Guidelines for the Acute Treatment of Cerebral Edema in Neurocritical Care Patients.

BACKGROUND: Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety. METHODS: The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy. RESULTS: The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy. CONCLUSION: The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.

Evaluation of a fixed, weight-based dose of 3-factor prothrombin complex concentrate without adjunctive plasma following warfarin-associated intracranial hemorrhage.

INTRODUCTION: Data regarding use of prothrombin complex concentrate (PCC) for international normalization ratio (INR) reversal in warfarin-associated intracranial hemorrhage (wICH) is variable with regards to dosages, adjunctive agents, and product choice. In 2012, we implemented a fixed, weight-based [30 IU/kg] dosing protocol of 3-factor PCC (3PCC) utilizing a rapid infusion rate and no requirement for fresh frozen plasma (FFP) following factor product administration. We aimed to evaluate the impact of this protocol on immediate and delayed INR reversal in patients admitted with wICH in the absence of FFP co-administration. METHODS: We conducted a retrospective review of patients receiving 3PCC following wICH between January 1, 2012 and December 10, 2013. The primary objective was to determine the percentage of patients achieving goal INR (≤1.4) following 3PCC administration. Patients were excluded if their bleed was not intracranial in origin, received a dose outside of the specified protocol, or were given FFP as an adjunctive agent. RESULTS: We included 35 patients with a mean presenting INR of 3.2 ± 1.3. Thirty patients (85.7%) achieved goal INR (≤1.4) following one dose of 3PCC. The mean INR after infusion of 3PCC was 1.3 ± 0.2. The median duration between 3PCC infusion and subsequent INR was 48.0 min (30-70.1 min). Vitamin K was utilized in 33 (94.3%) patients. No patient experienced a thromboembolic event within 7 days of 3PCC administration. CONCLUSIONS: Fixed, weight-based dosing of 3PCC without adjunctive FFP resulted in high rates of complete INR reversal without significant adverse events.

The Preventable Shunt Revision Rate: a potential quality metric for pediatric shunt surgery.

OBJECTIVE Shunt surgery consumes a large amount of pediatric neurosurgical health care resources. Although many studies have sought to identify risk factors for shunt failure, there is no consensus within the literature on variables that are predictive or protective. In this era of "quality outcome measures," some authors have proposed various metrics to assess quality outcomes for shunt surgery. In this paper, the Preventable Shunt Revision Rate (PSRR) is proposed as a novel quality metric. METHODS An institutional shunt database was queried to identify all shunt surgeries performed from January 1, 2010, to December 31, 2014, at Le Bonheur Children's Hospital. Patients' records were reviewed for 90 days following each "index" shunt surgery to identify those patients who required a return to the operating room. Clinical, demographic, and radiological factors were reviewed for each index operation, and each failure was analyzed for potentially preventable causes. RESULTS During the study period, there were 927 de novo or revision shunt operations in 525 patients. A return to the operating room occurred 202 times within 90 days of shunt surgery in 927 index surgeries (21.8%). In 67 cases (33% of failures), the revision surgery was due to potentially preventable causes, defined as inaccurate proximal or distal catheter placement, infection, or inadequately secured or assembled shunt apparatus. Comparing cases in which failure was due to preventable causes and those in which it was due to nonpreventable causes showed that in cases in which failure was due to preventable causes, the patients were significantly younger (median 3.1 vs 6.7 years, p = 0.01) and the failure was more likely to occur within 30 days of the index surgery (80.6% vs 64.4% of cases, p = 0.02). The most common causes of preventable shunt failure were inaccurate proximal catheter placement (33 [49.3%] of 67 cases) and infection (28 [41.8%] of 67 cases). No variables were found to be predictive of preventable shunt failure with multivariate logistic regression. CONCLUSIONS With economic and governmental pressures to identify and implement "quality measures" for shunt surgery, pediatric neurosurgeons and hospital administrators must be careful to avoid linking all shunt revisions with "poor" or less-than-optimal quality care. To date, many of the purported risk factors for shunt failure and causes of shunt revision surgery are beyond the influence and control of the surgeon. We propose the PSRR as a specific, meaningful, measurable, and-hopefully-modifiable quality metric for shunt surgery in children.

Fungus species isolated from commercial hatcheries in Alabama.

Selected locations (incubators, incubator rooms, hatchers, hatcher rooms, chick pools, and egg rooms) in six commercial broiler hatcheries in Alabama were sampled for fungus species over a 12-month period (May 1977-April 1978) by open-plate techniques (cornmeal agar or Sabouraud's dextrose agar). Colonies at each location were counted at 24, 48, and 72-120 hours postexposure. Thirty-five species representing 21 genera were identified. The most prevalent genera were Cladosporium, Penicillium, Aspergillus, Geotrichum, and Fusarium. Aspergillus fumigatus was associated with clinical disease in the baby chick on several occasions, and Cladosporium cladosporioides was the most prevalent species isolated. In general, isolations increased in early spring and summer.

