Retained colistin susceptibility in clinical Acinetobacter baumannii isolates with multiple mutations in pmrCAB and lpxACD operons.

The progressive increase in the resistance rates to first- and second-line antibiotics has forced the reuse of colistin as last-line treatment for Acinetobacter baumannii infections, but the emergence of colistin-resistant strains is not uncommon. This has been long linked to acquired chromosomal mutations in the operons pmrCAB and lpxACD. Hence, such mutations are routinely screened in colistin-resistant strains by most studies. The current study was designed to explore the possible existence of pmrCAB and lpxACD mutations in colistin-susceptible isolates. For this purpose, the whole genome sequences of eighteen multi-/extensively drug resistant A. baumannii were generated by Illumina sequencing and screened for missense mutations of the operons pmrCAB and lpxACD. Most of the isolates belonged to global clones (GCs) including GC1 (n=2), GC2 (n=7), GC7 (n=2), GC9 (n=3), and GC11 (n=1). The minimum inhibitory concentrations (MICs) of colistin were determined by the broth microdilution assay. Seventeen isolates were fully susceptible to colistin with MICs ranging from (≤0.125 to 0.5 µg/ml). Interestingly, all colistin-susceptible isolates carried missense mutations in pmrCAB and lpxACD operons with reference to A. baumannii ATCC 19606. Overall, 34 mutations were found. Most substitutions were detected in pmrC (n=20) while no mutations were found in pmrA or lpxA. Notably, the mutation pattern of the two operons was almost conserved among the isolates that belonged to the same sequence type (ST) or GC. This was also confirmed by expanding the analysis to include A. baumannii genomes deposited in public databases. Here, we demonstrated the possible existence of missense mutations in pmrCAB and lpxACD operons in colistin-susceptible isolates, shedding light on the importance of interpreting mutations with reference to colistin-susceptible isolates of the same ST/GC to avoid the misleading impact of the ST/GC-related polymorphism. In turn, this may lead to misinterpretation of mutations and, hence, overlooking the real players in colistin resistance that are yet to be identified.

Statistical optimization of a podoviral anti-MRSA phage CCASU-L10 generated from an under sampled repository: Chicken rinse.

Introduction: The insurgence of antimicrobial resistance is an imminent health danger globally. A wide range of challenging diseases are attributed to methicillin-resistant Staphylococcus aureus (MRSA) as it is weaponized with a unique array of virulence factors, and most importantly, the resistance it develops to most of the antibiotics used clinically. On that account, the present study targeted the optimization of the production of a bacteriophage active against MRSA, and evaluating some of its characters. Methods and results: The bacteriophage originated from a quite peculiar environmental source, raw chicken rinse and was suggested to belong to Podoviridae, order Caudovirales. It withstood a variety of extreme conditions and yield optimization was accomplished via the D-optimal design by response surface methodology (RSM). A reduced quadratic model was generated, and the ideal production conditions recommended were pH 8, glycerol 0.9% v/v, peptone 0.08% w/v, and 107 CFU/ml as the host inoculum size. These conditions led to a two-log fold increase in the phage titer (1.17x10¹² PFU/ml), as compared to the regular conditions. Discussion: To conclude, statistical optimization successfully enhanced the output of the podoviral phage titer by two-log fold and therefore, can be regarded as a potential scale-up strategy. The produced phage was able to tolerate extreme environmental condition making it suitable for topical pharmaceutical preparations. Further preclinical and clinical studies are required to ensure its suitability for use in human.

Genetic Configuration of Genomic Resistance Islands in Acinetobacter baumannii Clinical Isolates From Egypt.

