Streptococcal species as a prognostic factor for mortality in patients with streptococcal bloodstream infections.

PURPOSE: Streptococcal bloodstream infections (BSIs) are common, yet prognostic factors are poorly investigated. We aimed to investigate the mortality according to streptococcal species and seasonal variation. METHODS: Patients with streptococcal BSIs from 2008 to 2017 in the Capital Region of Denmark were investigated, and data were crosslinked with nationwide registers for the identification of comorbidities. A multivariable logistic regression analysis was performed to assess mortality according to streptococcal species and season of infection. RESULTS: Among 6095 patients with a streptococcal BSI (mean age 68.1 years), the 30-day mortality was 16.1% and the one-year mortality was 31.5%. With S. pneumoniae as a reference, S. vestibularis was associated with a higher adjusted mortality both within 30 days (odds ratio (OR) 2.89 [95% confidence interval (CI) 1.20-6.95]) and one year (OR 4.09 [95% CI 1.70-9.48]). One-year mortality was also higher in S. thermophilus, S. constellatus, S. parasanguinis, S. salivarius, S. anginosus, and S. mitis/oralis. However, S. mutans was associated with a lower one-year mortality OR 0.44 [95% CI 0.20-0.97], while S. gallolyticus was associated with both a lower 30-day (OR 0.42 [95% CI 0.26-0.67]) and one-year mortality (OR 0.66 [95% CI 0.48-0.93]). Furthermore, with infection in the summer as a reference, patients infected in the winter and autumn had a higher association with 30-day mortality. CONCLUSIONS: The mortality in patients with streptococcal BSI was associated with streptococcal species. Further, patients with streptococcal BSIs infected in the autumn and winter had a higher risk of death within 30 days, compared with patients infected in the summer.

Plasma concentration of orally administered amoxicillin and clindamycin in patients receiving haemodialysis.

OBJECTIVES: In the randomized controlled trial PANTHEM, the prophylactic effect of oral amoxicillin or clindamycin is investigated in patients receiving chronic haemodialysis (HD). However, data on plasma concentrations of these antibiotics during HD are sparse. This study aims to determine if the plasma concentration of amoxicillin and clindamycin is sufficient during HD after oral administration of amoxicillin and clindamycin at three different time intervals prior to the HD procedure. METHODS: Adult patients receiving chronic HD were investigated twice with an interval of at least 7 days starting with either a tablet of 500/125 mg amoxicillin/clavulanic acid or a tablet of 600 mg clindamycin. Patients were randomized to take the antibiotics either 30, 60 or 120 min prior to the HD procedure. Plasma antibiotic concentrations were measured at start, midway and at the end of HD. A lower threshold was set at 2.0 mg/L for amoxicillin and at 1.0 mg/L for clindamycin. In addition, a population pharmacokinetic (PK) analysis was performed, assessing PTA. RESULTS: In the amoxicillin cohort (n = 37), 84% of patients and 95% of all plasma amoxicillin concentrations were above or at the threshold throughout the dialysis procedure. In the clindamycin cohort (n = 33), all concentrations were above the threshold throughout the dialysis procedure. Further, in all patients, the mean plasma concentration of both amoxicillin and clindamycin across the HD period was well above the threshold. Finally, the PK model predicted a high PTA in the majority of patients. DISCUSSION: In patients on chronic HD, oral administration of amoxicillin/clavulanic acid (500/125 mg) or clindamycin (600 mg) within 30-120 min prior to HD leads to a sufficient prophylactic plasma concentration across the HD period.

Temporal changes in cardiovascular disease and infections in dialysis across a 22-year period: a nationwide study.

