Wild-type MECP2 expression coincides with age-dependent sensory phenotypes in a female mouse model for Rett syndrome.

Rett syndrome is characterized by an early period of typical development and then, regression of learned motor and speech skills in girls. Loss of MECP2 protein is thought to cause Rett syndrome phenotypes. The specific underlying mechanisms from typical developmental trajectory to regression features throughout life are unclear. Lack of established timelines to study the molecular, cellular, and behavioral features of regression in female mouse models is a major contributing factor. Due to random X-chromosome inactivation, female patients with Rett syndrome and female mouse models for Rett syndrome (Mecp2Heterozygous , Het) express a functional copy of wild-type MECP2 protein in approximately half of all cells. As MECP2 expression is regulated during early postnatal development and experience, we characterized the expression of wild-type MECP2 in the primary somatosensory cortex of female Het mice. Here, we report increased MECP2 levels in non-parvalbumin-positive neurons of 6-week-old adolescent Het relative to age-matched wild-type controls, while also displaying typical levels of perineuronal net expression in the barrel field subregion of the primary somatosensory cortex, mild tactile sensory perception deficits, and efficient pup retrieval behavior. In contrast, 12-week-old adult Het express MECP2 at levels similar to age-matched wild-type mice, show increased perineuronal net expression in the cortex, and display significant tactile sensory perception deficits. Thus, we have identified a set of behavioral metrics and the cellular substrates to study regression during a specific time in the female Het mouse model, which coincides with changes in wild-type MECP2 expression. We speculate that the precocious increase in MECP2 expression within specific cell types of adolescent Het may provide compensatory benefits at the behavioral level, while the inability to further increase MECP2 levels leads to regressive behavioral phenotypes over time.

Hive Panel Explorer: an interactive network visualization tool.

MOTIVATION: Networks are used to relate topological structure to system dynamics and function, particularly in ecology systems biology. Network analysis is often guided or complemented by data-driven visualization. Hive one of many network visualizations, distinguish themselves as providing a general, consistent and coherent rule-based representation to motivate hypothesis development and testing. RESULTS: Here, we present HyPE, Hive Panel Explorer, a software application that creates a panel of interactive hive plots. HyPE enables network exploration based on user-driven layout rules and parameter combinations for simultaneous of multiple network views. We demonstrate HyPE's features by exploring a microbial co-occurrence network constructed from forest soil microbiomes. AVAILABILITY AND IMPLEMENTATION: HyPE is available under the GNU license: https://github.com/hallamlab/HivePanelExplorer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy: An executive summary.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed in the main document.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed.

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment?

The treatment of human immunodeficiency virus (HIV) has greatly advanced over the past few decades from complex regimens, with high toxicities, multiple daily dosing, and incomplete viral suppression to more simplified, highly effective, daily oral regimens. Although these advancements greatly improved access and tolerability, the need for daily antiretroviral (ARV) administration remained until recently. With long-acting (LA) injectable ARV options emerging, patients may choose how they want to receive treatment. By eliminating the barrier of daily medication adherence, LA injectable ARV formulations have the potential to not only improve health outcomes for the individual, but also the community by reducing HIV transmission. At the time of this writing cabotegravir/rilpivirine (LA-CAB/RPV) is the only LA injectable ARV regimen approved as a complete regimen for the treatment of HIV in adults and adolescents (⩾35 kg and ⩾12 years of age) who are virologically suppressed. However, additional studies of LA-CAB/RPV in expanded populations, and of other LA ARVs, are underway. The goal of this article was to summarize clinical data and review pertinent clinical considerations for the use of LA-CAB/RPV in the management of HIV.

Impact of emergency department-based intensive care unit on outcomes of decompensating boarding emergency department patients.

