The relevance of genetic and epigenetic alterations in the pathogenesis of inflammatory bowel disease (IBD) is still poorly understood. So far, 240 risk gene loci have been associated with IBD. They are mainly involved in regulating innate and adaptive immunity, as well as maintaining intestinal epithelial barrier function. However, the functional consequences of the identified genetic polymorphisms for IBD pathogenesis in vivo are often unknown. Even less is known about the role for epigenetic modifications in IBD pathogenesis. Though a number of epigenetic events seem to be causatively involved IBD pathogenesis, our knowledge about the functional relevance of those epigenetic modifications is scanty. This opens up a broad research field that generates novel insights into the pathophysiology of intestinal and chronic inflammatory disease. Patterns of DNA methylation and histone modifications might serve not only as biomarkers of disease activity or disease course, but also as new targets in therapeutic interventions in IBD patients.
BACKGROUND
Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterised by activation of the mononuclear phagocytic system, and often leads to progressive multiple organ failure. The diagnosis of HLH is made late by most physicians.
METHODSTo confirm the diagnosis of acquired HLH made in a single-institution series of adult patients with HLH-04 criteria, we applied the HScore and evaluated prognostic factors associated with clinical outcome.
RESULTSA total of 174 patients with a median age of 51 years (range 17–90) were included. Male/female ratio was 111/63. In 92/174 (52.9%) patients, there were potential haematological diseases (4 acute leukaemia, 1 thrombotic thrombocytopenic purpura, 3 Hodgkin’s lymphoma [HL], 17 B-cell non-Hodgkin’s lymphoma [NHL], 67 T-cell NHL including 22 natural killer / T-cell NHL [NK/t-cell NHL). Six (3.4%) patients had autoimmune disease and 76 (43.7%) undiagnosed underlying disease. There were 44 (25.3%) patients with Epstein-Barr virus infection, 11 (6.3%) with cytomegalovirus, 1 (0.5%) syphilis, 9 (5.2%) hepatitis B virus and 3 (1.7%) human immunodeficiency virus. More than 95% of patients had hyperferritinaemia, high lactate dehydrogenase, fever and low albumin, whereas 89.1% of patients had bone marrow phagocytosis. By the HScore, 4/174 patients had a >50% and 16/174 patients had a >90% probability of not having HLH. All 174 patients fulfilled more than five of the HLH-04 diagnostic criteria, but 16 of them had a low probability of HLH by the HScore. In a multivariate analysis, lymphopenia and hypofibrinogenaemia were independent prognostic factors for death.
CONCLUSIONIn our study, viral infection was not an independent prognostic factor. NK/T-cell -NHL was associated with worse prognosis compared with B-cell NHL and T-cell NHL (p = 0.036) and similar to other aetiologies.
BACKGROUND
Hyponatraemia is the most common electrolyte disorder encountered in hospitalised patients and has an impact on outcome and survival. However, the risk factors are not yet sufficiently known.
AIMS OF THE STUDYThis retrospective analysis was conducted with the primary objective to identify the incidence of hyponatraemia in patients, who need hospitalisation from any medical reason, focusing on the quality of treatment and the risk factors for recurrent or prolonged stay due to hyponatraemia. The secondary objectives were the calculation of costs of hyponatraemia caused by hospital stays in the canton of Basel-Landschaft and the additional extrapolation of these costs for the whole country of Switzerland.
METHODS368 patients with a diagnosis of hyponatraemia admitted to three tertiary care centers in 2011 were included. We analysed the risk factors, causes and manifestations of hyponatraemia and their effects on length of stay and outcome.
RESULTSFemale gender (62%), advanced age (average 75 ± 12 years) and the use of thiazides (r = 0.69, p = 0.03) represented the main risk factors with negative prognostic value concerning hyponatraemia. Hyponatraemia was never asymptomatic. Seventy-three patients (20%) were diagnosed with hyponatraemia due to SIADH (syndrome of inappropriate antidiuretic hormone secretion). The in-hospital mortality rate was 9%, irrespective of the severity of hyponatraemia, and every fifth patient had persistent neurological deficits on discharge from the hospital. Age (r = 0.65, p = 0.03), female sex (r = 0.49, p =0.12; in combination with age >75years r = 0.58, p = 0.049), resumption of risk medication (r = 0.563, p = 0.02) and persistent hyponatraemia on discharge (r = −0.51, p = 0.04) were associated with higher probability of relapse. Our data, extrapolated for Switzerland, yield uncovered annual costs of 93 million CHF, mostly due to in-hospital treatment longer than that reimbursed by SwissDRG (observed median of 9 days, cost coverage by SwissDRG 5 days for non-SIADH hyponatraemia and 6.5 days for SIADH).
