Appendectomy is followed by increased risk of Crohn's disease

BACKGROUND & AIMS: Appendectomy is associated with a low risk of subsequent ulcerative colitis. This study analyzes the risk of Crohn's disease after appendectomy. METHODS: We followed-up 212,218 patients with appendectomy before age 50 years and a cohort of matched controls, identified from the Swedish Inpatient Register and the nationwide Census, for any subsequent diagnosis of Crohn's disease. RESULTS: An increased risk of Crohn's disease was found for more than 20 years after appendectomy, with incidence rate ratio 2.11 (95% confidence interval [CI], 1.21-3.79) after perforated appendicitis, 1.85 (95% CI, 1.10-3.18) after nonspecific abdominal pain, 2.15 (95% CI, 1.25-3.80) after mesenteric lymphadenitis, 2.52 (95% CI, 1.43-4.63) after other diagnoses. After nonperforated appendicitis, there was an increased risk among women but not among men (incidence rate ratio 1.37; 95% CI, 1.03-1.85, respectively, 0.89, 95% CI, 0.64-1.24). Patients operated on before age 10 years had a low risk (incidence rate ratio 0.48, 95% CI, 0.23-0.97). Crohn's disease patients with a history of perforated appendicitis had a worse prognosis. CONCLUSIONS: Appendectomy is associated with an increased risk of Crohn's disease that is dependent on the patient's sex, age, and the diagnosis at operation. The pattern of associations suggests a biologic cause.     

Does surgical removal of mucosal associated lymphoid tissue protect against adult coeliac disease? A case controlled study

BACKGROUND AND AIMS: Surgical resection of mucosa associated lymphoid tissue has been suggested as a protective mechanism against the development of inflammatory bowel disease. Mucosal T-cell activity plays a pivotal role in coeliac disease pathogenesis. We aimed to determine if the development of adult coeliac disease is influenced by appendectomy or tonsillectomy. METHODOLOGY: Three hundred patients over 16 years of age with biopsy proven coeliac disease were identified from two hospital databases in South Yorkshire. From these databases, appendectomy and tonsillectomy status was determined and compared with 1033 coeliac disease antibody-negative controls (volunteers recruited from general practice). Logistic regression was performed to correct for the age differences between the two groups; cross-table analysis was performed. RESULTS: Thirteen percent of coeliac disease patients and 12.2% of controls had previous appendectomy (P = 0.71; odds ratio 1.08; 95% confidence interval 0.72-1.62). 20.7% of coeliac disease patients and 24.5% of the controls had previous tonsillectomy (P = 0.17; odds ratio 0.80; 95% confidence interval 0.59-1.10). CONCLUSIONS: No significance was demonstrated in either the appendectomy or tonsillectomy group. Surgical removal of mucosal associated lymphoid tissue does not appear to prevent the development of adult onset coeliac disease.     

Prior appendectomy and the phenotype and course of Crohn＇s disease

AIM: To determine whether prior appendectomy modifies the phenotype and severity of Crohn's disease. METHODS: Appendectomy status and smoking habits were specified by direct interview in 2838 patients consecutively seen between 1995 and 2004. Occurrence of complications and therapeutic needs were reviewed retrospectively. Additionally, annual disease activity was assessed prospectively between 1995 and 2004 in patients who had not had ileocecal resection and of a matched control group. RESULTS: Compared to 1770 non-appendectomized patients, appendectomized patients more than 5 years before Crohn's disease diagnosis (n=716) were more often females, smokers, with ileal disease. Cox regression showed that prior appendectomy was positively related to the risk of intestinal stricture (adjusted hazard ratio, 1.24; 95% confidence interval, 1.13 to 1.36; P=0.02) and inversely related to the risk of perianal fistulization (adjusted hazard ratio, 0.75; 95% confidence interval, 0.68 to 0.83; P=0.002). No difference was observed between the two groups regarding the therapeutic needs, except for an increased risk of surgery in appendectomized patients, attributable to the increased prevalence of ileal disease. Between 1995 and 2004, Crohn's disease was active during 50% of years in appendectomized patients (1318 out of 2637 patient-years) and 51% in non-appendectomized patients (1454 out of 2841 patient-years; NS). CONCLUSION: Prior appendectomy is associated with a more proximal disease and has an increased risk of stricture and a lesser risk of anal fistulization. However, the severity of the disease is unaffected.     