Occurrence of Nigrospora Lint Rot Caused by Nigrospora oryzae on Cotton in Alabama.

During 2000 and 2001, a lint rot of cotton bolls (Gossypium hirsutum L.) was reported in the coastal region of Alabama when precipitation was 55% lower than the 5-year average. Bolls at an early stage of opening contained gray mycelium within the locules. At maturity, the lint within the infected locules was discolored, and the fibers were compact resulting in the characteristic "gray lock" sign and symptom attributed to Nigrospora oryzae (Berk. & Broome) Petch. Roots, petioles, leaves, and bolls when present were sampled at the seedling, first bloom, full bloom, and maturity stages of cotton development. A total of 640 sections of tissue (approximately 5 mm2) were surface sterilized for 20 s in 95% ethanol followed by 60 s in 0.525% NaOCl and aseptically plated on potato dextrose agar. Plates were incubated in the dark at 25°C for 3 to 10 days. N. oryzae was isolated at low frequencies from all plant tissues beginning at first bloom. Developing bolls at full bloom were colonized at a frequency of 48%. N. oryzae conidiophores were branched, flexuous, and pallid to brown with smooth walls 4 to 7 (5) µm thick. Conidiogenous cells were monoblastic, single, and 6 to 9 (7.5) µm in diameter. Conidia were single, smooth, broadly ellipsoidal, dark brown to black, single-celled, and 11 to 16 (14) µm in diameter (2). Principal component analysis was used to examine the relationship between disease incidence and weather parameters. Weather data was obtained from Auburn University Mesonet located in fields where the samples were collected. Principal components from weather data were ambient and soil maximum, minimum, and average temperature, maximum, minimum, and average relative humidity and precipitation. The first principal component, which is temperature, accounted for 61% of total joint variation among original observations. The second principal component, which was related to the moisture variables, accounted for 19% of the variation. The abundance of N. oryzae was correlated with the principal component factor moisture (r = -0.78**). The dry conditions experienced in this region were conducive to N. oryzae lint rot of cotton. This disease has been reported on cotton primarily in arid climates typical of the southwestern United States (1). To our knowledge, this is the first report of N. oryzae lint rot in the southeastern United States. References: (1) W. E. Batson. Boll rots. Pages 36-38 in: Compendium of Cotton Diseases. T. L. Kirkpatrick and C. S. Rothrock, eds. The American Phytopathological Society, St. Paul, MN. 2001. (2) M. B. Ellis. Dematiaceous Hyphomycetes, CAB, Kew, Surrey, England, 1971.

Potential for nematode control by mycofloras endemic in the tropics.

Results of mycological surveys of root-knot and cyst nematodes from tropical regions indicate that most fungal species associated with females or cysts of species of Globodera, Heterodera, and Meloidogyne are those found with nematodes from temperate areas. Some fungal species, however, were found in higher frequency in tropical regions than in temperate countries; e.g., Cylindrocarpon destructans and Ulocladium atrum were the most common species associated with G. pallida and G. rostochiensis cysts in Peru. These fungi are not so frequent in nematodes from temperate areas. Fungi associated with diseased nematodes in the tropics vary greatly in nutritional requirements and include thermophilic species as well as cold-tolerant fungi. Multi-cropping systems possible in most tropical regions may be designed to increase the frequency of occurrence of microbial species antagonistic to phytonematodes.

Interaction of Rotylenchulus reniformis with Seedling Disease Pathogens of Cotton.

The impact of 10 Fusarium species in concomitant association with Rotylenchulus reniformis on cotton seedling disease was examined under greenhouse conditions. In experiment 1, fungal treatments consisted of Fusarium chlamydosporum, F. equiseti, F. lateritium, F. moniliforme, F. oxysporum, F. oxysporum f.sp. vasinfectum, F. proliferatum, F. semitectum, F. solani, and F. sporotrichioides; Rhizoctonia solani; and Thielaviopsis basicola. The experimental design was a 2 x 14 factorial consisting of the presence or absence of R. reniformis and the 12 fungal treatments plus two controls in autoclaved field soil. In experiment 2, the same fungal and nematode treatments were examined in autoclaved or non-autoclaved soil. This experimental design was a 2 x 2 x 14 factorial consisting of field or autoclaved soil, presence or absence of R. reniformis, and the 12 fungal treatments plus two controls. In both tests, Fusarium oxysporum f. sp. vasinfectum, F. solani, R. solani, and T. basicola consistently displayed extensive root and hypocotyl necrosis that was more severe (P

Tenuazonic acid production by Alternaria alternata and Alternaria tenuissima isolated from cotton.

Cultures of Alternaria alternata (three isolates) and Alternaria tenuissima (three isolates) obtained from cottonseeds and bolls were toxigenic when cultured on various laboratory media. A mycotoxin was isolated and identified as tenuazonic acid by using solvent partition, thin-layer chromatography, and instrument analyses. Toxicity was monitored with brine shrimp and chicken embryo bioassays. All cultures except A. alternata 938 produced tenuazonic acid when grown on cottonseed and on yeast extract-sucrose broth. The most toxin (266 mg/kg) was produced by A. tenuissima 843 on cottonseed.

