The complement cascade in lung injury and disease.

BACKGROUND: The complement system is an important arm of immune defense bringing innate and adaptive immunity. Although originally regarded as a major complementary defense mechanism against pathogens, continuously emerging evidence has uncovered a central role of this complex system in several diseases including lung pathologies. MAIN BODY: Complement factors such as anaphylatoxins C3a and C5a, their receptors C3aR, C5aR and C5aR2 as well as complement inhibitory proteins CD55, CD46 and CD59 have been implicated in pathologies such as the acute respiratory distress syndrome, pneumonia, chronic obstructive pulmonary disease, asthma, interstitial lung diseases, and lung cancer. However, the exact mechanisms by which complement factors induce these diseases remain unclear. Several complement-targeting monoclonal antibodies are reported to treat lung diseases. CONCLUSIONS: The complement system contributes to the progression of the acute and chronic lung diseases. Better understanding of the underlying mechanisms will provide groundwork to develop new strategy to target complement factors for treatment of lung diseases.

Adrenal function in relation to cytokines and outcome in non-critically ill patients with COVID-19.

PURPOSE: We aimed to identify whether hypothalamic-pituitary-adrenal (HPA) axis dysfunction is related to deterioration in a percentage of patients who progress to severe COVID-19. METHODS: In this cohort observational study, we evaluated HPA axis activation by measuring cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate (DHEA-S) levels, whole blood expression levels of the key glucocorticoid receptor, GCR-α, and the glucocorticoid-induced leucine zipper (GILZ), and cytokines, as markers of the inflammatory phase, in 149 patients with respiratory infection admitted in the ward, without known adrenal disease and/or confounding medications (glucocorticoids). One hundred and four (104) patients were SARS-CoV-2 positive (C +) and controls consisted of 45 SARS-CoV-2-negative patients (NC). RESULTS: No differences in cortisol levels were observed between the C + and the NC patients. Cortisol levels correlated with ACTH (r = 0.284, p = 0.001) and IL-6 (r = 0.289, p = 0.04). In C + patients, cortisol levels mainly correlated with IL-6 levels (r = 0.28; p = 0.017). GCR-α expression was significantly higher in C + patients compared to NC. Patients with higher cortisol levels were more likely to progress to respiratory function deterioration or die. Both GCR-α and GILZ expression were significantly higher in C + non-survivors. CONCLUSION: Our findings indicate that cortisol serves as an indicator of disease severity. GILZ expression appears to be a more effective marker of mortality prediction in moderate COVID-19 cases. However, routine measurement of GILZ levels is currently unavailable. Elevated levels of cortisol may be indicative of patients with moderate COVID-19 who are at a higher risk of deterioration. This information can aid in identifying individuals who require early medical attention.

Accuracy of T2 magnetic resonance assays as point-of-care methods in the intensive care unit.

BACKGROUND: Novel molecular diagnostic methods are being evaluated in order to expedite pathogen identification in patients with bacteraemia. AIMS: To evaluate the feasibility and diagnostic accuracy of the T2 magnetic resonance (T2MR) assays - T2 Bacteria (T2B) and T2 Resistance (T2R) - as point-of-care tests in the intensive care unit compared with blood-culture-based tests. METHODS: Prospective cross-sectional study of consecutive patients with suspected bacteraemia. Diagnostic accuracy was evaluated using blood culture as the reference method. FINDINGS: In total, 208 cases were included in the study. The mean time from sampling to report was lower for the T2MR assays compared with blood-culture-based methods (P<0.001). The rate of invalid reports was 6.73% for the T2B assay and 9.9% for the T2R assay. For the T2B assay, overall positive percentage agreement (PPA) was 84.6% [95% confidence interval (CI) 71.9-93.1%], negative percentage agreement (NPA) was 64.3% (95% CI 55.4-72.6%), positive predictive value (PPV) was 48.9% (95% CI 42.5-55.3%) and negative predictive value (NPV) was 91.2% (95% CI 84.4-95.2%). Cohen's kappa coefficient was 0.402. For the T2R assay, overall PPA was 80% (95% CI 51.9-95.7%), NPA was 69.2% (95% CI 54.9-81.3%), PPV was 42.9% (95% CI 31.7-54.8%) and NPV was 92.3% (95% CI 81.1-97.1%). Cohen's kappa coefficient was 0.376. CONCLUSION: T2MR assays have high NPV for rapid exclusion of bacteraemia, and could potentially assist with antimicrobial stewardship when applied as point-of-care diagnostic tests in the intensive care unit.

