HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women

Aims/hypothesis Diabetes is known to increase mortality rate, but the degree to which mild hyperglycaemia may be associated with the risk of death is uncertain. We examined the association between HbA_1c measured in stored erythrocytes and mortality rate in women with and without diabetes. Methods We conducted a cohort study of 27,210 women ≥ 45 years old with no history of cardiovascular disease or cancer who participated in the Women’s Health Study, a randomised trial of vitamin E and aspirin. Results Over a median of 10 years of follow-up, 706 women died. Proportional hazards models adjusted for age, smoking, hypertension, blood lipids, exercise, postmenopausal hormone use, multivitamin use and C-reactive protein were used to estimate the relative risk of mortality. Among women without a diagnosis of diabetes and HbA_1c <5.60%, those in the top quintile (HbA_1c 5.19–5.59%) had a relative risk of mortality of 1.28 (95% CI 0.98–1.69, p value for linear trend = 0.14) compared with those with HbA_1c 2.27–4.79%. Women with HbA_1c 5.60–5.99% and no diagnosis of diabetes had a 54% increased risk of mortality (95% CI 1–136%) compared with those with HbA_1c 2.27–4.79%. HbA_1c was significantly associated with mortality across the range 4.50–7.00% (p value for linear trend = 0.02); a test of deviation from linearity was not statistically significant (p = 0.67). Diabetic women had more than twice the mortality risk of non-diabetic women. Conclusions/interpretation This study provides further evidence that chronic mild hyperglycaemia, even in the absence of diagnosed diabetes, is associated with increased risk of mortality. ClinicalTrials.gov ID no.: NCT00000479     

Risk factors for mortality–morbidity after emergency–urgent colorectal surgery

Background  The aim of this study was to assess the risk factors associated with mortality and morbidity following emergency or urgent colorectal surgery. Materials and methods  All data regarding the 462 patients who underwent emergency colonic resection in our institution between November 2002 and December 2007 were prospectively entered into a computerized database. Results  The median age of patients was 73 (range 17–98) years. The most common indications for surgery were: 171 adenocarcinomas (37%), 129 complicated diverticulitis (28%), and 35 colonic ischemia (7.5%). Overall mortality and morbidity rates were 14% and 36%, respectively. In multivariate analysis, the only parameter significantly associated with postoperative mortality was blood loss >500 cm³ (odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.63–6.82, p = 0.001). There were three parameters which correlated with postoperative morbidity: ASA score ≥3 (OR = 2.9, 95% CI 1.9–4.5, p < 0.001), colonic ischemia (OR = 3.4, 95% CI 1.4–7.7, p = 0.006), and stoma creation (OR = 2.2, 95% CI 1.4–3.4, p = 0.0003). Conclusions  The main risk factors for postoperative morbidity and mortality following emergency colorectal surgery are related to: (1) patients’ ASA score, (2) colonic ischemia, and (3) perioperative bleeding. These variables should be considered in the elaboration of future scoring systems to predict outcome of emergency colorectal surgery.     

Coffee consumption and incidence of impaired fasting glucose,impaired glucose tolerance,and type 2 diabetes: the Hoorn Study

Aims/hypothesis Coffee contains several substances that may affect glucose metabolism. The aim of this study was to evaluate the relationship between habitual coffee consumption and the incidence of IFG, IGT and type 2 diabetes.Methods We used cross-sectional and prospective data from the population-based Hoorn Study, which included Dutch men and women aged 50–74 years. An OGTT was performed at baseline and after a mean follow-up period of 6.4 years. Associations were adjusted for potential confounders including BMI, cigarette smoking, physical activity, alcohol consumption and dietary factors.Results At baseline, a 5 cup per day higher coffee consumption was significantly associated with lower fasting insulin concentrations (–5.6%, 95% CI –9.3 to –1.6%) and 2-h glucose concentrations (–8.8%, 95% CI –11.8 to –5.6%), but was not associated with lower fasting glucose concentrations (–0.8%, 95% CI –2.1 to 0.6%). In the prospective analyses, the odds ratio (OR) for IGT was 0.59 (95% CI 0.36–0.97) for 3–4 cups per day, 0.46 (95% CI 0.26–0.81) for 5–6 cups per day, and 0.37 (95% CI 0.16–0.84) for 7 or more cups per day, as compared with the corresponding values for the consumption of 2 or fewer cups of coffee per day (p=0.001 for trend). Higher coffee consumption also tended to be associated with a lower incidence of type 2 diabetes (OR 0.69, CI 0.31–1.51 for 7 vs 2 cups per day, p=0.09 for trend), but was not associated with the incidence of IFG (OR 1.35, CI 0.80–2.27 for 7 vs 2 cups per day, p=0.49 for trend).Conclusions/interpretation Our findings indicate that habitual coffee consumption can reduce the risk of IGT, and affects post-load rather than fasting glucose metabolism.     

