Treatment of inflammatory bowel disease with steroid-sparing medications is age-dependent - Results from a Danish nationwide cohort study, 2000-2018.

BACKGROUND: Paediatric-onset and elderly-onset inflammatory bowel disease (IBD) present unique treatment challenges. AIMS: We investigated treatment patterns following a first and second course of systemic steroids in paediatric- and elderly-onset IBD and compared them to adult-onset IBD. METHODS: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2000 and 2018 were identified through the Danish healthcare registries. Patients were divided into groups based on their age at diagnosis. Kaplan-Meier plots were prepared for medications and surgeries after diagnosis and after the first and second courses of systemic steroids. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox regression analysis for steroid-sparing medications. RESULTS: 1851 CD (13%) and 1687 (6%) UC patients were paediatric-onset, while 2952 (20%) CD and 5812 (23%) UC patients were elderly-onset. Paediatric-onset more frequently received immunomodulators [CD: HR: 1.64, CI: 1.52-1.77, UC: HR: 2.29, CI: 2.02-2.61] and biologics [CD: HR: 1.43, CI: 1.25-1.65, UC: HR: 1.27, CI: 0.99-1.64], while elderly-onset less frequently received immunomodulators [CD: HR: 0.39, CI: 0.35-0.44, UC: HR: 0.58, CI: 0.50-0.67] and biologics [CD: HR: 0.19, CI: 0.14-0.25, UC: HR: 0.36, CI: 0.27-0.48] compared to adult-onset age groups. After two courses of systemic steroids, elderly-onset still received less steroid-sparing medications. High frailty was associated with lower usage of medications for elderly-onset. CONCLUSION: There are significant differences in the use of steroid-sparing medication between age of onset, even after two courses with systemic steroids. High frailty could account for some of these differences in elderly-onset IBD.

Early intestinal ultrasound in severe ulcerative colitis identifies patients at increased risk of 1-year treatment failure and colectomy.

BACKGROUND AND AIMS: Reliable and easily accessible objective markers of disease activity to predict long-term treatment outcomes in severe ulcerative colitis (UC) are missing. We aimed to investigate if intestinal ultrasound (IUS) might predict long-term outcomes in hospitalized patients with severe UC treated with intravenous corticosteroids. METHODS: Hospitalized patients with severe UC and IUS inflammation (bowel wall thickness (BWT)>3.0mm) starting IV corticosteroids were recruited at three university hospitals in Denmark. IUS was performed before treatment, 48±24 hours (h), 6±1 days, and 3 months after treatment initiation. Time until colectomy or need for new interventions was registered together with Mayo score at 3 months and partial Mayo score (pMayo) at 12-months. Follow-up time was 12 months. RESULTS: Fifty-six patients were included in the final analysis. Forty-five (80%) patients needed intervention, including 9 colectomies, during the 12-month follow-up. After 48±24h: No patient with a BWT<3mm needed a colectomy, p=0.04. BWT≥4mm showed an increased risk of colectomy (odds ratio 9.5 (95%CI 1.5-186), p=0.03), while a BWT≥3mm showed an increased risk of intervention (3.6 (1.1-12.5), p=0.03). A BWT≥4mm resulted in a significantly shorter time until both colectomy, p=0.03, and treatment intensification (mean days 75 (95%CI24-127) vs. 176 (119-233), p=0.005. However, neither IUS parameters nor pMayo score, CRP, hemoglobin, or p-albumin could predict remission at 3- and 12-months. CONCLUSION: BWT assessed at 48h post intravenous corticosteroid initiation in patients hospitalized with severe UC may identify patients with an increased risk of short- and long-term colectomy and predict a more aggressive short-term disease course.

Effectiveness and safety of a third-line rescue treatment for acute severe ulcerative colitis refractory to infliximab or ciclosporin (REASUC study).

BACKGROUND: The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy. AIMS: To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin. METHODS: Multicentre retrospective cohort study of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment. RESULTS: Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy. CONCLUSION: Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy.

Early Intestinal Ultrasound Predicts Intravenous Corticosteroid Response in Hospitalised Patients With Severe Ulcerative Colitis.

