IL-6 and other biomarkers as predictors of severity in COVID-19.

OBJECTIVE: Cytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers. METHODS: We studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU. RESULTS: Patients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin. CONCLUSIONS: IL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19.

A massive binary black-hole system in OJ 287 and a test of general relativity.

Tests of Einstein's general theory of relativity have mostly been carried out in weak gravitational fields where the space-time curvature effects are first-order deviations from Newton's theory. Binary pulsars provide a means of probing the strong gravitational field around a neutron star, but strong-field effects may be best tested in systems containing black holes. Here we report such a test in a close binary system of two candidate black holes in the quasar OJ 287. This quasar shows quasi-periodic optical outbursts at 12-year intervals, with two outburst peaks per interval. The latest outburst occurred in September 2007, within a day of the time predicted by the binary black-hole model and general relativity. The observations confirm the binary nature of the system and also provide evidence for the loss of orbital energy in agreement (within 10 per cent) with the emission of gravitational waves from the system. In the absence of gravitational wave emission the outburst would have happened 20 days later.

Embryo development and embryo transfer in the European mink (Mustela lutreola), an endangered mustelid species.

The European mink is an endangered Mustelidae species and thus requires effective conservation measures, although little is known about reproduction in this species. In particular, preimplantation development has not been studied and, therefore, embryonic development and the growth of embryos was documented in the present study for European mink using light and fluorescent microscopy. Embryos develop in the oviducts and then migrate into the uterus on Day 6 post coitum (p.c.) at the morula stage. Embryos expanded as blastocysts from Day 7 until implantation on Day 12 p.c. Based on these findings, the use of embryo transfer for a conservation programme for the European mink was evaluated. Embryos were flushed from European mink resource females and transferred into the uterine horns of recipient hybrid females (honoriks and nohoriks). These hybrids were obtained by mating European polecat males with European mink females and vice versa. A total of 40 embryos was transferred and 20 live kits were born. The rates of pre- and postnatal survival were 50% and 70%, respectively. Both male and female offspring were lighter at birth in the embryo transfer group compared with naturally born controls, but there was no difference at 3 months of age.

Prophylaxis of sternal wound infections with gentamicin-collagen implant: randomized controlled study in cardiac surgery.

Postoperative infections may lead to prolonged hospital stay and increased morbidity, mortality and hospital costs, especially in heart surgery. Finding new means to prevent infections would benefit both the patient and society. The aim of this study was to assess if locally administered gentamicin prevents sternal wound infections in coronary artery bypass (CABG) surgery. We randomized 542 consecutive CABG patients to two groups: those who received gentamicin-collagen implant under their sternum before closure (N=272) and controls (N=270). The subjects received routine intravenous antimicrobial prophylaxis (85% cefuroxime, 14% cefuroxime and vancomycin), and were followed-up for three months. The sternal wound infection rate was 4.0% (11/272) in the gentamicin group and 5.9% (16/270) in the control group. The mediastinitis rates were 1.1 and 1.9%, respectively. This treatment was safe and easy to administer, and no side-effects occurred. No statistically significant difference was demonstrated between infection rates in the two groups. This is the first study on the use of gentamicin-collagen sponge as prophylaxis in cardiac surgery. Our data show that infection was reduced slightly in the gentamicin-collagen group compared with the control group, but the study population was too small to draw conclusions. Further evaluation is needed, and the results may warrant another larger, better-powered study.

Predictive value of interleukins 6, 8 and 10, and low HLA-DR expression in acute renal failure.

AIMS: HLA-DR expression and plasma levels of pro- and anti-inflammatory cytokines (IL-6, IL-8 and IL-10) and their predictive value concerning survival of critically ill systemic inflammatory response syndrome (SIRS) patients with and without acute renal failure (ARF) were evaluated. MATERIAL: A total of 103 consecutive adult patients with SIRS from 2 university hospital intensive care units participated in the study. METHOD: Laboratory data for all patients were prospectively collected on the day of admission and 2 days thereafter. Patients with acute renal failure (ARF) and non-ARF patients were compared by Mann-Whitney U-test. Independent predictors of mortality were tested using forward stepwise logistic multiple regression analysis. The discriminative power of different variables was tested using receiver operating characteristic (ROC) curve analysis. RESULTS: ARF developed in 36 patients (35%). ARF patients showed significantly lower HLA-DR expression and higher plasma levels of IL-6, IL-8 and IL-10 than non-ARF patients. In ARF, moderate discriminative power in predicting survival was observed for day 2 IL-6 and IL-10 plasma levels (AUCs 0.703 and 0.749, respectively). CONCLUSIONS: We found no clinically significant discriminative power in predicting survival of ARF patients for monocyte HLA-DR expression or cytokine plasma levels. Therefore, our results do not support the use of HLA-DR expression or cytokine plasma levels for that purpose.