In Acinetobacter baumannii (A. baumannii), a wide repertoire of resistance genes is often carried within genomic resistance islands (RIs), particularly in high-risk global clones (GCs). As the first in Egypt, the current study aimed at exploring the diversity and genetic configuration of RIs in the clinical isolates of A. baumannii. For this purpose, draft genomes of 18 isolates were generated by Illumina sequencing. Disk diffusion susceptibility profiling revealed multidrug resistance (MDR) and extensive drug resistance (XDR) phenotypes in 27.7 and 72.2%, respectively. The highest susceptibility was noted for tigecycline (100.0%) followed by colistin (94.4%), for which an MIC50 of 0.25 µg/ml was recorded by the broth microdilution assay. Sequence typing (ST) showed that the majority of the isolates belonged to high-risk global clones (GC1, GC2, and GC9). A novel Oxford sequence type (ST2329) that also formed a novel clonal complex was submitted to the PubMLST database. A novel bla ADC variant (bla ADC-258) was also identified in strain M18 (ST85Pas/1089Oxf). In addition to a wide array of resistance determinants, whole-genome sequencing (WGS) disclosed at least nine configurations of genomic RIs distributed over 16/18 isolates. GC2 isolates accumulated the largest number of RIs (three RIs/isolate) followed by those that belong to GC1 (two RIs/isolate). In addition to Tn6022 (44.4%), the comM gene was interrupted by AbaR4 (5.5%) and three variants of A. baumannii genomic resistance island 1(AbGRI)-type RIs (44.4%), including AbaR4b (16.6%) and two novel configurations of AbGRI1-like RIs (22.2%). Three of which (AbaR4, AbaR4b, and AbGRI1-like-2) carried bla OXA-23 within Tn2006. With less abundance (38.8%), IS26-bound RIs were detected exclusively in GC2 isolates. These included a short version of AbGRI2 (AbGRI2-15) carrying the genes bla TEM-1 and aphA1 and two variants of AbGRI3 RIs carrying up to seven resistance genes [mphE-msrE-armA-sul1-aadA1-catB8-aacA4]. Confined to GC1 (22.2%), sulfonamide resistance was acquired by an ISAba1 bracketed GIsul2 RI. An additional RI (RI-PER-7) was also identified on a plasmid carried by strain M03. Among others, RI-PER-7 carried the resistance genes armA and bla PER-7. Here, we provided a closer view of the diversity and genetic organization of RIs carried by a previously unexplored population of A. baumannii.

Tn7382, a novel composite transposon harboring blaNDM-1 and aphA6 in Acinetobacter baumannii.

OBJECTIVES: Co-transfer of carbapenem and amikacin resistance might contribute to the evolution of extensively drug resistant (XDR) Acinetobacter baumannii. The current study used bioinformatic tools and an in silico approach to investigate the potential mobility of a novel composite transposon co-harboring blaNDM-1 and aphA6. METHODS: The transposon, named here Tn7382, was recently identified in the chromosomes of two XDR A. baumannii isolates (M02 and M11) from Egypt. The draft genomes of M02 and M11 were generated by Illumina sequencing. Nucleotide homology of Tn7382 and flanking regions was analyzed using the Basic Local Alignment Search Tool. RESULTS: Tn7382 is derived from Tn125 and encompasses seven open reading frames [aphA6, ISAba125 transposase-coding gene, blaNDM-1, ble, iso, tat, cutA] enclosed by two direct copies of ISAba14. While described for the first time, Tn7382 was found in the chromosomes of five A. baumannii strains deposited in the NCBI database. Using the Artemis Comparison Tool, the potential mobility of Tn7382 was demonstrated in silico by comparative genomic analysis of two A. baumannii strains (TP1 and TP2) retrieved from the NCBI database. The transposon was acquired by TP2 at the same location as an ISAba14 element in the ancestral variant TP1 isolated from the same patient in the USA 11 days earlier. CONCLUSIONS: Here, we present the characteristics of Tn7382, a composite transposon flanked by ISAba14 and harboring the aphA6 and blaNDM-1 resistance genes. In silico analysis inferred the potential mobility of Tn7382, but experimental validation is still required.

Surgical nuances in corpus callosotomy as a palliative epilepsy surgery.

