Efficacy and safety of high dose versus low dose furosemide with or without dopamine infusion: The Dopamine in Acute Decompensated Heart Failure II (DAD-HF II) Trial

Aims

The role of low-dose dopamine infusion in patients with acute decompensated heart failure (ADHF) remains controversial. We aim to evaluate the efficacy and safety of high- versus low-dose furosemide with or without low-dose dopamine infusion in this patient population.

Methods and results

161 ADHF patients (78 years; 46% female; ejection fraction 31%) were randomized to 8-hour continuous infusions of: a) high-dose furosemide (HDF, n = 50, 20 mg/h), b) low-dose furosemide and low-dose dopamine (LDFD, n = 56, 5 mg/h and 5 μg kg^− 1 min^− 1 respectively), or c) low-dose furosemide (LDF, n = 55, furosemide 5 mg/h). The main outcomes were 60-day and one-year all-cause mortality (ACM) and hospitalization for HF (HHF). Dyspnea relief (Borg index), worsening renal function (WRF, rise in serum creatinine (sCr) ≥ 0.3 mg/dL), and length of stay (LOS) were also assessed. The urinary output at 2, 4, 6, 8, and 24 h was not significantly different in the three groups. Neither the ACM at day 60 (4.0%, 7.1%, and 7.2%; P = 0.74) or at one year (38.1%, 33.9% and 32.7%, P = 0.84) nor the HHF at day 60 (22.0%, 21.4%, and 14.5%, P = 0.55) or one year (60.0%, 50.0%, and 47%, P = 0.40) differed between HDF, LDFD, and LDF groups, respectively. No differences in the Borg index or LOS were noted. WRF was higher in the HDF than in LDFD and LDF groups at day 1 (24% vs. 11% vs. 7%, P < 0.0001) but not at sCr peak (44% vs. 38% vs. 29%, P = 0.27). No significant differences in adverse events were noted.

Conclusions

In ADHF patients, there were no significant differences in the in-hospital and post-discharge outcomes between high- vs. low-dose furosemide infusion; the addition of low-dose dopamine infusion was not associated with any beneficial effects.     

Proteinuric renal disease in type 2 diabetes—Is remission of proteinuria associated with improved mortality and morbidity?

Aims

Patients with type 2 diabetes and macroalbuminuria are at high risk for end stage renal disease (ESRD), cardiovascular disease and death, but remission of proteinuria may improve prognosis. We examine the effectiveness of currently recommended treatments on inducing remission of proteinuria, and on morbidity and mortality.

Methods

Observational study of 78 patients with type 2 diabetes (46 male) with mean age (SD) of 61.5 (11) years, with a urinary albumin/creatinine ratio (ACR) ≥ 50 mg/mmol. All were treated with agents blocking the renin–angiotensin system. Follow-up was from recognition of ACR ≥ 50 mg/mmol until death or March 2011 (median 6 years). Remission of proteinuria was defined as ≥70% reduction from peak ACR, sustained for ≥1 year.

Results

Only 22 of 78 patients (28%) achieved remission of proteinuria. Thirty-six (46%) had at least one major event (death, dialysis or cardiovascular). Remission of proteinuria was associated with lower incidence of ESRD/death (9% vs 36%; p = 0.02) but cardiovascular events were not reduced (32% vs 30%). A third of patients had no retinopathy when albuminuria was first recognised, suggesting that non-diabetic renal pathologies were prominent. There was a significant interaction between the severity of diabetic retinopathy and remission of proteinuria on the risk of ESRD/death (p = 0.0003).

Conclusions

Remission of proteinuria was achieved in only a third of patients despite efforts to achieve blood pressure targets <130/80 mmHg. Failure to attain remission of proteinuria was associated with increased risk of ESRD or death, a risk compounded by the presence of severe diabetic retinopathy.     

Diverticulosis and the Risk of Interval Colorectal Cancer

Background

Diverticulosis, a prevalent condition at screening colonoscopy, has been associated with colorectal cancers that develop after a clearing colonoscopy, or interval cancers.