CONCLUSIONSAs even mild hyponatraemia is associated with an increased risk of morbidity and mortality, it is highly important to recognise it. Initial diagnostic evaluation, treatment based on volume status and thorough follow-up are crucial to avoid relapse. Hyponatraemia, based on the results of this retrospective study, constitutes a considerable medical and economic burden in Switzerland and has a serious impact on the hospital balance sheets.
INTRODUCTION
In Switzerland, the outcome of vascular access creation in the 4500 current dialysis patients is unknown, mainly because there is no prospective registry for patients undergoing vascular access surgery for renal replacement therapy. The aim of the study was to assess the quality of vascular access creation and to compare it with the current literature and guidelines, in order to define strategies to improve clinical outcome.
METHODSRetrospective single-centre study in a tertiary referral centre. All consecutive patients over 18 years of age undergoing primary vascular access creation between January 2013 and December 2014 were included. Follow-up data for at least 12 months were collected.
RESULTSDuring the study period, 365 patients had a surgical intervention for renal replacement therapy. A primary vascular access was created in 74 patients (20%), who were further analysed in our study: 63 (85%) had an arteriovenous fistula (AVF) and 11 (15%) an arteriovenous graft (AVG). The intervention-free survival (primary patency rate) of the primary vascular access at 1 year was 46% (95% confidence interval [CI] 33–58%) for AVF and 30% (95% CI 7–58%) for AVG, with a secondary patency rate at 1 year of 75% (95% CI 63–84%) for AVF and 50% (95% CI 18–75%) for AVG. Twenty-seven patients (36%) with primary vascular access underwent central venous catheter (CVC) placement (tunnelled or non-tunnelled) before the access creation. Thirty-seven (50%) patients had their first dialysis through a CVC. Thirty-one patients (42%) never received a CVC.
CONCLUSIONSThe primary patency of vascular access was unexpectedly low, and the number of CVC requests unexpectedly high. In light of this, we consider it essential that centres creating vascular access should register their activities and compare their outcomes with current guidelines to check and improve clinical management. To facilitate this, there is an initiative starting in 2018 encouraging all Swiss vascular surgeons to provide data on vascular access interventions, including 1-year follow-up, in the national online registry “SwissVasc 2.0”.
AIMS OF THE STUDY
Paediatric musculoskeletal infections by Panton-Valentine leucocidin (PVL)-producing Staphylococcus aureus constitute a rare, but highly critical event. They are characterised by a rapid course of marked inflammation, worsening under conservative therapy and a high rate of recurrence. This study aimed to illustrate the importance of paediatric PVL-producing S. aureus musculoskeletal infections in western Switzerland.
METHODSCase records, clinical parameters and biological assessments of children with musculoskeletal infections due to PVL-producing S. aureus who attended the University Hospitals of Lausanne and Geneva from 2008 to 2016 were studied retrospectively.
RESULTSOf the nine cases (seven male), four presented with haematogenous acute osteomyelitis, two with septic arthritis, and three with skin and soft tissue infections. Laboratory analysis revealed mean values for white blood cell count of 12,700/mm3, C-reactive protein (CRP) 171mg/l, erythrocyte sedimentation rate (ESR) 62 mm/h and platelet count 241,000/mm3. Notably, fever and laboratory values were higher for osteoarticular infections. PVL was produced by methicillin-sensitive S. aureus (MSSA) in eight cases and by community-acquired methicillin-resistant S. aureus (CA-MRSA) in one case. PVL was identified in blood cultures (six cases), operative samples (seven cases) and an oral swab (one case). Treatment relied on surgical procedures, endorsed by two-agent antimicrobial therapy for up to 9 weeks. Complications included recurrent infections (five cases), pathological fracture (one case) and growth arrest (two cases), as well as an important psychological impact (one case).