BACKGROUND: Cardiovascular diseases (CVD) and infections are recognized as serious complications in patients with end stage kidney disease. However, little is known about the change over time in incidence of these complications. This study aimed to investigate temporal changes in CVD and infective diseases across more than two decades in chronic dialysis patients. METHODS: All patients that initiated peritoneal dialysis (PD) or hemodialysis (HD) between 1996 and 2017 were identified and followed until outcome (CVD, pneumonia, infective endocarditis (IE) or sepsis), recovery of kidney function, end of dialysis treatment, death or end of study (December 31st, 2017). The calendar time was divided into 5 periods with period 1 (1996-2000) being the reference period. Adjusted rate ratios were assessed using Poisson regression. RESULTS: In 4285 patients with PD (63.7% males) the median age increased across the calendar periods from 65 [57-73] in 1996-2000 to 69 [55-76] in 2014-2017, (p <  0.0001). In 9952 patients with HD (69.2% males), the overall median age was 71 [61-78] without any changes over time. Among PD, an overall non-significant decreasing trend in rate ratios (RR) of CVD was found, (p = 0,071). RR of pneumonia increased significantly throughout the calendar with an almost two-fold increase of the RR in 2014-2017 (RR 1.71; 95% CI 1.46-2.0), (p <  0.001), as compared to the reference period. The RR of IE decreased significantly until 2009 (RR 0.43; 95% CI 0.21-0.87), followed by a return to the reference level in 2010-2013 (RR 0.87; 95% CI 0.47-1.60 and 2014-2017 (RR 1.1; 95% CI 0.59-2.04). A highly significant (p <  0.001) increase in sepsis was revealed across the calendar periods with an almost 5-fold increase in 2014-2017 (RR 4.69 95% CI 3.69-5.96). In HD, the RR of CVD decreased significantly (p <  0.001) from 2006 to 2017 (RR 0.85; 95% CI 0.79-0.92). Compared to the reference period, the RR for pneumonia was high during all calendar periods (p <  0.05). The RR of IE was initially unchanged (p = 0.4) but increased in 2010-2013 (RR 2.02; 95% CI 1.43-2.85) and 2014-2017 (RR 3.39; 95% CI 2.42-4.75). No significant changes in sepsis were seen. CONCLUSION: Across the two last decades the RR of CVD has shown a decreasing trend in HD and PD patients, while RR of pneumonia increased significantly, both in PD and in HD. Temporal trends of IE in HD, and particularly of sepsis in PD were upwards across the last decades.

Influence of patient related factors on number of mesenchymal stromal cells reached after in vitro culture expansion for clinical treatment.

BACKGROUND: Number of stromal cells injected in patients with ischaemic heart disease (IHD) may be of importance for the treatment efficacy, which in turn may be influenced by various patient-related factors. In this study, we investigate whether patient-related factors influence the number of autologous stromal cells reached after in vitro culture expansion for clinical therapy. METHODS: Culture expansion data from 111 patients with IHD treated with autologous stromal cells in three clinical trials were used. We correlated the final cell count after two passages of cultivation with different patient factors. RESULTS: There was a significant relation between body mass index (BMI) and the number of adipose derived stromal cells (ASCs) reached after culture expansion and for all patients included into the three studies (r = 0.375, p = .019 and r = 0.200, p = .036, respectively). Moreover, there was a significantly higher number of ASCs reached in patients with hypertension compared to those without hypertension and for all patients overall (68.8 ± 39.6 × 106 vs. 39.1 ± 23.6 × 106, p = .020 and 62.0 ± 55.0 × 106 vs. 29.0 ± 19.3 × 106, p < .001, respectively). The same tendency was seen with bone marrow derived mesenchymal stromal cells (MSCs) in patients with hypertension compared to those without hypertension (58.4 ± 61.8 × 106 vs. 22.6 ± 13.3 × 106, p < .001) and in males compared to females (56.4 ± 61.5 × 106 vs. 30.9 ± 27.9 × 106, p = .041). Moreover, a significant negative correlation between left ventricular ejection fraction and number of MSCs was found (r = -0.287, p = .017). CONCLUSIONS: Patient related factors such as BMI, hypertension and gender may influence the number of MSCs reached after in vitro culture expansion.

Laser-induced forward transfer for flip-chip packaging of single dies.