Objectives: Emergency department (ED) boarding, or remaining in the ED after admission before transfer to an inpatient bed, is prevalent. Boarding patients may decompensate before inpatient transfer, necessitating escalation to the intensive care unit (ICU). We evaluated the impact of an ED-ICU on decompensating boarding ED patients. Methods: This is a retrospective single-center observational study. We identified decompensated boarding ED patients necessitating critical care before departure from the ED from October 2012 to December 2021. An automated query and manual chart review extracted data. Three cohorts were defined: pre-ED-ICU implementation (Group 1), post-ED-ICU implementation with ED-ICU care (Group 2), and post-ED-ICU implementation with inpatient ICU admission without ED-ICU care (Group 3). Primary outcome was ICU length of stay (LOS). Secondary outcomes included hospital LOS, in-hospital mortality, and ICU admissions with ICU LOS <24 hours. Between-groups comparisons used multiple regression analysis for continuous variables, χ2 tests and multivariable logistic regression analysis for binary variables, and follow-up contrasts for statistically significant omnibus tests. Results: A total of 1123 visits met inclusion criteria: 225 in Group 1, 780 in Group 2, and 118 in Group 3. Mean ICU LOS was shorter for Group 2 than Group 1 or 3 (47.4 vs 92.3 vs 103.9 hours, P < 0.001). Mean hospital LOS was shorter for Group 2 than Group 1 or 3 (185.1 vs 246.8 vs 257.3 hours, P < 0.01). In-hospital mortality was similar between groups. The proportion of ICU LOS <24 hours was lower for Group 2 than Group 1 or 3 (16.5 vs 27.1 vs 32.2%, P < 0.01). Conclusion: For decompensating boarding ED patients, ED-ICU care was associated with decreased ICU and hospital LOS, similar mortality, and fewer short-stay ICU admissions, suggesting ED-ICU care is associated with downstream resource preservation.

Mediterranean diet adherence, gut microbiota, and Alzheimer's or Parkinson's disease risk: A systematic review.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most prevalent neurodegenerative diseases, both without prevention or cure. The Mediterranean diet (MeDi) may be neuroprotective by modulating gut microbiota. We aimed to assess the effects of adherence to MeDi on the gut microbiota in relation to AD or PD risk. A search from inception to November 2020 was conducted in PubMed, CINAHL, EMBASE, Web of Science, Global Health, Biological Abstracts, and Grey Literature Report databases. Two searches were conducted: 1) (MeDi or Microbiota) and (PD or AD) and 2) MeDi and microbiota. Inclusion criteria for papers were specified prior to review. Of 4672 studies identified, 64 were eligible for inclusion. These studies were divided into five groups: MeDi and AD risk (n = 4), MeDi and PD risk (n = 2), MeDi and microbial composition or metabolomics (n = 21), AD and microbial composition or metabolomics (n = 7), and PD and microbial composition or metabolomics (n = 30). Adherence to the MeDi was associated with a lower risk of AD and PD development. Eight genera and two species of bacteria had an inverse relationship with MeDi and AD, and one family, eight genera and three species of bacteria had an inverse relationship with MeDi and PD. More studies are needed to investigate if MeDi, gut microbiota, and neurodegeneration are causally related.

Implementing a Weaning Protocol for Noninvasive Respiratory Support in Neonates Decreases Overuse and Length of Stay.

BACKGROUND: As part of efforts to decrease length of hospital stay, a protocol for weaning noninvasive respiratory support was implemented using quality improvement methodology. The objective of this study was to determine whether protocol implementation decreased the time to wean to no respiratory support by 24 h (30% reduction) over 3 months in preterm infants 30-34 weeks gestational age. METHODS: A quality improvement project was conducted with the following outcome measures: primary outcome measured was hours to wean; secondary outcomes included duration of respiratory support, length of stay, and postmenstrual age at feeding milestones; and balance measures were duration of oxygen exposure and growth velocity. RESULTS: Data from 89 subjects were included. Following implementation, decreases were seen in time to wean (40% reduction, P < .001), length of stay (25% reduction, P = .02), and growth velocity (21% reduction, P = .02). CONCLUSIONS: Implementing a weaning protocol decreases duration of support and length of stay in infants 30-34 weeks gestational age. Weaning respiratory support more quickly may decrease growth velocity.

