Effects of smoking in patients treated with cardiac resynchronization therapy

Smoking is associated with increased morbidity and mortality in cardiac patients. However, data on the prognostic impact of smoking in heart failure (HF) patients on cardiac resynchronization therapy with defibrillator (CRT-D) are absent. We investigated the effects of smoking on all-cause mortality and on a composite endpoint (all-cause death/appropriate device therapy), appropriate and inappropriate device therapy, in 649 patients with HF who underwent CRT-D between January 2003 and October 2011 in 6 Centers (4 in Italy and 2 in USA). 68 patients were current smokers, 396 previous-smokers (patients who had smoked in the past but who had quit before the CRT-D implant), and 185 had never smoked. The risk of each endpoint by smoking status was evaluated with both Kaplan–Meier and Cox proportional-hazard analysis. After adjusting for age, left ventricular ejection fraction, QRS width and ischemic etiology, both current and previous smoking were independent predictors of all-cause death [HR = 5.07 (95 % CI 2.68–9.58), p < 0.001 and HR = 2.43 (95 % CI 1.38–4.29), p = 0.002, respectively) and of composite endpoint [HR = 1.63 (1.04–2.56); p = 0.033 and HR = 1.46 (1.04–2.04) p = 0.027]. In addition, current smokers had a significantly higher rate of inappropriate device therapy compared to never smokers [HR = 21.74 (4.53–104.25), p = 0.005]. Our study indicates that in patients with HF who received a CRT-D device, current and previous smoking increase the event rate per person-time of death and of appropriate and inappropriate ICD therapy more than other known negative prognostic factors such as age, left ventricular dysfunction, prolonged QRS duration and ischemic etiology.     

Relationship Between Tobacco Consumption and Health-related Quality of Life in Adults Living in a Large Metropolitan Area

The aim of this study was to analyze the relationship between health-related quality of life (HRQOL) and tobacco consumption in adult individuals (over the age of 15). The study was based on individual data from the City of Madrid Health Survey (ESCM05). Subjects were divided into three groups according to tobacco consumption: smokers, nonsmokers, and ex-smokers. HRQOL was measured using the COOP/WONCA quality-of-life vignettes. A multivariate adjustment with multinomial logistic regression was made, including the following as covariables: sociodemographic characteristics, comorbidities, drug use, and lifestyles. A total of 7341 individuals were interviewed (53.7% women), with an average age of 46.7 (SD = 19.02) years. The percentage of smokers was 27%, that of ex-smokers was 16.5%, and that of nonsmokers was 56.5%. There were no significant differences between smokers, ex-smokers, and nonsmokers in the raw scores obtained as totals from the COOP/WONCA questionnaire. Multivariate analysis revealed that smokers consume more antidepressant drugs (OR = 1.54, 95% CI = 1.09–2.16) and tranquilizers (OR = 1.91, 95% CI = 1.45–2.51), drink more alcohol (OR = 2.55, 95% CI = 2.11–3.08), get less physical exercise (OR = 1.33, 95% CI = 1.11–1.60), and have a lower quality of life (OR = 1.02, 95% CI = 1.00–1.04) than nonsmokers. Following adjustment for a significant number of covariables, sociodemographic as well as health-related, smokers consume more antidepressant drugs and tranquilizers, drink more alcohol, get less physical exercise, and demonstrate a lower HRQOL than nonsmokers.     

