More than just the gene: investigating expression using a non-native plasmid and host and its impact on resistance conferred by ß-lactamase OXA-58 isolated from a hospital wastewater microbiome.

With the escalation of hospital-acquired infections by multidrug resistant bacteria, understanding antibiotic resistance is of paramount importance. This study focuses on the ß-lactamase gene, blaOXA-58, an important resistance determinant identified in a patient-facing hospital wastewater system. This study aimed to characterize the behaviour of the OXA-58 enzyme when expressed using a non-native plasmid and expression host. blaOXA-58 was cloned using a pET28a(+)/Escherichia coli BL21(DE3) expression system. Nitrocefin hydrolysis and antimicrobial susceptibility of OXA-58-producing cells were assessed against penicillin G, ampicillin, meropenem, and amoxicillin. blaOXA-58 conferred resistance to amoxicillin, penicillin G, and ampicillin, but not to meropenem. This was unexpected given OXA-58's annotation as a carbapenemase. The presence of meropenem also reduced nitrocefin hydrolysis, suggesting it acts as a competitive inhibitor of the OXA-58 enzyme. This study elucidates the phenotypic resistance conferred by an antimicrobial resistance gene (ARG) obtained from a clinically relevant setting and reveals that successful functional expression of ARGs is multifaceted. This study challenges the reliability of predicting antimicrobial resistance based solely on gene sequence alone, and serves as a reminder of the intricate interplay between genetics and structural factors in understanding resistance profiles across different host environments.

A novel characterized multi-drug-resistant Pseudocitrobacter sp. isolated from a patient colonized while admitted to a tertiary teaching hospital.

BACKGROUND: Reports of nosocomial infections typically describe recognised microorganisms. Here, a novel bacterial species was isolated, based on rectal swab screening for carbapenemases post-admission, then phenotypically and genetically characterized. METHODS: Sensititre, Vitek and API kits, MALDI and Illumina MiSeq were employed before profiles and phylogeny were compared with other related species. FINDINGS: Determined to be a possible Enterobacterales, the isolate was found to have 99.7% 16s rRNA identity to Pseudocitrobacter corydidari; an Asian cockroach-associated species. Given the highly conserved/low variability of 16S rRNA genes in Enterobacterales, average nucleotide identity (ANI) analysis compared the new isolate's genome with those of 18 Enterobacteriaceae species, including confirmed species of Pseudocitrobacter and unnamed Pseudocitrobacter species in the SILVA database. Of these, Pseudocitrobactercorydidari had the highest ANI at 0.9562. The published genome of the only known isolate of P.corydidari does not include Antimicrobial Resistance Genes (ARGs), with exception of potential drug efflux transporters. In contrast, our clinical isolate bears recognised antimicrobial resistance genes, including Klebsiella pneumoniae carbapenemase. The associated genome suggests resistance to carbapenems, ß-lactams, sulfonamides, fluoroquinolones, macrolides, aminoglycosides and cephalosporins. Phenotypic antimicrobial resistance was confirmed. CONCLUSION: Evident variations in ARG profiles, human colonization and origin in a clinically relevant niche that is geographically, physically and chemically disparate lend credibility for divergent evolution or, less likely, parallel evolution with P. corydidari. Genome data for this new species have been submitted to GENBANK using the proposed nomenclature Pseudocitrobacter limerickensis. The patient was colonized, rather than infected, and did not require antimicrobial treatment.

Large-scale characterization of hospital wastewater system microbiomes and clinical isolates from infected patients: profiling of multi-drug-resistant microbial species.