Mortality in Peripheral Arterial Disease: A Comparison of Patients Managed by Vascular Specialists and General Practitioners

BACKGROUND Peripheral arterial disease (PAD) is undertreated by general practitioners (GPs). However, the impact of the suboptimal clinical management is unknown. OBJECTIVE To assess the mortality rate of PAD patients in relation to the type of physician who provides their care (GP or vascular specialist). DESIGN Prospective study. SETTING Primary care practice and academic vascular laboratory. PARTICIPANTS GP patients (n = 60) were those of the Peripheral Arteriopathy and Cardiovascular Events study (PACE). Patients managed by specialists (n = 82) were consecutive subjects with established PAD who were referred to our vascular laboratory during the enrolment period of the PACE study. MEASUREMENTS All-cause and cardiovascular mortality. RESULTS After 32 months of follow-up, specialist management was associated with a lower rate of all-cause mortality (RR = 0.04; 95% CI 0.01–0.34; p = .003) and cardiovascular mortality (RR = 0.07; 95% CI 0.01–0.65; p = .020), after adjustment for patients’ characteristics. Specialists were more likely to use antiplatelet agents (93% vs 73%, p < .001), statins (62% vs 25%, p < .001) and beta blockers (28% vs 3%, p < .001). Survival differences between specialists and GPs disappeared once the use of pharmacotherapies was added to the proportional hazard model. The fully adjusted model showed that the use of statins was significantly associated with a reduced risk of all-cause mortality (RR = 0.02; 95% CI 0.01–0.73, p = .034) and cardiovascular mortality (RR = 0.02; 95% CI 0.01–0.71, p = .033). CONCLUSIONS Specialist management of patients with symptomatic PAD resulted in better survival than generalist management. This effect appears to be mainly caused by the more frequent use of effective medicines by specialists.     

Survival analysis of patients with dermatomyositis and polymyositis

To estimate the mortality rate and identify factors predicting survival in patients with polymyositis (PM) and dermatomyositis (DM). The medical records of 192 PM/DM patients who were treated at Chang Gung Memorial Hospital from 1999 through 2008 were retrospectively reviewed. The Taiwan National Death Registry (1999–2008) was used to obtain their survival status. Thirty-one (16.1%) of the 192 patients with PM/DM had an associated malignancy; 41 (21.4%) had interstitial lung disease (ILD). During the follow-up period, 55 (28.6%) patients died and the overall cumulative survival rate was 79.3% at 1 year, 75.7% at 2 years, 69.9% at 5 years, and 66.2% at 10 years. In univariate analysis, older age at PM/DM onset, anemia, thrombocytopenia, leukopenia, diabetes mellitus, ILD, cancer, and non-use of azathioprine were associated with higher mortality (p = 0.0172, 0.0484, <0.0001, 0.0008, 0.0001, 0.0036, 0.0010, and 0.0019, respectively). In multivariate Cox regression analysis, thrombocytopenia (hazard ratio [HR] 4.94, 95% confidence interval [CI] 2.60–9.37, p < 0.0001), diabetes mellitus (HR 2.57, 95% CI 1.38–4.80, p < 0.0001), cancer (HR 2.30, 95% CI 1.26–4.22, p = 0.0030), and ILD (HR 1.98, 95% CI 1.11–3.51, p = 0.0182) were positively associated with mortality. Use of azathioprine (HR 0.35, 95% CI 0.16–0.74, p = 0.0064) was negatively associated with mortality. This study confirmed the high mortality rate (28.6%) in PM/DM patients. Survival time was significantly reduced in patients with thrombocytopenia, diabetes mellitus, ILD, and cancer patients than in those without these conditions.     

