Recurrent episodes of febrile dyspnoea: hypersensitivity pneumonitis caused by a household ultrasonic humidifier.

Hypersensitivity pneumonitis is an immune-mediated interstitial lung disease that presents with respiratory symptoms, with or without systemic symptoms, following exposure to an identified or unidentified external factor. It can be caused by extrinsic factors including household items such as ultrasonic humidifiers.We present an intriguing case of a previously healthy 50-year-old man who displayed recurrent episodes of progressive dyspnoea and fever after repeated exposure to his household ultrasonic humidifier. He was treated with corticosteroids, followed by the removal of the humidifier, resulting in total recovery and absence of recurrence of further episodes.The clinical presentation of hypersensitivity pneumonitis can be dramatic, and the differential diagnosis is broad. The correct diagnosis is achieved by combining clinical, radiological and histopathological patterns. The key to finding the aetiology lies in a thorough history, with an important role for household investigations to identify the external factor.

Predictors for delayed antibiotic administration among bacteraemic patients in the Emergency Department: Differences between medical and surgical interns.

BACKGROUND: Bloodstream infections (BSIs) have been associated with high mortality. The aim of the study was to identify predictors of early (within 3 hours from triage) administration of first antibiotic dose among patients evaluated in the Emergency Department (ED) with BSI and their role in mortality. MATERIALS AND METHODS: All adult patients with BSI at the ED of the Hospital of Jura, Switzerland during a 3 year period (July 2014 to June 2017) were included. RESULTS: Among 364 BSI, the most common sites of infection were urinary tract (39.6% of BSIs), lower respiratory tract (15.4%), intra-abdominal (15.4%) and primary BSI (9.1%). One-hundred-seventy-eight patients (48.9%) received the first antibiotic dose within 3 hours from triage. Multivariate analysis identified evaluation by internal medicine intern, triage scales 1 and 2, as predictors of early antibiotic administration, while, primary BSI was associated with delayed antibiotic administration. Thirty-day mortality was 12.9% (47 patients). Charlson comorbidity index, septic shock, low respiratory tract infection were independently associated with mortality, while antibiotic administration within 3 hours from triage and source control within 48 hours from triage were associated with survival. CONCLUSIONS: The majority of patients received the first antibiotic dose after 3 hours Patients evaluated by surgical interns had a significant delay in administration of antibiotics as compared to those treated by medical interns.

Impact of universal infectious diseases consultation on the management of Staphylococcus aureus bloodstream infection in a Swiss community hospital.

We compared two periods, before and after systematic implementation of infectious diseases consultation for each Staphylococcus aureus bacteremia. Comparing these periods, we showed a significant increase in follow-up blood cultures (from 38% to 85%), transthoracic echocardiography (from 25% to 79%), and administration of appropriate antistaphylococcal agent (from 77% to 96%).

Predictors of mortality of influenza virus infections in a Swiss Hospital during four influenza seasons: Role of quick sequential organ failure assessment.

BACKGROUND: Influenza infections have been associated with high morbidity. The aims were to determine predictors of mortality among patients with influenza infections and to ascertain the role of quick Sequential Organ Failure Assessment (qSOFA) in predicting poor outcomes. METHODS: All adult patients with influenza infection at the Hospital of Jura, Switzerland during four influenza seasons (2014/15 to 2017/18) were included. Cepheid Xpert Xpress Flu/RSV was used during the first three influenza seasons and Cobas Influenza A/B and RSV during the 2017/18 season. RESULTS: Among 1684 influenza virus tests performed, 441 patients with influenza infections were included (238 for influenza A virus and 203 for B). The majority of infections were community onset (369; 83.7%). Thirty-day mortality was 6.0% (25 patients). Multivariate analysis revealed that infection due to A virus (P 0.035; OR 7.1; 95% CI 1.1-43.8), malnutrition (P < 0.001; OR 25.0; 95% CI 4.5-138.8), hospital-acquired infection (P 0.003; OR 12.2; 95% CI 2.3-65.1), respiratory insufficiency (PaO2/FiO2 < 300) (P < 0.001; OR 125.8; 95% CI 9.6-1648.7) and pulmonary infiltrate on X-ray (P 0.020; OR 6.0; 95% CI 1.3-27.0) were identified as predictors of mortality. qSOFA showed a very good accuracy (0.89) equivalent to other more specific and burdensome scores such as CURB-65 and Pneumonia Severity Index (PSI). CONCLUSION: qSOFA performed similarly to specific severity scores (PSI, CURB-65) in predicting mortality. Infection by influenza A virus, respiratory insufficiency and malnutrition were associated with worse prognosis.