Background: Corpus callosotomy is a well-established palliative procedure in selected patients with drug resistant epilepsy (DRE). It has a beneficial role in ameliorating generalized seizures mainly drop attacks. Here, we present some technical tips for performing callosotomy depending on the anatomical basis, to minimize craniotomy size and guard against inadvertently entering the lateral ventricles. Methods: This study was a retrospective review of patients who received corpus callosotomy at our institute as a palliative epilepsy surgery. We present our experience and surgical tips with the extraventricular technique of corpus callosotomy with comparison of surgery-related complications and operative time between extraventricular and conventional techniques in selected patients with DRE. Results: Our study included 34 patients. First group of patients included 14 patients who received conventional approach, while the extraventricular approach was done in 20 patients. Extraventricular approach showed significantly lower wound complications rate of 10% compared to 78% in intraventricular approach (P < 0.001). Mean operative time was significantly lower in extraventricular versus conventional technique with 52 min versus 94 min, respectively (P < 0.001). Planned extent of corpus callosotomy resection was achieved in all our patients using both approaches. Conclusion: The cleft of the septum pellucidum offers a natural pursuit to section corpus callosum strictly midline and completely extraventricular in well selected patients of DRE candidate for callosotomy. Performing corpus callosotomy in extraventricular approach provided better patients outcomes regarding surgery and wound-related complications when compared to conventional approach.

Outcome of pallidal stimulation of idiopathic generalized dystonia with predominant mobile truncal dystonia: case report.

BACKGROUND: Further reports are required to describe the outcome of truncal dystonia treated by bilateral pallidal stimulation (globus pallidus interna deep brain stimulation [GPi-DBS]), owing to the small number of reports and clinical variability and complexity of truncal dystonia. Retrospectively, we report our experience of treating three patients with idiopathic generalized dystonia, with predominant mobile truncal dystonia by bilateral GPi-DBS. METHODS: Three patients with idiopathic generalized dystonia underwent bilateral GPi-DBS. One patient had adult-onset dystonia, while two patients had childhood-onset dystonia. All patients had predominant mobile truncal dystonia of mixed abnormal postures (camptocormia and lateral tilt), while one patient had also truncal twist. Patients were assessed pre- and post-GPi-DBS using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Dystonia Disability Scale (DDS). RESULTS: The three patients showed marked improvement of global (94.78%, 92.4% and 80.95%) and truncal BFMDRS (all abnormal postures) (87.5%, 93.75% and 87.5%) and DDS (95.84% and 50%), using high amplitude monopolar settings, with a dramatic improvement of the mobile component. Improvement was persistent for 1.5, 3 and 6 years. CONCLUSION: Bilateral GPi-DBS improves markedly the mobile truncal dystonia and associated abnormal postures in patients with adult and childhood-onset idiopathic generalized dystonia. Improvement was persistent for up to 6 years.

Genomic Characterization of Extensively Drug-Resistant NDM-Producing Acinetobacter baumannii Clinical Isolates With the Emergence of Novel bla ADC-257.

Acinetobacter baumannii has become a major challenge to clinicians worldwide due to its high epidemic potential and acquisition of antimicrobial resistance. This work aimed at investigating antimicrobial resistance determinants and their context in four extensively drug-resistant (XDR) NDM-producing A. baumannii clinical isolates collected between July and October 2020 from Kasr Al-Ainy Hospital, Cairo, Egypt. A total of 20 A. baumannii were collected and screened for acquired carbapenemases (bla NDM, bla VIM and bla IMP) using PCR. Four NDM producer A. baumannii isolates were identified and selected for whole-genome sequencing, in silico multilocus sequence typing, and resistome analysis. Antimicrobial susceptibility profiles were determined using disk diffusion and broth microdilution tests. All bla NDM-positive A. baumannii isolates were XDR. Three isolates belonged to high-risk international clones (IC), namely, IC2 corresponding to ST570Pas/1701Oxf (M20) and IC9 corresponding to ST85Pas/ST1089Oxf (M02 and M11). For the first time, we report bla NDM-1 gene on the chromosome of an A. baumannii strain that belongs to sequence type ST164Pas/ST1418Oxf. Together with AphA6, bla NDM-1 was bracketed by two copies of ISAba14 in ST85Pas isolates possibly facilitating co-transfer of amikacin and carbapenem resistance. A novel bla ADC allele (bla ADC-257) with an upstream ISAba1 element was identified in M19 (ST/CC164Pas and ST1418Oxf/CC234Oxf). bla ADC genes harbored by M02 and M11 were uniquely interrupted by IS1008. Tn2006-associated bla OXA-23 was carried by M20. bla OXA-94 genes were preceded by ISAba1 element in M02 and M11. AbGRI3 was carried by M20 hosting the resistance genes aph(3`)-Ia, aac(6`)-Ib`, catB8, ant(3``)-Ia, sul1, armA, msr(E), and mph(E). Nonsynonymous mutations were identified in the quinolone resistance determining regions (gyrA and parC) of all isolates. Resistance to colistin in M19 was accompanied by missense mutations in lpxACD and pmrABC genes. The current study provided an insight into the genomic background of XDR phenotype in A. baumannii recovered from patients in Egypt. WGS revealed strong association between resistance genes and diverse mobile genetic elements with novel insertion sites and genetic organizations.