CONCLUSIONThe results of this study highlight the low prevalence of PVL-producing S. aureus musculoskeletal infections in the paediatric population in our region. Nevertheless, given the importance of complications, the recurrence rate and the duration of treatment, clinicians caring for children need to be especially well versed with the peculiarity of this entity. Retrospective case series. Level of evidence: IV
OBJECTIVE
Atrial fibrillation (AF) is considered to be a progressive disease, starting with intermittent episodes that progress over time to more sustained events. However, little is known about the prevalence of and predictors for AF type among patients with recent-onset AF. We aimed to address these issues among a selected population of patients with AF.
METHODSThe Basel atrial fibrillation cohort (BEAT-AF) study is an ongoing prospective multicentre cohort study among patients with AF. At baseline, we obtained information on the date of AF diagnosis, AF type, comorbidities, medication and lifestyle factors. For this analysis, 486 (31.4%) out of 1550 participants with recent-onset AF (defined as AF duration <24 months) were included. Predictors for AF type (non-paroxysmal vs paroxysmal) were obtained using multivariable adjusted logistic regression models.
RESULTSMean age was 67 (59–75) years and 136 (28%) were women. Recent-onset paroxysmal AF was observed in 301 (62%) participants, 185 (38%) had non-paroxysmal AF – persistent AF in 148 (30.4%) and permanent AF in 37 (7.6%). In multivariable models, odds ratios for having non-paroxysmal AF around AF diagnosis were 1.03 per year increasing in age (95% confidence interval [CI] 1.01–1.05, p = 0.01); 2.70 (1.5–4.68, p = 0.0004) for history of heart failure; 3.82 (1.05–13.87, p = 0.04) for a history of hyperthyroidism and 1.04 (1.02–1.05, p <0.0001) per beat increase in heart rate.
CONCLUSIONWe found a substantial proportion of AF patients with the non-paroxysmal form shortly after diagnosis. Predictors for non-paroxysmal AF were increasing age, history of heart failure or hyperthyroidism, and a higher heart rate.
AIMS
In comparison with other central European countries, Switzerland has a high prevalence of gun ownership and a high rate of suicide by shooting. After the Army XXI reform in 2003, which reduced personnel from about 400,000 to approximately 200,000, a decline in suicides by firearms and a decline in the total number of suicides was observed in national data spanning the period from 2000 to 2010. It is, however, unclear whether this decline can be linked to the reduced availability of military guns. This study explored whether the decline in suicide by firearms is related to the decline of suicides by army weapons.
METHODSIn 83.1% (n = 1112) of the 1338 suicides by firearm between 2000 and 2010 in Switzerland, the firearm could be categorised as an army weapon or a non-army weapon. The army weapon was used in 39.1% of these suicides. In comparison with other firearms, those who used army weapons tended to be younger and more likely to have a university degree. A prior suicide attempt was found less often in cases using a military weapon than other firearms. After the Army XXI reform, there was a significant drop in suicides by males aged 18 to 43 years using an army weapon, but no change in male suicide rates in the same age group who used a non-army weapon. The drop was statistically linked to a reduction of suicide by the army gun.
RESULTSThe army weapon was used in 39.1% of suicides by firearm between 2000 and 2010 in Switzerland. In comparison with other methods, those who used army weapons tended to be younger and more likely to have a university degree. A prior suicide attempt was found less often in cases using a military weapon than other methods. After the Army XXI reform, there was a significant drop in suicides by males aged 18 to 43 years using an army weapon, but no change in males’ suicide rates in the same age group who used a non-army weapon. The drop was statistically linked to a reduction of suicide by the army gun.
CONCLUSIONSMales who use army weapons differ from those who use other types of weapons. The significant drop in suicides was found in males aged 18 to 43 but there was no change in males of the same age group who used a non-army weapon. These results support the hypotheses that the observed drop in suicides is linked to the Army XXI reform and that restriction of access to guns is essential for reducing suicides by firearm.