Predictors of mortality of bloodstream infections among internal medicine patients in a Swiss Hospital: Role of quick Sequential Organ Failure Assessment.

BACKGROUND: Sepsis has been associated with high morbidity and mortality. The aims were to determine predictors of mortality among patients with bloodstream infections (BSIs) and to ascertain the role of quick Sequential Organ Failure Assessment (qSOFA) in predicting poor outcomes. METHODS: All internal medicine patients with BSIs at the Hospital of Jura, Switzerland during a three year period (July 2014 to June 2017) were included. RESULTS: Among 404 BSIs, Escherichia coli represented the most common species isolated (156 episodes; 38.6%), followed by Staphylococcus aureus (68; 16.8%). The most common site of infection was urinary tract accounting for 39.6% of BSIs (160 episodes). Thirty-day mortality was 18.1%. Multivariate analysis revealed BSI due to staphylococci, malignancy (haematologic or solid organ), qSOFA≥2 points, Pitt bacteraemia score as independent predictors of mortality, while appropriate empiric antibiotic therapy and administration of antibiotic therapy within three hours from infection's recognition were identified as a predictor of good prognosis. qSOFA showed the highest sensitivity (87.7%), negative predictive value (96.6%) and accuracy (0.83) as compared to other scores. Mortality among 141 septic patients was 45.4%. Malignancy (haematologic or solid organ), primary BSI, Pitt bacteraemia score, were independently associated with mortality, while appropriate empiric antibiotic therapy and administration of antibiotic therapy within the first hour from infection's recognition were associated with better prognosis. CONCLUSION: qSOFA as compared to other severity scores showed an excellent negative predictive value. Better prognosis was associated with administration of appropriate empiric antibiotic therapy and its timely initiation.

Indications and Outcomes of Helicopter Rescue Missions in Alpine Mountain Huts: A Retrospective Study.

Pasquier, Mathieu, Louis Marxer, Hervé Duplain, Vincent Frochaux, Florence Selz, Pierre Métrailler, Grégoire Zen Ruffinen, and Olivier Hugli. Indications and outcomes of helicopter rescue missions in alpine mountain huts: A retrospective study. High Alt Med Biol 18:355-362, 2017. AIMS: This retrospective study describes the rescue indications and outcome of patients rescued by helicopter from mountain huts in the Swiss Alps. The hospital course and operational data were also studied. RESULTS: Among 14,872 helicopter rescue missions undertaken during the 10-year study period, 309 (2.1%) were performed from mountain huts at a mean altitude of 2794 ± 459 m. The mean age of the patients was 43 ± 16 and 66% were male. Thirty-four percent of the patients had a National Advisory Committee for Aeronautics score ≥3. Most (89%) patients were transported to hospital and only 12 (3.9%) patients had to stay more than 48 hours. Hospital diagnoses were extremely varied. Trauma accounted for 50% and altitude diseases for 7% of the cases. A winching procedure was performed 18 times and 19 missions included a night flight. CONCLUSIONS: Helicopter rescue missions in mountain huts are a small part of all rescue missions. Our study provides a better understanding of medical emergencies arising in mountain huts. The diagnoses encountered are extremely varied in their type and severity. Hut keepers should be prepared for these situations as they will often have to act as first responders in the case of medical problems.

[Abiotrophia defectiva: an unusual cause of endocarditis]. / Endocardite à germe inhabituel: Abiotrophia defective.

This article reports one of the rare cases of Abiotrophia defectiva endocarditis with no underlying valvular condition. A sixty-three years old man was hospitalized because of complicated respiratory sepsis with acute heart failure. Hemocultures and echocardiogram enabled the diagnosis of A. defectiva endocarditis. The clinical course was favorable under combined aminoglycoside and cephalosporin. The patient ultimately required valvular replacement. A. defectiva is a micro-organism part of the Nutritionnaly Variant Streptococci (NVS) associated with a high mortality rate and often resistant to antibiotics. Although A. defectiva is a rare cause of endocarditis, prompt recognition and appropriate antibiotic treatment are essential to clinical course.

