Survival with Good Neurological Outcome despite Prolonged Cardiopulmonary Resuscitation and Extreme Acidosis after Out-of-Hospital Cardiac Arrest Due to Acute Myocardial Infarction: A Case Report and Review of the Literature.

We report the case of a 49-year-old male who suffered from a myocardial infarction with subsequent cardiac arrest. The emergency medical team began cardiopulmonary resuscitation, including defibrillation of ventricular fibrillation. Although a return of spontaneous circulation was achieved after approximately 30 min of continued efforts, the patient went back into cardiac arrest on the way to the hospital and resuscitation had to be resumed. On admission, the patient was severely acidotic with a pH of 6.67, lactatemia of 19 mmol/L, and pronounced hypercapnia (pCO2 127 mmHg). Despite the poor prognosis, all possible efforts including coronary intervention and therapeutic hypothermia were carried out and the patient made a quick recovery with discharge from the intensive care unit on day 5. Survival of extreme acidosis, such as in this case, is rare. This is the first report of survival with good neurologic outcome in a patient with myocardial infarction, cardiac arrest, and pH of under 6.7 on admission at the clinic.

Performance of galactomannan testing from endotracheal aspirate to guide bronchoalveolar lavage in the diagnosis of invasive aspergillosis.

PURPOSE: Invasive aspergillosis is a major threat to immunocompromised individuals. Galactomannan (GM) is used as a biomarker for invasive aspergillosis. Investigations recommended in current guidelines include GM testing of bronchoalveolar lavage (BAL) fluids. GM testing of endotracheal aspirate, the sampling of which is less invasive, less resource-intensive and less aerosol-generating, is not validated. We compared the performance of endotracheal aspirate GM as a screening tool to predict BAL fluid GM-positivity in patients with suspected invasive aspergillosis. METHODS: Of each patient, a pair of corresponding endotracheal aspirate and BAL fluid samples was tested and compared for GM results. Two sample sets were included. The first consisted of 140 consecutive BAL fluid/endotracheal aspirate pairs obtained from 133 patients. The pairs of the second sample set (n = 38) were selected based on the criterion that the BAL tested positive for GM. All specimens were obtained in a German 2,000 bed tertiary care center. RESULTS: Among BAL fluid GM-positive samples, endotracheal aspirate GM demonstrated poor specificity (72%) but high sensitivity (92% in predicting BAL fluid GM of ≥ 0.50 and 91% for BAL fluid GM of ≥ 1.00) and an excellent negative predictive value (98%). The use of a marginally elevated cutoff of 0.63 resulted in an improved specificity (72-81%), without loss of sensitivity. CONCLUSIONS: For screening purposes, one might consider testing endotracheal aspirate for GM, which could help avoid unnecessary BAL.

A Case of Self-salvation in a Determined Chloroquine Suicide Attempt.

This report concerns a young man who attempted suicide by ingesting a cocktail with a lethal dose of chloroquine phosphate and large amounts of diazepam. On presentation, the patient was drowsy, unresponsive and in cardiogenic shock with severely impaired left ventricular function. Active charcoal and vasopressors were administered, and despite his intoxication with diazepam, a high-dose diazepam treatment was initiated in the hospital. It is concluded that diazepam in the cocktail played a vital role in the survival of this patient. With a rise in numbers, every emergency and intensive care physician should be familiar with chloroquine poisoning.

What do international health electives and state examination scores have in common? - A cohort study to compare the results of written medical licensing examinations with the participation in international health electives during the final year of undergraduate medical education in Germany.

Objective: The final year of undergraduate medical education in Germany is called the practical year (PY), where emphasis is placed on developing practical skills requisite of soon-to-be physicians. Many students choose to spend part of this year abroad, yet little is known about their results on the medical licensing examinations. Is there a predisposition of high-performing students to go abroad as compared to lower performers? Are international health electives during the PY followed by higher scores in the final section of the German medical licensing examination (GMLE2)? Methods: We conducted a retrospective cohort study among undergraduate medical students at the LMU Munich, who participated in the final section of the German medical licensing examination between autumn 2009 and spring 2011. Of the 1,731 eligible students, 554 (32%) participated in our study. We analyzed for statistical associations of international health electives with written test scores of both sections of the medical licensing examination as well as grades earned during medical school training. We then used multiple regression analysis to identify relevant predictors of GMLE2 scores. Results: Approximately half of study participants pursued international health electives during the PY (51.1%). The number of students going abroad increased with the scores achieved on the first section of the medical licensing examination (GMLE1, p<0.001). Stratified by their GMLE1 scores students who pursued electives abroad during their PY achieved higher GMLE2 scores (p<0.001). The strongest predictor for GMLE2 scores were grades obtained during medical school training; age and study duration indicated lower scores; and those engaging in international health electives correlated with higher scores. Conclusions: Students with higher GMLE1 scores go abroad during PY more often. Beyond that, students who pursue international health electives achieve higher GMLE2 scores than those who stay in Germany during PY. There is an unmet need for additional research to identify which factors make these students perform better and what motivates them to go abroad.

