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Abstract BACKGROUND Stereotactic radiosurgery (SRS) has become popular as a standard treatment for cavernous sinus (CS) meningiomas. OBJECTIVE To summarize the published literature specific to the treatment of CS meningioma with SRS found through a systematic review, and to create recommendations on behalf of the International Stereotactic Radiosurgery Society. METHODS Articles published from January 1963 to December 2014 were systemically reviewed. Three electronic databases, PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials, were searched. Publications in English with at least 10 patients (each arm) were included. RESULTS Of 569 screened abstracts, a total of 49 full-text articles were included in the analysis. All studies were retrospective. Most of the reports had favorable outcomes with 5-yr progression-free survival (PFS) rates ranging from 86% to 99%, and 10-yr PFS rates ranging from 69% to 97%. The post-SRS neurological preservation rate ranged from 80% to 100%. Resection can be considered for the treatment of larger (>3 cm in diameter) and symptomatic CS meningioma in patients both receptive to and medically eligible for open surgery. Adjuvant or salvage SRS for residual or recurrent tumor can be utilized depending on factors such as tumor volume and proximity to adjacent critical organs at risk. CONCLUSION The literature is limited to level III evidence with respect to outcomes of SRS in patients with CS meningioma. Based on the observed results, SRS offers a favorable benefit to risk profile for patients with CS meningioma.

Abstract BACKGROUND Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. OBJECTIVE To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published. METHODS From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.). RESULTS Median tumor volume was 4.8 cm3, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up > 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P > .001), for female vs male patients (P > .001), for sporadic vs multiple meningiomas (P > .001), and for skull base vs convexity tumors (P > .001). Permanent morbidity rate was 6.6% at the last follow-up. CONCLUSION Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.

BACKGROUND:Gamma knife radiosurgery (GKRS) is one of the alternatives for treatment for classical trigeminal neuralgia (TN). OBJECTIVE:To retrospectively analyze long-term outcomes for TN using GKRS achieved at our institution. METHODS:One hundred seventeen patients with medically refractory TN treated by GKRS at our institution were followed up between 1993 and 2011. Mean maximum dose was 86.5 Gy (range80-90 Gy; median90 Gy). Clinical response was defined based on the Burchiel classification. We considered classes I and II as a complete response. For toxicity, we use the Barrow Neurological Institute facial numbness scale. Mean duration of follow-up was 66 months (range24-171 months). RESULTS:Complete response at last follow-up in our patients was 81%, with an excellent response while off medication in 52%. Pain-free rates without medication (class I) were 85% at 3 years (confidence interval [CI]78%-94%), 81% at 5 years (CI72%-91%), and 76% at 7 years (CI65%-90%). Complete response rates (classes I-II) were 91% at 3 years (CI86%-97%), 86% at 5 years (CI79%-93%), and 82% at 7 years (CI72%-93%). Poor treatment response rates differed significantly between patients who had undergone previous surgery and were refractory to management with medication prior to GKRS. New or worsening facial numbness was reported in 32.5% (30% score II and 2.5% score III). No anesthesia dolorosa was reported. Permanent recurrence pain rate was 12%. CONCLUSION:GKRS achieved favorable outcomes compared with surgery in terms of pain relief and complication rates in our cohort of patients, notwithstanding decreasing pain-free survival rates over time. We consider GKRS to be an initial treatment in the management of medically intractable TN in selected patients. ABBREVIATIONS:CI, confidence intervalGKRS, gamma knife radiosurgeryMVD, microvascular decompressionRS, radiosurgeryTN, trigeminal neuralgia

BackgroundCerebral cavernous malformations (CCMs) frequently manifest with haemorrhages. Stereotactic radiosurgery (SRS) has been employed for CCM not suitable for resection. Its effect on reducing haemorrhage risk is still controversial. The aim of this study was to expand on the safety and efficacy of SRS for haemorrhagic CCM.MethodsThis retrospective multicentric study included CCM with at least one haemorrhage treated with single-session SRS. The annual haemorrhagic rate (AHR) was calculated before and after SRS. Recurrent event analysis and Cox regression were used to evaluate factors associated with haemorrhage. Adverse radiation effects (AREs) and occurrence of new neurological deficits were recorded.ResultsThe study included 381 patients (median age: 37.5 years (Q1–Q3: 25.8–51.9) with 414 CCMs. The AHR from diagnosis to SRS excluding the first haemorrhage was 11.08 per 100 CCM-years and was reduced to 2.7 per 100 CCM-years after treatment. In recurrent event analysis, SRS, HR 0.27 (95% CI 0.17 to 0.44), p<0.0001 was associated with a decreased risk of haemorrhage, and the presence of developmental venous anomaly (DVA) with an increased risk, HR 1.60 (95% CI 1.07 to 2.40), p=0.022. The cumulative risk of first haemorrhage after SRS was 9.4% (95% CI 6% to 12.6%) at 5 years and 15.6% (95% CI% 9 to 21.8%) at 10 years. Margin doses> 13 Gy, HR 2.27 (95% CI 1.20 to 4.32), p=0.012 and the presence of DVA, HR 2.08 (95% CI 1.00 to 4.31), p=0.049 were factors associated with higher probability of post-SRS haemorrhage. Post-SRS haemorrhage was symptomatic in 22 out of 381 (5.8%) patients, presenting with transient (15/381) or permanent (7/381) neurological deficit. ARE occurred in 11.1% (46/414) CCM and was responsible for transient neurological deficit in 3.9% (15/381) of the patients and permanent deficit in 1.1% (4/381) of the patients. Margin doses >13 Gy and CCM volume >0.7 cc were associated with increased risk of ARE.ConclusionSingle-session SRS for haemorrhagic CCM is associated with a decrease in haemorrhage rate. Margin doses ≤13 Gy seem advisable.

