Shahram Bahmanyar

Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis

BACKGROUND & AIMS The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC. METHODS Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register. RESULTS The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohns disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9). CONCLUSIONS First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.

CANCER RISK AMONG PATIENTS WITH MULTIPLE SCLEROSIS AND THEIR PARENTS

Background: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. Methods: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. Results: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87–0.95). Increased risks were observed for brain tumors (1.44, 1.21–1.72) and urinary organ cancer (1.27, 1.05–1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. Conclusions: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible).

A Population-Based Nationwide Study of Cruciate Ligament Injury in Sweden, 2001-2009 Incidence, Treatment, and Sex Differences

Background: A few national cruciate ligament (CL) registers have been initiated with operative surveillance and outcome monitoring. No nationwide study describing CL injury has ever been done. Purpose: To study the incidence and characteristics of patients diagnosed with cruciate ligament injury in Sweden. Study Design: Descriptive epidemiology study. Methods: Data for all patients with a diagnosed CL injury between 2001 and 2009 were identified from the National Swedish Patient Register. Risk analysis and specific incidences were calculated according to age, sex, geographic region, and surgery. Results: A total number of 56,659 patients with CL injury were included in the study, and the overall incidence of CL injury in Sweden was 78 per 100,000 persons. Sixty percent of the patients were male. The mean age was 32 years (range, 1-98 years), and 50% of the cohort was younger than 30 years. There was an increased rate of injury among female patients younger than 20 years as compared with male patients in that age group. Among patients with CL injury, 36% underwent reconstructive surgery, with one-third of these performed within 1 year after injury. Among patients who underwent surgery, 59% were male; the mean age was 27 years (range, 5-89 years). Conclusion: This study defines the incidence of CL injury and also demonstrates sex differences in which men were more likely to sustain a CL injury, although female patients were injured at an earlier age. The findings in this study corroborate the results from recent surgical registers. Clinical Relevance: No data have hitherto been published including all patients with CL injury, treated both surgically and nonsurgically. Such baseline epidemiologic data are crucial to be able to validate and judge the generalizability of results from procedure registers and clinical studies.

Family stress and BMI in young children

Aim:  The aim of this study was to investigate if family stress and parental attachment style are associated with body mass index (BMI) in young children, and identify possible explanations.

Maternal smoking during pregnancy, other prenatal and perinatal factors, and the risk of Legg-Calvé-Perthes disease

OBJECTIVE. The causes of Legg-Calvé-Perthes disease are largely unknown, but this pediatric disease seems to result from interruption of the blood supply to the proximal femur and is considered a vascular disease. Because maternal smoking during pregnancy influences fetal development and is associated with cardiovascular diseases in offspring, we hypothesized that this exposure is a risk for Legg-Calvé-Perthes disease and also investigated other markers of impaired fetal development and early-life exposures. MATERIALS AND METHODS. The Swedish Inpatient Register identified 852 individuals with a diagnosis of Legg-Calvé-Perthes disease from 1983 to 2005, individually matched by year of birth, age, sex, and region of residence with 4432 randomly selected control subjects. Linkage with the Swedish Medical Birth Register provided information on prenatal factors, including maternal smoking. Conditional logistic regression examined associations of maternal smoking during pregnancy and the other measures with the risk of Legg-Calvé-Perthes disease in offspring, adjusted for socioeconomic index and other potential confounding factors. RESULTS. Maternal smoking during pregnancy was associated with an increased Legg-Calvé-Perthes disease risk, and heavy smoking was associated with a risk increase of almost 100%. Very low birth weight and cesarean section were independently associated with ∼240% and 36% increases in the risk of Legg-Calvé-Perthes disease, respectively. CONCLUSION. Maternal smoking during pregnancy and other factors indicated by impaired fetal development may be associated with an increased risk of Legg-Calvé-Perthes disease.

Maternal smoking during pregnancy and multiple sclerosis amongst offspring

Introduction:  An association between parental smoking and multiple sclerosis (MS) in offspring has been reported. This study examined whether maternal smoking during pregnancy is associated with MS in offspring.