Aims

To quantify the overall risk of diverticulosis in the development of interval cancers and examine this association in relevant subgroups.

Methods

Using a linked database containing SEER tumor registry data and Medicare claims, we identified patients aged ≥69 years with colorectal cancer who underwent colonoscopy within 6 months of diagnosis. Patients with an additional colonoscopy from 36 to 6 months prior to cancer diagnosis were characterized as having interval cancers. We compared characteristics of patients with interval cancers and detected cancers according to a diagnosis of diverticulosis not associated with a colonoscopy procedure from 1991 through the date of the most recent colonoscopy in both univariate and multivariate models.

Results

A previous diagnosis of diverticulosis was documented in 14,452 (26.9 %) patients with detected cancers compared to 2,905 (69.3 %) patients with interval cancers (p < 0.001); these results were consistent in multivariable analysis. Moreover, the association was found as well in the proximal colon (OR 2.88, 95 % CI 2.66, 3.12), distal colon (OR 3.56, 95 % CI 3.09, 4.11), and rectum (OR 4.07, 95 % CI 3.34, 4.95). The vast majority of diverticulosis diagnoses were without complications such as hemorrhage or diverticulitis.

Conclusions

Diverticulosis was strongly associated with interval colorectal cancers in all segments of the colon. Given its known predominance in the left colon, the findings argue against impaired visualization of lesions at colonoscopy as the only pathogenic factor.     

Stroke and Bleeding Risk in Atrial Fibrillation: Navigating the Alphabet Soup of Risk‐Score Acronyms (CHADS2, CHA2DS2‐VASc,R2CHADS2, HAS‐BLED,ATRIA, and More)

Stroke prevention is central to the management of patients with atrial fibrillation (AF). As effective stroke prophylaxis essentially requires oral anticoagulants, an understanding of the risks and benefits of oral anticoagulant therapy is needed. Although AF increases stroke risk 5‐fold, this risk is not homogeneous. Many stroke risk factors also confer an increased risk of bleeding. Various stroke and bleeding risk‐stratification schemes have been developed to help inform clinical decision‐making. These scores were derived and validated in different study cohorts, ranging from highly selected clinical‐trial cohorts to real‐world populations. Thus, their performance and classification accuracy vary depending on their derivation cohort(s). In the present review, we provide an overview of currently available stroke and bleeding risk‐stratification schemes. We particularly focus on the CHA₂DS₂‐VASc and HAS‐BLED schemes, as these are recommended by the latest European guidelines on AF management. Other risk‐stratification schemes (eg, CHADS₂, R₂CHADS₂, ATRIA, HEMORR₂HAGES, QStroke) and their place in the decision‐making are also considered.     

Ploidy effects on genes regulating growth mechanisms during fasting and refeeding in juvenile rainbow trout (Oncorhynchus mykiss)

Diploid and triploid rainbow trout weighing approximately 3 g were either fed for five weeks, or feed deprived for one week, followed by refeeding. During feed deprivation gastrointestinal somatic index decreased in diploids, but not triploids, and during refeeding, carcass growth rate recovered more quickly in triploids. Although not affected by ploidy, liver ghr2 and igfbp2b expression increased and igfbp1b decreased in fasted fish. Effects of ploidy on gene expression indicate potential mechanisms associated with improved recovery growth in triploids, which include decreased hepatic igfbp expression, which could influence IGF-I bioavailability, differences in tissue sensitivity to TGFbeta ligands due to altered tgfbr and smad expression, and differences in expression of muscle regulatory genes (myf5, mstn1a, and mstn1b). These data suggest that polyploidy influences the expression of genes critical to muscle development and general growth regulation, which may explain why triploid fish recover from nutritional insult better than diploid fish.     

A GCH1 haplotype confers sex‐specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21–5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry. Am. J. Hematol. 89:187–193, 2014. © 2013 Wiley Periodicals, Inc.