Elimination of the piperacillin/tazobactam combination during continuous venovenous haemofiltration and haemodiafiltration in patients with acute renal failure.

The elimination of the piperacillin/tazobactam combination was studied in six patients with acute renal failure undergoing either continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF) at 1 L/h and 2 L/h for 12 h. Piperacillin 4 g/tazobactam 0.5 g was given iv on three successive treatment periods and their concentrations in plasma, ultrafiltrate/dialysate and urine were determined for 12 h after each dose. The elimination half-life of piperacillin during CVVH (7.7 +/- 2.3 h; mean +/- s.d.) was significantly longer than during CVVHDF 1 L/h (6.7 +/- 1.9 h) or 2 L/h (6.1 +/- 2.0 h) (P< 0.05). Corresponding values for tazobactam were 13.9 +/- 3.9, 11.6 +/- 3.3 and 9.4 +/- 2.4 h, respectively (P< 0.05). Total piperacillin clearance during CVVH (3.89 +/- 1.23 L/h) was significantly lower than during CVVHDF 1 L/h (5.06 +/- 1.68 L/h) or 2 L/h (5.48 +/- 2.11 L/h) (P< 0.05). The corresponding tazobactam clearance values were 2.42 +/- 0.75, 3.13 +/- 0.66 and 3.75 +/- 1.43 L/h, respectively. The mean 12 h elimination of piperacillin and tazobactam in ultrafiltrate/dialysate was 29% and 37% during CVVH, 42% and 57% during CVVHDF (1 L/h), and 46% and 69% during CVVHDF (2 L/h). We recommend 8 hourly dosing of patients with renal failure on CVVH or CVVHDF with dialysis flow rates of 1 or 2 L/h treated with piperacillin 4 g/tazobactam 0.5 g.

Contents of vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms.

The aim of the study was to determine the contents of mineral elements (Ca, K, Mg, Na, P, Cu, Fe, Mn, Cd, Pb, and Se), vitamins (B(1), B(2), B(12), C, D, folates, and niacin), and certain phenolic compounds (flavonoids, lignans, and phenolic acids) in the cultivated mushrooms Agaricus bisporus/white, Agaricus bisporus/brown, Lentinus edodes, and Pleurotus ostreatus. Selenium, toxic heavy metals (Cd, Pb), and other mineral elements were analyzed by ETAAS, ICP-MS, and ICP methods, respectively; vitamins were detected by microbiological methods (folates, niacin, and vitamin B(12)) or HPLC methods (other vitamins), and phenolic compounds were analyzed by HPLC (flavonoids) or GC--MS methods (lignans and phenolic acids). Cultivated mushrooms were found to be good sources of vitamin B(2), niacin, and folates, with contents varying in the ranges 1.8--5.1, 31--65, and 0.30--0.64 mg/100 g dry weight (dw), respectively. Compared with vegetables, mushrooms proved to be a good source of many mineral elements, e.g., the contents of K, P, Zn, and Cu varied in the ranges 26.7--47.3 g/kg, 8.7--13.9 g/kg, 47--92 mg/kg, and 5.2--35 mg/kg dw, respectively. A. bisporus/brown contained large amounts of Se (3.2 mg/kg dw) and the levels of Cd were quite high in L. edodes (1.2 mg/kg dw). No flavonoids or lignans were found in the mushrooms analyzed. In addition, the phenolic acid contents were very low.

Adenosine in myocardial protection given through three windows of opportunity. An experimental study with pigs.

