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.

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.

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.

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.

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.

Can alcohol intoxication be excluded as the cause of confusion following head injury?

OBJECTIVE: To assess whether there is a breath alcohol level (BrAC) below which confusion in the head injured patient should not be attributed solely to the acute effects of alcohol. METHOD: Based in the Accident and Emergency Ward in Glasgow Royal Infirmary, a prospective observational study was carried out over a five month period. Patients admitted to the ward were recruited for the study if they had a primary diagnosis of head injury. The outcome measures recorded and analysed were sequential 2 hrly BrAC readings (mg/L) and Glasgow Coma Scale findings (Eye opening, motor and verbal responses). The relationship between these was investigated, which revealed additional relevant factors affecting level of consciousness. RESULTS: The breath alcohol analyser was found to be a useful non-invasive, quick and easy to use tool. The results obtained were consistent with the expected pattern of reducing BrAC levels over a 6 hour period. Within this group of patients, a poor correlation was found between each of the three responses of the Glasgow Coma Scale and BrAC readings. For those patients who remained confused, when their BrAC reading was less than 1 mg/L, other causes of a lowered level of consciousness were identified. CONCLUSION: Confusion in the head injured patient with a BrAC of less than 1 mg/L, should alert one to the likelihood of causes other than alcohol intoxication.

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.

Serum anticholinergic activity changes with acute illness in elderly medical patients.

BACKGROUND: Elevated serum anticholinergic activity levels have been associated with delirium in cross-sectional studies of ill older persons. This study used serial measures of serum anticholinergic activity levels to determine whether these levels change following illness resolution, and if such changes are specific to those with delirium. METHODS: Twenty-two nursing home residents with a febrile illness had serum specimens drawn and were evaluated for the presence of delirium during the acute illness and at 1-month follow-up. Delirium was diagnosed using the Confusion Assessment Method. Serum anticholinergic activity was determined using a previously described radionuclide competitive-binding assay. RESULTS: Delirium was present during illness in 8 of 22 subjects (36%), and had resolved by 1-month follow-up in all but one resident. Serum anticholinergic activity levels were significantly higher during illness than at 1-month follow-up in both the delirious (0.69 +/- 0.85 nM atropine equivalents/200 microL sample versus 0.10 +/- 0.16; p = .06) and non-delirious (0.65 +/- 0.51 nM atropine equivalents/200 microL sample versus 0.08 +/- 0.12; p < .001) groups. Medication changes did not seem to be related to changes in serum anticholinergic activity. CONCLUSIONS: In older nursing home residents with a fever, serum anticholinergic activity appears to be elevated during illness, and declines following recovery from illness. This effect does not seem to be specific to those residents with delirium, nor does it seem related to medication changes.

[Prolonged confusion syndrome in the course of cyclosporine treatment: a state of confusion?]. / Syndrome confusionnel prolongé au cours d'un traitement par ciclosporine: état de mal à expression confusionnelle?

Cyclosporine is a potent immunosuppressant that is more and more widely used, particularly after organ transplantations. Many neurological side effects, including convulsions, that could be related to this drug, have been previously observed, most often with high blood concentrations. We report, for the first time, a case of prolonged confusion where a non convulsive status epilepticus may be discussed. It occurred in a 64-year-old woman, 17 days after a liver transplantation. The whole blood cyclosporine value was 230 micrograms/l (normal range: 100-200 micrograms/l) at the beginning of the status epilepticus. The cyclosporine imputability and the part of other factors that could have facilite are discussed.

Postoperative confusion in schizophrenic patients is affected by interleukin-6.

STUDY OBJECTIVE: To investigate whether epidural analgesia with local anesthetics affects postoperative confusion in schizophrenic patients or the relationships between cortisol or interleukin-6 (IL-6) and postoperative confusion. DESIGN: Prospective, randomized study. SETTING: Hakodate Watanabe Hospital and Hirosaki National Hospital. PATIENTS: 105 patients who were scheduled to undergo abdominal surgery with general anesthesia. INTERVENTIONS: The schizophrenic patients were rendomly divided into two groups: patients in Group A received epidural anesthesia and patients in Group B did not receive epidural anesthesia. MEASUREMENTS AND MAIN RESULTS: Postoperative confusion during the first 48 hours after the end of operation occurred in 7 of 33 patients (21%) in Group A and 10 of 33 patients (30%) in Group B. There were no significant differences in the frequency of postoperative confusion between Groups A and B. Plasma cortisol concentrations in schizophrenic patients in Group A were significantly lower 15 minutes after incision and the end of surgery than those levels of patients in Group B; however, there was no significant difference between groups in plasma cortisol concentrations after anesthesia. Plasma IL-6 concentrations (51.7 +/- 22.0 and 31.4 +/- 8.2 pg mL(-1)) in patients with postoperative confusion at the end of surgery and 24 hours after surgery were significantly higher than those levels (34.4 +/- 16.2 and 16.9 +/- 7.7 pg mL(-1)) in patients without postoperative confusion. CONCLUSIONS: Epidural anesthesia does not significantly decrease the frequency of postoperative confusion in schizophrenic patients. Plasma IL-6 concentrations at the end of the operation and 24 hours after surgery in schizophrenic patients with postoperative confusion were significantly higher than those concentrations in patients without postoperative confusion.

[Recurrent encephalopathy after small bowel resection. Implication of D-lactate]. / Encéphalopathie complexe, transitoire et récidivante après résection étendue de l'intestin grêle. Responsabilité du D-Lactate.

Recurrent episodes of confusion are most commonly due to transient brain dysfunction related to vascular, epileptic or metabolic abnormalities. We report here a 54-year-old patient who, in the months following an extensive surgery of the small intestine, developed several acute confusional episodes characterized by encephalopathic signs (such as behavioral changes, desorientation and somnolence), ataxia, nystagmus and dysarthria. A number of metabolic changes were demonstrated during the episodes, including metabolic acidosis with increased anion gap and an elevated blood level of D-lactate. Symptoms disappeared after treatment with antibiotics. D-lactate encephalopathy is a rare cause of recurrent confusion which could be suspected based on a characteristic association of clinical signs. Diagnosis is confirmed by appropriate dosages. We discussed the possible mechanisms leading to confusional episodes.

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.