Ghrelin alterations during experimental and human sepsis.

BACKGROUND: Ghrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model. METHODS: All consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected. RESULTS: In patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ±â€¯213.4 vs 193.5 ±â€¯123.2, p < 0.001; 254.3 ±â€¯70.6 vs 56.49 ±â€¯16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouse endotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice. CONCLUSIONS: In a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process.

Adipose tissue lipolysis and circulating lipids in acute and subacute critical illness: effects of shock and treatment.

PURPOSE: The purpose of this study is to assess lipid metabolism at the tissue level in critically ill subjects. MATERIALS AND METHODS: We studied 182 patients with systemic inflammatory response syndrome/severe sepsis or shock during the acute (day 1) and subacute phase of critical illness (day 6). All subjects had a tissue microdialysis (MD) catheter placed in femoral adipose tissue upon admission to the intensive care unit (ICU). Plasma cholesterol, high-density lipoprotein, low-density lipoprotein, free fatty acids (FFAs), triglyceride, and MD glycerol (GLYC) were measured on days 1 and 6 in the ICU. RESULTS: On admission, 56% of the patients had increased levels (>200 µmol/L) of MD GLYC. Patients with shock displayed more pronounced subcutaneous tissue lipolysis and more profound derangements of circulating lipids vs patients without shock (but no appreciable differences in FFA levels). Furthermore, in patients with shock during the acute period, there were positive, albeit weak, correlations of subcutaneous tissue lipolysis (MD GLYC), plasma FFAs (r=0.260; P=.01), and norepinephrine's dose (r=0.230; P=.01), whereas during the subacute phase, MD GLY levels were higher in patients receiving glucocorticoids (344.7±276.0 µmol/L vs 252.2±158.4 µmol/L; P=.03). CONCLUSIONS: Subcutaneous tissue lipolysis is only one of the many determinants of plasma FFAs. Routinely applied therapeutic modalities in the ICU interfere with adipose tissue metabolism.

Elevated adipose tissue lactate to pyruvate (L/P) ratio predicts poor outcome in critically ill patients with septic shock: a microdialysis study.

BACKGROUND: Sepsis is a disease affecting tissue metabolism; in vivo microdialysis (MD) is a bedside technique enabling researchers to monitor tissue metabolic changes. We conducted this study aiming to evaluate the relationship between lactate to pyruvate (L/P) ratio, a sensitive marker of tissue oxygenation and perfusion, and mortality in critically ill septic patients. METHODS: We enrolled 105 patients with septic shock hospitalized in the mixed intensive care unit of a tertiary hospital. A MD catheter was inserted in the subcutaneous adipose tissue of the upper thigh and interstitial fluid samples were collected and analyzed for glucose, lactate, pyruvate, and glycerol. RESULTS: Multivariate regression analysis showed that among variables registered on day 1, APACHE II and SOFA scores, blood lactate and microdialysis-assessed tissue L/P ratio were independently associated with 28-day mortality. Even in patients with normal (<2 mmol/L) blood lactate, adipose tissue L/P ratio showed a strong trend to statistical significance. During the 6-day study period, non-survivors had significantly higher L/P ratios compared to survivors (P=0.001) and mixed model analysis revealed a different pattern of evolution in time with non-survivors experiencing an increase while survivors had a late decline in their L/P ratio. The AUC for L/P ratio was similar to that of APACHE II (P=0.67) and SOFA score (P=0.73). Comparison of the Kaplan-Meier 28-day survival curves of patients with normal (≤ 25) versus elevated (>25) L/P ratios showed that the latter survived significantly less (P=0.02; log-rank test). CONCLUSION: Elevated adipose tissue L/P ratio is associated with poor outcome in critically ill patients with septic shock. Microdialysis deserves to be further studied as a research tool in the multi-modal monitoring of septic critically ill patients.

