Etiologic discussion and clinical relevance of thyroid ultrasonography in subclinical hypothyroidism. A retrospective study in 1845 patients

Background

Acquired subclinical hypothyroidism in adulthood is mainly due to autoimmune thyroiditis. In the absence of a goiter or a palpable firm thyroid, measurement of thyroid antibodies can improve the diagnosis. Whether thyroid antibodies are detected or not, what might be the clinical relevance of ultrasonography in this setting?

Methods

We studied 1845 cases of subclinical hypothyroidism in adults recruited for symptoms indicative of hypothyroidism or thyroid pathology. All patients were screened for thyroid antibodies and underwent an ultrasonographic thyroid examination.

Localisation

Multicentric retrospective study.

Results

Chronic autoimmune thyroiditis was confirmed in 70% of patients. Thyroid antibodies were undetectable in 30% of patients. In all patients, thyroid ultrasound facilitated measurement of the thyroid volume and detection of non-palpable nodules and therefore allowed biopsy. In patients negative for thyroid antibodies, ultrasonography suggested autoimmune thyroiditis in 31% of cases. Ultrasonography did not contribute to diagnosis in a large number of patients without nodules and in case of normal echostructure. The strategy of thyroid hormone replacement therapy was not influenced by ultrasonographic data. Thyroid biopsies detected smears suspected to be cancerous in 10 patients (4%). Cancer was confirmed in nine patients after surgery. Ultrasonography displayed suspicious aspects in six patients.

Conclusion

In subclinical hypothyroidism, thyroid ultrasonography is not required for the diagnosis of autoimmune thyroiditis but is useful for patients with abnormal thyroid palpation and allows detection of non-palpable thyroid nodules. For patients that were negative for thyroid antibodies, thyroid ultrasonography can improve diagnosis for some patients, allowing detection of autoimmune thyroiditis.     

Potential celiac disease in type 1 diabetes: a multicenter study

Aims

To describe the prevalence of potential celiac disease (pot-CD) in young patients with type 1 diabetes mellitus (T1DM) and characterize their clinical features.

Methods

This cross-sectional multicenter study involved 8717 T1DM patients from 31 Italian centers. Information was collected on the total number of T1DM patients, CD patients and pot-CD patients. The following data were collected on pot-CD patients: gender, age at T1DM diagnosis, age at the first CD serological positivity, presence of CD-related symptoms, presence of other autoimmune disorders and treatment with gluten free diet (GFD). One thousand-three-hundred-sixty-one patients who were positive for CD serology were the control group.

Results

CD serological positivity was found in 7.2% T1DM patients. Prevalence of pot-CD was 12.2% (n = 77) among CD positive patients: symptoms were present in 12/77; a third autoimmune disorder was found in 15 patients. Prevalence of pot-CD in the control population was 8.4% (n = 114; p = 0.005). No difference was found with regard to clinical features. Only few symptomatic patients were on GFD both in T1DM and control patients.

Conclusions

A higher prevalence of pot-CD was found in T1DM patients, that may be ascribed to the routine screening, although the influence of genetic factors cannot be excluded.     

Comparison of 5 methods of QT interval measurements on electrocardiograms from a thorough QT/QTc study: effect on assay sensitivity and categorical outliers

Introduction

We studied moxifloxacin-induced QT prolongation and proportion of categorical QTc outliers when 5 methods of QT measurement were used to analyze electrocardiograms (ECGs) from a thorough QT study.

Methods

QT interval was measured by the threshold, tangent, superimposed median beat, automated global median beat, and longest QT methods in a central ECG laboratory in 2730 digital ECGs from 39 subjects during placebo and moxifloxacin treatment.

Results

All 5 methods were able to demonstrate statistically significant moxifloxacin-induced QTcF prolongation. However, lower bound of 95% 1-sided confidence interval of QTcF prolongation did not exceed 5 milliseconds with the longest QT method. More QTcF outliers were observed with the longest QT and tangent methods, whereas the other 3 methods were comparable. QTcF values greater than 500 milliseconds were observed only with moxifloxacin by the tangent method, and with moxifloxacin and placebo by the longest QT method.

Conclusion

The method of QT measurement must be considered when interpreting individual thorough QT/QTc studies.     

Developing a shortened measure of negative thinking for use in patients with heart failure

Objective

Negative thinking is a target for treatment of depressive symptoms in patients with heart failure (HF). A brief instrument is needed to measure negative thinking in these patients. The study objective was to shorten the Crandell Cognitions Inventory (CCI) for use in patients with HF.

