Improved Long-Term Preservation of Cannabis Inflorescence by Utilizing Integrated Pre-Harvest Hexanoic Acid Treatment and Optimal Post-Harvest Storage Conditions.

The effort to maintain cannabinoid and terpene levels in harvested medicinal cannabis inflorescence is crucial, as many studies demonstrated a significant concentration decrease in these compounds during the drying, curing, and storage steps. These stages are critical for the preparation and preservation of medicinal cannabis for end-use, and any decline in cannabinoid and terpene content could potentially reduce the therapeutic efficacy of the product. Consequently, in the present study, we determined the efficacy of pre-harvest hexanoic acid treatment alongside four months of post-harvest vacuum storage in prolonging the shelf life of high THCA cannabis inflorescence. Our findings indicate that hexanoic acid treatment led to elevated concentrations of certain cannabinoids and terpenes on the day of harvest and subsequent to the drying and curing processes. Furthermore, the combination of hexanoic acid treatment and vacuum storage yielded the longest shelf life and the highest cannabinoid and mono-terpene content as compared to all other groups studied. Specifically, the major cannabinoid's-(-)-Δ9-trans-tetrahydrocannabinolic acid (THCA)-concentration decreased by 4-23% during the four months of storage with the lowest reduction observed following hexanoic acid pre-harvest treatment and post-harvest vacuum storage. Hexanoic acid spray application displayed a more pronounced impact on mono-terpene preservation than storage under vacuum without hexanoic acid treatment. Conversely, sesqui-terpenes were observed to be less prone to degradation than mono-terpenes over an extended storage duration. In summation, appropriate pre-harvest treatment coupled with optimized storage conditions can significantly extend the shelf life of cannabis inflorescence and preserve high active compound concentration over an extended time period.

In Pursuit of Optimal Quality: Cultivar-Specific Drying Approaches for Medicinal Cannabis.

A limited number of studies have examined how drying conditions affect the cannabinoid and terpene content in cannabis inflorescences. In the present study, we evaluated the potential of controlled atmosphere drying chambers for drying medicinal cannabis inflorescence. Controlled atmosphere drying chambers were found to reduce the drying and curing time by at least 60% compared to traditional drying methods, while preserving the volatile terpene content. On the other hand, inflorescences subjected to traditional drying were highly infested by Alternaria alternata and also revealed low infestation of Botrytis cinerea. In the high-THC chemovar ("240"), controlled N2 and atm drying conditions preserved THCA concentration as compared to the initial time point (t0). On the other hand, in the hybrid chemovar ("Gen12") all of the employed drying conditions preserved THCA and CBDA content. The optimal drying conditions for preserving monoterpenes and sesquiterpenes in both chemovars were C5O5 (5% CO2, 5% O2, and 90% N2) and pure N2, respectively. The results of this study suggest that each chemovar may require tailored drying conditions in order to preserve specific terpenes and cannabinoids. Controlled atmosphere drying chambers could offer a cost-effective, fast, and efficient drying method for preserving cannabinoids and terpenes during the drying process while reducing the risk of mold growth.

Direct comparison of the diagnostic performance of growth differentiation factor 8 in pediatric versus adult heart failure.

INTRODUCTION: Growth differentiation factor 8 (GDF-8, myostatin) has been proposed for the management of adult heart failure (HF). Its potential role in pediatric HF patients is unknown. We sought to investigate its diagnostic performance in adult versus pediatric HF. METHODS: GDF-8 was measured prospectively in pediatric and adult HF patients and in matching controls. HF was defined as the combination of typical symptoms and impaired left ventricular systolic function. Diagnostic performance for the detection of HF was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: We enrolled 137 patients with HF (85 pediatric) and 67 healthy controls (47 pediatric). Neither pediatric nor adult HF patients had significantly different GDF-8 levels compared to the reference groups (3.53 vs 3.46 ng/mL, p = 0.334, and 6.87 vs 8.15 ng/mL, p = 0.063, respectively), but pediatric HF patients had significantly lower GDF-8 levels compared to adult patients (p < 0.001). ROC analysis showed no significant improvement adding GDF-8 to NT-proBNP, age and sex (area under the curve (AUC): 0.870 vs 0.868, p = 0.614) in children and neither in addition to age nor sex in adult HF patients (AUC: 0.74 vs 0.62, p = 0.110). CONCLUSION: GDF-8 did not accurately differentiate between HF patients and normal comparators in neither adults nor in children.