Assessment of lung function in a large cohort of patients with acromegaly.

OBJECTIVE: Acromegaly is associated with increased mortality due to respiratory disease. To date, lung function in patients with acromegaly has only been assessed in small studies, with contradicting results. We assessed lung function parameters in a large cohort of patients with acromegaly. DESIGN: Lung function of acromegaly patients was prospectively assessed using spirometry, blood gas analysis and body plethysmography. Biochemical indicators of acromegaly were assessed through measurement of growth hormone and IGF-I levels. This study was performed at the endocrinology outpatient clinic of a tertiary referral center in Germany. METHODS: We prospectively tested lung function of 109 acromegaly patients (53 male, 56 female; aged 24-82 years; 80 with active acromegaly) without severe acute or chronic pulmonary disease. We compared lung volume, air flow, airway resistance and blood gases to normative data. RESULTS: Acromegaly patients had greater lung volumes (maximal vital capacity, intra-thoracic gas volume and residual volume: P < 0.001, total lung capacity: P = 0.006) and showed signs of small airway obstruction (reduced maximum expiratory flow when 75% of the forced vital capacity (FVC) has been exhaled: P < 0.001, lesser peak expiratory flow: P = 0.01). There was no significant difference between active and inactive acromegaly. Female patients had significantly altered lung function in terms of subclinical airway obstruction. CONCLUSIONS: In our cross-sectional analysis of lung function in 109 patients with acromegaly, lung volumes were increased compared to healthy controls. Additionally, female patients showed signs of subclinical airway obstruction. There was no difference between patients with active acromegaly compared with patients biochemically in remission.

How well do final year undergraduate medical students master practical clinical skills?

INTRODUCTION: The clinical examination and other practical clinical skills are fundamental to guide diagnosis and therapy. The teaching of such practical skills has gained significance through legislative changes and adjustments of the curricula of medical schools in Germany. We sought to find out how well final year undergraduate medical students master practical clinical skills. METHODS: We conducted a formative 4-station objective structured clinical examination (OSCE) focused on practical clinical skills during the final year of undergraduate medical education. Participation was voluntary. Besides the examination of heart, lungs, abdomen, vascular system, lymphatic system as well as the neurological, endocrinological or orthopaedic examination we assessed other basic clinical skills (e.g. interpretation of an ECG, reading a chest X-ray). Participants filled-out a questionnaire prior to the exam, inter alia to give an estimate of their performance. RESULTS: 214 final year students participated in our study and achieved a mean score of 72.8% of the total score obtainable. 9.3% of participants (n=20) scored insufficiently (<60%). We found no influence of sex, prior training in healthcare or place of study on performance. Only one third of the students correctly estimated their performance (35.3%), whereas 30.0% and 18.8% over-estimated their performance by 10% and 20% respectively. DISCUSSION: Final year undergraduate medical students demonstrate considerable deficits performing practical clinical skills in the context of a formative assessment. Half of the students over-estimate their own performance. We recommend an institutionalised and frequent assessment of practical clinical skills during undergraduate medical education, especially in the final year.

A defect of CD16-positive monocytes can occur without disease.

The CD16-positive monocytes have been first described in 1988 but to date no selective defect in the number of these cells in blood has been reported. We now describe a family in which three of four siblings lack both CD16-positive monocyte subsets, i.e. the nonclassical and the intermediate monocytes. All three had CD16-positive monocytes of 2 cells/µl or less as compared to 52±18 cells/µl in healthy controls. The index case was affected by recurrent pleural effusion and infections and had evidence of an auto-inflammatory condition but no mutation of any of the relevant candidate genes. The other two siblings without CD16-positive monocytes were apparently healthy. There was no defect in serum M-CSF levels and no mutation in the M-CSF and M-CSFR genes. The data indicate that the absence of CD16-positive monocytes in blood does not lead to disease.