Methods

Baseline data from outpatients with HF (N = 179, 30% were female, age 60 ± 13 years) were used to evaluate psychometrics of the CCI. Internal consistency reliability was measured with Cronbach’s alpha construct validity with hypothesis testing. Principal components analysis was used in shortening. A separate sample of hospitalized patients with HF (N = 77, 49% were female, age 66 ± 11years) was used to validate the shortened CCI (CCI-SF).

Results

The CCI showed evidence of reliability and validity, but there was item redundancy in outpatients with HF. The 12-item CCI-SF showed good evidence of reliability and validity in inpatients with HF.

Conclusion

The results support the reliability and validity of the CCI-SF to measure negative thinking in hospitalized patients with HF.     

TRACKING OF INDIUM-111-OXINE LABELLED LYMPHOCYTES IN AUTOIMMUNE THYROID DISEASE

Peripheral lymphocytes (approximately 10(8)) from 4 subjects affected by autoimmune thyroid disease (2 Hashimoto's thyroiditis, 1 primary myxoedema, 1 Graves' disease) and 4 normal subjects were labelled in vitro with 40 microCi of indium-111-oxine and, following autologous injection, the distribution of the cells in the body was investigated by gamma camera imaging. Lymphocytes in the thyroid were observed 24 h after injection in both patients with Hashimoto's thyroiditis and in the patient with primary myxoedema, but not in the patient with Graves' disease or in any of the controls. To our knowledge, this is the first report using this method to try and demonstrate lymphocytes in the thyroid gland, and supports the concept that cell-mediated immunity may be playing an important role in the pathogenesis of Hashimoto's thyroiditis and primary myxoedema.     

A polymorphism within the vitamin D-binding protein gene is associated with Graves' disease but not with Hashimoto's thyroiditis

Graves' disease and Hashimoto's thyroiditis are common autoimmune thyroid disorders. Experimentally, 1,25(OH)(2) D(3) prevents Hashimoto's thyroiditis. Vitamin D serum levels in Graves' disease were found to be significantly lower than in nonautoimmune hyperthyroidism. The polymorphic vitamin D-binding protein (DBP) greatly facilitates vitamin D actions, and DBP alleles differ regarding their affinity for 1,25(OH)(2) D(3). Therefore, we investigated polymorphisms of the DBP gene for an association with thyroid autoimmunity. Families with an offspring affected by Graves' disease (95 pedigrees) or by Hashimoto's thyroiditis (92 pedigrees) encompassing 561 individuals of Caucasian origin were genotyped for three DBP polymorphisms [(TAAA)(N) in intron 8; StyI; and HaeIII in exon 11]. Indirect haplotyping and (extended) transmission disequilibrium testing were performed. There was a significant transmission disequilibrium of the intron 8 polymorphism in patients with Graves' disease (P < 0.03) but not of the exon 11 polymorphism. In contrast, neither the intron 8 nor the exon 11 polymorphism was associated with Hashimoto's thyroiditis. Maternal and paternal transmission as well as allele frequencies in DQ2(+) and DQ2(-) patients did not differ in either disease. Therefore, allelic variants of the DBP gene confer susceptibility to Graves' disease but not to Hashimoto's thyroiditis in our population. These findings support a role of the vitamin D endocrine system in thyroid autoimmunity.     

Patient awareness of the risks for heart disease posed by air pollution

Background

The purpose of this study was to assess patient awareness of the coronary heart disease (CHD) risks posed by air pollution.

Methods

We distributed a questionnaire to 500 patients at a University of Michigan cardiology clinic.

Results

More than half of patients (n = 264, 53%) did not believe that air pollution was “proven” or “likely” to cause CHD, whereas a similar percentage (n = 284, 57%) were not previously aware of its association with CHD. Most patients (n = 459, 92%) reported that a health care provider had not informed them of the potential CHD risks posed by air pollution nor discussed ways to lower their exposure (n = 471, 94%).

Conclusion

Patients were mostly unaware of the CHD risks posed by air pollution. These findings suggest that a serious knowledge gap exists among at-risk patients regarding this important CHD risk factor and support the need for educational efforts targeting patients and health care providers alike.     

Production of 8-OHdG and cytochrome c by cultured human mononuclear cells in patients with autoimmune thyroid disease

Since oxidative stress is related to autoimmune thyroid disease, we studied the production of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cytochrome c by culture of mononuclear cells from patients with Graves' disease and Hashimoto's thyroiditis. In patients with untreated Graves' disease, 8-OHdG and cytochrome c levels in culture supernatant of mononuclear cells were significantly higher than those of healthy control subjects, while the cytochrome c levels were significantly higher in patients with untreated Graves' disease and Hashimoto's thyroiditis than those of control subjects. Significant correlations between 8-OHdG and FT4, and cytochrome c were found. These results indicated that thyroid function has a potent influence on oxidative stress.     

