You're The Flight Surgeon.

Beauvais A, Tate J, Kluesner JK. You're the flight surgeon: hypoglycemia. Aerosp Med Hum Perform. 2019; 90(9):826-829.

The Relationship Between Inflammatory Biomarkers and Symptom Distress in Lung Cancer Patients Undergoing Chemotherapy.

BACKGROUND: Symptom distress often occurs in lung cancer patients undergoing chemotherapy. However, a biomarker has not been identified to reflect the severity of their symptom distress. OBJECTIVE: The aim of this study was to investigate the relationship between symptom distress and serum inflammatory biomarkers in lung cancer patients undergoing chemotherapy. METHODS: A longitudinal, repeated-measures design was used to assess subjective symptoms (fatigue, sleep disturbance, pain, depression, and confusion), serum biomarkers (tartrate-resistant acid phosphatase 5a [TRACP5a], interleukin 6 [IL-6], IL-8, and C-reactive protein), and white blood cells in 62 lung cancer patients recruited from a single medical center at 3 time points: T1 was the baseline, T2 was the eighth day after the first chemotherapy cycle, and T3 was prior to the second cycle. Symptom distress was measured individually by 5 questionnaires (General Fatigue Scale, Pittsburgh Sleep Quality Index, Brief Pain Inventory, Profile of Mood States-Depressive, and Confusion). RESULTS: The trend of TRACP5a was positively correlated to the trend of the patients' symptom distress. However, the trends of IL-6 and IL-8 did not correlate. CONCLUSIONS: Serum TRACP5a was associated with symptom distress in lung cancer patients. Therefore, TRACP5a might be a potential biomarker to assess symptom distress of lung cancer patients undergoing chemotherapy. IMPLICATIONS FOR PRACTICE: Oncology nurses may be able to apply TRACP5a expression to predict or monitor multiple distress symptoms in lung cancer patients undergoing chemotherapy. Furthermore, nurses can use these study findings to better understand the patients who need more attention to improve their quality of life.

N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Levels are Increased in Patients With Transient Ischemic Attack Accompanied by Nonfocal Symptoms.

BACKGROUND: Transient nonfocal neurological symptoms may serve as markers of cardiac dysfunction. We assessed whether serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, a biomarker of cardiac disease, are increased in patients with transient ischemic attack (TIA) accompanied by nonfocal symptoms and in patients with attacks of nonfocal symptoms (transient neurological attack [TNA]). METHODS AND RESULTS: We included 15 patients with TNA, 69 with TIA accompanied by nonfocal symptoms, 58 with large-vessel TIA, 32 with cardioembolic TIA, and 46 age- and sex-matched healthy control participants. Serum NT-proBNP levels were determined within 1 week after the attack. We compared log-transformed NT-proBNP levels of patients with cardioembolic TIAs and mixed or nonfocal TNAs, with those of patients with noncardioembolic TIAs as a reference group. Adjustments for age, sex, atrial fibrillation, and a history of nonischemic heart disease were made with a multiple linear regression model. Compared with large-vessel TIA (mean 14.2 pmol/L), mean NT-proBNP levels were significantly higher in patients with TIA accompanied by nonfocal symptoms (40.5 pmol/L, P=0.049) and with cardioembolic TIA (123.5 pmol/L; P=0.004) after adjustments for age, sex, atrial fibrillation, and a history of nonischemic heart disease. Patients with TNA also had higher mean NT-proBNP levels (20.8 pmol/L, P=0.38) than those with large-vessel TIA, but this difference was not statistically significant. CONCLUSION: NT-proBNP levels are increased in patients with TIA accompanied by nonfocal symptoms.

A lifetime of hypercalcemia and hypercalciuria, finally explained.

