Lateral medullary vascular compression manifesting as paroxysmal hypertension.

Neurovascular compression of the rostral ventrolateral medulla (RVLM) has been described as a possible cause of refractory essential hypertension. We present the case of a patient affected by episodes of severe paroxysmal hypertension, some episodes associated with vago-glossopharyngeal neuralgia. Classical secondary forms of hypertension were excluded. Imaging revealed a neurovascular conflict between the posterior inferior cerebellar artery (PICA) and the ventrolateral medulla at the level of the root entry zone of the ninth and tenth cranial nerves (CN IX-X REZ). A MVD of a conflict between the PICA and the RVLM and adjacent CN IX-X REZ was performed, resulting in reduction of the frequency and severity of the episodes. Brain MRI should be performed in cases of paroxysmal hypertension. MVD can be considered in selected patients.

Already low drug dose antagonism of the renin-angiotensin aldosterone system decreases 1-year mortality and rehospitalization in old heart failure patients.

AIMS: Hospitalization for heart failure treatment (HHF) is an incisive event in the course of HF. Today, the large majority of HHF patients is ≥ 65 years and discharge HF drugs are most often not applied at dose levels acknowledged to provide prognostic benefit. This study therefore aims to investigate the treatment effect size of discharge HF drugs in old HHF patients. METHODS: Drugs are analyzed according to pharmacological class. Individual discharge HF drug dose is reported as percentage of guidelines-recommended target dose. Primary endpoint was 1-year all-cause mortality (ACM) after discharge; the secondary endpoint combined 1-year ACM and first cardiovascular hospitalization within 1 year after discharge. Comparison between 65-80 years and > 80 years old study participants tested the relative treatment effect size as a function of respective age group. RESULTS: The 875 consecutive HHF patients had a median age of 82 years [76-87 years]; 48.6 % were females. Betablocker and diuretic treatment did not change the incidence of endpoints. Inhibition of the renin-angiotensin system (RASi), when compared to no treatment, decreased the incidence of endpoints both at the 1-25 % and the > 25 % target dose level. Antagonists of the mineralocorticoid receptor (MRA), when compared to no treatment, decreased the secondary endpoint at the 1-25 % target dose level but not at the > 25 % target dose level. The relative treatment effect size of RASi or MRA corresponded between the age strata for both endpoints. CONCLUSION: Low-dose RASi and MRA had beneficial effects in these old HHF patients.

Human genomics of the humoral immune response against polyomaviruses.

Human polyomaviruses are widespread in humans and can cause severe disease in immunocompromised individuals. To identify human genetic determinants of the humoral immune response against polyomaviruses, we performed genome-wide association studies and meta-analyses of qualitative and quantitative immunoglobulin G responses against BK polyomavirus (BKPyV), JC polyomavirus (JCPyV), Merkel cellpolyomavirus (MCPyV), WU polyomavirus (WUPyV), and human polyomavirus 6 (HPyV6) in 15,660 individuals of European ancestry from three independent studies. We observed significant associations for all tested viruses: JCPyV, HPyV6, and MCPyV associated with human leukocyte antigen class II variation, BKPyV and JCPyV with variants in FUT2, responsible for secretor status, MCPyV with variants in STING1, involved in interferon induction, and WUPyV with a functional variant in MUC1, previously associated with risk for gastric cancer. These results provide insights into the genetic control of a family of very prevalent human viruses, highlighting genes and pathways that play a modulating role in human humoral immunity.

[Thiamine-responsive megaloblastic anemia or Rogers syndrome: A literature review]. / L'anémie mégaloblastique thiamine dépendante ou syndrome de Rogers : une revue de la littérature.

Thiamine-responsive megaloblastic anemia (TRMA), also known as Rogers syndrome, is a rare autosomal recessive disease characterized by three main components: megaloblastic anemia, diabetes mellitus and sensorineural deafness. Those features occur in infancy but may arise during adolescence. Diagnosis relies on uncovering genetic variations (alleles) in the SLC19A2 gene, encoding for a high affinity thiamine transporter. This transporter is essentially present in hematopoietic stem cells, pancreatic beta cells and inner ear cells, explaining the clinical manifestations of the disease. Based on a multidisciplinary approach, treatment resides on lifelong thiamine oral supplementation at pharmacological doses, which reverses anemia and may delay development of diabetes. However, thiamine supplementation does not alleviate already existing hearing defects.