BACKGROUND: Hospital-acquired infections (HAIs) and infectious agents exhibiting antimicrobial resistance (AMR) are challenges globally. Environmental patient-facing wastewater apparatus including handwashing sinks, showers and toilets are increasingly identified as sources of infectious agents and AMR genes. AIM: To provide large-scale metagenomics analysis of wastewater systems in a large teaching hospital in the Republic of Ireland experiencing multi-drug-resistant HAI outbreaks. METHODS: Wastewater pipe sections (N=20) were removed immediately prior to refurbishment of a medical ward where HAIs had been endemic. These comprised toilet U-bends, and sink and shower drains. Following DNA extraction, each pipe section underwent metagenomic analysis. FINDINGS: Diverse taxonomic and resistome profiles were observed, with members of phyla Proteobacteria and Actinobacteria dominating (38.23 ± 5.68% and 15.78 ± 3.53%, respectively). Genomes of five clinical isolates were analysed. These AMR bacterial isolates were from patients >48 h post-admission to the ward. Genomic analysis determined that the isolates bore a high number of antimicrobial resistance genes (ARGs). CONCLUSION: Comparison of resistome profiles of isolates and wastewater metagenomes revealed high degrees of similarity, with many identical ARGs shared, suggesting probable acquisition post-admission. The highest numbers of ARGs observed were those encoding resistance to clinically significant and commonly used antibiotic classes. Average nucleotide identity analysis confirmed the presence of highly similar or identical genomes in clinical isolates and wastewater pipes. These unique large-scale analyses reinforce the need for regular cleaning and decontamination of patient-facing hospital wastewater pipes and effective infection control policies to prevent transmission of nosocomial infection and emergence of AMR within potential wastewater reservoirs.

Geo-analysis: the distribution of community health workers in relation to the HIV prevalence in KwaZulu-Natal province, South Africa.

BACKGROUND: The South African Ward Based Primary Health Care Outreach Team (WBPHCOT) policy framework states that the distribution of community health workers (CHWs) should be proportional to levels of poverty and disease within the population. We aimed to describe the spatial distribution of CHWs in relation to the prevalence of the Human Immunodeficiency Virus (HIV) which has itself been associated with poverty in previous studies. METHODS: This was a descriptive, cross-sectional study in which secondary data was used for geospatial analysis. Based on the extrapolation from the norm of one WBPHCOT per 6000 individuals, we utilized geographic information system (GIS) methods to visualize the distribution of CHWs in relation to the prevalence of HIV in KwaZulu-Natal (KZN). Dot density mapping was used to visualize the random distribution of CHWs in relation to HIV prevalence and population in the districts. The districts' HIV prevalence, number of PLWH, ratio of CHW: people living with HIV (PLWH), ratio of CHW: population and poverty scores were mapped using choropleth mapping. MapInfo Pro 17.0 was used to map geospatial presentation of the data. RESULTS: Overall, KZN province showed under allocation of CHWs with a CHW: people ratio of 1: 1156 compared to the estimated norm of 1: 600-1000. At district level, only two of 11 districts met the suggested norm of CHW: PLWH (1: 109-181). This indicates shortages and misallocation of CHWs in the nine remaining districts. Furthermore, our findings showed extensive geospatial heterogeneity with no clear pattern in the distribution of CHWs. There was no relationship between CHW distribution and HIV prevalence or poverty scores in the districts. CONCLUSION: This study shows inequality in the distribution of CHWs which may be associated with inequalities in the provision of HIV related services. It is critical to strengthen the response to the HIV epidemic through the appropriate distribution of CHWs especially in those districts with high levels of HIV prevalence and poverty.

Physical activity and the prevention, reduction, and treatment of alcohol and other drug use across the lifespan (The PHASE review): A systematic review.