OBJECTIVE: Adenosine (ADO) has been shown to have beneficial effects against tissue injury after myocardial ischemia. However, the timing and dose of ADO administration have not been defined. This study was designed to determine the cardioprotective effect of exogenous ADO in an experimental open heart surgery model in pigs. DESIGN: The animals were openly divided into two groups both undergoing 30 min of total cardiac arrest. In the control group animals received cold crystalloid cardioplegic solution. In the ADO group ADO was added to cardioplegic solution and in addition ADO was infused to the superior vena cava for 2 h starting 30 min before cardiac arrest. The pumping function of the heart was measured with echocardiography and myocardial blood flow was measured with microspheres and positron emission tomography (PET). Cardiomyocyte apoptosis was detected and tumor necrosis factor (TNF) levels were measured. RESULTS: Better post-ischemic pumping function was found in the ADO group (relative decrease 43.7% vs 55.4%, p = 0.20 between the groups). The cardiac output decreased significantly from the baseline values (p < 0.05 in both groups). There was a temporary decrease in myocardial blood flow post-ischemically, followed by a compensatory increase during the later reperfusion period. The cardiomyocyte apoptosis was induced significantly in both groups. CONCLUSIONS: In this experiment two important details were noticed. Firstly, cardiomyocyte apoptosis is involved in ischemia-reperfusion injury associated with open heart surgery. Secondly, PET is a comparable method with the microsphere technique when coronary flow is studied. No significant effects of ADO against ischemia-reperfusion injury could be shown. However, there were some signsof positive outcome, even though statistical significance could not be reached.

Elimination of meropenem during continuous veno-venous haemofiltration and haemodiafiltration in patients with acute renal failure.

Meropenem elimination was studied in six patients with acute renal failure on continuous venovenous haemofiltration (CVVH) or continuous veno-venous haemodiafiltration (CVVHDF) 1 L/h and 2 L/h for 12 h. Meropenem 1 g was given iv over three dialysis periods, and plasma, ultrafiltrate/dialysate and urine concentrations of meropenem were determined. The half-life of meropenem was significantly longer (P < 0.05) during CVVH (7.5 +/- 2.0 h; mean +/- S.D.) than during CVVHDF 1 L/h (5.6 +/- 1.4 h) or 2 L/h (4.8 +/- 1.2 h). Meropenem clearance was 3.27 +/- 2.30 L/h, 4.72 +/- 2.69 L/h and 5.71 +/- 3.58 L/h in CVVH, CVVHDF 1 L/h and CVVHDF 2 L/h, respectively (P < 0.05 between CVVH and CVVHDF). Patients with renal failure on CVVHDF 1 or 2 L/h should be treated with meropenem 1 g bid; 500 mg tid may be enough for patients on CVVH.

Disseminated hydatid disease causing paraplegia and destruction of the hip.

A patient who had had been treated by surgery for spinal echinococcosis in a Mediterranean country emigrated to northern Europe. After surgery, the echinococcosis disseminated and he developed chronic lytic and sinus-draining hydatid disease of the left hip and neuromuscular weakness of the left lower extremity. Seventeen years after the spinal surgery, he was referred to our hip service for a possible total hip replacement (THR) after receiving adequate chemotherapy against echinococcosis for nearly 3 years. Because of the poor results reported by others, we decided against THR; two of the four previous patients described in the current literature who had THR died due to complications.

Intramucosal pH and endotoxin and cytokine release in severe acute pancreatitis.

It has been postulated that in severely ill patients splanchnic hypoperfusion may cause endotoxin release from the gut, and this leakage of endotoxin into the circulation can trigger the cascade of inflammatory cytokines. We tested this hypothesis in 9 patients with acute severe pancreatitis by monitoring gastric intramucosal pH (pHi) as measure of splanchnic hypoperfusion at 12-h intervals trying to correlate it to endotoxin and cytokine release. Only 3 of 59 samples, obtained from 3 patients contained circulating endotoxin. Thirteen of 15 plasma samples drawn at pHi <7.20 did not contain endotoxin. The pHi was significantly lower in patients who subsequently developed 3 or more organ failures (P = 0.0017, analysis of variance). Although endotoxemia was only occasionally found, most patients had measurable interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) in their plasma. Concentrations of IL-6, IL-8, and IL-10 on admission correlated to degree of organ dysfunction as measured by the multiple organ system failure score (P = 0.035, r = 0.74; P = 0.010, r = 0.91; P = 0.021, r = 0.82, respectively). In conclusion, patients with acute, severe pancreatitis often have splanchnic hypoperfusion and produce a wide array of cytokines despite a rare occurrence of endotoxemia.