CONTEXT: Hypercalcemia, hypercalciuria, and recurrent nephrolithiasis are all common clinical problems. This case report illustrates a newly described but possibly not uncommon cause of this presenting complex. OBJECTIVE: We report on a patient studied for over 30 years, with the diagnosis finally made with modern biochemical and genetic tools. DESIGN AND SETTING: This study consists of a case report and review of literature conducted in a University Referral Center. PATIENT AND INTERVENTION: A single patient with hypercalcemia, hypercalciuria, and recurrent nephrolithiasis was treated with low-calcium diet, low vitamin D intake, prednisone, and ketoconazole. MAIN OUTCOME MEASURE: We measured the patient's clinical and biochemical response to interventions above. RESULTS: Calcium absorption measured by dual isotope absorptiometry was elevated at 37.4%. Serum levels of 24,25-dihydroxyvitamin D were very low, as measured in two laboratories (0.62 ng/mL [normal, 3.49 ± 1.57], and 0.18 mg/mL). Genetic analysis of CYP24A1 revealed homozygous mutation E143del previously described. The patient's serum calcium and renal function improved markedly on treatment with ketoconazole but not with prednisone. CONCLUSIONS: Chronic hypercalcemia, hypercalciuria, and/or nephrolithiasis may be caused by mutations in CYP24A1 causing failure to metabolize 1,25-dihydroxyvitamin D.

Hypophosphataemia as a cause of acute confusional state.

A 74-year-old gentleman presented with an acute onset of confusion and agitation. His symptoms were so severe that he had to be sedated and intubated for CT scan. All investigations were unremarkable, except a low serum phosphate. He was treated with intravenous phosphate and his symptoms improved in line with the rise in his serum phosphate. By discharge, he had returned to his previous state of health. The cause of the hypophosphataemia was not apparent; we have asked his general practitioner to monitor his serum phosphate.

Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology.

Biomarkers are useful in community-acquired pneumonia (CAP). Recently, midregional (MR) proadrenomedullin (proADM) has been shown to be of potential prognostic use. We sought to determine whether this prognostic role depends on the cause of CAP. We conducted a prospective cohort study of immunocompetent patients with CAP. Pneumonia Severity Index (PSI) and CURB-65 score (confusion (abbreviated mental test score of ≤ 8), urea ≥ 7 mol · L(-1), respiratory rate ≥ 30 breaths · min(-1), blood pressure <90 mmHg systolic or <60 mmHg diastolic, and age ≥ 65 yrs), blood C-reactive protein, procalcitonin, MR-proADM, and microbiological studies were systematically performed. Patients were grouped as bacterial, viral/atypical and mixed CAP, and were followed up at 30, 90 and 180 days, and 1 yr. We recruited 228 CAP patients. Identification of at least one pathogen was achieved in 155 (68%) patients. MR-proADM levels closely correlated with increasing severity scores, and showed an important predictive power for complications and short- and long-term mortality (1 yr). Its addition to PSI and CURB-65 significantly improved their prognostic accuracy. A MR-proADM cut-off of 0.646 nmol · L(-1) identified 92% of patients scored as PSI classes IV and V as high risk. MR-proADM outcome prediction power was not affected by different aetiologies. MR-proADM has high short- and long-term prognostic accuracy, and increases the accuracy of clinical scores. The prognostic value of MR-proADM is not modified by different possible CAP aetiologies.

False-positive ethanol blood concentrations leading to clinical confusion on Christmas Day.

A case of altered consciousness in which ethanol ingestion was one of the differential diagnoses is described. Three separate blood samples were conveyed to the hospital biochemistry laboratory and each returned a positive value when assayed via an indirect, enzymatic method. The family strongly denied alcohol ingestion and hence, a few days later, the samples were conveyed to an external laboratory using a 'specific', chromatographic method. These samples were all reported as negative for ethanol. Alternative causes of altered consciousness were restricted by the false-positive ethanol laboratory results.

Factors associated with inflammatory cytokine patterns in community-acquired pneumonia.