Flip-chip (FC) packaging is a key technology for realizing high performance, ultra-miniaturized and high-density circuits in the micro-electronics industry. In this technique the chip and/or the substrate is bumped and the two are bonded via these conductive bumps. Many bumping techniques have been developed and intensively investigated since the introduction of the FC technology in 1960(1) such as stencil printing, stud bumping, evaporation and electroless/electroplating2. Despite the progress that these methods have made they all suffer from one or more than one drawbacks that need to be addressed such as cost, complex processing steps, high processing temperatures, manufacturing time and most importantly the lack of flexibility. In this paper, we demonstrate a simple and cost-effective laser-based bump forming technique known as Laser-induced Forward Transfer (LIFT)3. Using the LIFT technique a wide range of bump materials can be printed in a single-step with great flexibility, high speed and accuracy at RT. In addition, LIFT enables the bumping and bonding down to chip-scale, which is critical for fabricating ultra-miniature circuitry.

A case of airway obstruction secondary to acute haemorrhage into a benign thyroid cyst.

A 70-year-old female, with a history of progressive dyspnoea, was admitted to the critical care unit after successful resuscitation following a witnessed, out of hospital cardiorespiratory arrest. A presumptive diagnosis of cardiorespiratory arrest secondary to an exacerbation of chronic obstructive pulmonary disease was made. However, on more detailed examination a large anterior, midline neck mass was noted. Following tracheal intubation, a computerised tomography scan of the patient's neck and thorax revealed a seven-centimetre, well-defined, nonenhancing, rounded homogeneous opacity at the thoracic inlet, consistent with a large midline thyroid cyst. Needle aspiration of the cyst was performed and yielded approximately 50 mL of frank blood. After an uncomplicated tracheal extubation and recovery, an elective subtotal thyroidectomy was performed prior to hospital discharge. Histology of the specimen revealed a benign thyroid cyst within a multinodular goitre. Euthyroid multinodular goitres are more likely to be managed conservatively due to an asymptomatic clinical course in most patients. However, the risk of respiratory distress and acute airway obstruction from tracheal compression or acute haemorrhage should be kept in mind. Patients at risk of this life threatening complication should be managed with elective thyroidectomy to reduce morbidity and mortality.

Treatment of ovarian cancer cells with nutlin-3 and resveratrol combination leads to apoptosis via caspase activation.

The current study was focused on the induction of apoptotic effects of resveratrol along with the combination treatments of nutlin-3 and transforming growth factor-ß (TGF-ß) against the human ovarian cancer cell line A2780/CP70. To determine the extent of apoptosis following the above-mentioned treatments, we assessed the execution of apoptotic events that proceed via caspase activation and cytochrome c release. We estimated the caspase-3 and -9 activities using a direct enzymatic assay that measures the cleavage of synthetic peptide substrate (N-acetyl-Asp-Glu-Val-Asp-p-nitroanilide). Our experiments showed an increase in caspase-3 and -9 activities in the cells that were treated with the combination of resveratrol (5 µM) with nutlin-3 (5 µM) or TGF-ß (1 µg/mL). Since activation of procaspase-3 by caspase-9 requires the release of cytochrome c into the cytoplasm, we measured the levels of cytochrome c in the cytoplasm by western blot experiments. The data indicated a considerable increase in caspase-3 and cytochrome c levels when cells were treated with drugs for 24 hours. Experiments with 4,6'-diamino-2-phenylindole dihydrochloride (DAPI) staining also confirmed the induction of apoptosis in all the above-mentioned treatments done at 24 and 48 hours. These results support our hypothesis that resveratrol combination can induce programmed cell death at doses that are less than half of what is typically needed for nutlin-3 and TGF-ß to induce apoptosis.

Influence of optical standing waves on the femtosecond laser-induced forward transfer of transparent thin films.

The effects of the formation of an optical standing wave during femtosecond laser-induced forward transfer of transparent films is analyzed using a numerical interference model. The dependence of the intensity distribution on a number of easily controllable experimental parameters is investigated. Results of the model are compared to experimental studies of the transfer of gadolinium gallium oxide (GdGaO) with a polymer sacrificial layer. The model allows us to explain the observed variation in deposit morphology with the size of the air gap, and why forward transfer of the GdGaO was possible below the ablation thresholds of polymer and oxide.