Reliability of reporting left ventricular systolic function by echocardiography: a systematic review of 3 methods

Background

An accurate assessment of left ventricular (LV) systolic function is of central importance to the diagnosis and management of heart failure. Echocardiography is currently the technique most widely used for this purpose.

Methods

A systematic review was performed of the evidence for the accuracy of 3 echocardiographic methods—Simpson's rule, wall motion index (WMI), and subjective visual assessment—compared with radionuclide or contrast ventriculography for the assessment of LV ejection fraction (LVEF).

Results

Twenty-five studies were identified in which data on agreement between echocardiography and reference methods were obtainable. A further 18 studies provided correlation data alone. For Simpson's rule, Bland-Altman limits of agreement (95% CI) ranged from LVEF ±7% to ±25% (median ±18%); for WMI ±13% to ±20% (median ±16%); and for subjective visual assessment ±16% to ±24% (median ±19%). Subject echogenicity, the nature of underlying disease, and the use of additional imaging technology, including secondary harmonic imaging and contrast agents, is likely to influence the accuracy of different methods. No method appears to systematically under- or overestimate LVEF to any major extent.

Conclusion

These findings have important implications for the investigation of heart failure and for the practice and reporting of echocardiography.     

Thresholds in the relationship between mortality and left ventricular hypertrophy defined by electrocardiography

Background

Electrocardiographic criteria for the diagnosis of left ventricular hypertrophy in current use were defined using autopsy results or echocardiography; criteria defined using mortality might be more clinically meaningful.

Methods

Using data from Third National Health and Nutrition Examination Survey (NHANES III), we selected electrocardiographic measures that best differentiated those surviving at 5 years from those who did not. We identified voltage thresholds using regression techniques and then compared survival for subjects above and below the thresholds.

Results

Cornell voltage, Cornell product, and Novacode estimate of left ventricular mass index were discriminative for mortality and had identifiable thresholds present in their relationships with mortality. Independent of systolic blood pressure, there were significant associations with 5-year mortality for Novacode index above threshold; hazard ratios were 1.58 for women and 1.27 for men, and for 5-year cardiovascular mortality were 1.78 for women and 2.34 for men.

Conclusions

Electrocardiographic criteria for left ventricular hypertrophy validated against mortality might be clinically useful.     

Pain and quality of life with chronic obstructive pulmonary disease

Background

Pain as a symptom may be underrecognized in patients with chronic obstructive pulmonary disease (COPD).

Objective

The aim of this study is to explore the prevalence and intensity of pain, its location, how demographic and clinical variables may be related to pain, and how pain is associated with quality of life (QOL).

Methods

In this cross-sectional study, 154 patients with COPD answered the Brief Pain Inventory, Respiratory Quality of Life Questionnaire, and Quality of Life Scale, and performed spirometry.

Results

Seventy-two percent of the patients indicated the location of pain on a body diagram. Lower lung function, higher score of pain intensity, and pain interference were associated with lower disease QOL. A higher score of pain interference was associated with lower global QOL. When controlling for disease QOL in the equation of global QOL, pain interference was no longer significant.

Conclusion

The experience of pain is related to disease QOL in patients with COPD.     

Attribution of functional limitation to cancer decreases in the year following breast cancer diagnosis in older patients

Objectives

To examine the prevalence of self-reported functional limitations in a breast cancer population, identify whether these reported limitations are attributed to breast cancer versus other coexisting illnesses, and examine how this attribution changes over time from early in treatment to 9 months later.

Design

Longitudinal, observational study.

Setting

Community dwelling adults in Detroit metropolitan area.

Participants

2033 participants (1011 breast cancer patients, 1022 controls) aged 40-84 years.

Measurements

Participants were asked about each of 23 possible coexisting illnesses in addition to breast cancer and whether or not each illness, including breast cancer, caused any activity limitation.

Results

Of the 933 cancer patients who completed both baseline and follow-up evaluations, 45% were aged 65 years and older. At baseline, 56% of patients 65 years and older reported functional limitation compared with 50% of patients younger than 65 years (p = 0.005). Of those patients who reported limitation at baseline, 59% of older patients and 78% of younger patients attributed their limitation to breast cancer (p < 0.001). At follow-up, 53% of older and 37% of younger patients reported functional limitation (p < 0.001), with 27% of older patients compared with 57% of younger patients (p < 0.001) attributing limitation to breast cancer.