BACKGROUND AND AIMS: Our aim was to determine if transabdominal intestinal ultrasound changes after 48 ±â€…24 h of intravenous corticosteroids can predict treatment outcomes in hospitalised patients with severe ulcerative colitis. METHODS: We performed a blinded observational multicentre study. Ultrasound parameters were assessed before treatment initiation, after 48 ±â€…24 h, and 6 ±â€…1 days. Treatment response was determined within 7 days by two outcome measures: 1] partial Mayo score reduction; 2] no administration of rescue therapy. RESULTS: Out of 69 recruited patients, 56 were included in the final analysis, with 37 responders. The colon segment with the highest baseline bowel wall thickness was analysed, being the sigmoid in all patients. There was no difference in baseline bowel wall thickness between responders and non-responders in the partial Mayo score outcome. At 48 ±â€…24 h, a significant difference between responders and non-responders was identified in both absolute bowel wall thickness [median 3.1 mm vs 4.9 mm; p <0.0001], absolute reduction [-1.9 mm vs -0.2 mm; p <0.001], and relative reduction [-35.9% vs -4.1%; p <0.0001]. A ≤20% reduction had a sensitivity of 84.2% (95% confidence interval [CI] 60.4, 96.6%) and a specificity of 78.4% [61.8, 90.2%] for determining non-response [area under the curve 0.85]. In the multivariable analysis, a >20% reduction had the highest odds ratio (22.6 [4.2, 201.2]; p = 0.001) for determining response. Similar results were seen for the rescue therapy outcome. CONCLUSIONS: Changes in bowel wall thickness, after 48 ±â€…24 h following intravenous corticosteroid treatment in hospitalised patients with severe ulcerative colitis, identify responders with high accuracy and might be used as an early marker to guide accelerated rescue therapy.

Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study): the protocol for a Copenhagen IBD Inception Cohort Study.

INTRODUCTION: Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment. METHODS AND ANALYSIS: IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis. ETHICS AND DISSEMINATION: This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.

The knowledge and skills needed to perform intestinal ultrasound for inflammatory bowel diseases-an international Delphi consensus survey.

BACKGROUND: Intestinal ultrasound (IUS) is a non-invasive modality for monitoring disease activity in inflammatory bowel diseases (IBD). IUS training currently lacks well-defined standards and international consensus on competency criteria. AIM: To achieve international consensus on what competencies should be expected from a newly certified IUS practitioner. METHODS: A three-round, iterative Delphi process was conducted among 54 IUS experts from 17 countries. Round 1 was a brainstorming phase with an open-ended question to identify the knowledge and skills that experts believe a newly certified IUS practitioner should possess. The experts' suggestions were then organised into statements by a Steering Committee. In round 2, the experts commented upon and rated the statements, which were revised accordingly. In round 3, the experts rated the revised statements. Statements meeting the pre-defined consensus criterion of at least 70% agreement were included in the final list of statements. RESULTS: In total, 858 items were suggested by the experts in the first round. Based on these suggestions, 55 statements were organised into three categories: knowledge, technical skills and interpretation skills. After the second round, 53 revised statements remained. After the final round, a total of 41 statements had achieved consensus. CONCLUSIONS: We established international, expert consensus on the knowledge and skills that should be expected from newly certified IUS practitioners. These consensus statements are the first step towards mastery learning for IUS training. Educators can utilise these statements to design training programmes and evaluate the competencies of trainees before they engage in independent practice.

Surgery due to Inflammatory Bowel Disease During Pregnancy: Mothers and Offspring Outcomes From an ECCO Confer Multicentre Case Series [Scar Study].

AIMS: i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery. METHODS: Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients' demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded. RESULTS: In all, 44 IBD patients were included, of whom 75% had Crohn's disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit]. CONCLUSIONS: IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.

The Use and Efficacy of Biological Therapies for Inflammatory Bowel Disease in a Danish Tertiary Centre 2010-2020.

Background: Patients with inflammatory bowel disease (IBD) who receive biologicals frequently experience lack or loss of response. Our aim was to describe the use and efficacy of biological therapy in a tertiary IBD center. Methods: We included all bio-naive IBD patients who initiated biological therapy between 2010 and 2020 at our centre. Their medical records were reviewed. Results: The population consisted of 327 Crohn's disease (CD) patients, 291 ulcerative colitis (UC) patients, and 3 patients with IBD unclassified (IBDU). The median follow-up was 3 years (interquartile range = 2-5) after initiating therapy. The annual number of patients initiating biological therapy rose from 29 (2010) to 85 (2019). Most patients (457, 73.6%) received 1 biological drug; 164 (26.4%) patients received 2 or more biologicals. Primary lack of response was observed in 36.4% (106/291) and 17.4% (57/327) of UC and CD patients; loss of response was observed in 27.1% (79/291) and 31.5% (103/327) of UC and CD patients, respectively. The 5-year surgery rates were 26.6% and 20.4% in UC and CD patients, respectively. Multivariate Cox regression showed that treatment with thiopurine reduced the likelihood of needing to switch biological therapy, requiring surgery or corticosteroids in UC patients (HR: 0.745, 95% CI: 0.559-0.993), but not in CD patients (HR: 0.996, 95% CI: 0.736-1.349). Conclusions: The annual number of IBD patients initiated on biological therapy increased considerably between 2010 and 2020. One-quarter of these patients required surgery after 5 years. Our findings suggest a beneficial effect of concurrent thiopurines for UC patients receiving biologicals, but this was not found for CD patients. This effect in UC patients was not observed when we included patients initiating thiopurines up to 6 months after the introduction of biological therapy.