The effect of homocysteine on the clinical outcomes of ventilated patients with severe sepsis.

BACKGROUND: There is considerable evidence that elevated plasma homocysteine levels are associated with a prothrombotic milieu, whereas activation of the coagulation cascade is an important component of the pathogenesis of sepsis. The protein C pathway has been reported to play a central role both in the propagation of sepsis and a hyperhomocysteinemia-induced hypercoagulable state. Our primary aim was to measure plasma homocysteine levels in mechanically ventilated patients with severe sepsis/septic shock and to assess the association of these levels with relevant clinical outcomes. METHODS: The study cohort included 102 mechanically ventilated patients with severe sepsis or septic shock. Demographics, comorbidities, clinical data and severity scores were recorded. Plasma homocysteine, vitamin B12, folate, creatinine, and protein C levels were measured in all study subjects upon enrollment, and genotyping for the C677T and A1298C polymorphisisms of the methylenetetrahydrofolate reductase (MTHFR) gene and for factor V Leiden (FVL) mutations was performed as well. The primary outcomes were mortality at 28 and 90 days; secondary outcomes included the number of days without renal or cardiovascular failure and the ventilator-free days during the study period. RESULTS: Homocysteine levels were not significantly associated with any primary or secondary outcomes in the multivariable analysis. In addition, a synergistic effect of homocysteine with protein C levels was not detected. CONCLUSION: Our data suggest that plasma homocysteine levels may not inform the prognosis of mechanically ventilated patients with severe sepsis/septic shock.

Failure of tigecycline to treat severe Clostridium difficile infection.

Clostridium difficile infection is an emerging and often difficult-to-treat iatrogenic complication. Recent data suggest that tigecycline, a novel antibiotic with broad-spectrum antibacterial activity, can be used successfully to treat patients with severe Clostridium difficile infection. We report a 70-year-old man who developed severe Clostridium difficile infection, was admitted to the intensive care unit and eventually succumbed to complications of his illness despite receiving tigecycline for approximately three weeks in combination with vancomycin, metronidazole and intravenous immunoglobulin. Additionally, we discuss the unique challenges that emerged during tigecycline treatment, such as the development of Proteus mirabilis bacteraemia and of colonisation with Acinetobacter baumannii resistant to tigecycline. Finally, we review data on other cases reported in the medical literature. Even though tigecycline looks promising for the treatment of Clostridium difficile infection, we urge caution against its indiscriminate use for off label indications.

Serum of patients with septic shock stimulates the expression of Trem-1 on U937 monocytes.

OBJECTIVES: To describe the concentrations of sTREM-1 in patients with sepsis and to explore the effects of their serum on the expression of TREM-1 on U937 monocytes. METHODS: Blood was sampled at regular time intervals in 56 patients with sepsis. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1alpha), IL-6, IL-8, IL-10 and IL-12p70 and sTREM-1 were measured. U937 monocytes were incubated in the presence of serum at sepsis onset. RESULTS: Median sTREM-1 concentration on day 1 for patients with septic shock was 915 pg/ml and 228.5 pg/ml for those without shock (p = 0.002). TNFalpha, IL-1alpha, IL-6, IL-8 and IL-10 did not differ between them. A positive correlation was found between changes of sTREM-1 and SOFA scores from day 1 to 7. Sera of patients with septic shock evoked a significant increase of the expression of TREM-1. The concentrations of TNFalpha and IL-8 in supernatants increased only after stimulating with sera of patients without shock, but not after stimulating with sera of patients with shock. CONCLUSIONS: Levels of sTREM-1 correlated with sepsis severity. sTREM-1 is considerably higher in patients with shock compared to patients without shock. The serum of shocked patients could stimulate the expression of TREM-1 on U937 monocytes.