Lower extremity muscular strength,sedentary behavior,and mortality

To examine whether lower extremity strength (LES) is predictive of all-cause mortality, independent of physical activity and among those with vary levels of sedentary behavior. Data from the 1999–2002 National Health and Nutrition Examination Survey was used (N = 2768; 50–85 years). Peak isokinetic knee extensor strength was objectively measured, sedentary behavior and physical activity were self-reported, and mortality was assessed via the National Death Index, with follow-up through 2011. Participants were followed for up to 12.6 years with the weighted average follow-up period lasting 9.9 years (standard error, 1.13). In the sample, 321,996 person-months occurred with a mortality rate of 2.1 deaths per 1000 person-months. After adjustments (including physical activity), for every 15 N increase in LES, participants had a 7 % reduced risk of all-cause mortality (HR = 0.93; 95 % CI 0.91–0.95; P < 0.001). When adding a three-level sedentary behavior variable (< 2, 2–4, 5+ h/day) as a covariate in this model, results were unchanged (HR = 0.93; 95 % CI 0.92–0.96; P < 0.001). Similarly, when sedentary behavior was included as a continuous covariate in the model, results regarding the relationship between LES and mortality were unchanged (HR = 0.94; 95 % CI 0.91–0.96; P < 0.001). There was no evidence of statistical interaction between LES and sedentary behavior on all-cause mortality (HR_interaction = 1.01; 95 % CI 0.92–1.10; P = 0.88). LES was inversely associated with all-cause mortality, and this association was unchanged when considering the participant’s sedentary behavior.     

Expression of the calpain system is associated with poor clinical outcome in gastro-oesophageal adenocarcinomas

Background

Surgery is critical in the management of gastro-oesophageal cancer, and the addition of neo-adjuvant chemotherapy has proved to be of benefit. The calpain system has been implicated in tumour progression and response to various anti-cancer therapies, and therefore expression of the system was determined in this tumour type.

Methods

Two cohorts of gastro-oesophageal adenocarcinomas were investigated for calpain-1, calpain-2, calpain-9 and calpastatin expression using conventional immunohistochemistry. 88 patients who received neo-adjuvant chemotherapy and 140 patients who received surgery alone were investigated using a tissue microarray approach.

Results

Calpain-1, calpain-2 and calpastatin expression was associated with adverse cancer-specific survival in the neo-adjuvant cohort (P = 0.004, P = 0.001 and P = 0.012 respectively); which remained significant in multivariate analysis (Hazard ratio (HR) = 0.337; 95 % confidence interval (CI) = 0.140–0.81; P = 0.015, HR = 0.375; 95 % CI = 0.165–0.858; P = 0.020 and HR = 0.481; 95 % CI = 0.257–0.900; P = 0.022 respectively). Calpain-1 and calpastatin expression was also associated with adverse cancer specific survival in the primary surgery cohort (P = 0.001 and P = 0.013 respectively); which remained significant in multivariate analysis (HR = 0.309; 95 % CI = 0.159–0.601; P = 0.001 and HR = 0.418; 95 % CI = 0.205–0.850; P = 0.016 respectively). Calpain-9 expression was not associated with cancer-specific survival in the neo-adjuvant and primary surgery cohorts.

Conclusion

Determining the expression levels of calpain-1, calpain-2 and calpastatin may provide clinically relevant prognostic information for gastro-oesophageal adenocarcinomas; these findings warrant further studies in larger cohorts of patients.     

The Association Between TP53 Arg72Pro Polymorphism and Lung Cancer Susceptibility: Evidence from 30,038 Subjects

Background

The TP53 codon 72 polymorphism has been associated with the individual susceptibility to lung cancer. However, the association remains uncertain and varies with ethnicity, smoking status, cancer histology, and stage.

Methods

We performed a meta-analysis to evaluate the relationship between TP53 Arg72Pro polymorphism and lung cancer susceptibility basing on 15,647 lung cancer patients and 14,391 controls from 36 published literatures. We also performed stratified analysis in populations of different ethnicities, smoking statuses, lung cancer stages, and histological types.

Results

The analysis showed a significantly increased lung cancer susceptibility among Pro allele carriers (P < 0.001, odds ratio (OR) = 1.14, 95 % confidence interval (CI) = 1.1–1.19), especially for smokers (P < 0.001, OR = 1.29, 95 % CI = 1.12–1.47). Stratified analysis indicated that Pro72 elevates lung cancer susceptibility in Asians, while it has no effect on lung cancer risk of Caucasians. Moreover, Pro carriers present an increased risk of developing squamous cell carcinoma and adenocarcinoma, instead of large cell carcinoma and small cell carcinoma. Interestingly, patients with the Pro allele seemed to be diagnosed with lung cancer at the early stages (stage I–II, P = 0.008, OR = 1.2, 95 % CI = 1.05–1.37).

