Trough anti-Xa activity after intermediate dose nadroparin for thrombosis prophylaxis in critically ill patients with COVID-19 and acute kidney injury.

Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. In patients on intermediate dose nadroparin (5700 IU once daily) we assessed the incidence of bioaccumulation (trough anti-Xa level > 0.2 IU/mL) stratified according to presence of AKI. We quantified this association using multilevel analyses. To assess robustness of our observations, we explored the association between AKI and anti-Xa activity in patients receiving high dose nadroparin (> 5700 IU). 108 patients received intermediate dose nadroparin, of whom 24 had AKI during 36 anti-Xa measurements. One patient with AKI (4.2% [95%CI 0.1-21%]) and 1 without (1.2% [95%CI 0.03-6.5%]) developed bioaccumulation (p = 0.39). Development of AKI was associated with a mean increase of 0.04 (95%CI 0.02-0.05) IU/ml anti-Xa activity. There was no statistically significant association between anti-Xa activity and AKI in 51 patients on high dose nadroparin. There were four major bleeding events, all in patients on high dose nadroparin. In conclusion, Bioaccumulation of an intermediate dose nadroparin did not occur to a significant extent in critically ill patients with COVID-19 complicated by AKI. Dose adjustment in AKI may be unnecessary.

Exercise training increases skeletal muscle mitochondrial volume density by enlargement of existing mitochondria and not de novo biogenesis.

AIMS: (i) To determine whether exercise-induced increases in muscle mitochondrial volume density (MitoVD ) are related to enlargement of existing mitochondria or de novo biogenesis and (ii) to establish whether measures of mitochondrial-specific enzymatic activities are valid biomarkers for exercise-induced increases in MitoVD . METHOD: Skeletal muscle samples were collected from 21 healthy males prior to and following 6 weeks of endurance training. Transmission electron microscopy was used for the estimation of mitochondrial densities and profiles. Biochemical assays, western blotting and high-resolution respirometry were applied to detect changes in specific mitochondrial functions. RESULT: MitoVD increased with 55 ± 9% (P < 0.001), whereas the number of mitochondrial profiles per area of skeletal muscle remained unchanged following training. Citrate synthase activity (CS) increased (44 ± 12%, P < 0.001); however, there were no functional changes in oxidative phosphorylation capacity (OXPHOS, CI+IIP ) or cytochrome c oxidase (COX) activity. Correlations were found between MitoVD and CS (P = 0.01; r = 0.58), OXPHOS, CI+CIIP (P = 0.01; R = 0.58) and COX (P = 0.02; R = 0.52) before training; after training, a correlation was found between MitoVD and CS activity only (P = 0.04; R = 0.49). Intrinsic respiratory capacities decreased (P < 0.05) with training when respiration was normalized to MitoVD. This was not the case when normalized to CS activity although the percentage change was comparable. CONCLUSIONS: MitoVD was increased by inducing mitochondrial enlargement rather than de novo biogenesis. CS activity may be appropriate to track training-induced changes in MitoVD.

Accurate and fast diagnostic algorithm for febrile urinary tract infections in humans.

BACKGROUND: The urine dipstick that detects nitrite and leukocyte esterase, and urine sediment is commonly used to diagnose or exclude urinary tract infections (UTIs) as the source of infection in febrile patients admitted to the emergency department of Dutch hospitals. However, the diagnostic accuracy of the urine dipstick and urine sediment has never been studied in this specific situation. METHODS: Urinary samples of 104 febrile consecutive patients were examined. Urine culture with ≥ 10(5) colonies/ml of one or two known uropathogen was used as the gold standard. The diagnostic value of the urine dipstick, urine sediment and Gram stain at various cut-off points was determined and used to develop a new diagnostic algorithm. This algorithm was validated in a new group of sepsis patients based on systemic inflammatory response syndrome (SIRS) criteria. RESULTS: A positive nitrite on the urine dipstick (specificity 99%) rules in UTI. This is the first step of our diagnostic algorithm. The second step is to exclude UTI by absence of bacteria in the urine sediment (sensitivity 94%). The third and last step is the number of leucocytes/high-power field (hpf) in the urine sediment. Less than 10 leucocytes/hpf makes UTI unlikely whereas ≥ 10 leucocytes/hpf indicates UTI. In contrast to urine dipstick and/or urine sediment results alone, our algorithm showed both a high sensitivity (92%) and specificity (92%) and was validated in a new sepsis population. CONCLUSION: Our accurate and fast diagnostic algorithm, which combines the selective results of urine dipstick and urine sediment, can be easily used to diagnose UTI in febrile patients at the emergency department of Dutch hospitals.