Large-cell neuroendocrine tumor of the prostate: a case report and review of the literature.

BACKGROUND: Primitive neuroendocrine prostate neoplasms are rarely reported. This entity comprises carcinoïd tumors and poorly differentiated neuroendocrine tumors, mainly those of the small-cell type. Large-cell-type primitive tumors are exceptional, and only nine cases are reported in the literature. Similar to neuroendocrine tumors of the prostate, large-cell-type primitive tumors may be observed in the context of conventional adenocarcinoma during androgen deprivation therapy or as prostatic metastasis of a distant neuroendocrine tumor, mainly pulmonary neoplasms. CASE PRESENTATION: We report a Caucasian case of a mixed prostatic carcinoma, with the largest component being the large-cell neuroendocine carcinoma, in a patient who underwent a total prostatectomy for a localized cancer. Diagnostic, histological, therapeutic and evolutive aspects are reported and discussed. CONCLUSIONS: Large-cell primitive prostate neuroendocrine carcinoma is a rare but aggressive histological entity, which can be associated or not with an adenocarcinomatous component. Mixed forms have a better outcome, mainly when diagnosed at an early stage.

Algorithm optimization for multitined radiofrequency ablation: comparative study in ex vivo and in vivo bovine liver.

PURPOSE: To prospectively optimize multistep algorithms for largest available multitined radiofrequency (RF) electrode system in ex vivo and in vivo tissues, to determine best energy parameters to achieve large predictable target sizes of coagulation, and to compare these algorithms with manufacturer's recommended algorithms. MATERIALS AND METHODS: Institutional animal care and use committee approval was obtained for the in vivo portion of this study. Ablation (n = 473) was performed in ex vivo bovine liver; final tine extension was 5-7 cm. Variables in stepped-deployment RF algorithm were interrogated and included initial current ramping to 105 degrees C (1 degrees C/0.5-5.0 sec), the number of sequential tine extensions (2-7 cm), and duration of application (4-12 minutes) for final two to three tine extensions. Optimal parameters to achieve 5-7 cm of coagulation were compared with recommended algorithms. Optimal settings for 5- and 6-cm final tine extensions were confirmed in in vivo perfused bovine liver (n = 14). Multivariate analysis of variance and/or paired t tests were used. RESULTS: Mean RF ablation zones of 5.1 cm +/- 0.2 (standard deviation), 6.3 cm +/- 0.4, and 7 cm +/- 0.3 were achieved with 5-, 6-, and 7-cm final tine extensions in a mean of 19.5 min +/- 0.5, 27.9 min +/- 6, and 37.1 min +/- 2.3, respectively, at optimal settings. With these algorithms, size of ablation at 6- and 7-cm tine extension significantly increased from mean of 5.4 cm +/- 0.4 and 6.1 cm +/- 0.6 (manufacturer's algorithms) (P <.05, both comparisons); two recommended tine extensions were eliminated. In vivo confirmation produced mean diameter in specified time: 5.5 cm +/- 0.4 in 18.5 min +/- 0.5 (5-cm extensions) and 5.7 cm +/- 0.2 in 21.2 min +/- 0.6 (6-cm extensions). CONCLUSION: Large zones of coagulation of 5-7 cm can be created with optimized RF algorithms that help reduce number of tine extensions compared with manufacturer's recommendations. Such algorithms are likely to facilitate the utility of these devices for RF ablation of focal tumors in clinical practice.

Two's a Company, Three's a Crowd: A Review of Initiating or Switching to a Two-Drug Antiretroviral Regimen in Treatment-Naïve and Treatment-Experienced Patients Living with HIV-1.