Conclusions

Our results suggest that the Pro allele acts as a risk factor for development of lung cancer, especially for smokers and Asians.     

A meta-analysis of the relation of polymorphism at sites −1082 and −592 of the IL-10 gene promoter with susceptibility and clearance to persistent hepatitis B virus infection in the Chinese population

Background

Up to now, many publications about the Chinese population have evaluated the correlation between interleukin-10 (IL-10) ?1082 and ?592 polymorphisms and persistent hepatitis B virus (HBV) infection. However, the results remain inconclusive. In order to resolve this conflict, a meta-analysis was performed.

Methods

Seven studies were included and dichotomous data are presented as the odds ratio (OR) with a 95% confidence interval (CI).

Results

The results of our study suggest that carriers of the IL-10 ?592A allele were more likely to clear HBV spontaneously in the Chinese pooled population (A vs. C: OR = 0.799, 95% CI = 0.678–0.941, P = 0.007; AC vs. AA: OR = 1.343, 95% CI = 1.017–1.684, P = 0.011; AA vs. AC + CC: OR = 0.736, 95% CI = 0.594–0.912; AA + AC vs. CC: OR = 0.588, 95% CI = 0.408–0.848, P = 0.004) and the IL-10 ?1082A allele was associated with significantly reduced persistent HBV infection risk in Chinese (A vs. G: OR = 0.701, 95% CI = 0.494–0.996, P = 0.047; AA vs. GG + GA: OR = 0.684, 95% CI = 0.476–0.982, P = 0.040).

Conclusions

Persistent HBV infection susceptibility is associated with the gene polymorphism IL-10 ?1082GA in the Chinese population and the clearance of HBV is associated with the gene polymorphism IL-10 ?592CA in the Chinese population.     

Long-Term Cigarette Smoking Trajectories Among HIV-Seropositive and Seronegative MSM in the Multicenter AIDS Cohort Study

To examine the association between demographic characteristics and long-term smoking trajectory group membership among HIV-seropositive and HIV-seronegative men who have sex with men (MSM). A cohort of 6552 MSM from the Multicenter AIDS Cohort Study were asked detailed information about their smoking history since their last follow-up. Group-based trajectory modeling was used to examine smoking behavior and identify trajectory group membership. Because participants enrolled after 2001 were more likely to be younger, HIV-seronegative, non-Hispanic black, and have a high school diploma or less, we also assessed time of enrollment in our analysis. Participants were grouped into 4 distinct smoking trajectory groups: persistent nonsmoker (n = 3737 [55.9 %]), persistent light smoker (n = 663 [11.0 %]), heavy smoker to nonsmoker (n = 531 [10.0 %]), and persistent heavy smoker (n = 1604 [23.1 %]). Compared with persistent nonsmokers, persistent heavy smokers were associated with being enrolled in 2001 and later (adjusted odds ratio [aOR] 2.35; 95 % CI 2.12–2.58), having a high school diploma or less (aOR 3.22; 95 % CI 3.05–3.39), and being HIV-seropositive (aOR 1.17; 95 % CI 1.01–1.34). These associations were statistically significant across all trajectory groups for time of enrollment and education but not for HIV serostatus. The overall decrease of smoking as shown by our trajectory groups is consistent with the national trend. Characteristics associated with smoking group trajectory membership should be considered in the development of targeted smoking cessation interventions among MSM and people living with HIV.     

Long-term effects of coffee and caffeine intake on the risk of pre-diabetes and type 2 diabetes: Findings from a population with low coffee consumption

Background and aim

Here, we examined the potential effect of coffee consumption and total caffeine intake on the occurrence of pre-diabetes and T2D, in a population with low coffee consumption.