Cancer risk among patients with cystic fibrosis and their first-degree relatives

Patients with cystic fibrosis (CF) are at increased risk of some cancers. Little is known about the cancer risks among carriers heterozygous for the CF mutation and it is hypothesized this may be associated with reduced cancer risk. Using Swedish general population‐based registers, we identified 884 patients with CF from 1968 to 2003 and 3,033 of their first‐degree relatives The subjects were followed from birth of index persons or 1958, whichever came later, until death, emigration or 2003, whichever came first. Cancer risks were compared with the general Swedish population using standardized incidence ratios (SIR) with 95% confidence intervals (CI). Patients, followed for an average of 21 years, were at a higher overall risk of cancer. Some 26 cancer diagnoses, after excluding multiple diagnoses of nonmelanoma skin cancer in one man, produced an overall SIR of 3.2 (95% CI 2.1–4.6). We found statistically significantly increased risks for kidney, thyroid, endocrine, lymphoma and nonmelanoma skin cancer. There was no modification of cancer risk among parents and siblings, with an average of 21 years of follow‐up. This study did not identify a heterozygote advantage for CF gene mutations in relation to cancer risk.

Multiple sclerosis clinical course and cardiovascular disease risk - Swedish cohort study.

Cardiovascular disease (CVD) risk amongst multiple sclerosis (MS) patients appears raised, but few studies have examined CVD risk amongst an unselected MS patient group. MS course may be relevant for CVD risk. Our aim was to assess CVD risk and variation by course in MS patients.

Cruciate ligament reconstruction and risk of knee osteoarthritis: the association between cruciate ligament injury and post-traumatic osteoarthritis. a population based nationwide study in Sweden, 1987-2009.

Objective To study the association between Cruciate Ligament (CL) injury and development of post-traumatic osteoarthritis in the knee in patients treated operatively with CL reconstruction compared with patients treated non-operatively. Design Population based cohort study; level of evidence II-2. Setting Sweden, 1987–2009. Participants All patients aged between 15–60 years being diagnosed and registered with a CL injury in The National Swedish Patient Register between 1987 and 2009. Main Outcome Measures Knee osteoarthritis. Results A total of 64,614 patients diagnosed with CL injury during 1987 to 2009 in Sweden were included in the study. Seven percent of the patients were diagnosed with knee OA in specialized healthcare during the follow-up (mean 9 years). Stratified analysis by follow-up showed that while those with shorter follow-up had a non-significant difference in risk (0.99, 95%CI 0.90–1.09 for follow-up less than five years compared with the non-operated cohort), those with longer follow-up had an increased risk of knee OA after CL reconstruction (HR = 1.42, 95%CI 1.27–1.58 for follow-up more than ten years compared with non-operated cohort). The risk to develop OA was not affected by sex. Conclusion CL reconstructive surgery does not seem to have a protective effect on long term OA in either men or women.

Long-term risk of gastric cancer by subsite in operated and unoperated patients hospitalized for peptic ulcer.

OBJECTIVE:We aimed to investigate whether the elevated risk of gastric cancer among patients with gastric ulcer (GU) and the enigmatic low risk among patients with duodenal ulcer (DU) pertain to both cardia and noncardia cancer. We also studied the risks among operated patients while taking the disparate baseline risks into consideration.METHODS:Retrospective cohorts of 59,550 and 79,412 unoperated patients with DU and GU, respectively, plus 12,840 patients with partial gastric resection and 8,105 with vagotomy, recorded in the Swedish Inpatient Register since 1970, were followed from the first hospitalization (date of operation for the surgery cohort) until occurrence of any cancer, death, emigration, definitive surgery, or December 31, 2003. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) expressed relative risk (RR), compared to the age-, sex-, and calendar period-matched Swedish population. Cox regression produced adjusted RR estimates among operated patients, relative to unoperated ones with the same ulcer type.RESULTS:While unoperated DU patients had a halved risk of noncardia cancer (SIR = 0.5, 95% CI 0.4–0.7), their risk of cardia cancer was slightly above expectation (SIR = 1.2, 95% CI 0.8–1.7). Unoperated GU patients had doubled risks for both cancers (SIR = 2.1, 95% CI 2.0–2.4 and SIR = 1.9, 95% CI 1.4–2.3, respectively). DU patients who underwent gastric resection had a 60% risk elevation (RR = 1.6, 95% CI 1.0–2.5) compared to unoperated ones. Vagotomy was associated with a greater risk in the first 10 yr, but this excess disappeared with further follow-up. Resected GU patients had a 40% risk reduction relative to their unoperated peers (RR = 0.6, 95% CI 0.5–0.8). This reduction persisted well beyond the first postoperative decade.CONCLUSION:The DU-related protection against gastric cancer does not seem to pertain to cardia cancer. With gastric resection, risks are shifted toward normality, regardless of underlying ulcer type.