Epizootic rabbit enteropathy (ERE) affects young rabbits and represents 32% of the enteropathies in rabbit production farms in Mexico. The etiology of this syndrome has not been clarified yet. A metataxonomic and histopathology study of ERE was carried out to compare the gastrointestinal microbiota and histopathological lesions of healthy and positive-ERE rabbits. The metataxonomic study was done using an Illumina MiSeq (MiSeq® system, Illumina, San Diego California, USA) massive segmentation platform, and a Divisive Amplicon Denoising Algorithm 2 (DADA2 algorithm) was used to obtain Shannon and Simpson diversity indices as well as the relative abundance of the identified communities. For the histopathological study, paraffin sections of the cecum, ileo-cecal valve, and colon were stained with eosin and hematoxylin. AxioVision 4.9 software (Carl Zeiss MicroImaging GmbH, Jena, Germany) was used to measure the crypt depths. Statistical analysis was done using PERMANOVA analysis for the metataxonomic study and ANOVA for the histopathology study. Histopathologic analysis showed smaller sizes of crypts in the colon of ERE rabbits. Differences were observed in the diversity and abundance of the gastrointestinal microbiota between the analyzed groups. The genus Clostridium and the species Cloacibacillus porcorum and Akkermansia muciniphila were associated with ERE. The results obtained from this study can provide information for future clarification of the etiology and proposals of effective treatments.

This study aimed to investigate the effect of feeding insoluble fiber on the microbiota and metabolites of the caecum and feces of rabbits recovering from epizootic rabbit enteropathy relative to non-infected rabbits. Rabbits that had either recovered from epizootic rabbit enteropathy or ones that had never had epizootic rabbit enteropathy were fed on a diet of 32% or 36% neutral detergent fiber until they were 70 days of age. At this point, the short-chain fatty acid and ammonia levels were measured in caecotroph and fecal samples and compared using 2 × 2 ANOVA. The microbial composition of the samples was also analyzed using next-generation sequencing and compared by PERMANOVA. Caecotrophic samples from previously affected rabbits on lower fiber diets had higher short-chain fatty acid contents and higher species diversity index values for some indices (p < 0.05), although the fecal samples showed lower species diversity levels (p < 0.05). In addition, the PERMANOVA analyses demonstrated that differences were detected in the microbial composition of both fecal and caecotrophic samples, depending on the disease status at the outset of the experiment (p < 0.05). The results of this work show that, although there is some potential in the use of high-fiber diets for the treatment of rabbits that have had epizootic rabbit enteropathy, they are not able to produce the same digestive tract properties as those seen in rabbits that have never had the condition. This is true even after the rabbits have recovered from epizootic rabbit enteropathy.

Brainstem cerebral cavernous malformations (CCM) are clinically more aggressive compared to superficial CCMs. Due to their location, resection can be challenging, making stereotactic radiosurgery (SRS) an attractive alternative for symptomatic patient. Brainstem CCM patients ( n  = 170) were treated with Gamma Knife SRS at 11 radiosurgical centers. Hemorrhagic risk reduction, risk factors of post-SRS hemorrhage, and clinical outcomes were retrospectively analyzed. Most patients had a single (165/170 patients) brainstem CCMs treated; the majority of CCMs (165/181) presented with bleeding. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM (HR: 0.17, p  < 0.001) using recurrent multivariate analysis. The annual hemorrhage rate decreased from 14.8 per 100 CCM-years before SRS to 2.3 after treatment. Using univariate Cox-analysis, the probability of a new hemorrhages after SRS was reduced for patient older than 35 years (HR = 0.21, p  = 0.002) and increased with a margin dose > 13 Gy (HR = 2.57, p  = 0.044). Adverse radiation effect (ARE) occurred in 9 patients (5.3%) and was symptomatic in four (2.4%). At a median follow-up of 3.4 years (Inter-quartile range: 5.4), 13 patients (8.0%) had a worsened clinical status, with the treated CCM being the cause in 5.6% (10) of the patients. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM and conveyed this benefit with a low risk of advrse radiation effects (ARE) and worsening clinical status.