Dual HIV Risk: Receptive Syringe Sharing and Unprotected Sex Among HIV-Negative Injection Drug Users in New York City

HIV-negative injection drug users (IDUs) who engage in both receptive syringe sharing and unprotected sex (“dual HIV risk”) are at high risk of HIV infection. In a cross-sectional study conducted in New York City in 2009, active IDUs aged ≥18 years were recruited using respondent-driven sampling, interviewed, and tested for HIV. Participants who tested HIV-negative and did not self-report as positive were analyzed (N = 439). Adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) were estimated using multinomial logistic regression. The sample was: 77.7 % male; 54.4 % Hispanic, 36.9 % white, and 8.7 % African-American/black. Dual risk was engaged in by 26.2 %, receptive syringe sharing only by 3.2 %, unprotected sex only by 49.4 %, and neither by 21.2 %. Variables independently associated with engaging in dual risk versus neither included Hispanic ethnicity (vs. white) (aOR = 2.0, 95 % CI = 1.0–4.0), married or cohabiting (aOR = 6.3, 95 % CI = 2.5–15.9), homelessness (aOR = 3.4, 95 % CI = 1.6–7.1), ≥2 sex partners (aOR = 8.7, 95 % CI = 4.4–17.3), ≥2 injecting partners (aOR = 2.9, 95 % CI = 1.5–5.8), and using only sterile syringe sources (protective) (aOR = 0.5, 95 % CI = 0.2–0.9). A majority of IDUs engaged in HIV risk behaviors, and a quarter in dual risk. Interventions among IDUs should simultaneously promote the consistent use of sterile syringes and of condoms.     

Paclitaxel-eluting stents versus sirolimus-eluting stents in patients with diabetes mellitus undergoing percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials

Uncertainties exist with regard to the efficacy of paclitaxel-eluting stents (PES) versus sirolimus-eluting stents (SES) in diabetes patients undergoing percutaneous coronary intervention (PCI). We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the outcome of PES versus SES in diabetes patients undergoing PCI. A literature search was started, and we found all studies conducted from 2005 to 2016. We systematically searched the literature through the MEDLINE, Cochrane library, and EMBASE. Quality assessments were evaluated with the Jadad scale. Data were extracted considering the characteristics of efficacy and the safety of the designs. 12 RCTs satisfy the inclusion criteria. There is a significant decrease of target lesion revascularization (TLR) (MD = 0.65, 95 % CI = 0.42–1.00, P = 0.05) in a year and more than 1 year (MD = 0.54, 95 % CI = 0.37–0.78, P = 0.00010). A significant decrease of target vessel revascularization (TVR) in more than 1 year is (MD = 0.62, 95 % CI = 0.47–0.81, P = 0.0004). A significant decrease of major adverse cardiac events (MACE) in more than 1 year is (MD = 0.73, 95 % CI = 0.60–0.89, P = 0.002). Nevertheless, there is no significant difference in mortality (MD = 0.85, 95 % CI = 0.66–1.11, P = 0.24), stent thrombosis (ST) (MD = 0.65, 95 % CI = 0.35–1.21, P = 0.18), or myocardial infarction (MD = 1.04, 95 % CI = 0.71–1.51, P = 0.84). SES may be more significant in decreasing TLR, TVR, and MACE than PES without significantly increasing mortality, ST and MI in diabetes patients.     

Obesity is associated with lower mortality risk in elderly diabetic subjects: the Casale Monferrato study

The relationship between obesity and mortality in people with type 2 diabetes has not been definitely assessed. We have examined this issue in a well-characterized population-based cohort of Mediterranean diabetic people. Standardized anthropometric data from the population-based Casale Monferrato Study have been prospectively analyzed. The cohort included 1,475 people (62.6% aged ≥65 years) who had been recruited in 1991 and followed-up to December 31, 2006. Cox proportional hazards modeling was employed to estimate the independent associations between all-cause and cardiovascular mortality and BMI. Out of 1,475 people, 972 deaths occurred during a 15-year follow-up. Cox regression analyses showed that with respect to BMI <24.2 kg/m², values of 30.0 kg/m² and over were associated with lower all-cause and cardiovascular mortality risk (HR = 0.68, 95% CI 0.56–0.85, P for trend = 0.001; HR = 0.59, 0.44–0.80, P for trend = 0.002), independently of classical and new risk factors. As interaction between age and BMI was significant, we performed a stratified analysis by age, providing evidence that our finding was entirely due to a significant protective effect of BMI of 30.0 kg/m² and over in the elderly (all-cause mortality HR = 0.75, 95% CI 0.58–0.96; cardiovascular mortality HR = 0.67, 95% CI 0.45–0.95). In contrast, obesity was not significantly associated with mortality risk in diabetic subjects aged <65 years. Results were confirmed even excluding from the analysis individuals who died within 2 years of follow-up, smokers and those with CHD. In Mediterranean diabetic people aged ≥65 years, obesity is significantly associated with lower 15-year mortality risk. In contrast, it was not significantly associated with mortality risk in diabetic subjects aged <65 years. As more than two-thirds of people with type 2 diabetes are elderly, our findings, if confirmed, could have clinical implications.     