Leptospirosis in a Dutch catfish farm.

A 51-year-old farm worker presented with jaundice and fever. There had been a rat infestation around the farm ponds and in the shed. He was admitted to our hospital with acute renal and liver failure, thrombocytopenia and rhabdomyolysis. Because of the clinical clues, leptospirosis was suspected and diagnosed in blood by polymerase chain reaction and serology. Also his son, a co-worker on the farm, showed a positive serology. Clinicians should be aware of these occupational outbreaks and should recognise the clinical picture.

Salivary cortisol as an alternative for serum cortisol in the low-dose adrenocorticotropic hormone stimulation test?

BACKGROUND: Salivary cortisol is unaffected by cortisol binding globulin and reflects free serum cortisol as compared to total serum cortisol. AIM: The aim of the present study was to compare the salivary cortisol response with the serum cortisol response in a low-dose (1-microg) ACTH test in a clinical setting and to determine the optimal cut-off value of salivary cortisol as an alternative to serum cortisol. MATERIAL/SUBJECTS AND METHODS: We measured serum and salivary cortisol responses to iv administration of 1-microg ACTH in 51 patients (17 males) referred to the Department of Clinical Chemistry for ACTH-testing. Serum cortisol was assessed before, 20, and 30 min after ACTH-administration, and salivary cortisol was assessed before and 30 min after ACTH administration. RESULTS: Mean cortisol at baseline, 20, and 30 min were 0.44 micromol/l (SD: 0.22), 0.64 micromol/l (SD: 0.24), and 0.70 micromol/l (SD: 0.25), respectively. Median basal salivary cortisol was 8.4 nmol/l [interquartile range (IQR): 3.8-14.2]. Salivary cortisol at 30 min equaled 35.9 nmol/l (IQR: 21.1-46.2). Basal salivary cortisol was significantly correlated with salivary cortisol at 30 min (r=0.53; p<0.001). Salivary cortisol at 30 min of 23.5 nmol/l had a sensitivity and specificity of 78.1% and 70.0%, respectively as compared to the serum cortisol cut-off values of >0.50 micromol/l. CONCLUSIONS: The salivary low-dose ACTH-test yields more dynamic responses than serum cortisol. However, the sensitivity and specificity of salivary cortisol are too low to be adequate as an alternative to the serum cortisol measurements. In women on estrogen therapy, however, the use of salivary cortisol might be superior to serum cortisol.

The effect of clinical characteristics on the lecithin/sphingomyelin ratio and lamellar body count: a cross-sectional study.

OBJECTIVES: To study the changes in the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) during pregnancy and to study the effect of clinical characteristics on these measurements. METHODS: We reviewed in retrospect the amniotic fluid samples for the assessment of fetal lung maturity of consecutive women between January 1996 and December 2000. We evaluated the effect of antenatal administration of glucocorticoids, the presence of diabetes, fetal growth restriction and the amount of amniotic fluid on the L/S ratio and LBC. We then constructed normal curves, by relating the L/S ratio and LBC to gestational age in the cases without respiratory distress syndrome (RDS). Data from the literature were added to these curves. RESULTS: From the 334 included women, 64 infants (19%) developed RDS. The LBC was lower in women with polyhydramnios (p = 0.04), and similar in women with oligohydramnios. Administration of glucocorticoids, the presence of maternal diabetes or fetal growth restriction did not affect the L/S ratio or the LBC. The median L/S ratio in cases without RDS showed a constant increase from a gestational age of 28 weeks onwards. The median LBC increased slowly between a gestational age of 28 weeks and 34 weeks, to increase more steeply thereafter. CONCLUSIONS: The amount of amniotic fluid affects the LBC, but not the L/S ratio. Since the L/S ratio and the LBC increase with gestation, differences in gestational age should be taken into account in the interpretation of these fetal lung maturity tests.