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is increasingly considered for selected olfactory groove meningiomas (OGMs). OBJECTIVE To investigate the safety and efficacy of SRS for OGMs. METHODS From 20 institutions participating in the International Radiosurgery Research Foundation, we pooled patients who underwent SRS for histologically confirmed or radiologically suspected WHO grade I OGMs and were followed for 6 mo or more after the SRS. RESULTS In total, 278 (median age 57 yr) patients underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) WHO grade I OGMs Median treatment volume was 4.60 cm3 (range: 0.12-27.3 cm3), median prescription dose was 12 Gy, and median dose to the olfactory nerve was 11.20 Gy. During median post-SRS imaging follow-up of 39 mo (range: 6-240 mo), 43% of patients had partial or marginal response, 54% of patients had stable disease, and 3% of patients experienced progression. During median post-SRS clinical follow-up of 51 mo (range: 6-240 mo), 36 (13%) patients experienced clinical and/or radiological adverse radiation events (AREs). Elevated risk of AREs was associated with larger OGM volume (P = .009) and pre-SRS peritumoral T2/fluid-attenuated inversion-recovery signal abnormalities (P < .001). After the SRS, olfaction remained stable, improved, or deteriorated in 90%, 8%, and 2% of patients, respectively. Complete post-SRS anosmia was predicted by partial/complete anosmia before the SRS (odds ratio [OR] = 83.125; 95% CI [24.589-281.01], P < .001) and prior resection of OGM (OR = 3.919; 95% CI [1.713-8.970], P = .001). CONCLUSION SRS is associated with durable local control of the majority of OGM patients with acceptable safety profile. SRS allows preservation or improvement of olfactory function in the majority of OGM patients. Graphical Abstract Graphical Abstract

Searching for generic behaviors has been one of the driving forces leading to a deep understanding and classification of diverse phenomena. Usually a starting point is the development of a phenomenology based on observations. Such is the case for power law distributions encountered in a wealth of situations coming from physics, geophysics, biology, lexicography as well as social and financial networks. This finding is however restricted to a range of values outside of which finite size corrections are often invoked. Here we uncover a universal behavior of the way in which elements of a system are distributed according to their rank with respect to a given property, valid for the full range of values, regardless of whether or not a power law has previously been suggested. We propose a two parameter functional form for these rank-ordered distributions that gives excellent fits to an impressive amount of very diverse phenomena, coming from the arts, social and natural sciences. It is a discrete version of a generalized beta distribution, given by f(r) = A(N+1-r)(b)/r(a), where r is the rank, N its maximum value, A the normalization constant and (a, b) two fitting exponents. Prompted by our genetic sequence observations we present a growth probabilistic model incorporating mutation-duplication features that generates data complying with this distribution. The competition between permanence and change appears to be a relevant, though not necessary feature. Additionally, our observations mainly of social phenomena suggest that a multifactorial quality resulting from the convergence of several heterogeneous underlying processes is an important feature. We also explore the significance of the distribution parameters and their classifying potential. The ubiquity of our findings suggests that there must be a fundamental underlying explanation, most probably of a statistical nature, such as an appropriate central limit theorem formulation.

Background. Antimicrobial resistance (AMR) poses a significant global health threat, necessitating a deeper understanding of bacterial adaptation mechanisms. Introduction. This study investigates the genotypic and phenotypic evolutionary trajectories of Escherichia coli under meropenem and gentamicin selection, and it benchmarks these findings against florfenicol-evolved strains. Methodology. Utilizing a downsized, three-layer acrylic modified “Microbial Evolution and Growth Arena (MEGA-plate) system”—scaled to 40 × 50 cm for sterile handling and uniform 37 °C incubation—we tracked adaptation over 9–13 days, enabling real-time visualization of movement across antibiotic gradients. Results. Meropenem exposure elicited pronounced genetic heterogeneity and morphological remodeling (filamentous and circular forms), characteristic of SOS-mediated division arrest and DNA-damage response. In contrast, gentamicin exposure produced a uniform resistance gene profile and minimal shape changes, suggesting reliance on conserved defenses without major morphological adaptation. Comprehensive genomic analysis revealed a core resistome of 22 chromosomal loci shared across all three antibiotics, highlighting potential cross-resistance and the central roles of baeR, gadX, and marA in coordinating adaptive responses. Gene ontology enrichment underscored the positive regulation of gene expression and intracellular signaling as key themes in resistance evolution. Discussion. Our findings illustrate the multifaceted strategies E. coli employs—combining metabolic flexibility with sophisticated regulatory networks—to withstand diverse antibiotic pressures. This study underscores the utility of the MEGA-plate system in dissecting spatiotemporal AMR dynamics in a controlled yet ecologically relevant context. Conclusions. The divergent responses to meropenem and gentamicin highlight the complexity of resistance development and reinforce the need for integrated, One Health strategies. Targeting shared regulatory hubs may open new avenues for antimicrobial intervention and help preserve the efficacy of existing drugs.