Incidence of type 2 diabetes, hypertension, and dyslipidemia in metabolically healthy obese and non-obese.

BACKGROUND AND AIMS: Metabolically healthy obese (MHO) individuals are devoid of many metabolic abnormalities, but how this condition is maintained over time remains debated. We assessed the prevalence of MHO over time and the incidence of hypertension (HTN), dyslipidemia, and type 2 diabetes mellitus (T2DM) in MHO as compared with metabolically healthy non obese (MHNO). METHODS AND RESULTS: Prospective, population-based study including 3038 participants (49.9 ± 9.9 years; 1753 women) free from metabolic syndrome and cardiovascular disease at baseline and examined after a follow-up of 5.6 years and 10.9 years on average. At each follow-up, prevalence of MHO, MHNO, metabolically unhealthy not obese (MUNO), and metabolically unhealthy obese (MUO), as well as of HTN, dyslipidemia, and T2DM, was calculated and stratified by sex, age group, and education. At baseline, 179 (5.7%) MHO participants were identified, of which 62 (34.6%) and 79 (44.1%) remained MHO at 5.6 and 10.9 years follow-up, respectively. At 5.6 years follow-up, MHO participants were more likely to develop low HDL or be on hypolipidemic medication [multivariable-adjusted OR (95% CI): 1.56 (1.02-2.38)], to have dyslipidemia [1.94 (1.33-2.82)], and high triglycerides [2.07 (1.36-3.14)] than MHNO. At 10.9 years follow-up, MHO participants were significantly more likely to develop T2DM [3.44 (1.84-6.43)], dyslipidemia [1.64 (1.14-2.38)], and low HDL or be prescribed hypolipidemic medication [1.57 (1.08-2.27)] than MHNO. Conversely, no differences were found regarding hypertension. CONCLUSION: A considerable fraction of MHO individuals lose their status over time, and in metabolically healthy adults, obesity confers a higher risk of developing cardiovascular risk factors.

Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study.

BACKGROUND: There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders. METHODS: The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models. RESULTS: Current combined MDD [ß = 0.29, 95% confidence interval (CI) 0.03-0.55] and current atypical MDD (ß = 0.32, 95% CI 0.10-0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up. CONCLUSIONS: The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated.

Correction: Plasma 1-deoxysphingolipids are early predictors of incident type 2 diabetes mellitus.

[This corrects the article DOI: 10.1371/journal.pone.0175776.].

Plasma 1-deoxysphingolipids are early predictors of incident type 2 diabetes mellitus.

1-Deoxysphingolipids (1-deoxySLs) are atypical sphingolipids, which are formed in a side reaction during sphingolipid de-novo synthesis. Recently, we demonstrated that 1-deoxySLs are biomarkers for the prediction of T2DM in obese, non-diabetic patients. Here we investigated the relevance of 1-deoxySLs as long-term predictive biomarkers for the incidence of T2DM in an asymptomatic population. Here, we analyzed the plasma sphingoid base profile in a nested group of non-diabetic individuals (N = 605) selected from a population-based study including 5 year follow-up data (CoLaus study). 1-DeoxySLs at baseline were significantly elevated in individuals who developed T2DM during the follow-up (p<0.001), together with increased glucose (p<5.11E-14), triglycerides (p<0.001) and HOMA-IR indices (p<0.001). 1-Deoxy-sphinganine (1-deoxySA) and 1-deoxy-sphingosine (1-deoxySO) were predictive for T2DM, even after adjusting for fasting glucose levels in the binary regression analyses. The predictive value of the combined markers 1-deoxySA+glucose were superior to glucose alone in normal-weight subjects (p<0.001) but decreased substantially with increasing BMI. Instead, plasma adiponectin and waist-to-hip ratio appeared to be better risk predictors for obese individuals (BMI>30kg/m2). In conclusion, elevated plasma 1-deoxySL levels are strong and independent risk predictors of future T2DM, especially for non-obese individuals in the general population.

A genetic risk score is significantly associated with statin therapy response in the elderly population.

The ability of statins to strongly reduce low-density lipoprotein cholesterol (LDL-C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population-based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL-C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population-based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL-C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL-C reduction to a considerable extent in the older population.