Acute appendicitis in the elderly patient: diagnostic problems, prognostic factors and outcomes

BACKGROUND AND AIMS: Acute appendicitis (AA) in the elderly (over 60 year-old) continues to pose diagnostic problems and carries a high morbidity and mortality rate. The aim of this article is to present our experience and outcomes and to evaluate influencing factors. METHODS: During a period of 5 years 63 patients with a definitive pathological diagnosis of AA were retrospectively analyzed. RESULTS: The primary admission diagnosis was established correctly in 44 patients (69.8%). Nineteen patients (30.1%) required further diagnostic investigations and the mean time to final diagnosis was 26 hours. For 3 patients (4.8%), the final diagnosis was established intra-operatively. The perforation rate was 31.8% (20 patients). Thirty-eight patients (63.3%) had associated co-morbidities. The overall mean duration of pre-hospitalization symptoms was 2.7 days, 2.3 days for non-perforated cases and 3.8 days for perforated AA (p=0.0025). The complication rate was 34.9% (22 patients), complications occurred in 75% of perforated appendicitis and in 16.2% of non-perforated cases (p=0.00001). Overall mortality rate was 6.3%, 15% in the perforated case group and 2.3% in the group with non-perforated appendicitis (p=0.0003). The mean hospital stay was significantly longer for cases with perforated AA (7.2 days) than non-perforated AA (5.1 days) (p=0.0056), and for patients developing complications (9.6 days) than those without complications (5.6 days) (p=0.0031). CONCLUSIONS: Advanced age adversely affects clinical diagnosis, the stage of the disease and the outcomes. Late presentation, delayed diagnosis, presence of perforation and co-morbidities are associated with a poor outcome from surgery.     

Incidence of appendicitis according to region of origin in first- and second-generation immigrants and adoptees in Sweden. A cohort follow-up study

Background. Geographic variations in incidence of appendicitis and proportion of perforations suggest environmental or genetic etiological factors. We study incidence of appendicitis and proportion of perforations according to geographical origin in immigrants and international adoptees in Sweden. Methods. A cohort of 11,557,566 Swedish residents – 277,104 first- and 377,773 second-generation immigrants and 57,304 adoptees – was followed from 1988 till 2010. Differences in proportion of operation for perforated appendicitis and negative appendectomy and standardized incidence ratios (SIR) of perforated and non-perforated appendicitis associated with geographic origin was analyzed. Results. High incidence rates are seen in first- and second-generation immigrants from South America for perforated (SIR 1.58 and 1.81, respectively) and non-perforated appendicitis (SIR 1.18 and 1.22, respectively), and in adoptees from South America for non-perforated appendicitis (SIR 1.07). Low incidence rates are seen for perforated appendicitis in first-generation immigrants and adoptees from Asia (SIR 0.74 and 0.56, respectively), and for non-perforated appendicitis in immigrants from Africa and Asia (SIR 0.69 and 0.76 in first-generation, 0.51 and 0.74 in second-generation, respectively) and in adoptees from Asia (SIR 0.71). A high proportion of perforated appendicitis is associated with a low incidence rate of non-perforated appendicitis but no increase in the incidence rate of perforated appendicitis. Conclusions. The association of different incidence of appendicitis with geographic origin which remains over generations and is seen in adoptees suggest genetic etiologic factors. The proportion of perforation can be high without an increased incidence rate of perforation and is therefore an imperfect indicator of quality of care.     

Coeliac disease characteristics, compliance to a gluten free diet and risk of lymphoma by subtype

Objective

Coeliac disease is associated with an increased risk of malignant lymphomas. We investigated the importance of coeliac disease characteristics and diet compliance for risk of lymphoma.

Methods

In a nested case–control design, we identified 59 patients with lymphoma and 137 matched controls from a population-based cohort of 11,650 inpatients with coeliac disease. We assessed coeliac disease characteristics at diagnosis and dietary compliance collected prospectively from medical records during follow-up.