Raised systemic levels of interleukin (IL)-6 and IL-10 cytokines have been associated with poorer outcome in community-acquired pneumonia. The aim of our study was to identify potential associated factors with increased levels of IL-6, IL-10, or both cytokines. We performed a prospective study of 685 patients admitted to hospital with community-acquired pneumonia. IL-6 and IL-10 were measured in blood in the first 24 h. 30-day mortality increased from 4.8% to 11.4% (p = 0.003) when both cytokines were higher than the median. Independent associated factors with an excess of IL-6 were neurologic disease, confusion, serum sodium < 130 mEq·L⁻¹, pleural effusion, and bacteraemia. The associated factors for an excess of IL-10 were respiratory rate ≥ 30 breaths·min⁻¹, systolic blood pressure < 90 mmHg and glycaemia ≥ 250 mg·dL⁻¹. The independent associated factors for an excess of both cytokines were confusion, systolic blood pressure < 90 mmHg, pleural effusion and bacteraemia. Protective factors were prior antibiotic treatment and pneumococcal vaccination. Different independent factors are related to an excess of IL-6 and IL-10. Confusion, hypotension, pleural effusion and bacteraemia were associated with the inflammatory profile with the highest mortality rate, whereas anti-pneumococcal vaccination and previous antibiotic treatment appeared to be protective factors.

Prognostic value of procalcitonin in community-acquired pneumonia.

The prognostic value of procalcitonin (PCT) levels to predict mortality and other adverse events in community-acquired pneumonia (CAP) remains undefined. We assessed the performance of PCT overall, stratified into four predefined procalcitonin tiers (< 0.1, 0.1-0.25, > 0.25-0.5, >0.5 µg·L⁻¹) and stratified by Pneumonia Severity Index (PSI) and CURB-65 (confusion, urea >7 mmol·L⁻¹, respiratory frequency ≥ 30 breaths·min⁻¹, systolic blood pressure < 90 mmHg or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 yrs) risk classes to predict all-cause mortality and adverse events within 30 days follow-up in 925 CAP patients. In receiver operating characteristic curves, initial PCT levels performed only moderately for mortality prediction (area under the curve (AUC) 0.60) and did not improve clinical risk scores. Follow-up measurements on days 3, 5 and 7 showed better prognostic performance (AUCs 0.61, 0.68 and 0.73). For prediction of adverse events, the AUC was 0.66 and PCT significantly improved the PSI (from 0.67 to 0.71) and the CURB-65 (from 0.64 to 0.70). In Kaplan-Meier curves, PCT tiers significantly separated patients within PSI and CURB-65 risk classes for adverse events prediction, but not for mortality. Reclassification analysis confirmed the added value of PCT for adverse event prediction, but not mortality. Initial PCT levels provide only moderate prognostic information concerning mortality risk and did not improve clinical risk scores. However, PCT was helpful during follow-up and for prediction of adverse events and, thereby, improved the PSI and CURB65 scores.

Coagulation and inflammation biomarkers may help predict the severity of community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: There are limited data on the relationship between the severity of community-acquired pneumonia (CAP) and biomarkers of inflammation and coagulation. The aim of this study was to evaluate the association between the severity of CAP and serum levels of antithrombin III (AT-III), protein C (P-C), D-dimers (D-D) and CRP, at hospital admission. METHODS: This was a prospective observational study in 77 adults (62.3% men), who were hospitalized for CAP. The severity of CAP was assessed using the confusion, uraemia, respiratory rate >or=30 breaths/min, low blood pressure, age >or=65 years (CURB-65) score. RESULTS: Forty patients (52%) had severe CAP (CURB-65 score 3-5). Serum levels of AT-III were lower and levels of D-D and CRP were higher in patients with severe CAP than in patients with mild CAP (CURB-65 score 0-2) (P < 0.001 for all comparisons). Levels of P-C were lower in patients with severe CAP compared with those with mild CAP, but the difference was not significant (P = 0.459). At a cut-off point of 85%, AT-III showed a sensitivity of 80% and a specificity of 75%, as a determinant of the need for hospitalization. At a cut-off point of 600 ng/mL, D-D showed a sensitivity of 90% and a specificity of 75% and at a cut-off point of 110 mg/L, CRP showed a sensitivity of 83% and a specificity of 79%, as determinants of the need for hospitalization. CONCLUSIONS: Serum levels of AT-III, D-D and CRP at admission appear to be useful biomarkers for assessing the severity of CAP.

The S-100B substudy of the GLUTAMICS trial: glutamate infusion not associated with sustained elevation of plasma S-100B after coronary surgery.