Subtotal Resection Followed by Adjuvant Radiosurgery for Large Vestibular Schwannomas: Outcomes with Regard to the Timing and Regimen of Irradiation.

OBJECTIVE: To evaluate the results of combined management of large vestibular schwannomas (VS) with initial subtotal resection (STR) followed by adjuvant stereotactic radiosurgery (SRS), with a particular emphasis on the timing and regimen of irradiation. METHODS: Seventeen patients underwent STR of a VS followed by SRS, whereas five others were observed after STR. Early SRS (<6 months after surgery) and late SRS (>6 months after surgery) were done in 8 and 9 patients, respectively. Single- and multisession SRS treatments were administered in 10 and 7 patients, respectively. The mean follow-up durations after surgery and SRS were 40 and 28 months, respectively. RESULTS: The rates of radiological and oncological tumor control after SRS were 82% and 100%, respectively. The tumor volume at the last follow-up and its relative changes after SRS did not differ significantly on the basis of the irradiation timing (early versus late) or on the basis of the irradiation regimen (single-session versus multisession). In no patient who was observed after STR of a VS was tumor regrowth noted during a mean follow-up period of 49 months. At 12 months after surgery, motor function of the ipsilateral facial nerve corresponded to House-Brackmann grades I, II, III, and IV in 16 patients (73%), 3 patients (14%), 1 patient (5%), and 2 patients (9%), respectively. Facial nerve function at the last follow-up did not differ significantly on the basis of the irradiation timing (early versus late) or on the basis of the irradiation regimen (single-session versus multisession). CONCLUSION: The combination of initial STR followed by adjuvant SRS is an effective treatment strategy for patients with a large VS. Although the optimal timing and regimen of postoperative irradiation of the residual lesion should be defined further, our preliminary data suggest that either early or late SRS after surgery may provide good tumor control and optimal functional results.

Emergence of colistin resistance in multidrug-resistant Klebsiella pneumoniae and Escherichia coli strains isolated from cancer patients.

BACKGROUND: Colistin resistance is mainly driven by alterations in the Gram-negative outer membrane lipopolysaccharides and is caused, in most cases, by mutations in mgrB gene. However, the recent emergence of plasmid-encoded colistin resistance among Enterobacteriaceae strains represents a serious threat to global public health. In this paper we have investigated the rates of colistin resistance and the underlying mechanisms in 450 Klebsiella pneumoniae and Escherichia coli isolates obtained from cancer patients in Egypt. METHODS: Colistin susceptibility and minimum inhibitory concentrations were determined according to the European Committee on Antimicrobial Susceptibility Testing, by broth microdilution, and by E-test. The mcr-1, mcr-2 and mgrB genes were detected by PCR and then sequenced. Clonal diversity in colistin-resistant K. pneumoniae was evaluated by multilocus sequence typing. RESULTS: Forty (8.8%) colistin-resistant isolates, including 22 K. pneumoniae and 18 E. coli, were isolated over 18 months. Of these, 50% were carbapenem-resistant, out of which nine were blaOXA-48 and seven blaNDM-1 positive. The mechanisms of colistin resistance could be revealed only in three of the 40 resistant strains, being represented by mcr-1 in one blaNDM-1-positive E. coli strain and in one K. pneumoniae ST11 and by mgrB mutations, detected in one K. pneumoniae isolate. None of the studied isolates harbored mcr-2. CONCLUSIONS: Our results demonstrate a high frequency of colistin resistance in enterobacterial strains isolated from cancer patients, but a low prevalence of the most well known resistance mechanisms.