Pulmonary toxicity from novel antineoplastic agents.

BACKGROUND: The pulmonary side-effects induced by novel antineoplastic agents have not been well characterized. METHODS: To further investigate this topic, relevant English and non-English language studies were identified through Medline. For our search we used the generic names of novel cytotoxic or non-cytotoxic antineoplastic agents and the key phrases pulmonary/lung toxicity, dyspnea, pneumonitis, acute lung injury, acute respiratory distress syndrome and alveolar damage. The references from the articles identified were reviewed for additional sources. Abstracts from International Meetings were also included. Furthermore, information was obtained from the Pneumotox website, which provides updated knowledge on drug-induced respiratory disease as well as from pharmaceutical websites. RESULTS: Most novel antineoplastic drugs may induce pulmonary toxicity, which involves mainly the parenchyma, and less frequently the airways, pleura or the pulmonary circulation. Furthermore, a subset of these agents impairs pulmonary function tests. The exact incidence of lung toxicity remains unclear. The most common patterns consist of dyspnea without further details and infiltrative lung disease (ILD), denoting changes in the interstitium or alveoli. The diagnosis is one of exclusion. ILD is usually benign and responds to appropriate treatment; however, fatalities have been reported. CONCLUSIONS: Clinicians should be aware of the potential of most novel antineoplastic agents to cause lung toxicity. A high index of suspicion is required if these are combined with other cytotoxic drugs or radiation.

Diabetes insipidus, secondary hypoadrenalism and hypothyroidism after traumatic brain injury: clinical implications.

Adequate ADH secretion, adrenal and thyroid functions are vital during the acute and post-acute phases of TBI. Deficiencies of these functions as a result of TBI are increasingly recognized. During the acute phase of TBI the incidence of severe DI is 2.9%; the incidence of less severe forms of DI is 21.6-26%. The development of DI seems to correlate with the severity of trauma. In most occasions DI is transient, but persisting DI may develop with an incidence of 6.9-7.5% amongst TBI victims. The assessment of the adequacy of adrenal function during the acute phase of TBI remains a diagnostic challenge. A few studies demonstrated an incidence of hypoadrenalism of 15-16% during the early phase of TBI. It should be noted that early hypoadrenalism may be due to either a structural damage at the level of the hypothalamo-pituitary unit or it may develop in the context of the so-called "relative adrenal insufficiency", a functional abnormality that is currently increasingly recognized during the course of severe illness. Secondary hypoadrenalism during the late phases of TBI appears with an incidence of 7.1-12.7%. The "low-T3 syndrome" compromises the assessment of thyroid function during the acute phase of TBI; the incidence of TSH insufficiency during the recovery phase varies widely between 1-21%. In summary, diabetes insipidus, secondary hypoadrenalism and hypothyroidism may develop in a small albeit significant proportion of patients during the course of TBI. Therefore, assessment of the integrity of ADH secretion, hypothalamic-pituitary adrenal (HPA) axis and thyroid axis is crucial to ensure survival and optimal rehabilitation of TBI patients.

A prospective study on lung toxicity in patients treated with gemcitabine and carboplatin: clinical, radiological and functional assessment.