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma

Purpose

To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).

Methods

Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR).

Results

One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48–0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42–0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53–1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48–1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39–0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred.

Conclusions

First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.

     

MGMT −535G>T polymorphism is associated with prognosis for patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy

Purpose

The present study analyzed the polymorphisms of DNA repair genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer.

Patients and methods

A total of 94 patients with recurrent or metastatic colorectal cancer treated with oxaliplatin-based combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 16 DNA repair genes were determined using a PCR–RFLP assay.

Results

During the median follow-up duration of 15.9 (2.1–53.0) months, 67 (71.3%) progressions and 29 (30.9%) deaths were observed. Among the 60 patients assessable for response, response to the oxaliplatin-based regimens was found in 27 (45%) patients (9 CR and 18 PR). In a logistic regression analysis adjusted to age, sex, primary site, disease status, and regimen, the POLR2C rs4937 and MSH2 rs3732183 polymorphisms were statistically associated with the response to the oxaliplatin-based chemotherapy. A multivariate survival analysis showed that the TT genotype of the MGMT (rs1625649) ?535G>T polymorphism was found to correlate with a worse progression-free survival (PFS) than the combined GG + GT genotypes (HR = 3.137; 95% CI = 1.423–6.914; P = 0.005), which was also observed among the 60 evaluable patients (HR = 2.653; 95% CI = 1.101–6.392; P = 0.030) For the clinical parameters, curative resection was the most significant prognostic factor in a Cox model for PFS and overall survival (HR = 0.229 and 0.205; P < 0.001 and 0.001, respectively).

Conclusion

The MGMT ?535G>T polymorphism (rs1625649) was found to be correlated with PFS in patients with advanced colorectal cancer treated with oxaliplatin-based chemotherapy.     

Associations between persistent organic pollutants and metabolic syndrome in morbidly obese individuals

Background and aims

Persons with “metabolically healthy” obesity may develop cardiometabolic complications at a lower rate than equally obese persons with evident metabolic syndrome. Even morbidly obese individuals vary in risk profile. Persistent organic pollutants (POPs) are widespread environmental chemicals that impair metabolic homeostasis. We explored whether prevalence of metabolic syndrome in morbidly obese individuals is associated with serum concentrations of POPs.

Answering Orientation Questions and Following Single-Step Verbal Commands: Effect on Aspiration Status

In the acute-care setting patients with altered mental status as a result of such diverse etiologies as stroke, traumatic brain injury, degenerative neurologic impairments, dementia, or alcohol/drug abuse are routinely referred for dysphagia testing. A protocol for dysphagia testing was developed that began with verbal stimuli to determine patient orientation status and ability to follow single-step verbal commands. Although unknown, it would be beneficial to ascertain if this information on mental status was predictive of aspiration risk. The purpose of this investigation was to determine if there was a difference in odds for aspiration based upon correctly answering specific orientation questions, i.e., 1. What is your name? 2. Where are you right now? and 3. What year is it?, and following specific single-step verbal commands, i.e., 1. Open your mouth. 2. Stick out your tongue. and 3. Smile. In a consecutive retrospective manner data from 4070 referred patients accrued between 1 December 1999 and 1 January 2007 were analyzed. The odds of liquid aspiration were 31% greater for patients not oriented to person, place, and time (odds ratio [OR] = 1.305, 95% CI = 1.134–1.501). The odds of liquid aspiration (OR = 1.566, 95% CI = 1.307–1.876), puree aspiration (OR = 1.484, 95% CI = 1.202–1.831), and being deemed unsafe for any oral intake (OR = 1.688, 95% CI = 1.387–2.054) were, respectively, 57, 48, and 69% greater for patients unable to follow single-step verbal commands. Being able to answer orientation questions and follow single-step verbal commands provides information on odds of aspiration for liquid and puree food consistencies as well as overall eating status prior to dysphagia testing. Knowledge of potential increased odds of aspiration allows for individualization of dysphagia testing thereby optimizing swallowing success.     