The aim of this review is to systematically describe and quantify the effects of PA interventions on alcohol and other drug use outcomes, and to identify any apparent effect of PA dose and type, possible mechanisms of effect, and any other aspect of intervention delivery (e.g. key behaviour change processes), within a framework to inform the design and evaluation of future interventions. Systematic searches were designed to identify published and grey literature on the role of PA for reducing the risk of progression to alcohol and other drug use (PREVENTION), supporting individuals to reduce alcohol and other drug use for harm reduction (REDUCTION), and promote abstinence and relapse prevention during and after treatment of alcohol and other drug use (TREATMENT). Searches identified 49,518 records, with 49,342 excluded on title and abstract. We screened 176 full text articles from which we included 32 studies in 32 papers with quantitative results of relevance to this review. Meta-analysis of two studies showed a significant effect of PA on prevention of alcohol initiation (risk ratio [RR]: 0.72, 95%CI: 0.61 to 0.85). Meta-analysis of four studies showed no clear evidence for an effect of PA on alcohol consumption (Standardised Mean Difference [SMD]: 0.19, 95%, Confidence Interval -0.57 to 0.18). We were unable to quantitatively examine the effects of PA interventions on other drug use alone, or in combination with alcohol use, for prevention, reduction or treatment. Among the 19 treatment studies with an alcohol and other drug use outcome, there was a trend for promising short-term effect but with limited information about intervention fidelity and exercise dose, there was a moderate to high risk of bias. We identified no studies reporting the cost-effectiveness of interventions. More rigorous and well-designed research is needed. Our novel approach to the review provides a clearer guide to achieve this in future research questions addressed to inform policy and practice for different populations and settings.

Prescription drug diversion among people living with HIV: a systematic scoping review.

OBJECTIVES: Globally, people living with HIV (PLWH) are at greater risk for various infections and chronic pain, therefore, vulnerable to prescription drug diversion which might negatively impact HIV care. The study purpose is to gather evidence on prescription drug diversion among PLWH. STUDY DESIGN: This is a systematic scoping review. METHODS: Arksey and O'Malley's framework and recommendation by Levac et al. were used to guide this study. Literature was searched in PubMed, Google Scholar, EBSCOhost (Academic Search Complete, MEDLINE and Newspaper Source) and Open Access Theses and Dissertations. Studies reporting evidence of prescription drug diversion from January 1996 to July 2017 were included. Thematic content analysis was performed to summarize data on the prevalence. RESULTS: Twenty-nine studies were eligible for data synthesis. Twenty-six studies were conducted in the United States of America (USA), one study in France and two multicountry studies; one study in Kenya and Uganda and the other study in Botswana, Kenya, Malawi, South Africa; Zimbabwe, India, Thailand, Brazil and the USA. Research evidence shows high prevalence of prescription drug diversion for analgesics and antiretroviral drugs; meanwhile, stimulants and erectile dysfunction drugs were the least diverted drugs among PLWH. There is a research gap in low- to middle-income countries (LMICs) investigating prescription drug diversion among PLWH. CONCLUSION: Our findings reveal that diversion of various prescription drug classes among PWLH exists. There is lack of research in LMICs. We recommend research in LMICs where there is high HIV prevalence. PROSPERO REGISTRATION NUMBER: CRD42017074076.

Evidence of factors influencing self-medication with antibiotics in low and middle-income countries: a systematic scoping review.

OBJECTIVES: Self-medication with antibiotics (SMA) is a practice of global concern with a higher incidence within the low- and middle-income countries (LMICs). Despite worldwide efforts to control and promote the rational use of antibiotics, the continuing practice of SMA systematically exposes individuals and communities to the risk of antibiotic resistance and a host of other antibiotic side-effects. This systematic scoping review maps evidence on the factors influencing SMA in these settings. STUDY DESIGN: Systematic scoping review. METHODS: The search strategy involved electronic databases including PubMed, Web of science, Science Direct, EBSCOhost, Google Scholar, BioMed Central, and the World Health Organization Library. PRISMA P guidelines and Arksey and O'Malley's framework were used. Thematic analysis was used to identify the factors that influence the practices of SMA in LMICs. The Mixed Method Appraisal Tool (MMAT), version 2011, was used to assess the quality of the included primary studies. RESULTS: Fifteen studies met the inclusion criteria. Studies included participants from the following LMICs: Guatemala, India, Indonesia, Kenya, Laos, Nepal, Nigeria, Pakistan, Sri Lanka, and Yemen. The findings of the review emphasized a considerable high prevalence of SMA, ranging from 8.1% to 93%, with an association with the level of education, monthly income, and gender of participants. Accessibility, affordability, and conditions of health facilities, as well as the health-seeking behavior, are factors that influence SMA in LMICs. Health conditions such as a sore throat, common cold, cough, headache, toothache, flu-like symptoms, pain relief, fever, runny nose, toothache, upper respiratory tract infections, and urinary tract infection were the major complaints that led to the practices of SMA. CONCLUSIONS: There is a considerable level of research evidence predominantly in some LMICs from Asia, with less evidence from African LMICs. Sociocultural determinants of health associated with the structure and conditions of health system as well as the health-seeking behavior are the main factors influencing SMA. Contextual and comprehensive studies on the factors influencing the non-prescribed use of antibiotics are needed to enable evidence-based strategies to correctly address the utilization of antibiotics and contain the problem of antimicrobial resistance, especially within the LMICs. PROSPERO REGISTRATION: CRD42017072954.