Developmental Origins of Hypoxic Pulmonary Hypertension and Systemic Vascular Dysfunction: Evidence from Humans.

Epidemiological studies have shown an association between pathologic events occurring during fetal/perinatal life and the development of cardiovascular and metabolic disease in adulthood. These observations have led to the so-called developmental origin of adult disease hypothesis. More recently, evidence has been provided that the pulmonary circulation is also an important target for the developmental programming of adult disease in both experimental animal models and in humans. Here we will review this evidence and provide insight into mechanisms that may play a pathogenic role.

Haemodynamic instability of uncommon aetiology in Switzerland.

In Switzerland, vitamin C deficiency is a rare condition. Nonetheless, in clinical practice, there are some patients exhibiting a vitamin C deficiency as a result of an unbalanced diet or intestinal malabsorption. We report the clinical history of a 55-year-old man known for alcoholism and insufficient intake of fresh fruits and vegetables. He was admitted to the intensive care unit, for haemodynamic instability caused by blood loss due to fragile vessels (skin, gastrointestinal). Further analyses revealed a severe lack of vitamin C. The patient received a high dose of intravenous substitutive treatment, leading to a favourable clinical outcome.

Acute and Chronic Altitude-Induced Cognitive Dysfunction in Children and Adolescents.

OBJECTIVE: To assess whether exposure to high altitude induces cognitive dysfunction in young healthy European children and adolescents during acute, short-term exposure to an altitude of 3450 m and in an age-matched European population permanently living at this altitude. STUDY DESIGN: We tested executive function (inhibition, shifting, and working memory), memory (verbal, short-term visuospatial, and verbal episodic memory), and speed processing ability in: (1) 48 healthy nonacclimatized European children and adolescents, 24 hours after arrival at high altitude and 3 months after return to low altitude; (2) 21 matched European subjects permanently living at high altitude; and (3) a matched control group tested twice at low altitude. RESULTS: Short-term hypoxia significantly impaired all but 2 (visuospatial memory and processing speed) of the neuropsychological abilities that were tested. These impairments were even more severe in the children permanently living at high altitude. Three months after return to low altitude, the neuropsychological performances significantly improved and were comparable with those observed in the control group tested only at low altitude. CONCLUSIONS: Acute short-term exposure to an altitude at which major tourist destinations are located induces marked executive and memory deficits in healthy children. These deficits are equally marked or more severe in children permanently living at high altitude and are expected to impair their learning abilities.

Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Clinical trials yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of community-acquired pneumonia. We assessed whether short-term corticosteroid treatment reduces time to clinical stability in patients admitted to hospital for community-acquired pneumonia. METHODS: In this double-blind, multicentre, randomised, placebo-controlled trial, we recruited patients aged 18 years or older with community-acquired pneumonia from seven tertiary care hospitals in Switzerland within 24 h of presentation. Patients were randomly assigned (1:1 ratio) to receive either prednisone 50 mg daily for 7 days or placebo. The computer-generated randomisation was done with variable block sizes of four to six and stratified by study centre. The primary endpoint was time to clinical stability defined as time (days) until stable vital signs for at least 24 h, and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00973154. FINDINGS: From Dec 1, 2009, to May 21, 2014, of 2911 patients assessed for eligibility, 785 patients were randomly assigned to either the prednisone group (n=392) or the placebo group (n=393). Median time to clinical stability was shorter in the prednisone group (3·0 days, IQR 2·5-3·4) than in the placebo group (4·4 days, 4·0-5·0; hazard ratio [HR] 1·33, 95% CI 1·15-1·50, p<0·0001). Pneumonia-associated complications until day 30 did not differ between groups (11 [3%] in the prednisone group and 22 [6%] in the placebo group; odds ratio [OR] 0·49 [95% CI 0·23-1·02]; p=0·056). The prednisone group had a higher incidence of in-hospital hyperglycaemia needing insulin treatment (76 [19%] vs 43 [11%]; OR 1·96, 95% CI 1·31-2·93, p=0·0010). Other adverse events compatible with corticosteroid use were rare and similar in both groups. INTERPRETATION: Prednisone treatment for 7 days in patients with community-acquired pneumonia admitted to hospital shortens time to clinical stability without an increase in complications. This finding is relevant from a patient perspective and an important determinant of hospital costs and efficiency. FUNDING: Swiss National Science Foundation, Viollier AG, Nora van Meeuwen Haefliger Stiftung, Julia und Gottfried Bangerter-Rhyner Stiftung.