Conclusion

Self-reported functional limitations are common 3 months after breast cancer diagnosis, being attributed primarily to breast cancer. By 1 year after diagnosis, much of the limitation due to breast cancer resolves. Older women are less likely to have resolution of their limitations, which are most commonly due to other coexisting illnesses.     

Depression and perceptions about heart failure predict quality of life in patients with advanced heart failure

Background

Mood is an independent predictor of mortality and quality of life (QoL) for people with heart failure. However, the underlying belief systems involved in mood are unknown.

Objective

We sought to identify psychological and clinical variables predicting mood and QoL for people diagnosed with heart failure (HF).

Methods

One hundred and forty-six HF patients were assessed with standardized measures, to determine their beliefs about HF, coping styles, mood, and QoL.

Results

Patients with more negative beliefs about the consequences of HF and with less perceived control over symptoms showed maladaptive coping styles such as denial and behavioral disengagement, and more severe levels of depression and anxiety. Depression also independently predicted QoL outcomes.

Conclusions

Anxious and depressed patients have more negative beliefs about HF, leading to negative coping behaviors and poor QoL. Our evidence suggests that changing negative beliefs may improve the psychological well-being and QoL of patients, irrespective of disease severity.     

Elevated serum chemerin concentrations are associated with renal dysfunction in type 2 diabetic patients

Aim

Chemerin, a new adipocytokine, has been suggested to be linked to obesity-induced insulin resistance and type 2 diabetes. The association of plasma chemerin levels with diabetic nephropathy, however, is unknown. Therefore, this study aims to determine whether plasma chemerin levels are associated with renal function in type 2 diabetic patients.

Methods

A total of 116 type 2 diabetic patients and 38 healthy subjects were enrolled in this study. Serum levels of chemerin were measured by enzyme-linked immunosorbent assay.

Results

Serum chemerin was significantly elevated in type 2 diabetic patients with macroalbuminuria compared with control subjects and diabetic patients with normoalbuminuria and microalbuminuria. No differences were found in the level of serum chemerin between diabetic patients with normoalbuminuria and microalbuminuria and control subjects. Serum chemerin was positively correlated with age, body mass index (BMI), systolic blood pressure (SBP), C-reactive protein (CRP), blood urea nitrogen (BUN), serum creatinine and serum triglycerides, and negatively correlated with creatinine clearance Stepwise regression analysis showed that creatinine clearance and serum creatinine remained significantly associated with serum chemerin.

Conclusion

Serum chemerin levels are strongly associated with renal function in diabetic patients.     

Enhanced detection of patent foramen ovale by systematic transthoracic saline contrast echocardiography

Objective

We aimed to evaluate the effectiveness of transthoracic saline contrast echocardiography (TSCE) in detecting patent foramen ovale (PFO).

Background

Transesophageal echocardiography (TEE) is semi-invasive and not ideal for PFO screening.

Methods

112 patients (48 males, 46 ± 14 years) with suspected PFO received intravenous agitated-saline contrast at rest and stress (strain and release phases of Valsalva maneuver and coughing). The presence of interatrial shunting was defined as > 5 bubbles appearing in the left heart within 3 cardiac cycles. The stage of the maneuver at which interatrial shunting occurred was recorded. The TSCE findings were validated by TEE.

Results

TEE identified PFO in 45% of patients. The sensitivities of TSCE in detecting PFO at rest, during strain and release of Valsalva maneuver, and coughing were 12.0%, 38.0%, 80.0% and 94.0% respectively (each p < 0.05 when compared to previous stage). Specificities were similar and > 95% for all stages. Moreover, the release phase of the maneuver improved the diagnostic accuracy [defined as (number of true positives + true negatives) divided by total in sample] with incremental value over the preceding strain phase (89.2 vs. 70.5%, p < 0.001).

Conclusions

Patent foramen ovale can be identified confidently with proper conduct of the Valsalva maneuver during the transthoracic saline contrast echocardiography.     

Asthma in US Seniors: Part 2. Treatment. Seeing Through the Glass Darkly

Background

We sought to identify the best evidence for treatment of asthmatic patients aged 65 years or more.

Methods

We used computer-assisted searches to identify randomized, controlled trials for asthma in the elderly that were published in English between 1950 and 2008.