[Multidisciplinary treatment of acute iron poisoning due to suicide attempt].

Intentional iron overdoses have an insidious and potentially fatal clinical course. This is a case report of a young woman, who deliberately ingested 300 tablets ferrous fumarate 330 mg, i.e. 400 mg elementary iron per kg body weight. Plain abdominal radiographs showed a conglomerate of iron tablets in the ventricle. Treatment consisted of endoscopic removal of tablets, deferoxamine antidote treatment, and whole bowel irrigation with macrogol laxatives. Toxicological risk evaluation of intentional iron overdoses is necessary to timely effectuate life-saving multidisciplinary empiric treatments.

[Myeloproliferative neoplasms and chronic inflammatory bowel disease].

Studies have suggested a possible association between inflammatory bowel disease (IBD) and the Philadelphia-negative chronic myeloproliferative neoplasms (MPNs). The mechanisms behind this association have not been investigated yet, but in this review, we find it most likely to involve complex interactions between genetic, treatment-related and inflammation- and immune-mediated factors. When patients with IBD present with persistent leukocytosis and/or thrombocytosis, it may reflect concomitant MPN, and early detection and treatment of MPNs may prevent some of the complications related to these diseases.

Anti-TNF Therapy in Pregnant Women With Inflammatory Bowel Disease: Effects of Therapeutic Strategies on Disease Behavior and Birth Outcomes.

BACKGROUND: Active inflammatory bowel disease (IBD) adversely affects pregnancy outcomes. Little is known about the risk of relapse after stopping anti-tumor necrosis factor (anti-TNF) treatment during pregnancy. We assessed the risk of relapse before delivery in women who discontinued anti-TNF treatment before gestational week (GW) 30, predictors of reduced infant birth weight, a marker associated with long-term adverse outcomes, and rates and satisfaction with counseling. METHODS: Pregnant women with IBD receiving anti-TNF treatment were prospectively invited to participate in an electronic questionnaire carried out in 22 hospitals in Denmark, Australia, and New Zealand from 2011 to 2015. Risk estimates were calculated, and birth weight was investigated using t tests and linear regression. RESULTS: Of 175 women invited, 153 (87%) responded. In women in remission, the relapse rate did not differ significantly between those who discontinued anti-TNF before GW 30 (1/46, 2%) compared with those who continued treatment (8/74, 11%; relative risk, 0.20; 95% confidence interval [CI], 0.02 to 1.56; P = 0.08). Relapse (P = 0.001) and continuation of anti-TNF therapy after GW 30 (P = 0.007) were independently associated with reduced mean birth weight by 367 g (95% CI, 145 to 589 g; relapse) and 274 g (95% CI, 77 to 471 g; anti-TNF exposure after GW 30). Of 134 (88%) women who received counseling, 116 (87%) were satisfied with the information provided. CONCLUSIONS: To minimize fetal exposure in women in remission, discontinuation of anti-TNF before GW 30 seems safe. Relapse and continuation of anti-TNF therapy after GW 30 were each independently associated with lower birth weight, although without an increased risk for birth weight <2500 g. Most women received and were satisfied with counseling.

Treatment of candidemia in a nationwide setting: increased survival with primary echinocandin treatment.