Incidence,consequences, and risk factors for anastomotic dehiscence after colorectal surgery: a prospective monocentric study

Background Anastomotic dehiscence is the most severe surgical complication after large bowel resection. This study was designed to assess the incidence, to observe the consequences, and to identify the risk factors associated with anastomotic leakage after colorectal surgery. Materials and methods All procedures involving anastomoses of the colon or the rectum, which were performed between November 2002 and February 2006 in a single institution, were prospectively entered into a computerized database. Results One thousand eighteen colorectal resections and 811 anastomoses were performed over this 40-month period. The most frequent procedures were sigmoid (276) and right colectomies (217). The overall anastomotic leak rate was 3.8%. The mortality rate associated with anastomotic leak was 12.9%. In univariate analysis, the following parameters were associated with an increased risk for anastomotic dehiscence: (1) ASA score ≥ 3 (p = 0.004), (2) prolonged (>3 h) operative time (p = 0.02), (3) rectal location of the disease (p < 0.001), (4) and a body mass index > 25 (p = 0.04). In multivariate analysis, ASA score ≥ 3 (OR = 2.5; 95% CI 1.5–4.3, p < 0.001), operative time > 3 h [OR = 3.0; 95% CI 1.1–8.0, p = 0.02), and rectal location of the disease (OR = 3.75; 95% CI 1.5–9.0 (vs left colon), p = 0.003; OR = 7.69; 95% CI 2.2–27.3 (vs right colon), p = 0.001] were factors significantly associated with a higher risk of anastomotic dehiscence. Conclusions Three risk factors for anastomotic leak have been identified, one is patient-related (ASA score), one is disease-related (rectal location), the third being surgery-related (prolonged operative time). These factors should be considered in perioperative decision-making regarding defunctioning stoma formation.     

Levels of soluble receptor for AGE are cross-sectionally associated with cardiovascular disease in type 1 diabetes, and this association is partially mediated by endothelial and renal dysfunction and by low-grade inflammation: the EURODIAB Prospective Complications Study

Aims/hypothesis  Plasma soluble receptor for AGE (sRAGE) may reflect the activity of the AGE–RAGE axis, which has been proposed as a potential mechanism linking hyperglycaemia to vascular complications in diabetes. We have therefore investigated: (1) whether sRAGE is associated with greater prevalence of cardiovascular disease (CVD) and microvascular complications in type 1 diabetic individuals; and (2) the extent to which any such associations are explained by markers of endothelial and renal dysfunction and inflammation. Methods  The study included 477 individuals (234 women; mean age 42 ± 10 [SD] years) from the EURODIAB Prospective Complications Study. We used linear regression analyses to investigate the differences in sRAGE levels between individuals with and without vascular complications. All analyses were adjusted for age, sex, HbA_1c, duration of diabetes and other risk factors. Results  Individuals with CVD (n = 116) had higher levels of sRAGE than those without CVD or any microvascular complications (n = 178): β = 0.15 (95% CI 0.04–0.27). Further adjustments for markers of endothelial (β = 0.13 [0.02–0.24]) and renal dysfunction (β = 0.10 [−0.01, 0.20]) and inflammation (β = 0.12 [0.01–0.23]) attenuated these differences; altogether these variables explained about 50% of the association between sRAGE and prevalent CVD. sRAGE levels tended to be higher in the presence and across the levels of severity of albuminuria (p for trend = 0.087) and retinopathy (p for trend = 0.057); adjustments for endothelial and renal dysfunction and inflammation also attenuated these differences. Conclusions/interpretation  sRAGE is associated with greater prevalence of CVD in type 1 diabetic individuals, and these associations may be partly explained by endothelial and renal dysfunction and low-grade inflammation. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study

Aims/hypothesis AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. Subjects and methods Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45–64 years. These participants were followed for 18 years for total, CVD and CHD mortality. Results Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p = 0.002) and CVD mortality (p = 0.021) in women, but not in men. Serum levels of AGEs in the highest sex-specific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14–1.99; p = 0.004), CVD (HR 1.56; 95% CI 1.12–2.19; p = 0.009), and CHD (HR 1.68; 95% CI 1.11–2.52; p = 0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. Conclusions/interpretation Increased serum levels of AGEs predict total and CVD mortality in women with type 2 diabetes. B. K. Kilhovd and A. Juutilainen contributed equally to this study.     

Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women

BACKGROUND: Coffee intake may be associated with reduced risk of type 2 diabetes mellitus because of minerals, phytochemicals, and antioxidants in coffee, but the role of caffeine is unclear. Our objective was to examine the association between total, caffeinated, and decaffeinated coffee intake, as assessed by food frequency questionnaire at baseline, and risk of incident type 2 diabetes mellitus. METHODS: This prospective analysis of the Iowa Women's Health Study (1986-1997) included 28 812 postmenopausal women free of diabetes and cardiovascular disease in the general community. The main outcome measure was incident type 2 diabetes mellitus as determined by mailed questionnaire. RESULTS: Coffee intake was categorized as 0, less than 1, 1 to 3, 4 to 5, and 6 or more cups per day. During 11 years of follow-up, there were 1418 incident cases of diabetes. Relative risks (RRs) were adjusted for a variety of demographic, adiposity, and lifestyle measures. Compared with women who reported 0 cups of coffee per day, women who consumed 6 or more cups per day had a 22% lower risk (RR = 0.78; 95% confidence interval [CI], 0.61-1.01) of diabetes (P for linear trend across categories, .06). This association appeared to be largely explained by decaffeinated coffee (RR = 0.67; 95% CI, 0.42-1.08; P for trend, .006) rather than regular coffee (RR = 0.79; 95% CI, 0.59-1.05; P for trend, .90). Intake of magnesium and phytate did not explain these associations. Intakes of caffeine from all sources was not associated with risk of diabetes. CONCLUSION: Coffee intake, especially decaffeinated, was inversely associated with risk of type 2 diabetes mellitus in this cohort of postmenopausal women.     

Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients

Aims/hypothesis  The aim of this study of type 2 diabetic patients in the Swedish National Diabetes Register was to study the associations of BMI, overweight (BMI 25–29.9 kg/m²) and obesity (BMI ≥ 30 kg/m²) with cardiovascular disease in type 2 diabetes, as these associations have not previously been clarified. Methods  Patients aged 30–74 years with no previous CHD or stroke (N = 13,087) were followed for a mean of 5.6 years until 2003 for fatal or non-fatal CHD, stroke, cardiovascular disease (CHD or stroke) and total mortality. In total, 1,922 cardiovascular-disease events occurred, based on 64,864 person-years. Results  The relative risks of CHD, stroke, cardiovascular disease and total mortality for a 5 unit increase in BMI at baseline were 15%, 11%, 13% and 27%, respectively, using Cox regression analysis, after adjusting for age, sex, diabetes duration, hypoglycaemic treatment and smoking (model 1), and were 9%, 4% (not significant), 7% and 20%, respectively, when adjusting also for HbA_1c, blood pressure, antihypertensive drugs, lipid-reducing drugs and microalbuminuria (model 2). Adjusted hazard ratios (model 1) for CHD, cardiovascular disease and total mortality with overweight were 1.27 (95% CI 1.09–1.48), 1.24 (1.09–1.41) and 1.16 (0.94–1.45), respectively, and 1.49 (1.27–1.76), 1.44 (1.26–1.64) and 1.71 (1.36–2.14) with obesity, as compared with normal weight. Significant hazard ratios were attenuated when adjusted according to model 2. For a 1 unit increase in BMI during follow-up, the relative risk of CHD (model 2) was 1.13 (1.04–1.23; p = 0.005). Conclusions/interpretation  Both overweight and obesity independently increased the risk of CHD and cardiovascular disease in patients with type 2 diabetes. The CHD risk was higher with increasing BMI than with stable or decreasing BMI during the study.     

Comment on “Association of coffee drinking with total and cause-specific mortality”