BACKGROUND: Small series and retrospective studies have suggested that treatment with gemcitabine may be associated with pulmonary toxicity. However, a prospective evaluation of cancer patients treated with gemcitabine-based chemotherapy without neoplastic involvement of the thorax and without administration of radiotherapy has not been performed. PATIENTS AND METHODS: To investigate this issue, 41 consecutive patients receiving gemcitabine and carboplatin underwent prospective evaluation of lung function, which included pulmonary symptoms, pulmonary function tests, arterial blood gases and radiographic studies. Assessment was performed before and after completion of chemotherapy in all patients. Patients with a substantial decline in diffusion capacity for carbon monoxide (DLCO), defined as a drop of > or = 20%, were reassessed 2 months later. RESULTS: After chemotherapy, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, alveolar volume or total lung capacity. In contrast, there was a significant decline in DLCO (73 +/- 22 versus 67 +/- 24% predicted; P = 0.017) and in carbon monoxide transfer coefficient (KCO) (89 +/- 24 versus 80 +/- 24% predicted; P = 0.004). Arterial blood gases did not change following treatment. Ten of the 41 patients (24%) exhibited a substantial decline in DLCO, which, however, recovered within 2 months (DLCO at baseline, immediately after therapy and at 2 months after completion of treatment, 84 +/- 14, 58 +/- 16 and 77 +/- 17% predicted, respectively; P < 0.001; baseline DLCO versus DLCO at 2 months, P > 0.05). Four of the 41 patients (10%) experienced dyspnea, which was self-limiting, with the exception of one patient who developed interstitial lung fibrosis. Among the various risk factors examined, older age, female gender and lower baseline DLCO were associated with more profound changes in DLCO post-treatment. CONCLUSIONS: This prospective analysis showed that the combination of gemcitabine and carboplatin induces a significant, but reversible, decrease in diffusion capacity, which is mostly asymptomatic. Thus, this regimen is safe as regards clinically significant lung toxicity.

Relationship between nosocomial Acinetobacter species occurring in two geographical areas (Greece and the UK).

Fifty-two isolates of Acinetobacter spp. obtained from three Greek and one UK hospital, were studied using partial 16 S ribosomal DNA sequence analysis, repetitive extragenic palindromic sequence-based polymerase chain reaction (REP-PCR) mediated fingerprinting and DNA macro-restriction analysis. The aim was twofold: first, to discern the major differences in the population of Acinetobacter spp. between the two countries. Second, to compare a simple PCR-based typing scheme with pulsed-field gel electrophoresis (PFGE). The multi-resistant Greek isolates were within DNA groups 2 and TU13, and clustered into three types both by REP-PCR and PFGE. By contrast, the more susceptible Oxford isolates were heterogeneous on 16 S RNA sequence analysis and distinguishable on typing. The need for studies that elucidate the phylogeny of Acinetobacter spp. inside and outside hospitals are important, as this will help clarify the relationship between organisms that are increasingly recognized as causes of severe infections.

Protein S-100b serum levels in trauma-induced brain death.

OBJECTIVE: To analyze the time course of serum protein S-100b in patients with traumatic brain injury deteriorating to brain death and to investigate the predictive value of initial S-100b levels in relation to clinical and radiologic measures of injury severity with regard to brain death. METHODS: Forty-seven patients who sustained severe head injury were studied. Blood samples for measurement of S-100b were drawn on admission in the intensive care unit and every 24 hours thereafter for a maximum of 6 consecutive days or until brain death occurred. Variables related to outcome were recorded, including age, sex, Glasgow Coma Scale (GCS), and brain CT findings on admission. Outcome was defined as deterioration to brain death or not. RESULTS: Of the 47 patients studied, 17 deteriorated to brain death and 30 did not. On admission, patients who became brain dead had higher median serum S-100b levels compared with those who did not (2.32 microg/L vs 1.04 micro g/L, p = 0.0028). Logistic regression analysis showed that initial S-100b was an independent predictor of brain death (p = 0.041), in the presence of advanced age (p = 0.043) and low GCS score (p = 0.013). The odds ratio of 2.09 (95% CI, 1.03 to 4.25) indicates a more than doubling of the probability of deteriorating to brain death per 1- micro g/L increase in S-100b on admission. At clinical brain death, median S-100b was higher in patients with brain death compared with the peak S-100b value obtained over a 6-day period in those who did not become brain dead (6.58 microg/L vs 1.49 microg/L, p < 0.0001). CONCLUSIONS: Prediction of brain death after severe head injury can be improved by combining clinical and S-100b data; thus, serum S-100b determination deserves to be included in the neuromonitoring of patients with severe traumatic brain injury.

Effects of severity of chronic obstructive pulmonary disease on thyroid function.