Modulation of monocytic lipopolysaccharide-induced tissue factor expression and tumor necrosis factor alpha release by estrogen and calcitriol.

OBJECTIVE: Modulatory effects of estrogens on both the immune and the coagulation system are only partially understood. In severe infections high estrogen levels have been observed both in men and postmenopausal women and are associated with increased mortality. Monocyte-derived tissue factor (TF) expression can activate the coagulation system and worsen the course of severe infection. T he aim of the current study was to evaluate the in vitro effect of estrogens on differentiation, TF expression and Tumor Necrosis Factor alpha (TNFalpha) release in human monocytes. DESIGN: Isolated peripheral blood monocytes, MM6- and T HP-1 cells were cultured and stimulated by lipopolysaccharides (LPS) in the presence of 17beta-estradiol (E2) and/or calcitriol. Proliferative responses were evaluated by determining the proliferation rate and by cell cycle analysis. Cell surface expression of C D14 and T F was determined by flow cytometry. TNFalpha was determined by ELISA. RESULTS: Although calcitriol induced the expression of the differentiation marker C D14 and decreased the expression of T F in both immature monocytic cell lines and primary monocytes, the LPS stimulation of T F expression was not significantly increased in immature monocytic cells and was decreased in mature monocytes. Calcitriol-treatment increased LPS-induced TNFalpha release in MM6 cells but inhibited TNFalpha release from peripheral blood monocytes. Treatment with E2 did not alter the phenotype or cell proliferation of resting monocytic cells. However, E2-treated monocytic cells and monocytes responded to LPS by increased TF expression and decreased TNFalpha. CONCLUSIONS: The results suggest that estrogens may modulate T F expression and cytokine production by monocytes and may thus be involved, at least in part, in the pathophysiology of acute inflammatory processes associated with high estrogen levels.

Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock.

OBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. DESIGN: Prospective randomized, placebo-controlled, multiple-center trial. SETTING: Eleven intensive care units in Germany. PATIENTS: Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. INTERVENTIONS: Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. CONCLUSIONS: The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.

New disseminated intravascular coagulation score: A useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores.

OBJECTIVE: To compare the performance of a coagulation score-the new scoring system for diagnosing disseminated intravascular coagulation (DIC)-with the Acute Physiology and Chronic Health Evaluation (APACHE) II and Logistic Organ Dysfunction score in mortality prediction. DESIGN: Single-center retrospective study. SETTING: Medical intensive care unit of the University of Munich. PATIENTS: A total of 797 patients admitted to the intensive care unit between January 1, 1996, and January 1, 2001. METHODS: A retrospective analysis of all patients was done if the coagulation variables d-dimer, platelet count, fibrinogen, and prothrombin index were available within the first 12 hrs after admission. Patients with missing values, fibrinolytic therapy, or unknown survival status were excluded from analysis. As a marker of fibrin generation, d-dimer was measured and integrated into the scoring system for DIC together with prothrombin time, fibrinogen, and platelet count. A coagulation score was calculated in analogy with the scoring system for DIC in patients not typically developing DIC. MEASUREMENTS AND RESULTS: Overall, the mean result of the scoring system for DIC was 2.2 points. An increasing scoring system for DIC was associated with increasing mortality in patients with serious infections. Use of the scoring system for DIC in addition to the APACHE II score helps to predict mortality better than the APACHE II score alone, especially in patients with infections. The Cox regression analysis showed that the DIC and APACHE II scores correlated independently with survival time with a greater effect of the DIC score than the APACHE II or the Logistic Organ Dysfunction score. Similar results were obtained using the coagulation score in patients with cardiocirculatory diseases. CONCLUSION: Our retrospective data suggest that a combination of the APACHE II score and the scoring system for DIC predicts mortality in critically ill patients with available variables better than the APACHE II score alone. This effect is most pronounced among patients with active infection. These results of our retrospective analysis have to be confirmed in a prospective study.

Outcome in elderly patients with severe infection is influenced by sex hormones but not gender.