BACKGROUND: In accordance with international guidelines, primary antifungal treatment (AFT) of candidemia with echinocandins has been nationally recommended in Denmark since 2009. Our nationwide cohort study describes the management of candidemia treatment focusing on the impact of prophylactic AFT on species distribution, the rate of adherence to the recommended national guidelines for AFT, and the effect of AFT on patient outcomes. MATERIALS AND METHODS: Incident candidemia cases from a 2-year period, 2010-2011, were included. Information on AFT was retrospectively collected from patient charts. Vital status was obtained from the Danish Civil Registration System. HRs of mortality were reported with 95% CIs using Cox regression. RESULTS: A total of 841 candidemia patients was identified. Prior to candidemia diagnosis, 19.3% of patients received AFT (162/841). The risk of non-albicans candidemia increased after prior AFT (59.3% vs 45.5% among nontreated). Echinocandins as primary AFT were given for 44.2% (302/683) of patients. Primary treatment with echinocandins resulted in adequate treatment in a higher proportion of patients (97.7% vs 72.1%) and was associated with lower 0- to 14-day mortality compared with azole treatment (adj. HR 0.76, 95% CI: 0.55-1.06). Significantly lower 0- to 14-day mortality was observed for patients with Candida glabrata and Candida krusei with echinocandin treatment compared with azole treatment (adj. HR 0.50, 95% CI: 0.28-0.89), but not for patients with Candida albicans or Candida tropicalis. CONCLUSION: The association shown between prior AFT and non-albicans species underlines the importance of treatment history when selecting treatment for candidemia. Compliance with national recommendations was low, but similar to previously reported international rates. Primary treatment of candidemia with echinocandins compared with azoles yielded both a higher proportion of adequately treated patients and improved mortality rates. This real-life setting supports guidelines recommendation, and further focus on compliance with these seems warranted.

Prognostic value of lectin pathway molecules and complement proteins in ascitic fluid and blood in patients with liver cirrhosis.

BACKGROUND AND AIM: Patients with liver cirrhosis and ascites have a poor prognosis with increased risk of infection related death, as advanced stages of cirrhosis are associated with immunodeficiency. We aimed to investigate immunologically active molecules in ascitic fluid and blood and their potential association to survival. MATERIALS AND METHODS: In an exploratory pilot study; blood and ascitic fluid from 34 patients with liver cirrhosis of different etiology were analyzed for pattern recognition molecules (ficolin-1, ficolin-2, ficolin-3 and MBL) and complement proteins (C4 and C3). An observational follow-up study (minimum 17 months) was conducted to assess the association to all-cause mortality or liver transplantation. RESULTS: Ficolin-1, ficolin-2, MBL, C4 and C3 in ascitic fluid and ficolin-1, C4 and C3 in blood were significantly (p = .001-.027) lower in patients with Child-Pugh stage C (n = 16, 47%) compared to Child-Pugh stage B cirrhosis (n = 18, 53%). In multivariate COX-regression analysis low levels of ficolin-1(p = .036) and C3 (p = .025) in ascitic fluid and C4(p = .005) and C3 (p = .032) in serum were associated with all-cause mortality or liver transplantation independent of Child-Pugh score. CONCLUSION: Levels of lectin-complement pathway molecules in ascitic fluid and blood are lower in patients with more advanced stage of cirrhosis. Low C4 and C3 in serum and C3 and ficolin-1 in ascitic fluid are risk factors for all-cause mortality or liver transplantation independently of liver function in patients with cirrhosis and ascites.

Impact of Infliximab and Cyclosporine on the Risk of Colectomy in Hospitalized Patients with Ulcerative Colitis Complicated by Cytomegalovirus-A Multicenter Retrospective Study.

BACKGROUND: Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA]). METHODS: This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months. RESULTS: A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy. CONCLUSIONS: IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.

[HIV-positive individuals still have shorter life-expectancy than the general population]. / Patienter med hiv-infektion lever stadig væsentlig kortere end baggrundsbefolkningen.

Despite more than 15 years of available highly active anti-retroviral therapy treatment, HIV-positive individuals still have a two-third shorter life-expectancy in comparison with the general population. Six studies of individuals with HIV (n = 235,854) were analysed with 7,898 deaths, of which 90% had a known cause. 42% were still due to AIDS, followed by liver-related deaths (12%), non-AIDS cancer (12%), cardiovascular disease (10%), suicide/overdose/accidents (8%), non-AIDS infection (7%) and other non-AIDS causes (11%). Recognising the causes of death among HIV-positive individuals may aid in reducing mortality.

[Gastric carcinoma is the most frequent Epstein-Barr virus-associated malignancy]. / Ventrikelcancer er den hyppigste Epstein-Barr-virus-associerede cancerform.

Epstein-Barr virus (EBV) is associated with 8% of gastric carcinomas (GC) worldwide, being the most frequent EBV-associated malignancy with 80,000 new cases per year. The association is based on the presence of clonal EBV products in gastric tumour cells, and elevated EBV antibodies in pre-diagnostic sera. EBV-associated GC are twice as common in males and often associated to cancer in the cardia-region. Gastric surgery increases the risk significantly. Until now, no clear interaction between Helicobacter pylori, the single most important risk factor for GC, and EBV has been established.