A longitudinal assessment of change in marijuana use with other substance use problems

Background: Despite increasing marijuana use rates over the past decade, the longitudinal association between marijuana use and other substance use problems among adults is unclear. Objectives: To examine associations of self-reported changes in marijuana use and marijuana use frequency with self-reported other substance use problems over a 12-month period. Methods: Two waves (W1 and W2) of the Population Assessment of Tobacco and Health Study provided data. The study sample (N = 26,204, female = 13,261; male = 12,943, aged 18+) included W1-W2 never marijuana users, W1-W2 ex-users (used prior to 12 months of W1), and those who either quit, initiated, resumed, or continued marijuana use between W1 and W2. We used multinomial and binary logistic regression analyses. Results: The past-year marijuana use rate was 12.4% at W2. A quarter of W1 users quit using marijuana in the 12 months preceding their W2 interview, and one-third of all the W2 users were new/resumed users since W1. Compared to W1-W2 ex-users, W2 quitters were more likely to report alcohol use problems and tobacco addiction at W2. Compared to quitters, continued users were more likely to report alcohol use problems (RRR = 1.62, 95% CI = 1.27–2.07) and tobacco addiction (RRR = 1.37, 95% CI = 1.11–1.69). New users (RRR = 2.05, 95% CI = 1.12–3.74), resumed users (RRR = 2.69, 95% CI = 1.55–4.70), and continued users (RRR = 3.40, 95% CI = 2.08–5.55) reported more drug use problems. Compared to less frequent marijuana users, frequent users had greater odds of reporting alcohol use problems (RRR = 1.44, 95% CI = 1.21–1.72) and drug use problems (OR = 1.63, 95% CI = 1.19–2.23). Conclusions: Given increased prevalence of marijuana use, polysubstance use problems among marijuana users should be assessed.     

Low blood pressure levels for fall injuries in older adults: the Health,Aging and Body Composition Study

Fall injuries cause morbidity and mortality in older adults. We assessed if low blood pressure (BP) is associated with fall injuries, including sensitivity analyses stratified by antihypertensive medications, in community-dwelling adults from the Health, Aging and Body Composition Study (N = 1819; age 76.6 ± 2.9 years; 53% women; 37% black). Incident fall injuries (N = 570 in 3.8 ± 2.4 years) were the first Medicare claims event from clinic visit (7/00–6/01) to 12/31/08 with an ICD-9 fall code and non-fracture injury code, or fracture code with/without a fall code. Participants without fall injuries (N = 1249) were censored over 6.9 ± 2.1 years. Cox regression models for fall injuries with clinically relevant systolic BP (SBP; ≤ 120, ≤ 130, ≤ 140, > 150 mmHg) and diastolic BP (DBP; ≤ 60, ≤ 70, ≤ 80, > 90 mmHg) were adjusted for demographics, body mass index, lifestyle factors, comorbidity, and number and type of medications. Participants with versus without fall injuries had lower DBP (70.5 ± 11.2 vs. 71.8 ± 10.7 mmHg) and used more medications (3.8 ± 2.9 vs. 3.3 ± 2.7); all P < 0.01. In adjusted Cox regression, fall injury risk was increased for DBP ≤ 60 mmHg (HR = 1.25; 95% CI 1.02–1.53) and borderline for DBP ≤ 70 mmHg (HR = 1.16; 95% CI 0.98–1.37), but was attenuated by adjustment for number of medications (HR = 1.22; 95% CI 0.99–1.49 and HR = 1.12; 95% CI 0.95–1.32, respectively). Stratifying by antihypertensive medication, DBP ≤ 60 mmHg increased fall injury risk only among those without use (HR = 1.39; 95% CI 1.02–1.90). SBP was not associated with fall injury risk. Number of medications or underlying poor health may account for associations of low DBP and fall injuries.     