Evidence on point-of-care diagnostics for assessment of nutritional biochemical markers as an integral part of maternal services in low- and middle-income countries: systematic scoping review protocol.

BACKGROUND: Malnutrition affects a third of the global population with low- and middle-income countries (LMICs) being the most affected. Most of those affected by malnutrition have limited means of determining their nutritional status. Recent developments of point-of-care (POC) diagnostics promise to enable early diagnosis of nutritional deficiencies or disease risk through biochemical indicator assessment. This provides potential opportunities for relatively simple interventions before the emergence of clinical symptoms. The main objective of this systematic scoping review is to map evidence on accessibility to POC diagnostic tests for the assessment of nutritional biochemical markers as an integral part of maternal health services in LMICs. METHODS AND ANALYSIS: We will search for relevant literature from the following databases: PubMed, Science Direct, EBSCOhost (Academic search complete, CINAHL with full text, MEDLINE with full text, MEDLINE), Google Scholar and World Health Organization library database. We will also search reference lists of included studies and existing networks such as organisations and conferences to source relevant literature. Primary research articles, published in peer-reviewed journals; review articles and grey literature that address the research question will be included. We will also search clinical trial registers to find relevant studies. Two independent reviewers will screen abstracts and full articles in parallel, from the included studies, using specific inclusion and exclusion criteria. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be used for reporting the screening results. NVivo version 10 will be employed to enable content thematic analysis of the review findings. A narrative summary of the results will be presented according to the emerging themes. DISCUSSION: We anticipate finding relevant literature on point-of-care diagnostic services for assessment of biochemical indicators as part of maternal services in low- and middle-income countries. The evidence obtained from the included studies when summarised will help to guide future research.

Operational assessment of point-of-care diagnostics in rural primary healthcare clinics of KwaZulu-Natal, South Africa: a cross-sectional survey.

BACKGROUND: The World Health Organization (WHO) called for new clinical diagnostic for settings with limited access to laboratory services. Access to diagnostic testing may not be uniform in rural settings, which may result in poor access to essential healthcare services. The aim of this study is to determine the availability, current usage, and need for point-of-care (POC) diagnostic tests among rural primary healthcare (PHC) clinics in South Africa's KwaZulu-Natal (KZN) province. METHODS: We used the KZN's Department of Health (DoH) clinic classification to identify the 232 rural PHC clinics in KZN, South Africa. We then randomly sampled 100 of 232 rural PHC clinics. Selected health clinics were surveyed between April to August 2015 to obtain clinic-level data for health-worker volume and to determine the accessibility, availability, usage and need for POC tests. Professional healthcare workers responsible for POC testing at each clinic were interviewed to assess the awareness of POC testing. Data were survey weighted and analysed using Stata 13. RESULTS: Among 100 rural clinics, the average number of patients seen per week was 2865 ± 2231 (range 374-11,731). The average number of POC tests available and in use was 6.3 (CI: 6.2-6.5) out of a potential of 51 tests. The following POC tests were universally available in all rural clinics: urine total protein, urine leukocytes, urine nitrate, urine pregnancy, HIV antibody and blood glucose test. The average number of desired POC diagnostic tests reported by the clinical staff was estimated at 15 (CI: 13-17) per clinic. The most requested POC tests reported were serum creatinine (37%), CD4 count (37%), cholesterol (32%), tuberculosis (31%), and HIV viral load (23%). CONCLUSION: Several POC tests are widely available and in use at rural PHC clinics in South Africa's KZN province. However, healthcare workers have requested additional POC tests to improve detection and management of priority disease conditions. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT02692274.