Randomized Trial of Macitentan/Tadalafil Single-Tablet Combination Therapy for Pulmonary Arterial Hypertension.

BACKGROUND: Endothelin receptor antagonist (ERA) and phosphodiesterase 5 inhibitor (PDE5i) combination therapy is recommended for low-/intermediate-risk pulmonary arterial hypertension (PAH) patients. A fixed-dose combination of the ERA macitentan and PDE5i tadalafil (M/T FDC) in a once-daily, single tablet would simplify treatment. OBJECTIVES: The multicenter, double-blind, adaptive phase 3 A DUE study investigated the efficacy and safety of M/T FDC vs macitentan 10 mg and vs tadalafil 40 mg monotherapies in PAH patients, including treatment-naïve and prior ERA or PDE5i monotherapy-treated patients. METHODS: World Health Organization functional class II-III patients were randomized to M/T FDC, macitentan, or tadalafil depending on their PAH treatment (treatment-naïve, ERA, or PDE5i monotherapy) at baseline. The primary endpoint was change in pulmonary vascular resistance (PVR) at week 16. RESULTS: In total, 187 patients were randomized to single-tablet M/T FDC (n = 108), macitentan (n = 35), or tadalafil (n = 44). PVR reduction with M/T FDC was significantly greater vs macitentan (29%; geometric mean ratio 0.71; 95% CL: 0.61-0.82; P < 0.0001) and vs tadalafil (28%; geometric mean ratio 0.72; 95% CL: 0.64-0.80; P < 0.0001). Three patients died in the M/T FDC arm (judged unrelated to treatment). Adverse events (AEs) leading to discontinuation, serious AEs, and those of special interest (anemia, hypotension, and edema) were more frequent with M/T FDC. CONCLUSIONS: Macitentan and tadalafil FDC significantly improved PVR vs monotherapies in PAH patients, with a safety and tolerability profile consistent with the individual components. The A DUE study supports M/T FDC as a once-daily, single-tablet combination for initial therapy and escalation to double combination therapy in patients with PAH. (Clinical Study to Compare the Efficacy and Safety of Macitentan and Tadalafil Monotherapies With the Corresponding Fixed-dose Combination Therapy in Subjects With Pulmonary Arterial Hypertension [PAH]) [A DUE]; NCT03904693).

Management of Colorectal Cancer Liver Metastases.

Ivey et al [...].

Whole-Body Magnetic Resonance Imaging Assessment of the Contributions of Adipose and Nonadipose Tissues to Cardiovascular Remodeling in Adolescents.