INTRODUCTION: As HIV has become a manageable chronic condition, a renewed and increased interest in challenging traditional three-drug HIV therapies and moving toward two-drug regimens (2DR) for initial or maintenance treatment in people living with HIV (PLWH) has developed. As PLWH are living longer, continual advancements in antiretroviral regimens have been a focus to provide optimal life-long therapy options. Although early studies may have shown poor outcomes in virologic suppression with 2DR, newer studies and treatment options have emerged to show promise in the management of HIV. The purpose of this review is to evaluate current literature and assess the efficacy of two-drug (2DR) antiretroviral therapy in treatment-naïve and -experienced people living with HIV. METHODS: A systematic search was performed between January 2009 to January 2020, using EMBASE, MEDLINE, Google Scholar, and bibliographies. Combinations of the following search terms were used: HIV-1 infection, antiretroviral therapy, dual therapy, two-drug regimen, two-drug therapy, two-drug regimen, and 2DR. Included studies were those in the adult population with at least one active comparator, outcomes assessing HIV-1 RNA viral load while on treatment, and written in English. RESULTS: Thirty-three studies were included, 13 where 2DRs were evaluated as initial therapy (3 studies with extension data) and 15 where 2DRs were evaluated as maintenance or switch therapy (2 studies with extension data). CONCLUSION: Although 2DRs may not be appropriate in all patient populations, they are being utilized more frequently and have the potential to reduce costs, adverse effects, and drug interactions.

Antiretroviral Stewardship: A Review of Published Outcomes with Recommendations for Program Implementation.

Persons living with HIV (PLWHs) are at high risk for medication errors when hospitalized, but antiretroviral medications are not often evaluated by antimicrobial stewardship programs (ASPs) because they are not specifically discussed in the standards of practice. However, antiretroviral (ARV) stewardship programs (ARVSPs) have been shown to decrease medication error rates and improve other outcomes. The goal of this article is to review published literature on ARVSPs and provide guidance on key aspects of ARVSPs. A MEDLINE search using the term "antiretroviral stewardship" was conducted. Original research articles evaluating ARVSPs in hospitalized, adult PLWHs were included. Six original research articles evaluating unique inpatient ARVSPs met inclusion criteria. All 6 studies evaluating medication errors as the primary outcome found a significant reduction in errors in the postimplementation phase. Based on current standards for ASPs, we propose core elements for ARVSPs. Future organizational guidelines for antimicrobial stewardship should include official recommendations for ARV medications.

Effectiveness of Single- and Multiple-Tablet Antiretroviral Regimens in Correctional Setting for Treatment-Experienced HIV Patients.

Minimal information is available regarding antiretroviral prescribing patterns and outcomes for HIV patients in correctional systems. This study analyzes single- (STR) and multiple- (MTR) tablet regimen effectiveness in patients receiving HIV telemedicine care through the Illinois Department of Corrections (IDOC). This study involves a retrospective review of HIV-positive adult patients in IDOC on either an STR (efavirenz, rilpivirine, elvitegravir based) or an MTR (emtricitabine/tenofovir with atazanavir/ritonavir, darunavir/ritonavir, or raltegravir). No significant differences in virologic suppression were seen between groups at baseline, weeks 24, 48, 96, and last clinic visit. Similar proportions of patient-reported adverse effects, self-reported adherence, and discontinuation rates were found in both groups. With similar rates of viral suppression, tolerability, adherence, and discontinuation, administering MTR in the incarcerated population is a viable alternative to STR.

99mTc-MIBI brain SPECT as an indicator of the chemotherapy response of recurrent, primary brain tumors.