To investigate thyroid function in chronic obstructive pulmonary disease (COPD), 46 consecutive patients (35 men) with stable, mild-to-severe disease, having a mean (SD) age of 67 +/- 7 years were studied. All subjects underwent pulmonary function tests (PFTs), arterial blood gas determination, and measurement of serum total thyroxine (TT4), total triiodothyronine (TT3), resin T3 uptake (RT3U), reverse triiodothyronine (rT3), and thyroid-stimulating hormone (TSH) levels. The free thyroxine and free triiodothyronine indexes (FT4I = RT3U/30TT4 and FT3I = RT3U/30TT3, respectively) along with the TT3/TT4 ratio were calculated; the latter was used as a marker of peripheral conversion of thyroxine into triiodothyronine. Interleukin (IL)-6 was also measured to evaluate its potential associations with thyroidal hormone levels. On the basis of forced expiratory volume in 1 second (FEV1), patients were divided in 2 groups: group 1, (FEV1 > or = 50% of predicted, n = 26), with mild-to-moderate COPD and group 2 (FEV1 < 50% of predicted, n = 20) having severe disease. All subjects had normal serum thyroid hormone levels; for the entire COPD population, mean values were 7.80 +/- 1.60 microg/dL for TT4, 1.12 +/- 0.20 ng/mL for TT3, 29.0 +/- 1.88 for RT3U, 7.54 +/- 1.34 for FT4I, 1.07 +/- 0.16 for FT3I, 18.71 +/- 5.89 ng/dL for rT3, and 1.15 +/- 0.6 microU/mL for TSH. Mean TT3/TT4 ratio was 0.14 +/- 0.03. In group 1, TT3, TT4, and TT3/TT4 ratio did not correlate with age, FEV1, PaO2, or inhaled corticosteroids. Similarly, in group 2, TT3 and TT4 were unrelated to the above-mentioned variables; however, there was a strong positive correlation between TT3/TT4 ratio and PaO2 (r =.61, P =.004). IL-6 was within normal limits in all subjects, and it did not correlate with any thyroid hormone either in group 1 or in group 2. It is concluded that in stable COPD, severity of disease through hypoxemia is important in determining the peripheral metabolism of thyroid hormones. Whether this constitutes an adaptation is not known.

Pattern of breathing during progressive exercise in chronic heart failure.

This descriptive study analyzed serial, individual changes in the exercise pattern of breathing (POB) of patients with stable chronic heart failure (CHF). Twenty-two CHF patients underwent maximal, symptom-limited cardiopulmonary exercise test on a treadmill. Minute ventilation (VE), tidal volume (VT), breathing frequency (f), the ventilatory equivalent for carbon dioxide (VE/VCO2) and estimated dead-space to tidal volume ratio (VD/VT) were continuously recorded. The VE/VCO2 slope was calculated in every subject as the slope of the regression line relating VE to VCO2 during exercising testing. Pattern of breathing was investigated by constructing the individual VT-f relationship for each patient separately. In 16 (73%) patients (group 1), the VT-f plot was initially linear, but subsequently exhibited an inflection point at which VT stopped increasing with further increases in f. In six (27%) patients (group 2) no inflection point was evident on the VT-f relation; in four of these patients the VT-f relation remained linear but shifted to the right throughout testing, and two patients decreased VT before peak exercise achieving high breathing frequencies. Comparing group 1 to group 2 patients, they had higher VEmax (68+/-23 vs. 44+/-10 l/min, P=0.02) and VO2max (17+/-5 vs. 12+/-3 ml/min/kg, P=0.01). In contrast, the two groups did not differ in terms of age, weight, height, diagnosis, ejection fraction or VE/VCO2 slope. In conclusion, patients with CHF adopt variable breathing patterns during exercise; specific patterns are associated with greater impairment in functional capacity.

Functional status and quality of life in long-term survivors of cardiac arrest after cardiac surgery.