Background Greater body mass index is associated with cardiovascular remodeling in adolescents. However, body mass index cannot differentiate between adipose and nonadipose tissues. We examined how visceral and subcutaneous adipose tissue are linked with markers of early cardiovascular remodeling, independently from nonadipose tissue. Methods and Results Whole-body magnetic resonance imaging was done in 82 adolescents (39 overweight/obese; 36 female; median age, 16.3 [interquartile range, 14.4-18.1] years) to measure body composition and cardiovascular remodeling markers. Left ventricular diastolic function was assessed by echocardiography. Waist, waist:height ratio, and body mass index z scores were calculated. Residualized nonadipose tissue, subcutaneous adipose tissue, and visceral adipose tissue variables, uncorrelated with each other, were constructed using partial regression modeling to allow comparison of their individual contributions in a 3-compartment body composition model. Cardiovascular variables mostly related to nonadipose rather than adipose tissue. Nonadipose tissue was correlated positively with left ventricular mass (r=0.81), end-diastolic volume (r=0.70), stroke volume (r=0.64), left ventricular mass:end-diastolic volume (r=0.37), and systolic blood pressure (r=0.35), and negatively with heart rate (r=-0.33) (all P<0.01). Subcutaneous adipose tissue was associated with worse left ventricular diastolic function (r=-0.42 to -0.48, P=0.0007-0.02) and higher heart rates (r=0.34, P=0.007) but linked with better systemic vascular resistance (r=-0.35, P=0.006). There were no significant relationships with visceral adipose tissue and no associations of any compartment with pulse wave velocity. Conclusions Simple anthropometry does not reflect independent effects of nonadipose tissue and subcutaneous adipose tissue on the adolescent cardiovascular system. This could result in normal cardiovascular adaptations to growth being misinterpreted as pathological sequelae of excess adiposity in studies reliant on such measures.

Hydroponic versus soil-based cultivation of sweet basil: impact on plants' susceptibility to downy mildew and heat stress, storability and total antioxidant capacity.

BACKGROUND: In recent years, hydroponically cultivated basil has gained extensive popularity over soil-based cultivation. Evidence for potential differences between both cultivation methods, in terms of resistance to biotic and abiotic stress factors, storage properties and shelf-life, is still lacking and the potential effect of cultivation method on the antioxidant capacity has not yet been fully explored. This study aimed to determine which of the two basil cultivation methods produces plants that are more resilient to downy mildew and external heat treatment and that exhibit better storage and shelf-life performance. RESULTS: Hydroponically grown basil was significantly more affected by browning than the soil-grown basil at the end of the storage and end of the shelf-life period. Under both cultivation methods, the extent of browning increased significantly between the end of the storage and end of the shelf-life period, by a factor of 1.4. Moreover, hydroponically grown plants were significantly more sensitive to heat treatment than soil-grown basil. However, the soil-grown basil exhibited significantly greater susceptibility to downy mildew than the hydroponically grown basil. At harvest, and at the end of the storage period, the antioxidant capacity of hydroponically cultivated basil was significantly greater than that of soil-grown basil. CONCLUSIONS: Hydroponically cultivated basil exhibited greater resistance to downy mildew, but less resilience to heat and browning during storage and a shelf-life period, resulting in poorer storage and shelf-life performance as compared to soil-cultivated basil. The greater total antioxidant capacity of the hydroponically cultivated basil seems to be the major cause for the observed phenomena. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Novel fluorescence spectroscopy method coupled with N-PLS-R and PLS-DA models for the quantification of cannabinoids and the classification of cannabis cultivars.

INTRODUCTION: Cannabis sativa L. inflorescences are rich in secondary metabolites, particularly cannabinoids. The most common techniques for elucidating cannabinoid composition are expensive technologies, such as high-pressure liquid chromatography (HPLC). OBJECTIVES: We aimed to develop and evaluate the performance of a novel fluorescence spectroscopy-based method coupled with N-way partial least squares regression (N-PLS-R) and partial least squares discriminant analysis (PLS-DA) models to replace the expensive chromatographic methods for preharvest cannabinoid quantification. METHODOLOGY: Fresh medicinal cannabis inflorescences were collected and ethanol extracts were prepared. Their excitation-emission spectra were measured using fluorescence spectroscopy and their cannabinoid contents were determined by HPLC-PDA. Subsequently, N-PLS-R and PLS-DA models were applied to the excitation-emission matrices (EEMs) for cannabinoid concentration prediction and cultivar classification, respectively. RESULTS: The N-PLS-R model was based on a set of EEMs (n = 82) and provided good to excellent quantification of (-)-Δ9-trans-tetrahydrocannabinolic acid, cannabidiolic acid, cannabigerolic acid, cannabichromenic acid, and (-)-Δ9-trans-tetrahydrocannabinol (R2 CV and R2 pred  > 0.75; RPD > 2.3 and RPIQ > 3.5; RMSECV/RMSEC ratio < 1.4). The PLS-DA model enabled a clear distinction between the four major classes studied (sensitivity, specificity, and accuracy of the prediction sets were all ≥0.9). CONCLUSIONS: The fluorescence spectral region (excitation 220-400 nm, emission 280-550 nm) harbors sufficient information for accurate prediction of cannabinoid contents and accurate classification using a relatively small data set.