Factors associated with study attrition in a pilot randomised controlled trial to explore the role of exercise-assisted reduction to stop (EARS) smoking in disadvantaged groups.

BACKGROUND: Study attrition has the potential to compromise a trial's internal and external validity. The aim of the present study was to identify factors associated with participant attrition in a pilot trial of the effectiveness of a novel behavioural support intervention focused on increasing physical activity to reduce smoking, to inform the methods to reduce attrition in a definitive trial. METHODS: Disadvantaged smokers who wanted to reduce but not quit were randomised (N = 99), of whom 61 (62 %) completed follow-up assessments at 16 weeks. Univariable logistic regression was conducted to determine the effects of intervention arm, method of recruitment, and participant characteristics (sociodemographic factors, and lifestyle, behavioural and attitudinal characteristics) on attrition, followed by multivariable logistic regression on those factors found to be related to attrition. RESULTS: Participants with low confidence to quit, and who were undertaking less than 150 mins of moderate and vigorous physical activity per week at baseline were less likely to complete the 16-week follow-up assessment. Exploratory analysis revealed that those who were lost to follow-up early in the trial (i.e., by 4 weeks), compared with those completing the study, were younger, had smoked for fewer years and had lower confidence to quit in the next 6 months. Participants who recorded a higher expired air carbon monoxide reading at baseline were more likely to drop out late in the study, as were those recruited via follow-up telephone calls. Multivariable analyses showed that only completing less than 150 mins of physical activity retained any confidence in predicting attrition in the presence of other variables. CONCLUSIONS: The findings indicate that those who take more effort to be recruited, are younger, are heavier smokers, have less confidence to quit, and are less physically active are more likely to withdraw or be lost to follow-up.

Evaluating the accessibility and utility of HIV-related point-of-care diagnostics for maternal health in rural South Africa: a study protocol.

INTRODUCTION: Poor healthcare access is a major barrier to receiving antenatal care and a cause of high maternal mortality in South Africa (SA). 'Point-of-care' (POC) diagnostics is a powerful emerging healthcare approach to improve healthcare access. This study focuses on evaluating the accessibility and utility of POC diagnostics for maternal health in rural SA primary healthcare (PHC) clinics in order to generate a model framework of implementation of POC diagnostics in rural South African clinics. METHOD AND ANALYSES: We will use several research methods, including a systematic review, quasi-experiments, survey, key informant interviews and audits. We will conduct a systematic review and experimental study to determine the impact of POC diagnostics on maternal health. We will perform a cross-sectional case study of 100 randomly selected rural primary healthcare clinics in KwaZulu-Natal to measure the context and patterns of POC diagnostics access and usage by maternal health providers and patients. We will conduct interviews with relevant key stakeholders to determine the reasons for POC deficiencies regarding accessibility and utility of HIV-related POC diagnostics for maternal health. We will also conduct a vertical audit to investigate all the quality aspects of POC diagnostic services including diagnostic accuracy in a select number of clinics. On the basis of information gathered, we will propose a model framework for improved implementation of POC diagnostics in rural South African public healthcare clinics. Statistical (Stata-13) and thematic (NVIVO) data analysis will be used in this study. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the University of KwaZulu-Natal (BE 484/14) and the KwaZulu-Natal Department of Health based on the Helsinki Declaration (HRKM 40/15). Findings of this study will be disseminated electronically and in print. They will be presented to conferences related to HIV/AIDS, diagnostics, maternal health and strengthening of health systems.