OBJECTIVE: The influence of gender as a prognostic variable in patients with severe infections is still controversial. Sex steroid hormones have an important impact on the immune system and vice versa, and prospective studies on the hormonal changes during severe infection are lacking. The objective was to compare the influences of gender and adrenal sex steroid hormone levels on hospital mortality rate in patients with infections. DESIGN: Prospective observational study conducted between January 1995 and December 2000. SETTING: University-based level I intensive care unit. PATIENTS: Included were 208 males and 100 females with severe infection at admission to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality rate during hospitalization was analyzed for correlation to gender and the levels of testosterone, 17beta-estradiol, and progesterone; source and clinical signs of infection; Acute Physiology and Chronic Health Evaluation II score; or age. There were no differences in demographic or infectious characteristics between males and females; the survival rate was similar. Males had significantly reduced testosterone levels. Elevation of the steroid hormones 17beta-estradiol (1.5-fold), progesterone (5-fold), and cortisol (1.5-fold) occurred in both genders to the same extent. In addition, testosterone was elevated in septic females and correlated with 17beta-estradiol. Nonsurvivors of both genders had significantly elevated 17beta-estradiol levels. Progesterone was particularly high in nonsurviving males, whereas testosterone was elevated in nonsurviving females. Mortality rate was correlated with high 17beta-estradiol and progesterone in males but with 17beta-estradiol and testosterone in females. Cortisol or dehydroepiandrostenedione sulfate levels were not associated with mortality rates. CONCLUSIONS: In elderly patients with infections, mortality was not dependent on gender but was correlated with elevated 17beta-estradiol in both genders, with elevated progesterone in males and elevated testosterone in females. Although the latter sex hormones may derive from the adrenals, cortisol levels were only moderately increased and not associated with survival. The high 17beta-estradiol concentrations implicate an increased aromatase activity. Therefore, other pathways of sex steroid production must be involved.

Selenium substitution has no direct effect on thyroid hormone metabolism in critically ill patients.

BACKGROUND: In severe illness, plasma selenium levels are decreased; a decreased activity of the selenoenzyme 5'-deiodinase has been hypothesized to contribute to low tri-iodothyronine (T3) levels in non-thyroidal illness (NTI) syndrome in these patients. OBJECTIVE: To analyse the influence of selenium substitution on thyroid hormone metabolism in patients with severe sepsis. DESIGN: A prospective, randomized, controlled study at the medical internal intensive care unit of the University of Munich. Results are for 41 consecutive patients with severe sepsis with an APACHE II score >15. Patients received either sodium selenite (500 microg/day for the first 3 days, reducing to 250 and then 125 microg/day every 3 days) or a placebo. RESULTS: At study entry, APACHE II score and demographics were identical in both groups. The mean levels of TSH, free tri-iodithyronine and total T3, as well as plasma selenium and selenium-dependent peroxidase (GSH-Px) activity, were decreased. Plasma selenium and GSH-Px activity were normalized on days 3, 7 and 14 in patients receiving selenium (n=21), but remained below normal in the control patients. Patients receiving selenium had a better clinical outcome and thyroid hormone levels normalized earlier. Thyroid hormone levels increased in patients who showed clinical improvement, independent of selenium levels or selenium substitution. CONCLUSIONS: Selenium substitution in patients with NTI improves morbidity, but has no direct effect on the free and total thyroid hormones. In severely ill patients, decreased deiodinase activity due to low plasma selenium levels seems unlikely. After clinical revival, TSH and then the thyroidal hormones normalize independently of selenium substitution.

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Treatment of intoxication with Cortinarius speciosissimus using an antioxidant therapy.

The authors present the case reports of a 30-year-old man and his 29-year-old wife who ingested a mushroom meal containing Cortinarius speciosissimus. Features of this intoxication include gastrointestinal symptoms such as nausea, vomiting, and diarrhea as well as back pain. The toxin orellanine is nephrotoxic and can lead to acute renal failure. A long symptom-free interval of 2 to 21 days is characteristic of this poisoning. The diagnosis can be made by mycologic testing or by toxicologic analysis of a renal biopsy specimen. Reported therapeutic options include hemodialysis, plasmapheresis, or drug therapy with corticosteroids, all of which have yielded variable results. Here the authors report the use of antioxidant therapy in 2 patients with acute renal failure caused by Cortinarius speciosissimus intoxication.

Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations.

In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml. The primary end point of the study was the change in TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation. Patients were randomized into 2 age- and antibody (TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium selenite/d, orally, for 3 months, and 34 patients received placebo. All patients were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, TgAb, TSH, and free thyroid hormones were determined by commercial assays. The echogenicity of the thyroid was monitored with high resolution ultrasound. The mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction in the selenium-treated patients compared with a 10% increase in TPOAb in the placebo group. TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased (P = 0.018), but were unchanged in the selenium group. Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T(4), and free T(3) levels were unchanged in both groups. We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.