Disruption of the topologically associated domain at Xp21.2 is related to 46,XY gonadal dysgenesis.

BACKGROUND: Duplications at the Xp21.2 locus have previously been linked to 46,XY gonadal dysgenesis (GD), which is thought to result from gene dosage effects of NR0B1 (DAX1), but the exact disease mechanism remains unknown. METHODS: Patients with 46,XY GD were analysed by whole genome sequencing. Identified structural variants were confirmed by array CGH and analysed by high-throughput chromosome conformation capture (Hi-C). RESULTS: We identified two unrelated patients: one showing a complex rearrangement upstream of NR0B1 and a second harbouring a 1.2 Mb triplication, including NR0B1. Whole genome sequencing and Hi-C analysis revealed the rewiring of a topological-associated domain (TAD) boundary close to NR0B1 associated with neo-TAD formation and may cause enhancer hijacking and ectopic NR0B1 expression. Modelling of previous Xp21.2 structural variations associated with isolated GD support our hypothesis and predict similar neo-TAD formation as well as TAD fusion. CONCLUSION: Here we present a general mechanism how deletions, duplications or inversions at the NR0B1 locus can lead to partial or complete GD by disrupting the cognate TAD in the vicinity of NR0B1. This model not only allows better diagnosis of GD with copy number variations (CNVs) at Xp21.2, but also gives deeper insight on how spatiotemporal activation of developmental genes can be disrupted by reorganised TADs causing impairment of gonadal development.

Quality Control Procedures for Genome-Wide Association Studies.

Genome-wide association studies (GWAS) are being conducted at an unprecedented rate in population-based cohorts and have increased our understanding of the pathophysiology of many complex diseases. Regardless of the context, the practical utility of this information ultimately depends upon the quality of the data used for statistical analyses. Quality control (QC) procedures for GWAS are constantly evolving. Here, we enumerate some of the challenges in QC of genotyped GWAS data and describe the approaches involving genotype imputation of a sample dataset along with post-imputation quality assurance, thereby minimizing potential bias and error in GWAS results. We discuss common issues associated with QC of the GWAS data (genotyped and imputed), including data file formats, software packages for data manipulation and analysis, sex chromosome anomalies, sample identity, sample relatedness, population substructure, batch effects, and marker quality. We provide detailed guidelines along with a sample dataset to suggest current best practices and discuss areas of ongoing and future research. © 2022 Wiley Periodicals LLC.

Wireless, fully implantable cardiac stimulation and recording with on-device computation for closed-loop pacing and defibrillation.

Monitoring and control of cardiac function are critical for investigation of cardiovascular pathophysiology and developing life-saving therapies. However, chronic stimulation of the heart in freely moving small animal subjects, which offer a variety of genotypes and phenotypes, is currently difficult. Specifically, real-time control of cardiac function with high spatial and temporal resolution is currently not possible. Here, we introduce a wireless battery-free device with on-board computation for real-time cardiac control with multisite stimulation enabling optogenetic modulation of the entire rodent heart. Seamless integration of the biointerface with the heart is enabled by machine learning-guided design of ultrathin arrays. Long-term pacing, recording, and on-board computation are demonstrated in freely moving animals. This device class enables new heart failure models and offers a platform to test real-time therapeutic paradigms over chronic time scales by providing means to control cardiac function continuously over the lifetime of the subject.