Impact of point-of-care diagnostics on maternal outcomes in HIV-infected women: systematic review and meta-analysis protocol.

INTRODUCTION: Studies indicate substandard diagnostic care, delayed and missed diagnosis as some of the contributing factors to maternal mortality. The clinical impact of point-of-care (POC) diagnostics has been shown in the monitoring and treatment of a variety of infectious diseases, including HIV/AIDS and tuberculosis. The objective of this systematic review is to investigate the impact of POC diagnostics on maternal outcomes for HIV-infected women. METHODS: We will conduct a systematic review to evaluate the impact of POC diagnostics for improving desired healthcare outcomes for HIV-infected women. The search strategy will involve electronic databases including: Cochrane Infectious Disease Group Specialised Register; Cochrane Central Register of Control Trials, published in The Cochrane Library; PubMed; EBSCOhost and LILACS. The studies will be mapped in 2 stages: stage 1 will map studies descriptively by focus and method; stage 2 will involve additional inclusion criteria, quality assessment and data extraction undertaken by 2 reviewers in parallel. Evidence will be synthesised using relevant systematic research tools: meta-analysis and subgroup analysis will be conducted using RevMan and Stata 13 will be used for meta-regressions. We will follow recommendations described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Cochrane Handbook for Intervention Reviews. ETHICS AND DISSEMINATION: We anticipate finding a large number of studies on POC diagnostic interventions on maternal outcomes in HIV-infected women, which, once summarised, will be useful to guide future diagnostic interventions. The protocol for the systematic review has been registered in PROSPERO. The study will be disseminated electronically and in print. It will also be presented to conferences related to HIV/AIDS, POC diagnostics and maternal health. TRIAL REGISTRATION NUMBER: PROSPERO CRD42014015439.

Primum non nocere: Multimodality management strategies when multiple mass lesions strike a single patient.

BACKGROUND: The management of multiple symptomatic intracranial pathological processes in a single patient presents a rare and challenging problem for the neurosurgeon and the patient. Neurosurgeons must utilize a full spectrum of neurosurgical options to achieve the best patient outcome. CASE DESCRIPTION: We present a unique case of a 63-year-old woman who presented with a large convexity meningioma causing headaches, an acoustic neuroma causing deafness and imbalance and a suprasellar arachnoid cyst compromising the visual fields. Therapeutic intervention was staged based on the primum non nocere concept. First, the patient underwent stereotactic intracavitary cyst irradiation using colloidal 32P. Secondly, microsurgical resection of the convexity meningioma was performed. Finally, Gamma Knife radiosurgery of the acoustic neuroma was performed. One year after multimodality management, the patient was neurologically improved. There was no evidence of meningioma or cyst recurrence and the growth of the acoustic neuroma was arrested. CONCLUSION: This case demonstrates the value of multi-modality treatment of neurosurgical pathology, utilizing minimally invasive techniques when possible.

Radiosurgery for childhood intracranial arteriovenous malformations.