Cooccurrence of NDM-1, ESBL, RmtC, AAC(6')-Ib, and QnrB in Clonally Related Klebsiella pneumoniae Isolates Together with Coexistence of CMY-4 and AAC(6')-Ib in Enterobacter cloacae Isolates from Saudi Arabia.

The aim of this study was to investigate the mechanisms responsible for resistance to antimicrobials in a collection of enterobacterial isolates recovered from two hospitals in Saudi Arabia. A total of six strains isolated from different patients showing high resistance to carbapenems was recovered in 2015 from two different hospitals, with four being Klebsiella pneumoniae and two Enterobacter cloacae. All isolates except one K. pneumoniae were resistant to tigecycline, but only one K. pneumoniae was resistant to colistin. All produced a carbapenemase according to the Carba NP test, and all were positive for the EDTA-disk synergy test for detection of MBL. Using PCR followed by sequencing, the four K. pneumoniae isolates produced the carbapenemase NDM-1, while the two E. cloacae isolates produced the carbapenemase VIM-1. Genotyping analysis by Multilocus Sequence Typing (MLST) showed that three out of the four K. pneumoniae isolates were clonally related. They had been recovered from the same hospital and belonged to Sequence Type (ST) ST152. In contrast, the fourth K. pneumoniae isolate belonged to ST572. Noticeably, the NDM-1-producing K. pneumoniae additionally produced an extended-spectrum ß-lactamase (ESBL) of the CTX-M type, together with OXA-1 and TEM-1. Surprisingly, the three clonally related isolates produced different CTX-M variants, namely, CTX-M-3, CTX-M-57, and CTX-M-82, and coproduced QnrB, which confers quinolone resistance, and the 16S rRNA methylase RmtC, which confers high resistance to all aminoglycosides. The AAC(6')-Ib acetyltransferase was detected in both K. pneumoniae and E. cloacae. Mating-out assays using Escherichia coli as recipient were successful for all isolates. The bla NDM-1 gene was always identified on a 70-kb plasmid, whereas the bla VIM-1 gene was located on either a 60-kb or a 150-kb plasmid the two E. cloacae isolates, respectively. To the best of our knowledge, this is the first report of the coexistence of an MBL (NDM-1), an ESBL (CTX-M), a 16S rRNA methylase (RmtC), an acetyltransferase (AAC[6']-Ib), and a quinolone resistance enzyme (QnrB) in K. pneumoniae isolates recovered from different patients during an outbreak in a Saudi Arabian hospital.

Combined Unilateral Posteroventral Pallidotomy and Ventral Intermediate Nucleus Thalamotomy in Tremor-Dominant Parkinson's Disease versus Posteroventral Pallidotomy Alone: A Prospective Comparative Study.

BACKGROUND: The optimum target in surgery for Parkinson's disease (PD) is still controversial, especially in patients with tremor-dominant PD. We aim to compare results in tremor-dominant patients undergoing pallidotomy vs. those undergoing simultaneous posteroventral pallidotomy (PVP) and ventral intermediate nucleus (VIM) thalamotomy. METHODS: Twenty-four patients with tremor-dominant PD were included in this study. Twelve patients received unilateral PVP contralateral to the most affected side. The other 12 patients received simultaneous unilateral PVP and VIM thalamotomy contralateral to the most affected side. Assessment of results in both groups was achieved using both UPDRS "off" motor scores and UPDRS rest tremor subscores. RESULTS: The mean UPDRS off motor score improved in the pallidotomy group from 61.3 preoperatively to 36.8 at 12 months. In the combined group, it improved from 59.6 to 35.2 at 12 months, with no statistically significant difference between both groups. On the other hand, while the mean tremor subscore in the pallidotomy group improved from a mean of 2.3-0.8, the tremors were abolished in all of the patients in the combined group except for 1 patient who showed slight infrequent tremors at 12 months. CONCLUSION: Patients with tremor-dominant PD achieve more improvement in tremor control after combined PVP and VIM thalamotomy.

Characterization of carbapenemases, ESBLs, and plasmid-mediated quinolone determinants in carbapenem-insensitive Escherichia coli and Klebsiella pneumoniae in Riyadh hospitals.