Use of near-infrared spectroscopy for the classification of medicinal cannabis cultivars and the prediction of their cannabinoid and terpene contents.

Cannabis sativa L. is used to treat a wide variety of medical conditions, in light of its beneficial pharmacological properties of its cannabinoids and terpenes. At present, the quantitative chemical analysis of these active compounds is achieved through the use of laborious, expensive, and time-consuming technologies, such as high-pressure liquid-chromatography- photodiode arrays, mass spectrometer detectors (HPLC-PDA or MS), or gas chromatography-mass spectroscopy (GC-MS). Hence, we aimed to develop a simple, accurate, fast, and cheap technique for the quantification of major cannabinoids and terpenes using Fourier transform near infra-red spectroscopy (FT-NIRS). FT-NIRS was coupled with multivariate classification and regression models, namely partial least square-discriminant analysis (PLS-DA) and partial least squares regression (PLS-R) models. The PLS-DA model yielded an absolute major class separation (high-THC, high-CBD, hybrid, and high-CBG) and perfect class prediction. Using only three latent variables (LVs), the cross-validation and prediction model errors indicated a low probability of over-fitting the data. In addition, the PLS-DA model enabled the classification of chemovars with genetic-chemical similarities. The classification of high-THCA chemovars was more sensitive and more specific than the classifications of the remaining chemovars. The prediction of cannabinoid and terpene concentrations by PLS-R yielded 11 robust models with high predictive capabilities (R2CV and R2pred > 0.8, RPD >2.5 and RPIQ >3, RMSECV/RMSEC ratio <1.2) and additional 15 models whose performance was acceptable for initial screening purposes (R2CV > 0.7 and R2pred < 0.8, RPD >2 and RPIQ <3, 1.2 < RMSECV/RMSEC ratio <2). Our results confirm that there is sufficient information in the FT-NIRS to develop cannabinoid and terpene prediction models and major-cultivar classification models.

Lithium salts: assessment of their chronic and acute toxicities to honey bees and their anti-Varroa field efficacy.

BACKGROUND: Varroa control is essential for the maintenance of healthy honey bee colonies. Overuse of acaricides has led to the evolution of resistance to those substances. Studies of the short-term acaricidal effects and safety of various lithium (Li) salts recently have been reported. This study examined the long-term in vitro and in vivo bee toxicities, short-term motor toxicity to bees and long-term anti-Varroa field efficacy of several Li salts. RESULTS: In an in vitro chronic-toxicity assay, lithium citrate (18.8 mm) was the most toxic of the examined salts, followed by lithium lactate (29.5 mm), and lithium formate (32.5 mm). In terms of acute locomotor toxicity to bees, all of the Li salts were well-tolerated and none of the treatment groups differed from the negative control group. In an in vitro survival study, all of the Li treatments significantly reduced bee life spans by a factor of 1.8-7.2, as compared to the control. In terms of life expectancy, lithium citrate was the most toxic salt, with no significant differences noted between lithium formate and lithium lactate. In the bee-mortality field study, none of the examined treatments differed from the negative control. Amitraz and lithium formate exhibited similar acaricide effects, which were significantly different from those observed for lithium lactate and the negative control. CONCLUSION: In light of lithium formate's honey bee safety and efficacy as an acaricide, additional sublethal toxicity studies in brood, drones and queens, as well as tests aimed at the optimization of administration frequency are warranted. © 2022 Society of Chemical Industry.

Increased activity of the metalloproteinase PAPP-A promotes diabetes-induced glomerular hypertrophy.