Antioxidants improve vascular function in children conceived by assisted reproductive technologies: A randomized double-blind placebo-controlled trial.

AIMS: Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability. METHODS AND RESULTS: In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children. CONCLUSIONS: Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.

Corticosteroid treatment for community-acquired pneumonia--the STEP trial: study protocol for a randomized controlled trial.

BACKGROUND: Community-acquired pneumonia (CAP) is the third-leading infectious cause of death worldwide. The standard treatment of CAP has not changed for the past fifty years and its mortality and morbidity remain high despite adequate antimicrobial treatment. Systemic corticosteroids have anti-inflammatory effects and are therefore discussed as adjunct treatment for CAP. Available studies show controversial results, and the question about benefits and harms of adjunct corticosteroid therapy has not been conclusively resolved, particularly in the non-critical care setting. METHODS/DESIGN: This randomized multicenter study compares a treatment with 7 days of prednisone 50 mg with placebo in adult patients hospitalized with CAP independent of severity. Patients are screened and enrolled within the first 36 hours of presentation after written informed consent is obtained. The primary endpoint will be time to clinical stability, which is assessed every 12 hours during hospitalization. Secondary endpoints will be, among others, all-cause mortality within 30 and 180 days, ICU stay, duration of antibiotic treatment, disease activity scores, side effects and complications, value of adrenal function testing and prognostic hormonal and inflammatory biomarkers to predict outcome and treatment response to corticosteroids. Eight hundred included patients will provide an 85% power for the intention-to-treat analysis of the primary endpoint. DISCUSSION: This largest to date double-blind placebo-controlled multicenter trial investigates the effect of adjunct glucocorticoids in 800 patients with CAP requiring hospitalization. It aims to give conclusive answers about benefits and risks of corticosteroid treatment in CAP. The inclusion of less severe CAP patients will be expected to lead to a relatively low mortality rate and survival benefit might not be shown. However, our study has adequate power for the clinically relevant endpoint of clinical stability. Due to discontinuing glucocorticoids without tapering after seven days, we limit duration of glucocorticoid exposition, which may reduce possible side effects. TRIAL REGISTRATION: 7 September 2009 on ClinicalTrials.gov: NCT00973154.

Nitric oxide mediates the blood pressure response to mental stress in humans.

OBJECTIVE: Nitric oxide (NO) regulates arterial pressure by modulating peripheral vascular tone and sympathetic vasoconstrictor outflow. NO synthesis is impaired in several major cardiovascular disease states. Loss of NO-induced vasodilator tone and restraint on sympathetic outflow could result in exaggerated pressor responses to mental stress. METHODS: We, therefore, compared the sympathetic (muscle sympathetic nerve activity) and haemodynamic responses to mental stress performed during saline infusion and systemic inhibition of NO-synthase by NG-monomethyl-L-arginine (L-NMMA) infusion. RESULTS: The major finding was that mental stress which during saline infusion increased sympathetic nerve activity by ~50 percent and mean arterial pressure by ~15 percent had no detectable sympathoexcitatory and pressor effect during L-NMMA infusion. These findings were not related to a generalised impairment of the haemodynamic and/or sympathetic responsiveness by L-NMMA, since the pressor and sympathetic nerve responses to immersion of the hand in ice water were preserved during L-NMMA infusion. CONCLUSION: Mental stress causes pressor and sympathoexcitatory effects in humans that are mediated by NO. These findings are consistent with the new concept that, in contrast to what has been generally assumed, under some circumstances, NO has a blood pressure raising action in vivo.

Systemic and pulmonary vascular dysfunction in children conceived by assisted reproductive technologies.