Natural transfer of viable microbes in space.

The possibility and probability of natural transfer of viable microbes from Mars to Earth and Earth to Mars traveling in meteoroids during the first 0.5 Ga and the following 4 Ga are investigated, including: --radiation protection against the galactic cosmic ray nuclei and the solar rays, dose rates as a function of the meteorite's radial column mass (radius x density), combined with dose rates generated by natural radioactivity within the meteorite; and survival curves for some bacterial species using NASA's HZETRN transport code --other factors affecting microbe survival: vacuum; central meteorite temperatures at launch, orbiting, and arrival; pressure and acceleration at launch; spontaneous DNA decay; metal ion migration --mean sizes and numbers of unshocked meteorites ejected and percentage falling on Earth, using current semiempirical results --viable flight times for the microbe species Bacillus subtilis and Deinococcus radiodurans R1 --the approximate fraction of microbes (with properties like the two species studied) viably arriving on Earth out of those ejected from Mars during the period 4 Ga BP to the present time, and during the 700 Ma from 4.5 to 3.8 Ga. Similarly, from Earth to Mars. The conclusion is that if microbes existed or exist on Mars, viable transfer to Earth is not only possible but also highly probable, due to microbes' impressive resistance to the dangers of space transfer and to the dense traffic of billions of martian meteorites which have fallen on Earth since the dawn of our planetary system. Earth-to-Mars transfer is also possible but at a much lower frequency.

Central nervous system involvement in gyrate atrophy of the choroid and retina with hyperornithinaemia.

In gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), a genetically determined deficiency of ornithine delta-aminotransferase activity leads to high ornithine concentrations in body fluids. GA is characterized by centripetally progressing retinal and choroidal destruction and selective atrophy with tubular aggregates in type II skeletal muscle fibres. These findings have been suggested to be mediated by hyperornithinaemia-induced deficiency of high-energy creatine phosphate. As abnormal brain magnetic resonance images and electroencephalograms are found in another disorder of creatine metabolism, guanidinoacetate methyltransferase deficiency, we investigated the central nervous system involvement in GA, which seems to be associated with a milder degree of phosphocreatine deficiency. We compared 23 untreated GA patients with age-matched healthy controls, and with 9 patients who had received creatine or creatine precursor supplementation daily for several years. The mean age of the patients (32 +/- 18 years) was similar to that of the controls (36 +/- 22 years). The MRI or EEG findings of the patients on creatine supplementation did not differ from those of the untreated group. Brain MRI revealed degenerative lesions in the white matter in 50% of the GA patients, and 70% of the patients had premature atrophic changes, with a striking increase in the number of Virchow's spaces. Of the patients whose EEG was recorded, 58% had abnormal slow background activity, focal lesions or high-amplitude beta rhythm (> 50 microV). The EEG findings were not associated with the MRI changes or with the age or the sex of the patients. Early degenerative and atrophic brain changes and abnormal EEG are thus features of GA, in addition to the well-characterized eye and muscle manifestations.

Life-threatening Mycoplasma hominis mediastinitis.

Mycoplasma hominis infections are easily missed because conventional methods for bacterial detection may fail. Here, 8 cases of septic mediastinitis due to M. hominis are reported and reviewed in the context of previously reported cases of mediastinitis, sternum wound infection, pleuritis, or pericarditis caused by M. hominis. All 8 patients had a predisposing initial condition related to poor cardiorespiratory function, aspiration, or complications related to coronary artery surgery or other thoracic surgeries. Mediastinitis was associated with purulent pleural effusion and acute septic symptoms requiring inotropic medication and ventilatory support. Later, the patients had a tendency for indolent chronic courses with pleuritis, pericarditis, or open sternal wounds that lasted for several months. M. hominis infections may also present as mild sternum wound infection or as chronic local pericarditis or pleuritis without septic mediastinitis. Treatment includes surgical drainage and debridement. Antibiotics effective against M. hominis should be considered when treating mediastinitis of unknown etiology.

Muscle creatine phosphate in gyrate atrophy of the choroid and retina with hyperornithinaemia--clues to pathogenesis.