OBJECTIVE: To assess long-term survival, functional status, and quality of life in patients who experienced cardiac arrest after cardiac surgery. DESIGN: Prospective, observational study. SETTING: An 18-bed, adult cardiac surgery intensive care unit in a tertiary teaching center. PATIENTS: Twenty-nine cardiac surgery patients who suffered an unexpected cardiac arrest in the immediate postoperative period. INTERVENTIONS: The New York Heart Association classification and a questionnaire based on the Nottingham Health Profile were used to evaluate functional status and quality of life 4 yrs after hospital discharge. MEASUREMENTS AND MAIN RESULTS: Of the 29 patients who experienced cardiac arrest during the first 24 hrs after cardiac surgery, 27 patients (93%) were successfully resuscitated and 23 patients (79%) survived to hospital discharge. Evaluation 4 yrs postdischarge showed that, of the 29 patients, 16 patients (55%) were still alive (long-term survivors). Functional status assessment of long-term survivors revealed that 12 patients (75%) were grouped in New York Heart Association class I, 3 patients (19%) in class II, and 1 patient (6%) in class III. None of them had a neurologic deficit. They all were living independently at home, without need of any nursing care. No patient reported any abnormal emotional reactions, and six patients (38%) had mild sleep disturbances, such as early awaking. Regarding activities of daily living, 20% returned to work, 94% were able to look after their home, 96% had a social life, 63% were sexually active, 81% were involved in their hobbies, and 75% had gone on holidays. CONCLUSIONS: Cardiac surgery patients who experience an unexpected cardiac arrest in the immediate postoperative period have a 55% chance of being alive 4 yrs postdischarge. The majority of these long-term survivors has a good outcome with respect to functional status and quality of life.

Epidemiological studies of large resistance plasmids in Haemophilus.

The distribution of large conjugative Haemophilus influenzae plasmids in the nasopharyngeal haemophili of a group of people and in a large collection of 541 H. influenzae type b (Hib) isolates was studied. A newly developed PCR-based assay was used to detect the plasmids. The target sequences were chosen from sequence analysis of part of p1056, a large multiresistance plasmid isolated from a clinical Hib isolate, 1056. Fifty-nine per cent of people were found to carry beta-lactamase-positive (beta-lac(+)), ampicillin-resistant (ampR) haemophili with detectable plasmid sequences. Of these, 83% were in Haemophilus parainfluenzae and 17% were in H. influenzae. In the collection of 541 Hib, antibiotic resistance [beta-lac(+)ampR, beta-lac(+)ampR plus tetracycline resistance (tetR) or tetR] was highly correlated with large plasmids. It was found that 2.3% of the isolates contained large cryptic plasmids (i.e. these isolates were susceptible to antibiotics). The distribution of plasmids between invasive and carried Hib did not differ significantly (25 of 245 and 23 of 276, respectively). Isolates with large plasmids occur at high frequency in the nasopharynx of the normal human population and consist of two populations in Hib, one associated with specific antibiotic resistance traits and the other cryptic. These plasmids do not appear to influence the invasiveness of Hib.

Respiratory function in patients with thalassaemia and iron overload.

Iron deposition in the respiratory system has been proposed as a potential cause of the ventilatory restrictive impairment seen in patients with thalassaemia major (TM) and iron overload. In this study, magnetic resonance imaging (MRI) measurements of the liver (T2 relaxation time) were used as a surrogate index of total body iron burden and the extent to which these measurements correlated with total lung capacity (TLC) in patients with TM was examined. Twenty-one patients (aged 25+/-5 yrs) with TM participated in the study. Standard pulmonary function tests were undertaken and the T2 relaxation time of the liver was measured in all patients. Ventilatory restrictive impairment (mean TLC 74+/-11 (SD)% predicted) was the most common abnormality found in 71% of TM patients. There was no correlation between TLC (% pred) and T2 relaxation time (r=0.06, p=0.78). T2 relaxation time correlated weakly with average serum ferritin levels (r=-0.56, p=0.008). In conclusion, the data do not support the notion that the restrictive impairment in patients with thalassaemia major and iron overload is related to iron deposition in the respiratory system.