The main objective of this work was to characterize carbapenemases, extended-spectrum ß-lactamases (ESBLs), and plasmid-mediated quinolone resistance (PMQR) among carbapenem-insensitive Klebsiella pneumoniae and Escherichia coli clinical isolates which were isolated from three hospitals in Riyadh. Thirty-one carbapenem-insensitive isolates (21 K. pneumoniae and 10 E. coli) were recovered from March 2014 to May 2014. Susceptibility testing and phenotypic detection tests were used to characterize the classes of ß-lactamases. PCR assays were performed for the detection of the genes encoding ESBL (blaCTX-M, blaTEM,blaSHV, and blaOXA-1), carbapenemase (blaKPC,blaGES,blaVIM, blaIMP, blaNDM, and blaOXA-48), and PMQR (qnrA, qnrB, qnrS, aac(6)-Ib-cr, qepA, oqxA, and oqxB) genes. All carbapenem-insensitive isolates were carbapenemase producers, with 41.9% and 58.1% being class B carbapenemases class D OXA-48, respectively. While the prevalence of ESBL producers was 80.6%. The following resistance genes were detected; OXA-48-like (58.1%), NDM-type (41.9%), CTX-M-1-like (77.4%), CTX-M-9-like (9.6%), TEM-1 (74.2%), OXA-1 (54.8%), SHV-1 (4.4%), qnrS (58.1%), qnrB (3.2%), and aac(6)-Ib-cr (51.6%). The predominant carbapenemases in the isolates that had carbapenem MIC≤4µg/ml and MIC≥12µg/ml were blaOXA-48-type and blaNDM-type respectively. CTX-M-1-like and qnrS were the dominant ESBL and PMQR genes, respectively. This is the first report in which qnrS was described in the isolates from Saudi Arabia.

Early versus late Gamma Knife radiosurgery following transsphenoidal surgery for nonfunctioning pituitary macroadenomas: a multicenter matched-cohort study.

OBJECTIVE Gamma Knife radiosurgery (GKRS) is frequently used to treat residual or recurrent nonfunctioning pituitary macroadenomas. There is no consensus as to whether GKRS should be used early after surgery or if radiosurgery should be withheld until there is evidence of imaging-defined progression of tumor. Given the high incidence of adenoma progression after subtotal resection over time, the present study intended to evaluate the effect of timing of radiosurgery on outcome. METHODS This is a multicenter retrospective review of patients with nonfunctioning pituitary macroadenomas who underwent transsphenoidal surgery followed by GKRS from 1987 to 2015 at 9 institutions affiliated with the International Gamma Knife Research Foundation. Patients were matched by adenoma and radiosurgical parameters and stratified based on the interval between last resection and radiosurgery. Operative results, imaging data, and clinical outcomes were compared across groups following early (≤ 6 months after resection) or late (> 6 months after resection) radiosurgery. RESULTS After matching, 222 patients met the authors' study criteria (from an initial collection of 496 patients) and were grouped based on early (n = 111) or late (n = 111) GKRS following transsphenoidal surgery. There was a greater risk of tumor progression after GKRS (p = 0.013) and residual tumor (p = 0.038) in the late radiosurgical group over a median imaging follow-up period of 68.5 months. No significant difference in the occurrence of post-GKRS endocrinopathy was observed (p = 0.68). Thirty percent of patients without endocrinopathy in the early cohort developed new endocrinopathies during the follow-up period versus 27% in the late cohort (p = 0.84). Fourteen percent of the patients in the early group and 25% of the patients in the late group experienced the resolution of endocrine dysfunction after original presentation (p = 0.32). CONCLUSIONS In this study, early GKRS was associated with a lower risk of radiological progression of subtotally resected nonfunctioning pituitary macroadenomas compared with expectant management followed by late radiosurgery. Delaying radiosurgery may increase patient risk for long-term adenoma progression. The timing of radiosurgery does not appear to significantly affect the rate of delayed endocrinopathy.

Prognostic significance of corticotroph staining in radiosurgery for non-functioning pituitary adenomas: a multicenter study.