Results

Poor compliance was not significantly associated with risk of lymphoma overall (odds ratio 1.83, 95% confidence interval 0.78–4.31) nor of lymphoma subtypes. Risk estimates differed by subtype; risk of T-cell lymphoma (odds ratio 1.01, confidence interval 0.32–3.15) or intestinal lymphoma (odds ratio 0.66, confidence interval 0.17–2.56) was unelevated, whereas there was an indication of a risk increase of B-cell lymphoma (odds ratio 4.74, confidence interval 0.89–25.3) or extraintestinal lymphoma (odds ratio 3.00, confidence interval 0.73–12.3) following poor compliance. History of weight loss (odds ratio 2.89, confidence interval 1.00–8.29) at coeliac disease diagnosis was associated with an increased risk of lymphoma when excluding tumours occurring with short latency (<3 years).

Conclusions

Compliance to a gluten-free diet did not significantly alter lymphoma risk, but a moderate effect cannot be excluded. Weight loss, a potential marker of coeliac disease severity, may be associated with lymphoma risk.     

Delayed-onset primary cytomegalovirus disease and the risk of allograft failure and mortality after kidney transplantation.

BACKGROUND: During the contemporary era of antiviral prophylaxis, the impact of delayed-onset primary cytomegalovirus (CMV) disease on the outcome of kidney transplantation is not known. We evaluated the incidence, clinical features, risk factors, and outcomes of CMV disease among high-risk kidney transplant recipients. METHODS: The medical records of CMV-seronegative recipients of kidney transplants from CMV-seropositive donors were reviewed. Cox proportional hazards regression was used to identify factors associated with CMV disease and to assess its impact on allograft loss and mortality. RESULTS: None of the 176 CMV-seronegative recipients of kidney transplants from CMV-seropositive donors developed breakthrough CMV disease during a median of 92 days (interquartile range, 90-92 days) of oral ganciclovir or valganciclovir prophylaxis. Thereafter, 51 patients (29%) developed CMV disease at a median of 61 days (interquartile range, 40-143 days) after stopping antiviral prophylaxis. Early-onset bacterial and fungal infection (hazard ratio, 3.61; 95% confidence interval, 1.78-7.33; p < .001) and a Charlson comorbidity index > or =3 (hazard ratio, 2.21; 95% confidence interval, 1.15-4.22; p = .011) were associated with a higher risk of delayed-onset primary CMV disease, and postrejection antiviral prophylaxis (hazard ratio, 0.29; 95% confidence interval, 0.09-0.94; P = .039) was associated with a lower risk of such CMV disease. A time-dependent Cox regression analysis revealed a statistically significant association between tissue-invasive CMV disease and allograft loss or mortality (hazard ratio, 2.85; 95% confidence interval, 1.22-6.67; P = .016). CONCLUSION: This study of a large cohort of CMV-seronegative recipients of kidney transplants from CMV-seropositive donors illustrates the ongoing challenge of delayed-onset primary CMV disease and its impact on transplantation outcomes despite antiviral prophylaxis. Better strategies for CMV disease prevention after kidney transplantation are warranted.     

Fracture experience of patients with coeliac disease: a population based survey

BACKGROUND: While coeliac disease is now recognised as being associated with both osteoporosis and osteomalacia, the size of any increase in the risk of fracture in patients with coeliac disease compared with the general population has not been quantified. Aim: To examine the fracture experience of adults with coeliac disease compared with the general population. SUBJECTS: Patients with coeliac disease diagnosed in adulthood and born before 1950, selected from two large population based disease registers, and age and sex frequency matched controls identified from local general practitioner lists. METHODS: A four page lifestyle and general health questionnaire which included specific questions about fracture experience. RESULTS: Analysis was performed on 244 patients with coeliac disease and 161 controls, giving response rates of 89% and 72%, respectively. Eighty two (35%) coeliac patients and 53 (33%) controls reported ever having sustained one or more fractures, giving an age and sex adjusted odds ratio of 1.05 (95% confidence interval (CI) 0.68-1.62). The most common fracture site reported was the forearm or wrist, with an adjusted odds ratio of 1.21 (95% CI 0.66-2.25) for patients with coeliac disease having had a forearm or wrist fracture. Low trauma fractures were reported by 37 patients with coeliac disease (15.7%) and by 21 controls (13.8%), with an adjusted odds ratio of 1.16 (95% CI 0.65-2.10). The risk of low trauma fracture was slightly higher in coeliac men than women (odds ratio 1.28 compared with 1.12), but this difference was not statistically significant (p=0.84). After adjustment for age, sex, body mass index, and smoking status, patients with coeliac disease reported 13% more low trauma fractures than controls (odds ratio 1.13, 95% CI 0.60-2.12). There was no difference in low trauma fracture risk before and after diagnosis of coeliac disease. CONCLUSION: No overall increased fracture risk in patients with coeliac disease was observed. Although severe osteoporosis may develop in a subset of patients, as a whole patients with coeliac disease do not represent a population at particularly high risk of osteoporotic fracture and thus targeting them for osteoporosis screening and treatment is not justified.     