At least partial hematological response after first cycle of treatment predicts organ response and long-term survival for patients with AL amyloidosis receiving bortezomib-based treatment

AL amyloidosis is a rare plasma cell dyscrasia characterized by multi-organ involvement and poor prognosis. We retrospectively evaluated the organ response (OR) and long-term survival of newly diagnosed AL amyloidosis patients who received first-line bortezomib-containing induction therapy, aiming to identify the clinical indication of a 50% reduction in the difference between involved and uninvolved free light chains (dFLC) after first cycle of treatment. Among the 89 patients included, 78.7% had cardiac involvement and 42.7% were diagnosed with 2004 Mayo stage III disease, while 75.3% of patients achieved a hematological response, including 37.1% with complete response and a median response time of 1 month. Cardiac and renal responses were observed in 44.3 and 53.1% of patients, respectively. Sixty-one (68.5%) patients achieved at least 50% reduction in dFLC after the first cycle of therapy. After a median follow-up duration of 12 months, the estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 61.3 and 61.7% respectively. At least 50% reduction in dFLC after the first cycle of therapy was predictive of achieving an OR (p = 0.002), as well as superior PFS (HR = 0.119; 95% CI = 0.045–0.313; p < 0.001) and OS (HR = 0.206; 95% CI = 0.078–0.541; p = 0.001). Additionally, the median PFS and OS were not reached for patients with rapid reduction of dFLC. These results demonstrated that early reduction of dFLC after the first cycle of treatment is predictive of achieving an OR and long-term survival in AL patients receiving bortezomib.     

A Functional Aryl Hydrocarbon Receptor Genetic Variant,Alone and in Combination with Parental Exposure,is a Risk Factor for Congenital Heart Disease

Recent experimental studies showed that ablation of the aryl hydrocarbon receptor (AhR) as well as its activation by exogenous ligands disrupt the molecular networks involved in heart formation and function, leading to congenital heart disease (CHD). However, no evidence is available about the role of AhR in humans. We assessed the prevalence of a functional AhR genetic variant (p.Arg554Lys) in CHD patients as well as its joint effects with parental exposure. A total of 128 CHD patients (76 males; age 6.2 ± 6.7 years) and 274 controls (160 males; age at birth) were genotyped for the AhR polymorphism by using the TaqMan^® Drug Metabolism Genotyping assay. Both case and control parents completed a structured questionnaire on demographic, lifestyle and preconception exposures. Genotype (p = 0.001) and allele (p < 0.0001) distributions of AhR p.Arg554Lys differed significantly between patients and controls. A significant elevated CHD risk was found under dominant (OR = 2.9, 95% CI 1.9–4.6, p < 0.0001) and additive genetic models (OR = 6.2, 95% CI 2–19, p = 0.001). There was a significant interaction between 554-Lys allele and paternal smoking exposure (OR_smoking = 1.6, 95% CI = 0.9–2.9; OR_allele = 2.6, 95% CI = 1.3–5; OR_interaction = 4.9, 95% CI = 2.4–9.9, p _interaction < 0.0001). Additionally, 554-Lys allele exacerbated the effect of maternal periconceptional exposure (OR_exposure = 1.6, 95% CI = 0.8–3; OR_allele = 2.6, 95% CI = 1.5–4.5; OR_interaction = 5.7; 95% CI = 2.6–12, p _interaction < 0.0001). Our findings showed that the AhR p.Arg554Lys polymorphism, alone and in combination with parental exposures, is associated with the CHD risk, highlighting the significant role of AhR in the cardiovascular development.