Background: Coffee is one of the most widely consumed beverages, but the association between coffee consumption and the risk of death remains unclear.Methods: We examined the association of coffee drinking with subsequent total and cause-specific mortality among 229 119 men and 173 141 women in the National Institutes of Health – AARP Diet and Health Study who were 50–71 years of age at baseline. Participants with cancer, heart disease, and stroke were excluded. Coffee consumption was assessed once at baseline.Results: During 5 148 760 person-years of follow-up between 1995 and 2008, a total of 33 731 men and 18 784 women died. In age-adjusted models, the risk of death was increased among coffee drinkers. However, coffee drinkers were also more likely to smoke, and, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality. Adjusted hazard ratios for death among men who drank coffee as compared with those who did not were as follows: 0.99 (95% confidence interval [CI], 0.95 to 1.04) for drinking less than 1 cup per day, 0.94 (95% CI, 0.90 to 0.99) for 1 cup, 0.90 (95% CI, 0.86 to 0.93) for 2 or 3 cups, 0.88 (95% CI, 0.84 to 0.93) for 4 or 5 cups, and 0.90 (95% CI, 0.85 to 0.96) for 6 or more cups of coffee per day (P < 0.001 for trend); the respective hazard ratios among women were 1.01 (95% CI, 0.96 to 1.07), 0.95 (95% CI, 0.90 to 1.01), 0.87 (95% CI, 0.83 to 0.92), 0.84 (95% CI, 0.79 to 0.90), and 0.85 (95% CI, 0.78 to 0.93) (p < 0.001 for trend). Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. Results were similar in subgroups, including persons who had never smoked and persons who reported very good to excellent health at baseline.Conclusions: In this large prospective study, coffee consumption was inversely associated with total and cause-specific mortality. Whether this was a causal or associational finding cannot be determined from our data.

Comment

Coffee is the most widely used stimulant beverage in the world. Caffeine is the active substance of coffee and belongs to the methylxanthine pharmacological group.Coffee is a complex mixture of thousands of chemical components, including carbohydrates, nitrogenates, lipids, minerals, vitamins, alkaloids and phenols.Due to its widespread consumption, coffee constitutes a major concern for many people, and, it must be admitted, does not have a good reputation: some of my students, when presenting a case at the bedside, include coffee alongside smoking as a major cardiovascular risk factor.This myth – because it really is a myth – is very hard to contradict, even though there are many studies showing that coffee prevents type 2 diabetes mellitus,¹ dementia,² Parkinson's disease³ and liver cancer.⁴ With regard to cardiovascular disease, coffee seems to have very little effect on normal individuals but may slightly increase blood pressure in hypertensive patients⁵, and probably increases atrial fibrillation incidence⁶.The present study⁷ looks at the relationship between coffee intake and subsequent total and cause-specific mortality among 229 119 men and 173 141 women in the National Institutes of Health AARP Diet and Health Study. Analyzing a total of 5 148 760 person-years of follow-up between 1995 and 2008, the author found that the risk of death was increased among coffee drinkers but, after adjustment for tobacco-smoking status and other potential confounders, there was a significant inverse association between coffee consumption and mortality, with hazard ratios between 1.01 and 0.84, i.e. ranging from a small increase of 0.1% to a decrease of 16%. Inverse associations were observed for deaths due to heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer.This study, by showing that coffee consumption was inversely associated with total and cause-specific mortality, should put to rest fears about this beverage, which, like anything else, should be taken in moderation.

Conflicts of interest

The author has no conflict of interest to declare.     

Interstitial lung disease in polymyositis and dermatomyositis

The aim of the study was to estimate the prevalence, characteristics, and prognostic factors of interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM). The medical records of 151 PM/DM patients treated at Chang Gung Memorial Hospital between January, 2000 and June, 2007 were retrospectively reviewed. Thirty of 151 (19.9%) PM/DM patients had developed ILD. Older age at PM/DM onset, anti-Jo-1 antibody, and arthritis/arthralgia were associated with the presence of ILD (p = 0.004, p = 0.008, and p = 0.026, respectively). Anti-Jo-1 was initially excluded from the multivariate analysis because only 80 patients underwent the test. An older age at onset above 45 years (odds ratio 3.28, 95% confidence interval (CI) 1.15–9.34, p = 0.026) and arthritis/arthralgia at onset (odds ratio (OR) 2.57, 95% CI 1.09–6.08, p = 0.032) were the two independent risk factors for developing ILD. If anti-Jo-1 was included in the multivariate analysis (n = 80), then an older age at onset above 45 years (OR 7.30, 95% CI 1.70–31.40, p = 0.008) and anti-Jo-1 positive (OR 7.89, 95% CI 1.18–52.87, p = 0.033) were associated with ILD, while arthritis/arthralgia was no longer significant (OR 2.64, 95% CI 0.70–10.01, p = 0.153). Of the 30 ILD patients, 16 (53.3%) died. The survival time was significantly shorter in ILD patients than in patients without ILD (p < 0.001). Poor survival in ILD patients was associated with male gender (p = 0.039), a Hamman–Rich-like presentation (p = 0.039), and a clinical diagnosis of acute interstitial pneumonia (p = 0.007).     