Silent corticotroph staining pituitary adenoma (SCA) represents an uncommon subset of Non-Functioning adenomas (NFAs), hypothesized to be more locally aggressive. In this retrospective multicenter study, we investigate the safety and effectiveness of Stereotactic Radiosurgery (SRS) in patients with SCA compared with other non-SCA NFA's. Eight centers participating in the International Gamma-Knife Research Foundation (IGKRF) contributed to this study. Outcomes of 50 patients with confirmed SCAs and 307 patients with confirmed non-SCA NFA's treated with SRS were evaluated. Groups were matched. SCA was characterized by a lack of clinical evidence of Cushing disease, yet with positive immunostaining for corticotroph. Median age was 55.2 years (13.7-87). All patients underwent at least one trans-sphenoidal tumor resection prior to SRS. SRS parameters were comparable as well. Median follow-up 40 months (6-163). Overall tumor control rate (TCR) 91.2% (n = 280). In the SCA group, TCR were 82% (n = 41) versus 94.1% (n = 289) for the control-NFA (p = 0.0065). The SCA group showed a significantly higher incidence of new post-SRS visual deficit (p < 0.0001) assigned to tumor progression and growth, and post-SRS weakness and fatigue (p < 0.0001). In univariate and multivariate analysis, only the status of silent corticotroph staining (p = 0.005, p = 0.009 respectively) and margin dose (p < 0.0005, p = 0.0037 respectively) significantly influenced progression rate. A margin dose of ≥17 Gy was noted to influence the adenoma progression rate in the entire cohort (p = 0.003). Silent corticotroph staining represents an independent factor for adenoma progression and hypopituitarism after SRS. A higher margin dose may convey a greater chance of TCR.

Fractal Analysis May Improve the Preoperative Identification of Atypical Meningiomas.

Background: There is no objective and readily accessible method for the preoperative determination of atypical characteristics of a meningioma grade. Objective: To evaluate the feasibility of using fractal analysis as an adjunctive tool to conventional radiological techniques in visualizing histopathological features of meningiomas. Methods: A group of 27 patients diagnosed with atypical (WHO grade II) meningioma and a second group of 27 patients with benign (WHO grade I) meningioma were enrolled in the study. Preoperative brain magnetic resonance (MR) studies (T1-wieghted, post-gadolinium) were processed and analyzed to determine the average fractal dimension (FDa) and maximum fractal dimension (FDm) of the contrast-enhancing region of the tumor using box-count method. FDa and FDm as well as particular radiological features were included in the logistic regression model as possible predictors of malignancy. Results: The cohort consisted of 34 women and 20 men, mean age of 62 ± 15 yr. Fractal analysis showed good interobserver reproducibility (Kappa >0.70). Both FDa and FDm were significantly higher in the atypical compared to the benign meningioma group (P < .0001). Multivariate logistic regression model reached statistical significance with P = .0001 and AUC = 0.87. The FDm, which was greater than 1.31 (odds ratio [OR], 12.30; P = .039), and nonskull base localization (OR, .052; P = .015) were confirmed to be statistically significant predictors of the atypical phenotype. Conclusion: Fractal analysis of preoperative MR images appears to be a feasible adjunctive diagnostic tool in identifying meningiomas with potentially aggressive clinical behavior.

A Randomized Trial on the Efficacy of Topical Anesthesia for Pain Reduction during Frame Placement for Gamma Knife Radiosurgery.

BACKGROUND/AIMS: Frame application for gamma knife radiosurgery (GKR) may be perceived as painful by patients. This study was designed to assess the efficacy of EMLA (2.5% lidocaine/2.5% prilocaine) in pain reduction. METHODS: This was a prospective, randomized, and controlled trial approved by our institutional review board. Fifty-four patients undergoing outpatient GKR were divided into EMLA and placebo groups. Prior to frame placement, EMLA/placebo was applied to the patient's forehead. A visual analog scale (VAS) was used to measure pain during 4 intervals: frontal injections, occipital injections, frontal screw insertion, and overall discomfort. This study was designed to observe a difference of 1.0 on the VAS at a power of 95%. RESULTS: VAS for EMLA versus placebo for frontal injections (5.2 ± 2.7 vs. 5.7 ± 2.0, respectively; p < 0.45), back injections, (6.5 ± 2.2 vs. 5.9 ± 2.3, respectively; p < 0.30), frontal pins (4.6 ± 2.7 vs. 4.6 ± 2.2, respectively; p < 0.99), and overall discomfort (p < 0.29) were not significantly different. A comparison between back and frontal injections for EMLA (6.54 vs. 5.19, respectively; p < 0.16) and placebo (5.89 vs. 5.68, respectively; p < 0.69) showed no significant difference between group and location (p < 0.21). CONCLUSION: Application of EMLA did not significantly reduce pain when used preoperatively for frame fixation. EMLA is no longer used as part of our routine for patients undergoing GKR.