BACKGROUND: Assisted reproductive technology (ART) involves the manipulation of early embryos at a time when they may be particularly vulnerable to external disturbances. Environmental influences during the embryonic and fetal development influence the individual's susceptibility to cardiovascular disease, raising concerns about the potential consequences of ART on the long-term health of the offspring. METHODS AND RESULTS: We assessed systemic (flow-mediated dilation of the brachial artery, pulse-wave velocity, and carotid intima-media thickness) and pulmonary (pulmonary artery pressure at high altitude by Doppler echocardiography) vascular function in 65 healthy children born after ART and 57 control children. Flow-mediated dilation of the brachial artery was 25% smaller in ART than in control children (6.7 ± 1.6% versus 8.6 ± 1.7%; P<0.0001), whereas endothelium-independent vasodilation was similar in the 2 groups. Carotid-femoral pulse-wave velocity was significantly (P<0.001) faster and carotid intima-media thickness was significantly (P<0.0001) greater in children conceived by ART than in control children. The systolic pulmonary artery pressure at high altitude (3450 m) was 30% higher (P<0.001) in ART than in control children. Vascular function was normal in children conceived naturally during hormonal stimulation of ovulation and in siblings of ART children who were conceived naturally. CONCLUSIONS: Healthy children conceived by ART display generalized vascular dysfunction. This problem does not appear to be related to parental factors but to the ART procedure itself. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00837642.

Reproducibility of acute mountain sickness in children and adults: a prospective study.

OBJECTIVE: Although a history of previous acute mountain sickness (AMS) is commonly used for providing advice and recommending its prophylaxis during subsequent exposure, the intraindividual reproducibility of AMS during repeated high-altitude exposure has never been examined in a prospective controlled study. METHODS: In 27 nonacclimatized children and 29 adults, AMS was assessed during the first 48 hours after rapid ascent to 3450 m on 2 consecutive occasions 9 to 12 months apart. RESULTS: During the first exposure, 18 adults (62%) and 6 children (22%) suffered from AMS; during the second exposure, 14 adults (48%) and 4 children (15%) suffered from this problem (adults versus children, P ≤ .01). Most importantly, the intraindividual reproducibility of AMS was very different (P < .001) between children and adults. None of the 6 children having suffered from AMS during the first exposure suffered from AMS during the second exposure, but 4 children with no AMS during the first exposure did experience this problem during the second exposure. In contrast, 14 of the 18 adults who suffered from AMS on the first occasion also presented with this problem during the second exposure, and no new case developed in those who had not experienced AMS on the first occasion. CONCLUSIONS: In adults, a history of AMS is highly predictable of the disease on subsequent exposure, whereas in children it has no predictive value. A history of AMS should not prompt practitioners to advise against reexposure to high altitude or to prescribe drugs for its prophylaxis in children.

Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice.

Obesity and insulin resistance represent a problem of utmost clinical significance worldwide. Insulin-resistant states are characterized by the inability of insulin to induce proper signal transduction leading to defective glucose uptake in skeletal muscle tissue and impaired insulin-induced vasodilation. In various pathophysiological models, melatonin interacts with crucial molecules of the insulin signaling pathway, but its effects on glucose homeostasis are not known. In a diet-induced mouse model of insulin resistance and normal chow-fed control mice, we sought to assess the effects of an 8-wk oral treatment with melatonin on insulin and glucose tolerance and to understand underlying mechanisms. In high-fat diet-fed mice, but not in normal chow-fed control mice, melatonin significantly improved insulin sensitivity and glucose tolerance, as evidenced by a higher rate of glucose infusion to maintain euglycemia during hyperinsulinemic clamp studies and an attenuated hyperglycemic response to an ip glucose challenge. Regarding underlying mechanisms, we found that melatonin restored insulin-induced vasodilation to skeletal muscle, a major site of glucose utilization. This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin-induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin-treated high-fat diet-fed mice. In contrast, melatonin had no effect on the ability of insulin to promote glucose uptake in skeletal muscle tissue in vitro. These data demonstrate for the first time that in a diet-induced rodent model of insulin resistance, melatonin improves glucose homeostasis by restoring the vascular action of insulin.