OBJECTIVE: The optimal management of intracranial arteriovenous malformations (AVMs) in children remains controversial. Children with intracranial AVMs present a special challenge in therapeutic decision-making because of the early recognition of their future life-long risks of hemorrhage if they are treated conservatively. The goals of radiosurgery are to achieve complete AVM obliteration and to preserve neurological function. We present long-term outcomes for a series of children treated using radiosurgery. METHODS: The findings for 53 consecutive children who underwent at least 36 months of imaging follow-up monitoring after radiosurgery were reviewed. The median age at the time of treatment was 12 years (range, 2-17 yr). Thirty-one children (58%) presented after their first intracranial hemorrhaging episodes, two (4%) after their second hemorrhaging episodes, and one (2%) after five hemorrhaging episodes. Nineteen children (36%) presented with unruptured AVMs, and a total of 25 children (47%) exhibited neurological deficits. AVMs were graded as Spetzler-Martin Grade I (2%), Grade II (23%), Grade III (36%), Grade IV (9%), or Grade VI (30%). The median AVM volume was 1.7 ml (range, 0.11-10.2 ml). The median marginal dose was 20 Gy (range, 15-25 Gy). RESULTS: Results were stratified according to AVM volumes (Group 1, < or =3 ml; Group 2, >3 ml to < or =10 ml; Group 3, >10 ml). Twenty-eight patients (80%) in Group 1 and 11 (64.7%) in Group 2 achieved complete obliteration. The only patient in Group 3 did not achieve obliteration. Complications included brainstem edema (n = 1) and transient pulmonary edema (n = 1). Four patients experienced hemorrhaging episodes, 30, 40, 84, and 96 months after radiosurgery. Multivariate logistic regression analysis demonstrated that only volume was significantly correlated with obliteration rates (P = 0.0109). CONCLUSION: Radiosurgery is safe and efficacious for selected children with AVMs. The obliteration rates and the attendant low morbidity rates suggest a primary role for stereotactic radiosurgery for pediatric AVMs.

Radiosurgery for hemangiomas of the cavernous sinus and orbit: technical case report.

OBJECTIVE AND IMPORTANCE: Hemangiomas of neurosurgical interest are histologically benign vascular tumors that most often occur in the orbit or cavernous sinus. Hemangiomas can be diagnosed by their characteristic radiographic and angiographic appearance and their tendency to bleed excessively during attempted removal. Intracranial or intraorbital hemangiomas require treatment when they become symptomatic. CLINICAL PRESENTATION: We report four hemangioma patients who presented with ocular symptoms or signs, such as orbital pain, ophthalmoplegia, proptosis, or impaired visual acuity. Before our evaluation, two patients had each had incomplete resections aborted because of excessive blood loss, one patient had undergone a nondiagnostic transsphenoidal biopsy, and one patient had had an unsuccessful embolization. INTERVENTION: All four patients were treated with gamma knife radiosurgery. Tumors received a minimal tumor dose that ranged from 14 to 19 Gy. Follow-up evaluations were performed 6 to 24 months after radiosurgery and revealed a reduction in tumor volume in three patients and no tumor progression in the fourth. All patients had symptomatic improvement, but one had persistent diplopia. CONCLUSION: In this early experience, stereotactic radiosurgery proved to be an effective management strategy that avoided the potentially serious complications associated with surgery or embolization of cavernous sinus hemangiomas.

Brain metastases in patients with no known primary tumor.

BACKGROUND: The care of patients with a brain metastasis from unknown primary site is controversial. The authors reviewed the results of stereotactic radiosurgery in this group of patients to better define clinical expectations. METHODS: During an 11-year interval, radiosurgery was performed in 421 patients with brain metastases at the University of Pittsburgh. Fifteen patients had solitary or multiple (< or = 5) brain metastases without a detectable primary site at the time of initial presentation. In five patients, a histologic diagnosis of cancer was obtained from extracranial metastatic sites. In 10 patients, a diagnosis was obtained from the brain. A total of 31 tumors with a mean volume of 4.3 mL (range, 0. 05-18.6 mL) underwent radiosurgery with a mean marginal dose of 16.2 Gray (Gy) (range, 12-20 Gy). Fourteen patients (93.3%) also received whole brain fractionated radiation therapy. RESULTS: The median survival was 15 months after radiosurgery (range, 1-48 months) and 27 months after their initial diagnosis of cancer. In 4 patients (26. 7%), the primary tumor was discovered later (lung in 3 patients and liver in 1). Three of these four patients died due to progression of their primary tumor. Of the remaining 11 patients, 4 died of progression of extracranial metastases, 2 died of other systemic diseases, and 3 patients died because of progression of brain metastasis. Three patients (20%) were still living between 21-48 months after radiosurgery. The presence of active systemic disease and brain stem location both were associated with a poor outcome (P = 0.004 and 0.04). The actuarial imaging-defined local tumor control rate was 91.3 +/- 5.9% at 4 years. CONCLUSIONS: Radiosurgery was an effective strategy for patients with brain metastases from an unknown primary site. Disease progression outside of the brain was the usual cause for patient death.

