer clinics. We estimated the hazard ratio (HR) for female carriers relative to the population, and hence the penetrance, using a modified segregation analysis of cancer family histories conditioned on ascertainment. The breast cancer HR estimates 95 % confidence interval (CI) for
BRCA1
and
BRCA2
mutation carriers were 18 (3–103) and 11 (5–27), respectively. The breast cancer penetrance estimates (95 % CI) to age 70 years were 49 % (11–98) and 35 % (16–65) for
BRCA1
and
BRCA2
mutation carriers, respectively. The breast cancer HR and penetrance estimates were similar for Korean and Western women (all
P
> 0.4). The point estimates of breast cancer penetrance were similar to age 50 years, though less for Korean carriers at older ages. Breast cancer risk for Korean and Western mutation carriers might reflect underlying population risks which in turn likely reflect differences in environmental and lifestyle factors. This raises the possibility of identifying modifiers of cancer risk for carriers with implications for prevention.
Management of pituitary incidentalomas Westall, Samuel J; Aung, Ei Thuzar; Kejem, Helmine ...
Clinical medicine,
March 2023, 2023-03-00, 20230301, Letnik:
23, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Pituitary incidentalomas are common findings with increasing use of modern neuroradiological imaging undertaken for symptoms unrelated to pituitary disease. The prevalence of these lesions is ∼10% in ...autopsy studies and the incidence varies from 10% to 38% on magnetic resonance imaging in the published literature. They are almost always benign in nature and most are non-functioning (non-secreting) adenomas. Although many individuals are asymptomatic at diagnosis, some with functioning (secreting) pituitary adenomas or larger non-functioning adenomas have symptoms. All identified cases should have a thorough clinical and endocrinological evaluation to help with precise management, which depends on the size of the lesion, hormonal status (functioning versus non-functioning adenoma) and the presence of visual deficits resulting from optic nerve compression by the pituitary adenoma. Here, we provide an overview of the initial assessment and management of pituitary incidentalomas for clinicians not routinely involved in the management of pituitary disease.
Summary
Linear IgA bullous dermatosis (LABD) is a subepidermal autoimmune bullous disease characterized by linear IgA deposition at the basement membrane zone, which is visualized by direct ...immunofluorescence. Patients with LABD typically present with widespread vesicles and bullae; however, this is not necessarily the case, as the clinical presentation of this disease is heterogeneous. LABD clinically presenting as Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) is an infrequent, yet well‐described phenomenon. Most cases of LABD are idiopathic, but some cases are drug‐induced. Multiple drugs have been implicated in the development of LABD. We report a case of piperacillin–tazobactam‐induced LABD presenting clinically as SJS/TEN overlap. This is the first reported case of a strong causal association between piperacillin‐tazobactam and the development of LABD.
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