QT<Subscript>c</Subscript> interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

Aims/hypothesis We evaluated the association of QT interval corrected for heart rate (QT_c) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. Methods We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 ± 0.6 years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. Results In subjects with type 1 diabetes QT_c, but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10 ms increase in QT_c, 95% CI 1.02–1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02–1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03–1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QT_c was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15–1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18–1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19–1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21–1.90, p < 0.001). Effect modification of QT_c by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). Conclusions/interpretation QT_c is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabetes.     

A/ASP/VAL allele combination of IGF1R, IRS2, and UCP2 genes is associated with better metabolic profile, preserved energy expenditure parameters, and low mortality rate in longevity

A large array of gene involved in human longevity seems to be in relationship with insulin/IGF1 pathway. However, if such genes interact each other, or with other genes, to reduce the age-related metabolic derangement and determine the long-lived phenotype has been poorly investigated. Thus, we tested the role of interchromosomal interactions among IGF1R, IRS2, and UCP2 genes on the probability to reach extreme old age in 722 unrelated Italian subjects (401 women and 321 men; mean age, 62.83 ± 25.30 years) enrolled between 1998 and 1999. In particular, the G/A-IGF1R, Gly/Asp-IRS2, and Ala/Val-UCP2 allele combination was tested for association with longevity, metabolic profile and energy expenditure parameters. The effect on all-cause and cause-specific mortality rate was also assessed after a mean follow-up of 6 years. The analysis revealed that AAV allele combination is associated with a decreased all-cause mortality risk (HR, 0.72; 95% CI, 0.63–0.91; p = 0.03) and with a higher probability to reach the extreme of old age (OR, 3.185; 95% CI, 1.63–6.19; p = 0.0006). The analysis also revealed lower HOMA-IR (Diff, −0.532, 95% CI, 0.886–0.17; p = 0.003), higher respiratory quotient (Diff, 0.0363, 95% CI, 0.014–0.05; p = 0.001), and resting metabolic rate (Diff, 101.80693, 95% CI, −5.26–204.278; p = 0.038) for AAV allele combination. In conclusion, A-IGF1R/Asp-IRS2/Val-UCP2 allele combination is associated with a decreased all-cause mortality risk and with an increased chance of longevity. Such an effect is probably due to the combined effect of IGF1R, IRS2, and UCP2 genes on energy metabolism and on the age-related metabolic remodeling capacity.     

Autologous hematopoietic stem cell transplantation—what determines the outcome: an experience from North India

Limited information is available from developing countries about complications, pattern of infections, and long-term outcome of patients following high-dose chemotherapy (HDCT) and autologous blood stem cell transplantation (ASCT). Between April, 1990 and December 2009, 228 patients underwent ASCT. Patients’ median age was 48 years, ranging from 11 to 68 years. There were 158 males and 70 females. Indications for transplant included multiple myeloma, n = 143; lymphoma, n = 44 (Hodgkin’s, n = 25 and non-Hodgkin’s, n = 19); leukemia, n = 22; and solid tumors, n = 18. Patients received HDCT as per standard protocols. Following ASCT, 175 (76.7%) patients responded; complete, 98 (43%); very good partial response, 37 (16.2%); and partial response, 40 (17.5%). Response rate was higher for patients with good Eastern Cooperative Oncology Group (ECOG) performance status (0–2 vs. 3–4, p < 0.001), pretransplant chemo-sensitive disease (p < 0.001) and those with diagnosis of hematological malignancies (p < 0.003). Mucositis, gastrointestinal, renal, and liver dysfunctions were major nonhematologic toxicities, 3.1% of patients died of regimen-related toxicities. Infections accounted for 5.3% of deaths seen before day 30. At a median follow-up of 66 months (range, 9–234 months), median overall (OS) and event-free survival (EFS) were 72 months (95% CI 52.4–91.6) and 24 months (95% CI 17.15–30.9), respectively. For myeloma, OS and EFS were 79 months (95% CI 52.3–105.7) and 30 months (95% CI 22.6–37.4), respectively. Pretransplant good performance status and achievement of significant response following transplant were major predictors of survival. Our analysis demonstrates that such procedure can be successfully performed in a developing country with results comparable to developed countries.     