Prospective associations of depression subtypes with cardio-metabolic risk factors in the general population.

The mechanisms and temporal sequence underlying the association between major depressive disorder (MDD) and cardio-metabolic diseases are still poorly understood. Recent research suggests subtyping depression to study the mechanisms underlying its association with biological correlates. Accordingly, our aims were to (1) assess the prospective associations of the atypical, melancholic and unspecified subtypes of MDD with changes of fasting glucose, high-density lipoprotein-cholesterol, triglycerides, systolic blood pressure and the incidence of the metabolic syndrome, (2) determine the potential mediating role of inflammatory marker or adipokine concentrations, eating behaviors and changes in waist circumference during follow-up. Data stemmed from CoLaus|PsyCoLaus, a prospective cohort study including 35-66-year-old randomly selected residents of an urban area. Among the Caucasian participants who underwent the physical and psychiatric baseline evaluations, 2813 (87% participation rate) also accepted the physical follow-up exam (mean follow-up duration=5.5 years). Symptoms of mental disorders were elicited using a semi-structured interview. The atypical MDD subtype, and only this subtype, was prospectively associated with a higher incidence of the metabolic syndrome (OR=2.49; 95% CI 1.30-4.77), a steeper increase of waist circumference (ß=2.41; 95% CI 1.19-3.63) and independently of this, with a steeper increase of the fasting glucose level (ß=131; 95% CI 38-225) during follow-up. These associations were not attributable to or mediated by inflammatory marker or adipokine concentrations, eating behaviors, comorbid psychiatric disorders or lifestyle factors. Accordingly, our results further support the subtyping of MDD and highlight the particular need for prevention and treatment of metabolic consequences in patients with atypical MDD.

Trends in vitamin, mineral and dietary supplement use in Switzerland. The CoLaus study.

BACKGROUND/OBJECTIVES: Vitamin/mineral (VMS) and dietary supplements (DS) use is common in Switzerland, but nothing is known regarding the factors associated with their initiation, discontinuation or continuation of intake. SUBJECTS/METHODS: Prospective study conducted between 2003-2006 and 2009-2012 in Lausanne, Switzerland among 4676 participants (2525 women, age range 35-75 years). VMS were defined as single or multivitamin/multimineral preparations; DS were defined as any dietary supplement. RESULTS: VMS use was 20.6% at baseline and 20.3% at follow-up (P=0.69): 559 (12.0%) participants discontinued; 545 (11.7%) initiated and 404 (8.6%) continued VMS use. On multivariable analysis, men had a lower relative risk ratio (RRR) of discontinuing, initiation or continuing; older age and being physically active were associated with a higher RRR of initiation or continuing; lower education and higher body mass index were associated with a lower RRR of discontinuing or continuing of VMS. DS use decreased from 10.4 to 6.8% (P<0.001): 405 (8.7%) participants discontinued; 239 (5.1%) initiated and 81 (1.7%) continued DS use. On multivariable analysis, men had a lower RRR of discontinuing, initiation or continuing; older age had a higher RRR of initiation, discontinuing or continuing; being physically active was associated with a higher RRR of initiation or continuing; Swiss citizens and former smokers had a higher RRR of discontinuing. CONCLUSIONS: VMS use is stable in the Lausanne population, whereas DS use appears to be decreasing. Individuals can be categorized either as users or non-users depending on the study period, and consistent users are only a small fraction of prevalent users.

[Social networks and medicine]. / Réseaux sociaux: de nouveaux outils de communication et de formation pour les médecins?

Social networks (social media or #SoMe) have entered medical practice within the last few years. These new media--like Twitter or Skype--enrich interactions among physicians (telemedicine), among physicians and patients (virtual consultations) and change the way of teaching medicine. They also entail new ethical, deontological and legal issues: the extension of the consultation area beyond the medical office and the access of information by third parties were recently debated. We develop here a review of some social networks with their characteristics, applications for medicine and limitations, and we offer some recommendations of good practice.

[Taking into account spiritual dimension of the patient in multidisciplinary team]. / Prendre en compte la dimension spirituelle du patient: plus pertinent à plusieurs.