BACKGROUND: Malignant brain tumors carry a pejorative prognosis and necessitate aggressive therapy. Chemotherapy can be used in cases of tumor recurrence. With limited response rate and potential toxicity to chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. AIM: To define the place of 99mTc hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) Single Positron Emission Computed Tomography (SPECT) in monitoring chemotherapy response in recurrent primary brain tumors. METHODS: In a retrospective analysis, thirty patients were investigated with MIBI SPECT. Imaging was performed 1h after the intravenous injection of 555 MBq of 99mTc-MIBI using a dedicated SPECT system. A MIBI uptake index (UI) was computed as the ratio of counts in the lesion to those in contralateral region. For all patients, we compared changes over time in UI with MRI and clinical data. RESULTS: The changes in UI agreed well with the clinical and MRI-based assessments in 97% of cases. In 44% of these cases, the scintigraphic response appeared before the MRI response. In instances of treatment failure or rebound, the concordance between scintigraphy and MRI was 52%, and the scintigraphic response appeared before the MRI response in 48% of cases. CONCLUSION: This study confirms our previous results obtained on a short series of patients with recurrent glioma, concerning the usefulness of MIBI SPECT in prediction of chemotherapy response. Moreover, in cases of tumor progression, we show that MIBI SPECT is an earlier indicator of escape from chemotherapy, an average 4 months before MRI changes.

Clinical utility of dronabinol in the treatment of weight loss associated with HIV and AIDS.

Since the beginning of the HIV/AIDS epidemic, weight loss has been a common complaint for patients. The use of various definitions defining HIV wasting syndrome has made it difficult to determine its actual prevalence. Despite the use of highly active antiretroviral therapy, it is estimated that the prevalence of HIV wasting syndrome is between 14% and 38%. HIV wasting syndrome may stem from conditions affecting chewing, swallowing, or gastrointestinal motility, neurologic disease affecting food intake or the perception of hunger or ability to eat, psychiatric illness, food insecurity generated from psychosocial or economic concerns, or anorexia due to medications, malabsorption, infections, or tumors. Treatment of HIV wasting syndrome may be managed with appetite stimulants (megestrol acetate or dronabinol), anabolic agents (testosterone, testosterone analogs, or recombinant human growth hormone), or, rarely, cytokine production modulators (thalidomide). The goal of this review is to provide an in-depth evaluation based on existing clinical trials on the clinical utility of dronabinol in the treatment of weight loss associated with HIV/AIDS. Although total body weight gain varies with dronabinol use (-2.0 to 3.2 kg), dronabinol is a well-tolerated option to promote appetite stimulation. Further studies are needed with standardized definitions of HIV-associated weight loss and clinical outcomes, robust sample sizes, safety and efficacy data on chronic use of dronabinol beyond 52 weeks, and associated virologic and immunologic outcomes.

New Antiretroviral Treatment for HIV.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set the global goal of ending the AIDS world epidemic by 2030. In order to end this epidemic they have established a 90-90-90 goal to be achieved by 2020, which may be problematic, especially in low- and middle-income countries. This goal includes 90% of individuals with HIV globally being diagnosed, on treatment, and virologically suppressed. Based on global estimates from 2014-2015, approximately 36.9 million individuals are living with HIV. Of those, 53% have been diagnosed with HIV, 41% are on antiretroviral therapy (ART), and 32% have viral suppression with <1000 copies/ml. Comprehensive approaches are needed to improve the number of people living with HIV (PLWH) who are diagnosed, linked, and engaged in care. Once PLWH are retained in care, treatment is key to both HIV prevention and transmission. The development and advancement of new ART is necessary to assist in reaching these goals by improving safety profiles, decreasing pill burden, improving quality of life and life expectancy, and creating new mechanisms to overcome resistance. The focus of this review is to highlight and review data for antiretroviral agents recently added to the market as well as discuss agents in various stages of development (new formulations and mechanisms of action).

Acute disseminated encephalomyelitis presenting as a brainstem encephalitis.