BACKGROUND: In gyrate atrophy of the choroid and retina with hyperornithinaemia (GA), inherited deficiency of ornithine-o-aminotransferase leads to progressive fundus destruction and atrophy of type II skeletal muscle fibres. Because high ornithine concentrations inhibit creatine biosynthesis, the ensuing deficiency of high-energy creatine phosphate may mediate the pathogenesis. MATERIALS AND METHODS: Relative concentrations of inorganic phosphate (Pi), creatine phosphate (PCr) and ATP in resting calf muscle were recorded in 23 GA patients and 33 control subjects using 31P-magnetic resonance spectroscopy (MRS). Eight patients with autosomal recessive retinitis pigmentosa with matched control subjects constituted an additional reference group. RESULTS: The PCr/Pi and PCr/ATP ratios (means +/- SD) were lower for the GA patients than for healthy control subjects [4.66 +/- 0.37 vs. 9.75 +/- 2.17 (P < 0.0001) and 2.85 +/- 0.37 vs. 3.70 +/- 0.50 (P < 0.05) respectively]. In retinitis pigmentosa the respective values were 9.12 +/- 2.57 and 4.25 +/- 0.45. Age and stage of the disease had no effect. CONCLUSION: Muscle 31P-MRS spectra were markedly abnormal in all GA patients.

Interleukin 1 receptor antagonist and E-selectin concentrations: a comparison in patients with severe acute pancreatitis and severe sepsis.

PURPOSE: This prospective clinical study was designed to compare interleukin 1 receptor antagonist (IL-1ra) and E-selectin concentrations in patients with severe acute pancreatitis to those with severe sepsis. MATERIALS AND METHODS: Nine consecutive patients with severe acute pancreatitis and 11 consecutive patients with severe sepsis admitted to a medical/surgical intensive care unit were included in the study. Plasma concentrations of IL-1ra and E-selectin were serially measured daily for 7 days or throughout their stay in the intensive care unit if shorter. RESULTS: The concentrations of IL-1ra were significantly higher on admission in patients with severe sepsis compared with the patients with severe pancreatitis (median levels 10,500 and 2,600 pg/mL, respectively, P = .007). When the data from the first 3 days were analyzed using analysis of variance (ANOVA), the levels of IL-1ra and E-selectin were similar in both groups. The concentrations of IL-1ra and E-selectin correlated to the development of multiorgan dysfunction as assessed by sequential organ failure assessment (SOFA) score (P = .032 and .043, respectively). CONCLUSION: This study shows that IL-1ra and E-selectin are released in acute severe pancreatitis, and the levels seem to be comparable to those in patients with severe sepsis. Concentrations of IL-1ra and E-selectin correlate to the development of multiorgan failure as indicated by high SOFA scores during the first week of disease.

Infrarenal endoluminal bifurcated stent graft infected with Listeria monocytogenes.

Prosthetic graft infection as a result of Listeria monocytogenes is an extremely rare event that recently occurred in a 77-year-old man who underwent endoluminal stent grafting for infrarenal abdominal aortic aneurysm. The infected aortic endoluminal prosthesis was removed by means of en bloc resection of the aneurysm and contained endograft with in situ aortoiliac reconstruction. At the 10-month follow-up examination, the patient was well and had no signs of infection.

Fluconazole orally dispersible tablets for the treatment of patients with oropharyngeal candidiasis.

The efficacy and tolerability of fluconazole orally dispersible tablets (ODT) in the treatment of oropharyngeal candidiasis was evaluated in this multicentre non-comparative study. A total of 89 adults with signs and symptoms of oropharyngeal candidiasis were enrolled; 70 of whom completed therapy with fluconazole ODT 100 mg once daily for 7 - 14 days. Acquired immunodeficiency syndrome (AIDS)/ AIDS-related complex was an underlying illness in 69% of patients (61). An antimicrobial and corticosteroid therapy was given in 52% (46) and 20% (18) of patients, respectively. Of the 60 patients who had baseline signs and symptoms of infection and a culture positive for Candida albicans, 90% (54) were cured or had improved at the end of therapy, and the fungal pathogen was eradicated in 19/57 (33%) patients. At the 4-week posttreatment follow-up, signs and symptoms of oropharyngeal candidiasis were absent in 73% (27/37) patients. The adverse events and laboratory abnormalities recorded during the study period were attributable to underlying illnesses rather than to fluconazole therapy. These results indicate that this novel dosage form of fluconazole is effective and well tolerated in the treatment of oropharyngeal candidiasis.