Cigarette smoking,appendectomy, and tonsillectomy as risk factors for the development of primary sclerosing cholangitis: a case control study

BACKGROUND AND AIMS: The strong clinical association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) suggests common factors in their pathogenesis. Smoking, previous appendectomy, and tonsillectomy have been associated with a decreased risk of developing UC. In this study, our aim was to examine these risk factors in patients with PSC with and without underlying inflammatory bowel disease (IBD). METHODS: The smoking habits and history of previous appendectomy and/or tonsillectomy of 170 patients with PSC, 41 without underlying IBD, 170 patients with UC but normal liver function tests, and 170 age and sex matched community controls were obtained by questionnaire. RESULTS: A total of 112 PSC patients (66%) had never smoked compared with 66 controls (39%). Only 12 PSC patients (7%) were current smokers versus 43 controls (25%). The resultant odds ratio of having PSC was 0.17 (95% confidence interval (CI) 0.08-0.35) among current smokers and 0.33 (95% CI 0.21-0.52) among ever (former+current) smokers. Among former smokers, the odds of having PSC were also significantly decreased (odds ratio 0.45, 95% CI 0.26-0.73; p<0.05). In the subgroup of PSC patients without IBD, only 5% were current smokers versus 26% of matched controls, and never smokers were overrepresented (68% v 37%). The rate of previous appendectomy was similar in all three study groups (14%, 12%, and 13%) but the frequency of tonsillectomy was reduced in the PSC group (21% v 31%; p=0.05). CONCLUSION: PSC, like UC, is a disease of non-smokers as the odds of having PSC was significantly decreased among current and former smokers. The association between non-smoking and PSC was independent of whether the PSC patient had underlying IBD. Previous tonsillectomy but not appendectomy may also be associated with a decreased risk of PSC but this warrants further study.     

Sex differences in coeliac disease risk: A Swedish sibling design study

Background

For unknown reasons girls are at an increased risk of coeliac disease compared to boys. However, the observed association might be confounded, since maternal coeliac disease is associated with both an increased risk of the disease in first-degree relatives as well as an increased ratio of girls to boys in offspring.

Aims

We investigate the effect of sex on the risk of coeliac disease before the age of two years using sibling design.

Methods

We identified all singleton children (n = 792,401) born between 1987 and 1993 in Sweden using the Swedish Medical Birth Registry. Coeliac disease cases (2264) were identified using the Swedish National Inpatient Registry. We applied both conventional population-based Cox regression models and sibling designs modelling the association in sex discordant siblings.

Results

We observed a conclusively increased risk of coeliac disease in girls compared to boys, using both sibling design (hazard ratio 1.67, 95% confidence interval 1.44–1.93) and conventional Cox regression analysis (hazard ratio 1.75, 95% confidence interval 1.61–1.91) that could not be explained by perinatal factors previously associated with the disease.

Conclusions

We confirm that female sex is causally associated with childhood coeliac disease, but the reasons remains unknown.     

Is the risk of adult coeliac disease causally related to cigarette exposure?