In the current healthcare environment, there is an increasing consensus for a holistic approach to the patient by means of a bio-psychosocial and spiritual model. The first part of this article describes how, in the context of a laic healthcare environment, physicians, nurses and spiritual caregivers are asked to change their way to communicate and to take into account this spiritual dimension. In the second part we will discuss some of the challenges of this interdisciplinary approach of the spiritual dimension in the hospital and the community. We will describe potential benefits for the patients, their family members and the caregivers. At the end, taking into account the spiritual dimension of the patient without proselytism will depend on the capacity of each caregiver to speak about it and to share this information in multidisciplinary team.

[Delivering bad news in a Swiss internal medicine ward: a medical and nurse partnership]. / L'annonce de mauvaises nouvelles en binôme médico-infirmier: mise en pratique en médecine interne.

Delivering bad news to a patient has a major impact for patients, their relatives and caregivers. The way this information is delivered can affect the way the patient sees his disease and potentially how he adheres to its treatment. To improve this communication with the patient the service of internal medicine at the Swiss university hospital of Lausanne set up a process including the coordination between all involved caregivers, and to break the bad news in a setting including a medical and nurse partnership. It also underscores that the resident in charge of the patient remains the coordinator of delivering new information. Moreover, the service provides communication tools to the caregivers to improve the communication skills.

Five year trends in dyslipidaemia prevalence and management in Switzerland: the CoLaus study.

BACKGROUND AND AIMS: Data from prospective cohorts describing dyslipidaemia prevalence and treatment trends are lacking. Using data from the prospective CoLaus study, we aimed to examine changes in serum lipid levels, dyslipidaemia prevalence and management in a population-based sample of Swiss adults. METHODS AND RESULTS: Cardiovascular risk was assessed using PROCAM. Dyslipidaemia and low-density lipoprotein cholesterol (LDL-C) target levels were defined according to the Swiss Group for Lipids and Atherosclerosis. Complete baseline and follow up (FU) data were available for n = 4863 subjects during mean FU time of 5.6 years. Overall, 32.1% of participants were dyslipidaemic at baseline vs 46.3% at FU (p < 0.001). During this time, lipid lowering medication (LLM) rates among dyslipidaemic subjects increased from 34.0% to 39.2% (p < 0.001). In secondary prevention, LLM rates were 42.7% at baseline and 53.2% at FU (p = 0.004). In multivariate analysis, LLM use among dyslipidaemic subjects, between baseline and FU, was positively associated with personal history of CVD, older age, hypertension, higher BMI and diabetes, while negatively associated with higher educational level. Among treated subjects, LDL-C target achievement was positively associated with diabetes and negatively associated with personal history of CVD and higher BMI. Among subjects treated at baseline, LLM discontinuation was negatively associated with older age, male sex, smoking, hypertension and parental history of CVD. CONCLUSIONS: In Switzerland, the increase over time in dyslipidaemia prevalence was not paralleled by a similar increase in LLM. In a real-life setting, dyslipidaemia management remains far from optimal, both in primary and secondary prevention.

Iron metabolism and incidence of metabolic syndrome.

BACKGROUND AND AIMS: Whether iron metabolism affects metabolic syndrome (METS) is debated. We assessed the association between several markers of iron metabolism and incidence of METS. METHODS AND RESULTS: Data from 3271 participants (1870 women, 51.3 ± 10.4 years), free of METS at baseline and followed for 5.5 years. The association of serum iron, ferritin and transferrin with incident METS was assessed separately by gender. Incidence of METS was 22.6% in men and 16.5% in women (p < 0.001). After multivariate adjustment, a positive association was found between transferrin and incident METS in men: odds ratio (OR) and 95% confidence interval for the fourth relative to the first quartile 1.55 (1.04-2.31), p for trend = 0.03, while no association was found for iron OR = 0.81 (0.53-1.24), p for trend = 0.33 and ferritin OR = 1.30 (0.88-1.92), p for trend = 0.018. In women, a negative association was found between iron and incident METS: OR for the fourth relative to the first quartile 0.51 (0.33-0.80), p for trend<0.03; the association between transferrin and incident METS was borderline significant: OR = 1.45 (0.97-2.17), p for trend = 0.07 and no association was found for ferritin: OR = 1.11 (0.76-1.63), p for trend = 0.58. CONCLUSION: Transferrin, not ferritin, is independently associated with an increased risk of incident METS; the protective effect of iron in women should be further explored.

Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.

Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study.

BACKGROUND: Sleep-disordered breathing is associated with major morbidity and mortality. However, its prevalence has mainly been selectively studied in populations at risk for sleep-disordered breathing or cardiovascular diseases. Taking into account improvements in recording techniques and new criteria used to define respiratory events, we aimed to assess the prevalence of sleep-disordered breathing and associated clinical features in a large population-based sample. METHODS: Between Sept 1, 2009, and June 30, 2013, we did a population-based study (HypnoLaus) in Lausanne, Switzerland. We invited a cohort of 3043 consecutive participants of the CoLaus/PsyCoLaus study to take part. Polysomnography data from 2121 people were included in the final analysis. 1024 (48%) participants were men, with a median age of 57 years (IQR 49-68, range 40-85) and mean body-mass index (BMI) of 25·6 kg/m(2) (SD 4·1). Participants underwent complete polysomnographic recordings at home and had extensive phenotyping for diabetes, hypertension, metabolic syndrome, and depression. The primary outcome was prevalence of sleep-disordered breathing, assessed by the apnoea-hypopnoea index. FINDINGS: The median apnoea-hypopnoea index was 6·9 events per h (IQR 2·7-14·1) in women and 14·9 per h (7·2-27·1) in men. The prevalence of moderate-to-severe sleep-disordered breathing (≥15 events per h) was 23·4% (95% CI 20·9-26·0) in women and 49·7% (46·6-52·8) in men. After multivariable adjustment, the upper quartile for the apnoea-hypopnoea index (>20·6 events per h) was associated independently with the presence of hypertension (odds ratio 1·60, 95% CI 1·14-2·26; p=0·0292 for trend across severity quartiles), diabetes (2·00, 1·05-3·99; p=0·0467), metabolic syndrome (2·80, 1·86-4·29; p<0·0001), and depression (1·92, 1·01-3·64; p=0·0292). INTERPRETATION: The high prevalence of sleep-disordered breathing recorded in our population-based sample might be attributable to the increased sensitivity of current recording techniques and scoring criteria. These results suggest that sleep-disordered breathing is highly prevalent, with important public health outcomes, and that the definition of the disorder should be revised. FUNDING: Faculty of Biology and Medicine of Lausanne, Lausanne University Hospital, Swiss National Science Foundation, Leenaards Foundation, GlaxoSmithKline, Ligue Pulmonaire Vaudoise.

Alcohol consumption and incidence of type 2 diabetes. Results from the CoLaus study.

BACKGROUND AND AIMS: Moderate alcohol consumption has been shown to decrease the risk of type 2 diabetes (T2DM), but whether this association is also valid for impaired fasting glucose (IFG) is less well known. We aimed at assessing the impact of alcohol consumption and of type of alcoholic beverage on the incidence of T2DM and T2DM + IFG. METHODS AND RESULTS: As many as 4765 participants (2613 women, mean age 51.7 ± 10.5 years) without T2DM at baseline and followed for an average of 5.5 years. The association between alcohol consumption, type of alcoholic beverage and outcomes was assessed after adjustment for a validated T2DM risk score. During follow-up 284 participants developed T2DM and 643 developed IFG. On bivariate analysis, alcohol consumption was positively associated with the risk of developing T2DM or T2DM + IFG. Moderate (14-27 units/week) alcohol consumption tended to be associated with a lower risk of T2DM, but no protective effect was found for T2DM + IFG. Multivariable-adjusted odds ratio (OR) and (95% confidence interval) for T2DM: 0.89 (0.65-1.22), 0.66 (0.42-1.03) and 1.63 (0.93-2.84) for 1-13, 14-27 and 28 + units/week, respectively (p for quadratic trend < 0.005). For T2DM + IFG, the corresponding ORs were 1.09 (0.90-1.32), 1.33 (1.02-1.74) and 1.54 (0.99-2.39), respectively, p for trend = 0.03. No specific effect of alcoholic beverage (wine, beer or spirits) was found for T2DM or for T2DM + IFG. CONCLUSION: Moderate alcohol consumption is associated with a reduced risk of developing T2DM, but not of developing T2DM + IFG. No specific effect of type of alcoholic beverage was found.