Effect of coffee consumption on dyslipidemia: A meta-analysis of randomized controlled trials

Background and aimDyslipidemia is a common metabolic disease worldwide and also an important predisposing factor for cardiovascular diseases (CVDs). Coffee is loved by people all over the world; however, the association between coffee consumption and blood lipids has yielded inconsistent results. So we carried this meta-analysis to explore the effects of coffee consumption on blood lipids.Methods and resultsMedline, PubMed, Web of science, Embase, and Cochrane Library databases were systematically searched until April 2020. Combined weighted mean differences (WMD) with their 95% confidence interval (CI) were calculated using random-effects models, and between-study heterogeneity was assessed by Cochran's Q test and I² statistics. Subgroup analysis and meta-regression analysis were also conducted to explore the potential heterogeneity. A total of 12 RCT studies involving the association between coffee consumption and blood lipid levels were included in the meta-analysis. The pooled results showed that coffee consumption significantly increased total cholesterol (TC) (WMD: 0.21 mmol/L, 95% CI: 0.04; 0.39, P = 0.017), triglyceride (TG) (WMD: 0.12 mmol/L, 95% CI: 0.03; 0.20, P = 0.006) and low-density lipoprotein (LDL-C) (WMD: 0.14 mmol/L, 95% CI: 0.05; 0.24, P = 0.003) while had no significant effect on high-density lipoprotein (HDL-C) (WMD: −0.01 mmol/L, 95% CI: −0.06; 0.04, P = 0.707). Dose–response analysis results revealed significant positive nonlinear associations between coffee consumption and the increase in TC, LDL-C, and TG levels.ConclusionsEvidence from this meta-analysis suggested that coffee consumption may be associated with an elevated risk for dyslipidemia and CVDs. So a reasonable habit of coffee consumption (<3 cups/d) is essential for the prevention of dyslipidemia.     

Prevalence of Musculoskeletal Pain and Statin Use

Background  Muscle effects are the most common reported adverse effects of 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins). However, in placebo-controlled trials the incidence of muscle pain is most often similar for placebo and active control groups. Objective  We sought to evaluate whether statin use was associated with a higher prevalence of musculoskeletal pain in a nationally representative sample. Methods  Cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2002. Participants were 3,580 adults ≥40 years without arthritis who were interviewed at home and examined in a mobile examination center. Participants were asked about sociodemographic characteristics, health conditions, medication use, and musculoskeletal pain. Height, weight, blood pressure, ankle brachial index, and cholesterol were measured. Measurements and Main Results  Prevalence and adjusted odds ratios (OR) of any musculoskeletal pain and musculoskeletal pain in 4 different anatomical regions (neck/upper back, upper extremities, lower back, and lower extremities) by statin use during the last 30 days. Among statin users (n = 402), 22.0% (95%CI 18.0–26.7%) reported musculoskeletal pain in at least 1 anatomical region during the last 30 days, compared with 16.7% (95%CI 15.1–18.4%) of those who did not use a statin. Compared to persons who did not use statins, those who used statins had multivariable-adjusted odds ratios (95%CI; p value) of 1.50 (1.07–2.11; p = .01) for any musculoskeletal pain, 1.59 (1.04–2.44, p = .03) for lower back pain, and1.50 (1.02–2.22, p = .03) for lower extremity pain. Conclusion  Musculoskeletal pain is common in adults ≥40 years without arthritis. In this nationally representative sample, statin users were significantly more likely to report musculoskeletal pain.     

Sodium Intake and Mortality Follow-Up in the Third National Health and Nutrition Examination Survey (NHANES III)