OBJECTIVE: Previous studies have shown an association between cigarette smoking and coeliac disease, but it has yet to be established whether this relationship is causal. The aim of this study was to assess causality using the Bradford Hill criteria. METHODS: A matched case-control study using a questionnaire to establish a detailed smoking history for 138 incident cases of adult coeliac disease and 276 age-matched and sex-matched controls. Subjects were categorized according to their active cigarette exposure prior to diagnosis of the matched case, and odds ratios and tests for linear trends were calculated. RESULTS: At the time of diagnosis, 10% of cases and 30% of controls were current smokers (odds ratio, 0.21 and 95% confidence interval, 0.11-0.40 for coeliac disease in current smokers versus never smokers). A biological gradient was demonstrated for total, recent and current cigarette exposure. The greatest risk reduction related to current exposure (odds ratio, 0.15, and 95% confidence interval, 0.06-0.37 for coeliac disease in current heavy smokers versus never smokers). CONCLUSIONS: This study strengthens the case for a causal relationship between smoking and coeliac disease by demonstrating a strong, temporally appropriate and dose-dependent effect, thus meeting the Bradford Hill criteria. This suggests that cigarette smoking truly protects against the development of adult coeliac disease.     

Coeliac disease: Oral ulcer prevalence, assessment of risk and association with gluten-free diet in children

AIMS: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet. METHODS: A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet. RESULTS: Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441). CONCLUSIONS: The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration.     

Appendectomy in adulthood and the risk of inflammatory bowel diseases

BACKGROUND: There is controversy as to whether appendectomy protects against the development of ulcerative colitis, but the possible impact of appendectomies performed in adulthood has not been systematically investigated. METHODS: We conducted a large case-control study based on inpatient records from Veterans Affairs hospitals in the United States for the period 1969-96. We identified 6,172 male patients with ulcerative colitis (age range 19-101 years, mean 57.4 years) and 4,498 male patients with Crohn disease (age range 18-99 years, mean 52.9 years). Each of these case patients was individually age- and race-matched to five other male veterans without recorded history of inflammatory bowel disease. We compared records of prior appendectomies in adulthood for the matched case-control sets using conditional logistic regression. RESULTS: Overall, both ulcerative colitis (odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.3-2.1) and Crohn disease (OR = 2.5, 95% CI: 2.0-3.3) were significantly and positively associated with history of appendectomy in adulthood. However, risks were not increased at intervals of 15 years or more between appendectomy and inflammatory bowel disease (ulcerative colitis: OR = 0.9, 95% CI: 0.4-2.1; Crohn disease: OR = 1.2. 95% CI: 0.5-2.5). CONCLUSIONS: The elevated risk of inflammatory bowel disease, notably Crohn disease, after appendectomy probably reflects differential diagnostic difficulties in patients with abdominal pain. Appendectomy carried out during adulthood seems not to confer protection against ulcerative colitis.     

Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death

BACKGROUND: Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. METHODS: We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and > or = 10.0 mIU/L). RESULTS: Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of > or = 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure.     

Renal function and heart failure risk in older black and white individuals: the Health, Aging, and Body Composition Study

BACKGROUND: Chronic kidney disease is a risk factor for heart failure, an association that may be particularly important in blacks who are disproportionately affected by both processes. Our objective was to determine whether the association of chronic kidney disease with incident heart failure differs between blacks and whites. METHODS: The study population comprised participants in the Health, Aging, and Body Composition Study without a diagnosis of heart failure (1124 black and 1676 white community-dwelling older persons). The main predictors were quintiles of cystatin C and creatinine concentrations and estimated glomerular filtration rate. The main outcome measure was incident heart failure. RESULTS: Over a mean 5.7 years, 200 participants developed heart failure. High concentrations of cystatin C and low estimated glomerular filtration rate were each associated with heart failure, but the magnitude was greater for blacks than for whites (cystatin C concentration: adjusted hazard ratio for quintile 5 [> or =1.18 mg/dL] vs quintile 1 [<0.84 mg/dL] was 3.0 [95% confidence interval 1.4-6.5] in blacks and 1.4 [95% confidence interval, 0.8-2.5] in whites; estimated glomerular filtration rate: adjusted hazard ratio for quintile 5 (<59.2 mL/min) vs quintile 1 (>86.7 mL/min) was 2.7 [95% confidence interval, 1.4-4.9] in blacks and 1.8 [95% confidence interval, 0.9-3.6] in whites). For cystatin C, this association was observed at more modest decrements in kidney function among blacks as well. The population attributable risk of heart failure was 47% for blacks with moderate or high concentrations of cystatin C (> or =0.94 mg/dL) (56% prevalence) but only 5% among whites (64% prevalence). CONCLUSION: The association of kidney dysfunction with heart failure appears stronger in blacks than for whites, particularly when cystatin C is used to measure kidney function.     