Platelet activation in the Dutch haemocytometry quality assessment programme: correlation between P-selectin expression and variation in platelet count.

Since 1990, our laboratory has prepared a set of 8 fresh whole blood samples for use in a countrywide quality assessment (QA) programme. The samples are intended as external controls for haemocytometry analysers. These samples are of 8 different haematocrit levels and each one is prepared from a single donor. About 210 laboratories participate in this QA programme. From the start of this programme large interlaboratory variations in platelet counts were encountered in some of the samples. This variability was much higher than would be expected and was independent of the platelet count of the samples. The main cause was thought to be formation of platelet aggregates. The aim of the present study was to find a parameter that can predict a high interlaboratory variation in the QA programme. Therefore we investigated the initial platelet activation status in the donors and the activation status of platelets in the prepared QA blood. As a marker for platelet activation P-selectin expression on the platelets was measured using flow cytometry. During 5 rounds of the QA programme we found a good correlation of r = 0.53 (p < 0.001) between P-selectin expression on platelets in the reconstituted QA blood and the interlaboratory platelet count variability. We conclude that P-selectin expression in the prepared QA blood is an important parameter to exclude samples that lead to high CVs of platelet counts in the QA programme.

[Iatrogenic tension pneumothorax following faulty positioning of gastric tube]. / Iatrogene spanningspneumothorax na verkeerd geplaatste maagsonde.

A 74-year-old man was admitted with respiratory insufficiency and required mechanical ventilation. Enteral nutrition was given via a nasogastric feeding tube, but persistent food retention occurred. The chest X-ray showed the nasogastric tube to be in the right pleural space. After the tube was withdrawn the patient developed a tension pneumothorax and a closed-tube thoracostomy was performed. The patient's recovery was uneventful, with resolution of the pneumothorax. It is necessary to be alert with respect to the tube position, which, if doubtful, should be checked by chest X-ray. Recognition of an aberrant position is necessary to minimize related morbidity.

Influence of low dose ciprofloxacin on microbial colonization of the digestive tract in healthy volunteers during normal and during impaired colonization resistance.

Ciprofloxacin in low doses is, in volunteers, effective for decontaminating the digestive tract [elimination of aerobic Gram-negative bacilli (GNB)] without disturbing colonization resistance. Before using this concept in neutropenic patients, we investigated if a low dose quinolone is still effective when the colonization resistance is disturbed by another antimicrobial agent. Ciprofloxacin 20 mg daily was effective in eliminating Gram-negative bacilli from the digestive tract in 4/5 volunteers, in 1 volunteer the GNB persisted in low concentration. No colonization with exogenous resistant GNB occurred. Following impairment of colonization resistance by addition of clindamycin 300 mg daily, 3/5 volunteers became colonized by spontaneously acquired exogenous GNB resistant to ciprofloxacin. We conclude that selective decontamination with a quinolone in low dosage cannot be recommended in neutropenic patients because there is, in the case of disturbed colonization resistance, a real risk of acquisition of quinolone-resistant strains.

Concentration of pefloxacin in feces during infection prophylaxis in neutropenic patients.

Pefloxacin (400 mg twice daily) was administered orally for infection prophylaxis in neutropenic patients. Diffusible fecal pefloxacin concentration was determined by bioassay during 24 neutropenic periods. The median diffusible fecal pefloxacin concentration was 187 micrograms/g. This concentration was comparable with those found in volunteers following oral and intravenous administration of pefloxacin (400 mg twice daily) (median of 171 and 155 micrograms/g, respectively). From this study, it is concluded that pefloxacin administered orally results in a predictable high diffusible fecal concentration which leads to effective elimination of susceptible aerobic gram-negative bacilli from the colonic flora.