Mycoflora of activated sewage sludge.

Thirty-eight species of fungi were identified in pure culture after isolation from activated sewage sludge by serial dilution. Nine species and genera were identified that had not been previously reported. In 1963, Cooke (1) published an excellent laboratory guide on the identification of fungi from polluted water, sewage, and sewage treatment systems; of approximately 30 papers cited only one (2) dealt with fungi from activated sewage sludge. Later (1970), Cooke & Pipes (3) enumerated 47 fungi consisting of 4 genera of yeasts and 33 genera of filamentous fungi that had been isolated from activated sludge. This paper reports the mycoflora of anaerobically digested sludge from a residential area in Auburn, Alabama.

Toxigenic thermophilic and thermotolerant fungi.

Twenty-three isolates of fungi, representing 13 thermophilic and thermotolerant species, were bioassayed for toxigenicity to brine shrimp, chicken embryos, and rats. Thirteen isolates representing nine genera were highly toxic to at least two of the three systems. Seven additional isolates of five genera were slightly toxic.

Toxigenic fungi in food.

Forty-five fungal isolates from moldy supermarket foods were tested for toxicity to brine shrimp, and twenty-two of these isolates were subsequently tested for toxicity to chicken embryos. Highly toxigenic fungi were Cladosporium sphaerospermum from a bakery product, Fusarium oxysporum from carrots, F. solani from cabbage, Aspergillus niger and Penicillium corylophilum from bread, P. cyclopium and P. herguei from corn meal, P. lanosum from onions,P. steckii from chocolate syrup, Penicillium sp. from jelly, and Rhizopus nigricans isolates from sweet potato, applesauce, and strawberries. Approximately one-third of the fungal cultures were moderately to highly toxigenic to brine shrimp and chicken embryos, while several additional cultures were slightly toxigenic.

Frequency and diversity of fungi colonizing tissues of upland cotton.

A study of the mycoflora of upland cotton in Alabama was conducted throughout the 2000 and 2001 growing seasons. Plants were sampled at seedling, first bloom, full bloom, and maturity stages of development. Thirty-seven genera representing 58 species of fungi were isolated, including 9 species of Fusarium. Fusarium oxysporum, F. solani, and F. equiseti were the most common members of this genus occurring at all four sampling stages in both years. Eight species accounted for 67% of the total fungi isolated during the two-year study. Alternaria alternata was the most common fungus encountered, accounting for 19 and 10% of the total fungi isolated in 2000 and 2001, respectively. Twenty species of fungi are reported for the first time colonizing upland cotton tissues.

Toxigenicity of fungi from grain sorghum.

The mycoflora of nine varieties of grain sorghum was determined by plating serial dilutions of ground samples on rose bengal-streptomycin agar. Seventeen species of fungi representing 10 genera were identified. Curvularia, Penicillium, Mucor, and Aspergillus were dominant genera. Extracts of P. herquei were highly toxic to brine shrimp, while those of C. clavata, C. lunata, and Mucor mucedo showed low to moderate toxicity. Extracts of C. clavata, C. lunata, and M. mucedo were highly toxic to chicken embryos; those of six other species showed low to moderate toxicity. Extracts of C. clavata, C. lunata, M. mucedo, Fusarium moniliforme, Alternaria tenuissima. P. herquei, and P. steckii showed varying degrees of toxicity to day-old cockerels.

Human phaeohyphomycotic osteomyelitis caused by the coelomycete Phomopsis saccardo 1905: criteria for identification, case history, and therapy.

The Sphaeropsidales, coelomycetous fungi producing asexual conidia within enclosed conidiomata (pycnidia), are saprobic on numerous vascular plants. Despite their ubiquitous nature, only a limited number of genera have been documented as causing human disease. We report what we believe to be the first human case of osteomyelitis due to a Phomopsis species in a chronically immunosuppressed female. The patient developed a subcutaneous abscess on the distal phalanx of the right fourth finger complicated by osteomyelitis. Operative specimens revealed fungal hyphae and a pure culture of mould. The patient was treated with a 6-month course of itraconazole. At 16 months of follow-up, she remained free of recurrence. Phomopsis species differ from the similar, more frequently reported Phoma species by having immersed, thick-walled, multiloculate conidiomata and by the production of alpha (short, ellipsoidal) and beta (long, filamentous) conidia.

Two toxic indole alkaloids from Penicillium islandicum.

Two new isomeric metabolites, toxins A and B, were isolated from culture extracts of Penicillium islandicum. Both toxins had a molecular formula of C16H15O2N2Cl, and physical and chemical analyses indicated that they were indole alkaloids. LD50 of toxin A was about 75-125 mg/kg in day-old cockerels. Insufficient toxin B was available to determine accurate LD50 values. Toxin A moderately inhibited growth of wheat coleoptiles but did not inhibit growth of week-old intact corn and bean plants. Toxin B showed no plant-growth inhibition.