Results

Small trials of an inhaled corticosteroid versus a leukotriene antagonist and an oral beta₂-agonist versus placebo compose the controlled trial data on asthma therapy in seniors. Epidemiologic evidence suggests that the side effects of corticosteroids and beta-agonists may be more common in the elderly than in younger populations.

Conclusion

Seniors with asthma or comorbid conditions that are common in the elderly have been systematically excluded from asthma treatment trials. There is no compelling evidence to demonstrate the superiority of any pharmacologic therapy in these asthmatic patients. Evaluation of response to asthma treatment in clinical trials remains primarily symptom-based when symptoms have been shown to underestimate the severity of disease in seniors.     

Exercise at ventilatory threshold aggravates left ventricular remodeling in patients with extensive anterior acute myocardial infarction

Background

The effects of physical training on ventricular remodeling after extensive anterior acute myocardial infarction (AMI) have not yet been defined. This randomized controlled study examines whether exercise aggravates left ventricular (LV) remodeling in patients with extensive anterior AMI.

Methods

Forty-eight consecutive patients with a first extensive anterior AMI and an LV ejection fraction (EF) of <45% assessed with left ventriculography (LVG) within 3 days of onset were randomly allocated to a training group (n = 24) or a control group (n = 24). Exercise intensity was determined by the heart rate of each patient at ventilatory threshold (VT). Three weeks after onset, a second LVG was performed, followed by a supervised exercise program at VT for 12 weeks. The LVG was reassessed after the exercise program. We then calculated the global LV volume (end-diastolic volume index [EDVI], end-systolic volume index [ESVI]) and systolic expansion volume index (SEVI), a new parameter for measuring the infarction site expansion at the end-systolic phase.

Results

Both EDVI and ESVI significantly decreased in the control group from 1 to 4 months after onset (91.2 ± 26.1 to 83.3 ± 24.0 mL/m², P <.05; 52.4 ± 22.5 to 45.7 ± 18.8mL/m², P <.01, respectively), but not in the exercise group. The SEVI also significantly decreased in the control group from 1 to 4 months (33.1 ± 16.9 to 25.7 ± 13.9 mL/m², P <.05), but not in the training group (34.2 ± 12.9 to 36.5 ± 15.5 mL/m², P = not significant).

Conclusion

Exercise while healing in patients with extensive anterior AMI, even at the VT level, induces LV enlargement and thus might aggravate LV remodeling. Therefore, in these patients, clinicians should consider withholding exercise training for at least 8 weeks, versus the 3-week period used in this trial.     

Nasosinusal and cervical sarcoidosis: a case series of three patients and literature review

Introduction

Sinonasal sarcoidosis is difficult to treat. Infliximab seems to be useful in the treatment of sarcoidosis of the upper respiratory tract.

Case series

We report three cases of sinonasal sarcoidosis in two women of 36 and 42-year-old and in a 64-year-old man. Resistance or dependence to corticosteroids and absence of efficacy of methotrexate therapy in one patient led to administer anti-TNFα therapy with infliximab. Outcome was favourable on sarcoid lesions but treatment was discontinued because of infectious complications and worsening of sarcoid chest involvement.

Conclusion

This case series suggests that infliximab might be useful for the treatment of sarcoidosis with sinonasal involvement.     

Danish multicenter randomized study on fibrinolytic therapy versus acute coronary angioplasty in acute myocardial infarction: rationale and design of the DANish trial in Acute Myocardial Infarction-2 (DANAMI-2)

Background

Randomized trials have indicated that primary coronary angioplasty performed in patients admitted directly to highly-experienced angioplasty centers offers certain advantages over intravenous fibrinolytic therapy. However, the large majority of patients with acute myocardial infarction are submitted to hospitals without a catheterization laboratory. This means that additional transportation will be necessary for many patients if a strategy of acute coronary angioplasty is to be introduced as routine treatment. The delay of treatment caused by transportation might negate (part of) the benefits of primary angioplasty compared to fibrinolytic therapy given immediately at the local hospital.

Study design

The DANish trial in Acute Myocardial Infarction-2 (DANAMI-2) is the first large-scale study to clarify, in a whole community, which of the 2 treatment strategies is best. A total of 1900 patients with ST-elevation myocardial infarction are to be randomized: 800 patients will be admitted to invasive hospitals and 1100 patients will be admitted to referral hospitals. Half of the 1100 patients admitted to referral hospitals will immediately be transferred to an invasive center to be treated with primary angioplasty.

Implications

If acute transfer from a local hospital to an angioplasty center is the superior strategy, primary angioplasty should be offered to all patients as routine treatment on a community basis.