Subclinical thyroid dysfunction as a risk factor for cardiovascular disease

BACKGROUND: There have been few large epidemiological studies examining the association between thyroid dysfunction and cardiovascular disease. In particular, it is uncertain if subclinical hypothyroidism is a risk factor for cardiovascular disease. METHODS: Serum thyrotropin and free thyroxine concentrations were measured in 2108 archived serum samples from a 1981 community health survey in Busselton, Western Australia (Busselton Health Study). In a cross-sectional study, we examined the prevalence of coronary heart disease in subjects with and without subclinical thyroid dysfunction. In a longitudinal study, we examined the risk of cardiovascular mortality and coronary heart disease events (fatal and nonfatal combined) to the end of 2001 (excluding subjects who had coronary heart disease at baseline). RESULTS: In the cross-sectional analysis, subjects with subclinical hypothyroidism (n = 119) had a significantly higher prevalence of coronary heart disease than euthyroid subjects (n = 1906) (age- and sex-adjusted prevalence odds ratio, 1.8; 95% confidence interval, 1.0-3.1; P = .04). In the longitudinal analysis of subjects with subclinical hypothyroidism (n = 101), there were 21 cardiovascular deaths observed compared with 9.5 expected (age- and sex-adjusted hazard ratio, 1.5; 95% confidence interval, 1.0-2.4; P = .08) and 33 coronary heart disease events observed compared with 14.7 expected (age- and sex-adjusted hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P < .01). The increased risk of coronary heart disease events remained significant after further adjustment for standard cardiovascular risk factors. Subjects with subclinical hyperthyroidism (n = 39) had no adverse outcomes. CONCLUSION: Subclinical hypothyroidism may be an independent risk factor for coronary heart disease.     

Performance-based physical function and future dementia in older people

BACKGROUND: The association of physical function with progression to dementia has not been well investigated. We aimed to determine whether physical function is associated with incident dementia and Alzheimer disease (AD). METHODS: We performed a prospective cohort study of 2288 persons 65 years and older without dementia. Patients were enrolled from 1994 to 1996 and followed up through October 2003. Main outcome measures included incident dementia and AD. RESULTS: During follow-up 319 participants developed dementia (221 had AD). The age-specific incidence rate of dementia was 53.1 per 1000 person-years for participants who scored lower on a performance-based physical function test at baseline (< or = 10 points) compared with 17.4 per 1000 person-years for those who scored higher (> 10 points). A 1-point lower performance-based physical function score was associated with an increased risk of dementia (hazard ratio, 1.08; 95% confidence interval, 1.03-1.13; P < .001), an increased risk of AD (hazard ratio, 1.06; 95% confidence interval, 1.01-1.12; P = .01), and an increased rate of decline in the Cognitive Ability Screening Instrument scores (0.11 point per year; 95% confidence interval, 0.08-0.14; P < .001) after adjusting for age, sex, years of education, baseline cognitive function, APOE epsilon4 allele, family history of AD, depression, coronary heart disease, and cerebrovascular disease. CONCLUSIONS: Lower levels of physical performance were associated with an increased risk of dementia and AD. The study suggests that poor physical function may precede the onset of dementia and AD and higher levels of physical function may be associated with a delayed onset.     

Women who had appendectomy have increased risk of systemic lupus erythematosus: a nationwide cohort study

The appendix is involved in immune function, and an appendectomy may alter the immune system. Studies evaluating the relationship between previous appendectomy and the risk of systemic lupus erythematosus (SLE) are lacking. This nationwide cohort study investigated the incidence and risk of SLE in patients who underwent appendectomy. Patients aged >?20 years who received appendectomy from 2000 to 2011 were identified from the National Health Insurance Research Database and assigned to the appendectomy cohort. Patients without appendectomy were randomly selected from the NHIRD and assigned to the control cohort; they were frequency matched to each study patient at a 4:1 ratio by sex, age, and index year. All patients were followed until SLE diagnosis, withdrawal from the National Health Insurance program, or the end of 2011. We used Cox models to estimate the hazard ratio (HR) and 95% confidence interval (CI) to compare the risk of SLE between the appendectomy and control cohorts. From 23.74 million people in the cohort, 80,582 patients undergoing appendectomy and 323,850 patients without appendectomy were followed for 723,438 and 2,931,737 person-years, respectively. The appendectomy cohort had a 2.04-fold higher risk of SLE than the control cohort (adjusted HR?=?2.04, 95% CI?=?1.52–2.76). Women aged ≤?49 years who underwent appendectomy had a 2.27-fold higher risk of SLE than the corresponding controls (adjusted HR?=?2.27, 95% CI?=?1.62–3.19). Women aged ≤?49 years who underwent appendectomy have a significantly higher risk of SLE.     