Outcomes in Patients with Vestibular Schwannoma after Subtotal Resection and Adjuvant Radiosurgery.

BACKGROUND: The debate continues with a limited number of publications describing outcomes in patients with vestibular schwannoma (VS) treated with planned subtotal resection (STR) plus stereotactic radiosurgery (SRS). Here we present our experience. METHODS: This is a retrospective review of 22 patients with VS Koos grade III and IV who were treated with STR followed by SRS. Tumor volumes, facial nerve function, hearing preservation, and the presence of trigeminal neuropathy were noted. Spearman's rank test was used to correlate facial nerve grade with postoperative tumor residual tumor volume. RESULTS: Tumor control was achieved in all patients with a mean follow-up of 28 months. No patient required other treatment beyond the original surgery and adjuvant SRS during this period. After a mean postoperative period of 28 months, 19/22 patients had excellent (House-Brackmann I or II) facial nerve function grading. Improved facial nerve function was positively correlated with larger residual tumor volume (rs = 0.63). Kaplan-Meier curve showed around 80% probability for regaining facial nerve function after initial deterioration. Four patients reported postoperative facial numbness at the side of surgery, with 3 cases showing improvement within a month. Temporary postoperative caudal cranial nerve dysfunction was observed in 2 patients. CONCLUSION: Hybrid strategy of STR and adjuvant SRS provides patients with large VS excellent tumor control and a good clinical outcome.

Distribution of ß-lactamases in carbapenem-non-susceptible Acinetobacter baumannii in Riyadh, Saudi Arabia.

In this study, the distribution of ß-lactamase genes among 55 consecutive Acinetobacter baumannii isolates with reduced susceptibility to imipenem collected at Prince Salman Hospital (Riyadh, Saudi Arabia) from February-June 2011 was investigated. Minimum inhibitory concentrations (MICs) were determined by Etest and were interpreted against Clinical and Laboratory Standards Institute (CLSI) breakpoints. PCR was used to search for ß-lactamase genes, insertion sequence ISAba1 and class 1 integrons. Imipenem MICs ranged from 2µg/mL to ≥32µg/mL and resistance to aztreonam, cefepime and ceftazidime was widespread, with MIC90 values (MIC required to inhibit 90% of the isolates) of >256µg/mL. blaTEM, blaADC and blaOXA-51-like genes were universal, whilst blaOXA-23, blaPER, blaGES and blaOXA-24 were found in 60.0%, 49.1%, 34.5% and 3.6% of isolates, respectively. Genes for SHV, CTX-M, VEB, KPC, OXA-58 and metallo-ß-lactamases (MBLs) were not detected. ISAba1 was universal and consistently present upstream of blaOXA-51, blaOXA-23, blaOXA-24 and blaADC; class 1 integrons also were universal. Notably, 28/55 isolates had both an extended-spectrum ß-lactamase (ESBLs) and an acquired blaOXA-23 gene. High-level carbapenem resistance (MIC≥32µg/mL) was consistently associated with blaOXA-23 or blaOXA-24, whereas low-level resistance (MIC of 2-8µg/mL) was associated with the presence of ESBLs of GES or PER type and/or ISAba1-upregulated blaOXA-51-like. In conclusion, blaTEM, blaOXA-23, blaPER and blaGES-like genes were prevalent, often in combination. MBLs remained absent and high-level carbapenem resistance consistently correlated with the presence of blaOXA-23 or blaOXA-24.