BACKGROUND: Diabetic nephropathy (DN) is a serious complication of diabetes and a common cause of end stage renal failure. Insulin-like growth factor (IGF)-signaling has been implicated in DN, but is mechanistically poorly understood. Here, we assessed the activity of the metalloproteinase PAPP-A, an activator of IGF activity, and its possible interaction with the endogenous PAPP-A inhibitors stanniocalcin (STC)-1 and -2 in the mammalian kidney under normal and hyperglycemic conditions. METHODS AND RESULTS: Immunohistochemistry demonstrated that PAPP-A, its proteolytic substrate IGF binding protein-4, STC1 and STC2 are present in the human kidney. Endogenous inhibited complexes of PAPP-A (PAPP-A:STC1 and PAPP-A:STC2) were demonstrated in media conditioned by human mesangial cells (HMCs), suggesting that PAPP-A activity is regulated by the STCs in kidney tissue. A method for the selective detection of active PAPP-A in tissue was developed and a significant increase in glomerular active PAPP-A in human diabetic kidney relative to normal was observed. In DN patients, the estimated glomerular filtration rate correlated with PAPP-A activity. In diabetic mice, glomerular growth was reduced when PAPP-A activity was antagonized by adeno-associated virus-mediated overexpression of STC2. CONCLUSION: We propose that PAPP-A activity in renal tissue is precisely balanced by STC1 and STC2. An imbalance in this equilibrium causing increased PAPP-A enzymatic activity potentially contributes to the development of DN, and thus, therapeutic targeting of PAPP-A activity may represent a novel strategy for its treatment.

Multivariate classification of cannabis chemovars based on their terpene and cannabinoid profiles.

Cannabis is used to treat various medical conditions, and lines are commonly classified according to their total concentrations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Based on their ratio of total THC to total CBD, cannabis cultivars are commonly classified into high-THC, high-CBD, and hybrid classes. While cultivars from the same class have similar compositions of major cannabinoids, their levels of other cannabinoids and their terpene compositions may differ substantially. Therefore, a more comprehensive and accurate classification of medicinal cannabis cultivars, based on a large number of cannabinoids and terpenes is needed. For this purpose, three different chemometric-based classification models were constructed using three sets of chemical profiles. We examined those models to determine which provides the most accurate "chemovar" classification. This was done by analyzing profiles of cannabinoids, terpenes, and the combination of these substances using the partial least square-discriminant analysis multivariate (PLS-DA) technique. The chemical profiles were selected from the three major classes of medicinal cannabis that are most commonly prescribed to patients in Israel: high-THC, high-cannabigerol (CBG), and hybrid. We studied the correlations between cannabinoids and terpenes to identify major bio-indicators representing the plant's terpene and cannabinoid content. All three PLS-DA models provided highly accurate classifications, utilizing six to nine latent variables with an overall accuracy ranging from 2 to 11% CV. The PLS-DA model applied to the combined cannabinoid-and-terpene profile did the best job of differentiating between the chemovars in terms of misclassification error, sensitivity, specificity, and accuracy. The combined cannabinoid-and-terpene PLS-DA profile had cross-validation and prediction misclassification errors of 4% and 0%, respectively. This is the first study to demonstrate the highly accurate classification of samples of medicinal cannabis based on their cannabinoid and terpene profiles, as compared to cannabinoid profiles alone. Furthermore, our correlation analysis indicated that 11 cannabinoids and terpenes might serve as bio-indicators for 32 different active compounds. These findings suggest that the use of multivariate statistics could assist in breeding studies and serve as a tool for minimizing the mislabeling of cannabis inflorescences.

Independent of Renox, NOX5 Promotes Renal Inflammation and Fibrosis in Diabetes by Activating ROS-Sensitive Pathways.