High-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, and outcome after ischemic stroke

BACKGROUND: Inflammatory markers have been associated with ischemic stroke risk and prognosis after cardiac events. Their relationship to prognosis after stroke is unsettled. METHODS: A population-based study of stroke risk factors in 467 patients with first ischemic stroke was undertaken to determine whether levels of high-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A(2) (Lp-PLA2) predict risk of stroke recurrence, other vascular events, and death. RESULTS: Levels of Lp-PLA2 and hs-CRP were weakly correlated (r = 0.09; P = .045). High-sensitivity CRP, but not Lp-PLA2, was associated with stroke severity. After adjusting for age, sex, race and ethnicity, history of coronary artery disease, diabetes mellitus, hypertension, hyperlipidemia, atrial fibrillation, smoking, and hs-CRP level, compared with the lowest quartile of Lp-PLA2, those in the highest quartile had an increased risk of recurrent stroke (adjusted hazard ratio, 2.08; 95% confidence interval, 1.04-4.18) and of the combined outcome of recurrent stroke, MI, or vascular death (adjusted hazard ratio, 1.86; 95% confidence interval, 1.01-3.42). After adjusting for confounders, hs-CRP was not associated with risk of recurrent stroke or recurrent stroke, myocardial infarction, or vascular death but was associated with risk of death (adjusted hazard ratio, 2.11; 95% confidence interval, 1.18-3.75). CONCLUSIONS: Inflammatory markers are associated with prognosis after first ischemic stroke and may offer complementary information. Lipoprotein-associated phospholipase A(2) may be a stronger predictor of recurrent stroke risk. Levels of hs-CRP, an acute-phase reactant, increase with stroke severity and may be associated with mortality to a greater degree than recurrence.     

Fused TU complexes as a new electrocardiographic marker of poor prognosis after myocardial infraction

To date, the clinical significance of fused T and U waves, termed as TU complexes, has not been evaluated. The aim of the study was to present the clinical characteristics of the patients with TU complexes and to assess the value of this ECG abnormality in risk stratification after myocardial infarction. In the group of 330 postinfarction patients (mean age 61 +/- 10 years, 279 men and 51 women), 50 (15%) had TU complexes in one or more leads of a standard ECG. In patients with TU complexes, the decreased left ventricular ejection fraction, frequent (> or = 10/hour) ventricular premature beats and non-sustained ventricular tachycardia detected on 24-hours ECG monitoring, increased QT dispersion, ST-segment depression and ST-segment elevation on a routine ECG were more common than in patients without TU complexes. During a follow-up period of 43 +/- 17 months, 88 patients died from all causes. At univariate Cox analysis the presence of TU complexes (hazard ratio 3.30; 95% confidence interval 2.09-5.21) and left ventricular ejection fraction < 40% (hazard ratio 3.82; 95% confidence interval 2.51-5.82) were the best predictors of mortality among the 9 evaluated clinical and electrocardiographic variables. The multivariate, stepwise Cox analysis selected ejection fraction < 40% (hazard ratio 3.09; 95% confidence interval 2.00-4.80), TU complexes (hazard ratio 2.28; 95% confidence interval 1.42-3.69), RR interval < 800 ms (hazard ratio 1.62; 95% confidence interval 1.06-2.47), and age of patients > 65 years (hazard ratio 1.58; 95% confidence interval 1.03-2.42) as an independent predictors of all cause mortality. CONCLUSION: The presence of TU complexes on a routine ECG is associated with impaired left ventricular function, increased predisposition to ventricular arrhythmias and higher risk of mortality. TU complexes may be considered as a new electrocardiographic marker of poor prognosis in patients after myocardial infarction.