Successful management of sellar and suprasellar arachnoid cysts with stereotactic intracavitary irradiation: an expanded report of four cases.

OBJECTIVE: Sellar and suprasellar arachnoid cysts may be asymptomatic or may cause headache, optic nerve compression, endocrine dysfunction, or hydrocephalus. We propose a minimally invasive treatment strategy when intervention is indicated. METHODS: Four patients with sellar and suprasellar arachnoid cysts presented with headache, visual compromise, and endocrine dysfunction. Two of the four patients previously had undergone unsuccessful surgical intervention. The imaging studies of two patients were diagnostic of an arachnoid cyst. RESULTS: All four patients underwent stereotactic intracavitary radiation with cyst regression and symptomatic improvement. In each patient, the optic chiasm was decompressed successfully. There were no complications from the procedure. CONCLUSION: Stereotactic intracavitary irradiation of arachnoid cysts proved to be safe and effective. The procedure obviated the need for open cyst fenestration or shunting.

Thalamic stimulation for choreiform movement disorders in children. Report of two cases.

Surgery for movement disorders is most commonly performed in patients with dyskinesia and tremor associated with Parkinson's disease or in those with essential tremor. The role of ablative surgery or deep brain stimulation in patients with choreiform movements is poorly defined. The authors placed thalamic stimulation systems in two children with disabling choreiform disorders due to intracerebral hemorrhage or cerebral palsy. Each patient displayed choreiform movements in the upper extremities both at rest and with intention, which interfered with daily activities and socialization. Both children obtained significant improvement in their choreiform movements, and their upper extremity function improved with no incidence of morbidity. Thalamic stimulation appears to be a promising and nonablative approach for children with choreiform movement disorders.

Iatrogenic pneumocephalus secondary to intravenous catheterization. Case report.

The presence of pneumocephalus in a patient without a history of undergoing intracranial or intrathecal procedures is a significant radiographic finding that portends a violation of the dural barrier or the presence of infection. The authors report a case of iatrogenic pneumocephalus that confounded the evaluation of a patient with unrelated neurological disorders, resulting in unnecessary transfer of the patient and utilization of medical resources. A review of 100 sequential computerized tomography scans obtained in patients for any indication in the emergency department revealed a 6% incidence of iatrogenic intravenous pneumocephalus. Computerized tomography scans revealing pneumocephalus had been obtained for altered mental status, focal motor deficit, seizure, and trauma. More careful intravenous catheterization and recognition of the condition on imaging may avoid similar problems.

Restorative neurosurgery: opportunities for restoration of function in acquired, degenerative, and idiopathic neurological diseases.

Historically, neurosurgery has improved the environment of the nervous system to promote maximal spontaneous recovery of function. The population of patients whom we treat at present is a small portion of those who suffer from disabling neurological illnesses. Based on a combination of new technology, and advances in neuroscience, restorative neurosurgery is advancing the frontiers of our specialty, and providing the potential to restore lost function. Significant advancements in gene therapy, the discovery and delivery of neurotrophic factors, and cell transplantation now require neurosurgeons to broaden the scope of our practice so that it includes the restoration of function in an enormous number of patients with acquired, degenerative and idiopathic neurological diseases. In order to meet the present challenge, neurosurgeons must broaden our vision, our role, and our future educational goals. In this review, we summarize the landmark advances in the basic and clinical neurosciences and the results of clinical trials that are driving our evolution from passive reaction to disease to active attempts to restore lost central nervous system function.