Excessive production of renal reactive oxygen species (ROS) plays a major role in diabetic kidney disease (DKD). Here, we provide key findings demonstrating the predominant pathological role of the pro-oxidant enzyme NADPH oxidase 5 (NOX5) in DKD, independent of the previously characterized NOX4 pathway. In patients with diabetes, we found increased expression of renal NOX5 in association with enhanced ROS formation and upregulation of ROS-sensitive factors early growth response 1 (EGR-1), protein kinase C-α (PKC-α), and a key metabolic gene involved in redox balance, thioredoxin-interacting protein (TXNIP). In preclinical models of DKD, overexpression of NOX5 in Nox4-deficient mice enhances kidney damage by increasing albuminuria and augmenting renal fibrosis and inflammation via enhanced ROS formation and the modulation of EGR1, TXNIP, ERK1/2, PKC-α, and PKC-ε. In addition, the only first-in-class NOX inhibitor, GKT137831, appears to be ineffective in the presence of NOX5 expression in diabetes. In vitro, silencing of NOX5 in human mesangial cells attenuated upregulation of EGR1, PKC-α, and TXNIP induced by high glucose levels, as well as markers of inflammation (TLR4 and MCP-1) and fibrosis (CTGF and collagens I and III) via reduction in ROS formation. Collectively, these findings identify NOX5 as a superior target in human DKD compared with other NOX isoforms such as NOX4, which may have been overinterpreted in previous rodent studies.

The effects of avoiding extended antimicrobial drain prophylaxis on Clostridioides difficile and postprocedural infection rates: a 5-year retrospective.

OBJECTIVE: Postprocedural infection is a consequential complication of neurosurgical intervention. Periprocedural antimicrobial prophylaxis is routinely administered to prevent infection, and in some cases, continued for extended periods while surgical drains remain in place. However, there is little evidence that extended antimicrobial administration is necessary to reduce postprocedural infection, and extended antimicrobials can be associated with harm, such as Clostridioides difficile infection. The authors sought to evaluate whether shortening the duration of postprocedural antimicrobial prophylaxis would decrease the incidence of C. difficile infection without increasing the incidence of postprocedural infection. METHODS: In this retrospective study, two general neurosurgical cohorts were examined. In one cohort, postoperative antimicrobial prophylaxis was limited to 24 hours; in the other, some patients received extended postoperative antimicrobial prophylaxis while surgical drains or external ventricular drains (EVDs) remained in place. Rates of infection with C. difficile as well as postprocedural infection after surgery and EVD placement were compared. RESULTS: Seven thousand two hundred four patients undergoing 8586 surgical procedures and 413 EVD placements were reviewed. The incidence of C. difficile infection decreased significantly from 0.5% per procedural encounter to 0.07% with the discontinuation of extended postprocedural antibiotics within 90 days of a procedure. Rates of postprocedural infection and EVD infection did not significantly change. Results were similar in subgroups of patients with closed suction drains as well as cranial and spine subgroups. CONCLUSIONS: Discontinuation of extended antimicrobial prophylaxis was associated with a significant decrease in the incidence of C. difficile infection without a concomitant change in postprocedural infections or EVD-associated infection. This study provides evidence in support of specialtfy-wide discontinuation of extended postoperative antimicrobial prophylaxis, even in the presence of closed suction drains.

[Stroke alarm-Arterial ischemic stroke as one of the most time-critical emergencies in children and adolescents]. / Notfall-Neuropädiatrie ­ Der arteriell ischämische Schlaganfall als einer der zeitkritischsten Notfälle bei Kindern und Jugendlichen.

Arterial ischemic stroke in childhood and adolescence is one of the most time-critical emergencies in pediatrics. Nevertheless, it is often diagnosed with a considerable time delay which may be associated with low awareness, the sometimes nonspecific clinical presentation with a wide variety of differential diagnoses, and less established 'acute care structures'. The revascularisation strategies in adult stroke care are also potential and promising treatment options for children, even if available evidence is still limited. In the post-acute phase, the etiological work-up is complex due to the multitude of risk factors to be considered. But it is essential to identify each child's individual risk profile as it determines secondary prevention, risk of recurrence and outcome. Long-term care in a multiprofessional, interdisciplinary team must take into account the bio-psycho-social aspects to integrate the child into its social and educational, and later professional environment.