Acute disseminated encephalomyelitis (ADEM) is a disease characterized by inflammation and destruction of myelin. Acute hemorrhagic leukoencephalitis (AHLE) is a severe form of ADEM known for its particularly poor outcome. We present a case of a young Caucasian female who presented with drowsiness and slurred speech followed by rapid brainstem involvement resembling rhomboencephalitis. Despite multiple diagnostic tests and empiric therapy with immunosuppressants, immunoglobulins, and antimicrobials, she lost most brainstem reflexes within a few weeks and ultimately passed away. Magnetic resonance imaging (MRI) showed progression of lesions from the brainstem to eventually involve bilateral cerebral hemispheres. Autopsy and microscopic examination of the brain revealed several hemorrhagic lesions throughout the brain and rendered a diagnosis of AHLE. AHLE was initially described in 1941 and is thought to be autoimmune related, possibly related to cross reactivity between the immune system and CNS tissues like myelin. While a definitive inciting pathogen was not discovered, this case emphasizes the importance of considering AHLE in the differential diagnosis of patients with rapid loss of neurologic function and highlights an atypical presentation of ADEM/AHLE.

Multiple injections of thyrotropin releasing hormone fail to reverse learning and memory deficits in rats with lesions of the nucleus basalis of meynert.

The learning and memory enhancing effects of thyrotropin releasing hormone (TRH) was examined in an animal model of Alzheimer's disease. Adult rats were prepared with either sham surgeries or cholinergic lesions of the nucleus basalis of Meynert (nbM). Subjects were injected (ip) with one of three doses of TRH (0, 5, 10 mg/kg) starting on the day of surgery and continuing once every other day for a total of four injections. Performance (four trials/day for 4 days, 30 m inter-trial interval) in a Morris water maze was assessed one week after the last TRH injection (i.e., 2 weeks postoperatively). Latency to find the hidden platform served as the dependent variable. Results indicated that damage to the nbM impaired task performance in that animals with nbM lesions generally required more time to find the platform and showed less trial-to-trial improvement. Treatment with TRH failed to reverse this lesion-induced deficit. These results suggest that multiple injections of TRH do not provide residual protection against the deleterious effects on learning and memory produced by cholinergic lesions of the basal forebrain. Other doses and administration parameters, however, need to be studied in order to determine the generalizability of these findings.

Technetium-99m sestamibi brain SPECT in the follow-up of glioma for evaluation of response to chemotherapy: first results.

The initial treatment of high-grade glioma often consists of surgery and radiation therapy. Chemotherapy is used in cases of recurrence or after incomplete surgery. Because of the many potential serious side-effects of chemotherapy, early tumour response evaluation is necessary to enable clinicians to adapt the treatment. However, response monitoring with computed tomography (CT) or magnetic resonance imaging (MRI) is often difficult. The aim of this study was to assess the value of repeated technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) single-photon emission computerised tomography (SPECT) for this purpose. Fifteen patients with malignant glioma were investigated with MIBI SPECT. Imaging was performed 1 h after the intravenous injection of 555 MBq of (99m)Tc-MIBI, using a dedicated SPECT system (Tomomatic 564, Medimatic, Denmark). Overall, 57 investigations were performed. A MIBI uptake index was computed as the ratio of counts in the lesion to those in the contralateral region. Previous study had shown a cut-off value of 2.0 to be appropriate. SPECT indices were compared with neurological evaluation, CT or MRI. This assessment was performed every 4 months during and after the treatment. Six patients showed an increased MIBI index associated with clinical or radiological progression of disease during chemotherapy. After an initial response to therapy, three patients showed an increased MIBI index despite chemotherapy, demonstrating secondary resistance to therapy. Six patients showed a decreased MIBI index, demonstrating a good response to therapy. The first nine patients died shortly after the last SPECT scan (average duration of survival, 4 months). The therapeutic protocol was modified in six cases, but successfully so in only two. In some cases, tumour progression was diagnosed earlier with SPECT than on the basis of clinical or MRI signs. Early response or resistance to chemotherapy is detectable by(99m)Tc-MIBI SPECT. Therefore this functional imaging modality could be considered as a valuable tool to permit effective adaptation of the therapeutic regimen in patients treated for recurrent high-grade glioma.