BACKGROUND & AIMS: Concerns have been raised about potential neurological injury related to exogenous glutamate. In cardiac surgery glutamate has been administered as a putative cardioprotective agent by cardioplegia or intravenous infusion. In the GLUTAMICS trial, in addition to surveillance of clinical neurological injuries, a prespecified subgroup was analyzed with regard to postoperative S-100B levels to detect potential subclinical neurological injury related to glutamate infusion. METHODS: Sixty-nine patients operated on for unstable coronary syndrome were randomized to intravenous infusion of glutamate (n=35) or saline (n=34) perioperatively. Plasma levels of S-100B were obtained on the third postoperative day. RESULTS: S-100B in the glutamate group and the control group were 0.079+/-0.034microg/L and 0.090+/-0.042microg/L respectively (p=0.245). There were no patients with stroke or mortality. Three patients in the control group and two in the glutamate group had postoperative confusion. These patients had significantly elevated S-100B compared with those without confusion (0.132+/-0.047vs 0.081+/-0.036microg/L; p=0.003). Overall, 21 patients had S-100B above reference level (> or =0.10microg/L) and these patients had significantly more calcifications in the ascending aorta on epiaortic scanning. CONCLUSIONS: Intravenous glutamate infusion during surgery for unstable coronary artery disease did not initiate a sustained elevation of plasma S-100B. Thus, no evidence for subclinical neurological injury related to glutamate infusion was found. In contrast, postoperative elevation of plasma S-100B was linked to calcification of the ascending aorta and postoperative confusion.

Non-fatal overdose of duloxetine in combination with other antidepressants and benzodiazepines.

The pharmaco-toxicological profile of duloxetine, a novel SNRI antidepressant, is still not completely known; in particular, intoxication cases have been scarcely studied. Here a duloxetine overdose case, in combination with other antidepressants and benzodiazepines, is reported and the chemical-clinical correlations discussed; this is probably the first detailed report of such a case. The patient referred to have ingested nine tablets of Cymbalta (more than 500 mg of duloxetine) and high amounts of four other drugs (venlafaxine, trazodone, sertraline and clonazepam). The patient was dozy and confused and some electrolyte imbalances were found. After gastrolavage, toxicological analyses revealed high plasma levels of duloxetine (384 ng/ml) and low levels of the other supposedly involved drugs. The overdose resulted to be not fatal and the outcome was relatively benign, also thanks to the fast emergency assistance. This case suggests that clinicians should be alerted to the possibility of toxic effects caused by simultaneous overdoses of duloxetine and other antidepressants and that caution should be used when prescribing more than one of these drugs to patients at risk of suicide.

Plasma homocysteine and vascular disease in psychogeriatric patients.

BACKGROUND: There is a high frequency (40-50%) of elevated plasma total homocysteine (tHcy) concentrations in elderly patients with mental disorders, and patients with a history of vascular disease exhibit significantly higher plasma tHcy concentration than patients without vascular disease. METHOD: The main objective of the present study was to further investigate the association between plasma tHcy concentration and vascular disease in psychogeriatric patients. We have therefore investigated 304 psychogeriatric patients and determined plasma tHcy and its most important determinants (folate and cobalamin status and renal function), and the natriuretic peptide N-terminal-pro brain natriuretic peptide (NT-proBNP). The patients were classified into several groups of vascular disease according to the findings of brain imaging and presence of a history/symptoms indicating manifest occlusive arteriosclerotic vascular disease. RESULTS: Plasma tHcy concentration is associated with the presence of vascular disease in psychogeriatric patients. The presence of vascular disease is also associated with higher age, higher serum NT-proBNP, renal impairment and lower serum folate concentration than in patients without vascular disease. The significant association between plasma tHcy concentration and vascular disease remained after correction for age and for cystatin C differences between the groups of patients without and with vascular disease. In the present population with only 16% of the patients showing elevated plasma tHcy, renal function was a more important determinant for plasma tHcy concentration than folate status. CONCLUSION: Plasma tHcy concentration is associated with vascular disease. In the present population of psychogeriatric patients renal function is associated with vascular disease and elevated plasma tHcy concentration. Thus, the association between plasma tHcy concentration and vascular disease might partially be explained by impairment of renal function.