Epstein-Barr virus-associated gastric carcinoma among patients with pernicious anemia.

Approximately 9% of gastric carcinomas worldwide are associated with Epstein-Barr virus (EBV), making it the most frequent EBV-associated malignancy. Pernicious anemia, a condition with chronic gastritis and achlorhydria, is strongly associated with gastric carcinoma. Both chronic inflammation and the lack of stomach acid may influence the likelihood of EBV infection of the neoplastic gastric epithelium, but the prevalence of EBV-associated gastric carcinoma among patients with pernicious anemia is unknown. Therefore, we conducted a Danish nationwide case-control study comparing gastric carcinoma patients with pernicious anemia (PA-GC) with those without pernicious anemia (nonPA-GC), frequency matched 1:2. Tumor tissues were reclassified by expert histopathologists blinded to pernicious anemia and EBV status. In total, 186 samples (55 PA-GC and 131 nonPA-GC) were identified. EBV-associated gastric carcinoma (EBV-GC) was more common among PA-GC compared with nonPA-GC, adjusted odds ratio (OR) = 2.53 (CI: 0.88; 7.14), p = 0.08, with further adjustment for lymphocytic infiltrate OR = 2.94 (0.99-8.67), p = 0.05. Gastric carcinomas with signet-ring cell morphology were significantly less common in patients with PA-GC compared with nonPA-GC (OR = 0.05, CI 0.01; 0.24). Although these conditions are rare, we found suggestive evidence that EBV-associated gastric carcinomas are more common among gastric carcinoma patients with pernicious anemia compared with those without.

The Inuit cancer pattern--the influence of migration.

The Inuit cancer pattern is characterized by high frequencies of Epstein-Barr Virus (EBV)-associated carcinomas of the nasopharynx and salivary glands. The reasons are unknown, but genetic and environmental factors are believed to be involved. Using data from the well-defined Inuit population in Greenland we investigated whether migration to Denmark influenced their risk of cancer. Greenland is part of the Danish Kingdom, and population-based registries cover both countries. Using rates for Denmark as reference, sex-specific standardized incidence ratios (SIR) were calculated for Inuit who never lived in Denmark and for those who at least once were registered with a Danish address. During 1973-2003, we observed 3,567 cancers in a cohort of 77,888 persons. Of these, 862 among 26,214 Inuit ever living in Denmark, and 2,705 among 51,674 nonmigrating Inuit. High SIRs for cancers of the nasopharynx [31.7 (CI 22.0-45.5)] and salivary glands [3.1 (CI 1.4-6.9)] observed among Inuit migrating to Denmark were comparable to those observed among Inuit never living in Denmark. Significant higher risk of cancer of the bladder, breast, prostate gland, skin, brain and stomach was observed among Inuit following migration to Denmark. The SIR was not generally influenced by duration of stay. The high risk of carcinoma of the nasopharynx and salivary glands observed in Inuit populations is maintained after migration to a low incidence area. This indicates that genetic factors or environmental factors acting early in life are etiologically important for these cancers.

A case of acute liver failure caused by herpes simplex type 2.

Unlike mucocutaneous infections, disseminated herpes simplex virus infections are rare and often fatal owing to acute liver failure (ALF). Typically, the course of the disease is rapid and the lack of specific symptoms may result in delay in diagnosis. This study reports a case of genital herpes caused by herpes simplex-type 2 that resulted in ALF. The patient was a 24-y-old woman with a 1 y history of Crohn's disease, treated with oral prednisolone. She was hospitalized with fatigue, anorexia and abdominal pain. Blood tests showed pancytopenia, renal failure and coagulopathy. Pelvic examination revealed signs of severe colpitis and prompt therapy with parenteral acyclovir was initiated. Despite the early institution of antiviral therapy, progressive hepatic coma, gastrointestinal bleeding, oliguria and severe intracranial hypertension characterized the clinical course. The patient received intensive supportive care and recovered without liver grafting. A subsequent screening for immunodeficiency diseases revealed an immeasurable blood mannose-binding lectin (MBL) concentration. 10 weeks after admission, she was discharged for further rehabilitation. This case stresses the importance of suspecting disseminated herpes virus infection in patients with ALF without known aetiology as it may secure prompt initiation of antiviral therapy and reduce the risk that transplantation is needed for survival.