Background  Sodium restriction is commonly recommended as a measure to lower blood pressure and thus reduce cardiovascular disease (CVD) and all-cause mortality. However, some studies have observed higher mortality associated with lower sodium intake. Objective  To test the hypothesis that lower sodium is associated with subsequent higher cardiovascular disease (CVD) and all cause mortality in the Third National Health and Nutrition Examination Survey (NHANES III). Design  Observational cohort study of mortality subsequent to a baseline survey. Participants  Representative sample (n = 8,699) of non-institutionalized US adults age ≥30, without history of CVD events, recruited between 1988–1994. Measurements and main results  Dietary sodium and calorie intakes estimated from a single baseline 24-h dietary recall. Vital status and cause of death were obtained from the National Death Index through the year 2000. Hazard ratio (HR) for CVD mortality of lowest to highest quartile of sodium, adjusted for calories and other CVD risk factors, in a Cox model, was 1.80 (95% CI 1.05, 3.08, p = 0.03). Non-significant trends of an inverse association of continuous sodium (per 1,000 mg) intake with CVD and all-cause mortality were observed with a 99% CI of 0.73, 1.06 (p = 0.07) and 0.86, 1.04 (p = 0.11), respectively, while trends for a direct association were not observed. Conclusion  Observed associations of lower sodium with higher mortality were modest and mostly not statistically significant. However, these findings also suggest that for the general US adult population, higher sodium is unlikely to be independently associated with higher CVD or all-cause mortality.     

Outcome of patients with seronegative spondyloarthritis continuing sulphasalazine and methotrexate after a short course of infliximab therapy—experience from a tertiary care teaching hospital in South India

The objective of the study is to evaluate the outcome of patients with seronegative spondyloarthritis continuing on sulphasalazine (SSZ) and methotrexate (MTX) after a short course of infliximab. Patients with seronegative spondyloarthritis on MTX and SSZ were given short course of infliximab therapy at 0, 2, 6 and 14 weeks. Outcome of these patients while continuing on MTX and SSZ was assessed. Clinical features, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were noted at baseline (pre-infliximab), 1 month, 3 months and last follow-up after last dose of infliximab infusion. Twenty-four patients were included in this study. The mean duration of follow-up was 9.1 months. Statistically significant reduction in tender and swollen joint count was noted at all the three visits as compared to baseline. Fall in ESR and CRP was statistically significant at 1 and 3 months, but not at last follow-up. Mean reduction in BASDAI at 1 month ,3 month and last follow-up after last infliximab dose were 3.907 (95% CI 2.98–4.83; p < 0.001), 4.53 (95% CI 3.56–5.49; p < 0.001) and 2.48 (95% CI 1.12–3.84; p = 0.002), respectively. Mean reduction in BASFI at 1 month, 3 months and last follow-up after last infliximab dose were 4.13 (95% CI 3.23–5.04; p < 0.001), 4.34 (95% CI 2.8–5.88; p < 0.001) and 2.38 (95% CI 0.86–3.90; p = 0.005), respectively. Continuing SSZ and MTX after short course of infliximab results in sustained improvement in our patients with seronegative spondyloarthritis in India.     

Outpatient treatment with intravenous antimicrobial therapy and oral levofloxacin in patients with febrile neutropenia and hematological malignancies

The purpose of this study was to evaluate outcomes such as success of the initial therapy, failure of outpatient treatment, and death in outpatient treatment during intravenous antimicrobial therapy in patients with febrile neutropenia (FN) and hematological malignancies. In addition, clinical and laboratory data and the Multinational Association for Supportive Care of Cancer index (MASCC) were compared with failure of outpatient treatment and death. In a retrospective study, we evaluated FN following chemotherapy events that were treated initially with cefepime, with or without teicoplanin and replaced by levofloxacin after 48 h of defervescence in patients with good general conditions and ANC >500/mm³. Of the 178 FN episodes occurred in 126 patients, we observed success of the initial therapy in 63.5% of the events, failure of outpatient treatment in 20.8%, and death in 6.2%. The success rate of oral levofloxacin after defervescence was 99% (95 out of 96). Using multivariate analysis, significant risks of failure of outpatient treatment were found to be smoking (odds ratio (OR) 3.14, confidence interval (CI) 1.14–8.66; p = 0.027) and serum creatinine levels >1.2 mg/dL (OR 7.97, CI 2.19–28.95; p = 0.002). With regard to death, the risk found was oxygen saturation by pulse oximetry <95% (OR 5.8, IC 1.50–22.56; p = 0.011). Using the MASCC index, 165 events were classified as low risk and 13 as high risk. Failure of outpatient treatment was reported in seven (53.8%) high-risk and 30 (18.2%) low-risk episodes (p = 0.006). In addition, death occurred in seven (4.2%) low-risk and four (30.8%) high-risk events (p = 0.004). Ours results show that MASCC index was able to identify patients with high risk. In addition, non-smoking, serum creatinine levels ≤1.2 mg/dL, and oxygen saturation by pulse oximetry ≥95% were protection factors.