Comparative effectiveness of frame-based and mask-based Gamma Knife stereotactic radiosurgery in brain metastases: A 509 patient meta-analysis.

PURPOSE: Stereotactic Radiosurgery (SRS) is the primary treatment for patients with limited numbers of small brain metastases. Head fixation is usually performed with framed-based (FB) fixation; however, mask-based (MB) fixation has emerged as a less invasive alternative. A comparative meta-analysis between both approaches has not been performed. METHODS: Databases were searched until August 28th, 2023, to identify studies comparing MB and FB SRS in the treatment of brain metastases. Our outcomes of interest included local tumor control (LTC), radiation necrosis (RN), mortality, and treatment time (TT). Mean difference (MD), risk ratio (RR), and hazard ratio (HR) were used for statistical comparisons. RESULTS: From 295 articles initially identified, six studies (1 clinical trial) involving 509 patients were included. LTC revealed comparable RR at 6-months (RR = 0.95[95%CI = 0.89-1.01], p = 0.12) and a marginal benefit in FB SRS at 1-year (RR = 0.87[95%CI = 0.78-0.96], p = 0.005). However, in oligometastases exclusively treated with single-fraction SRS, LTC was similar among groups (RR = 0.92 [95%CI = 0.89-1.0], p = 0.30). Similarly, in patients with oligometastases treated with single-fraction SRS, RN (HR = 1.69; 95%CI = 0.72-3.97, p = 0.22), TT (MD = -29.64; 95%CI = -80.38-21.10, p = 0.25), and mortality were similar among groups (RR = 0.62; 95%CI = 0.22-1.76, p = 0.37). CONCLUSION: Our findings suggest that FB and MB SRS, particularly oligometastases treated with single-fraction, are comparable in terms of LTC, RN, TT, and mortality. Further research is essential to draw definitive conclusions.

Antioxidant Activity and Oxidative Damage Associated with Seeding Surgery for Pearl Culture in the Winged Pearl Oyster Pteria sterna.

To evaluate the antioxidant activity and oxidative damage by relaxing, wounding, and seeding of a saibo of different origin on Pteria sterna hosts, five oyster treatments were included: (1) relaxed (REL) but neither wounded nor seeded; (2) relaxed and wounded (WOU) but not seeded; (3) relaxed, wounded, and seeded with an allograft (ALL); (4) relaxed, wounded, and seeded with an autograft (AUT); and (5) unrelaxed, unwounded, and unseeded as control (CTR). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and thiobarbituric acid (TBARS) activity were quantified between 3 and 24 h post-seeding. Compared to the CTR oysters, which did not suffer oxidative stress, SOD activity significantly decreased in the gonad and digestive gland in all treatments and decreased in mantle tissue in AUT oysters; this indicates that the entire process of preparing oysters for pearl culture (relaxing, wounding, and seeding) generates oxidative stress in the host. CAT was not a sensitive enzyme for measuring the short-term response of oysters to the wounding-seeding processes but rather a more prolonged or chronic stress. Similar to SOD, the lowest GPx and TBARS activity in seeded oysters evidenced their susceptibility to oxidative stress and damage, particularly in the WOU treatment. Evidence from this study indicates that SOD is a more sensitive enzyme for measuring the short-term response of the host oyster to the wounding and seeding of a saibo. It is also clear that the host undergoes stress at all stages of the pearl culture process, mostly during gonad wounding and regardless of the origin of saibo.

Pleomorphic Xanthoastrocytoma: Multi-Institutional Evaluation of Stereotactic Radiosurgery.

BACKGROUND AND OBJECTIVES: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA. METHODS: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used. RESULTS: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS. CONCLUSION: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.

Synergy of the Tropical Earthworm Pontoscolex corethrurus and Oil Palm Bagasse in the Removal of Heavy Crude Oil.

The tropical endogeic earthworm Pontoscolex corethrurus, a non-standard species used in ecotoxicity, has been found in crude oil-contaminated habitats. We estimated the removal of total hydrocarbons from heavy crude "Maya" oil on an artificially contaminated soil with a median lethal concentration of P. corethrurus and an addition of oil palm bagasse. P. corethrurus had a high survival rate, and the addition of oil palm bagasse led to a greater growth and an increase in abundance of bacteria and fungi. The activity of P. corethrurus and the nutritional quality of oil palm bagasse had a significant impact on the removal of a larger amount of petroleum hydrocarbons from contaminated soil. We concluded that the endogeic earthworm P. corethrurus and oil palm bagasse acted synergistically to achieve a more effective removal of total petroleum hydrocarbons from soil. These results show the potential for using P. corethrurus to remove, either directly or indirectly, crude oil from soil.

Metastatic Neoplasm Volume Kinetics Following 2-Stage Stereotactic Radiosurgery.

BACKGROUND: Multisession staged stereotactic radiosurgery (SRS) represents an alternative approach for management of large brain metastases (LBMs), with potential advantages over fractionated SRS. This study investigated clinical efficacy and safety of 2-stage stereotactic radiosurgery (2-SSRS) in patients with LBMs. METHODS: Patients with LBMs treated with 2-SSRS between 2014 and 2020 were evaluated. Demographic, clinical, and radiologic data were obtained. Volumetric measurements at first SRS session, second SRS session, and follow-up imaging studies were obtained. Characteristics that might predict response to 2-SSRS were evaluated through Fisher exact or Mann-Whitney U test. RESULTS: The study included 24 patients with 26 LBMs. Median (range) marginal doses for first and second SRS sessions were 15 Gy (14-18 Gy) and 15 Gy (12-16 Gy), respectively. Median (range) tumor volumes at first SRS session, second SRS session, and 3-month follow-up were 8.1 cm3 (1.5-28.5 cm3), 3.3 cm3 (0.8-26.1 cm3), and 2.2 cm3 (0.2-10.1 cm3), respectively. Of 26 lesions, 24 (92%) demonstrated early local control following the first SRS session, with 17 lesions (71%) demonstrating a decrease of ≥30% in T1 postcontrast MRI volume before the second SRS session and 3 lesions (12%) remaining stable. Eventually, 4 lesions showed disease progression after 2-SSRS. The median time to local progression was not reached; the median time to intracranial progression was 9.1 months. CONCLUSIONS: Our study supports the effectiveness and safety of 2-SSRS as a treatment modality for patients with LBMs, especially in poor surgical candidates. The local failure rate and low occurrence of adverse effects are comparable to other staged radiosurgery studies.

Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma.

INTRODUCTION: Recurrent glioblastoma (rGBM) prognosis is dismal. In the absence of effective adjuvant treatments for rGBM, re-resections remain prominent in our arsenal. This study evaluates the impact of reoperation on post-progression survival (PPS) considering rGBM genetic makeup. METHODS: To assess the genetic heterogeneity and treatment-related changes (TRC) roles in re-operated or medically managed rGBMs, we compiled demographic, clinical, histopathological, and next-generation genetic sequencing (NGS) characteristics of these tumors from 01/2005 to 10/2019. Survival data and reoperation were analyzed using conventional and random survival forest analysis (RSF). RESULTS: Patients harboring CDKN2A/B loss (p = 0.017) and KDR mutations (p = 0.031) had notably shorter survival. Reoperation or bevacizumab were associated with longer PPS (11.2 vs. 7.4-months, p = 0.006; 13.1 vs 6.2, p < 0.001). Reoperated patients were younger, had better performance status and greater initial resection. In 136/273 (49%) rGBMs undergoing re-operation, CDKN2A/B loss (p = 0.03) and KDR mutations (p = 0.02) were associated with shorter survival. In IDH-WT rGBMs with NGS data (n = 166), reoperation resulted in 7.0-month longer survival (p = 0.004) than those managed medically. This reoperation benefit was independently identified by RSF analysis. Stratification analysis revealed that EGFR-mutant, CDKN2A/B-mutant, NF1-WT, and TP53-WT rGBM IDH-WT subgroups benefit most from reoperation (p = 0.03). Lastly, whether or not TRC was prominent at re-operation does not have any significant impact on PPS (10.5 vs. 11.5-months, p = 0.77). CONCLUSIONS: Maximal safe re-resection significantly lengthens PPS regardless of genetic makeup, but reoperations are especially beneficial for IDH-WT rGBMs with EGFR and CDKN2A/B mutations with TP53-WT, and NF1-WT. Histopathology at recurrence may be an imperfect gauge of disease severity at progression and the imaging progression may be more reflective of the prognosis.

NUT Carcinoma of the Submandibular Gland: A Case at This Uncommon Site with Review of the Literature.

Nuclear protein in testis (NUT) carcinoma is a rare, highly aggressive, undifferentiated carcinoma that harbors a characteristic rearrangement of the NUTM1 gene. The majority arise in adolescents and young adults especially from the midline structures of the thorax, head, and neck. Until the present, there have only been three reported cases of NUT carcinoma of the submandibular gland, two of which were reported in children and another one in an adult from Korea. Here, we report the first case of NUT carcinoma arising in the submandibular gland of an adult female in the United States, representing the fourth case worldwide. A fine needle aspiration and biopsy was performed, and the diagnosis was confirmed by NUT immunohistochemical staining and fusion of the BRD4 (19p13.12) and NUTM1 (15q14) gene loci by fluorescence in-situ hybridization on the resection specimen. Salivary gland is an unusual site for NUT carcinoma and is rarely described in submandibular gland. We reviewed the clinicopathologic features of this entity at this site along with role of NUTM1 gene rearrangements in NUT tumorigenesis.

Oxytocinergic cells of the posterior hypothalamic paraventricular nucleus participate in the food entrained clock.

The mechanisms underlying food anticipatory activity are still poorly understood. Here we explored the role of oxytocin (OT) and the protein c-Fos in the supraoptic nucleus (SON), medial (PVNm) and posterior (PVNp) regions of the paraventricular hypothalamic nucleus. Adult rats were assigned to one of four groups: scheduled restricted feeding (RF), ad libitum (AL), fasting after restricted feeding (RF-F), to explore the possible persistence of oscillations, or ad libitum fasted (AL-F). In the SON and in the PVNm, OT cells were c-Fos positive after food intake; in contrast, OT cells in the PVNp showed c-Fos activation in anticipation to food access, which persisted in RF-F subjects. We conclude that OT and non-OT cells of the SON and PVNm may play a role as recipients of the entraining signal provided by food intake, whereas those of the PVNp which contain motor preautonomic cells that project to peripheral organs, may be involved in the hormonal and metabolic anticipatory changes in preparation for food presentation and thus, may be part of a link between central and peripheral oscillators. In addition, due to their persistent activation they may participate in the neuronal network for the clock mechanism that leads to food entrainment.

Genomic alterations predictive of response to radiosurgery in recurrent IDH-WT glioblastoma.

INTRODUCTION: Despite aggressive treatment, glioblastoma invariably recurs. The optimal treatment for recurrent glioblastoma (rGBM) is not well defined. Stereotactic radiosurgery (SRS) for rGBM has demonstrated favorable outcomes for selected patients; however, its efficacy in molecular GBM subtypes is unknown. We sought to identify genetic alterations that predict response/outcomes from SRS in rGBM-IDH-wild-type (IDH-WT). METHODS: rGBM-IDH-WT patients undergoing SRS at first recurrence and tested by next-generation sequencing (NGS) were reviewed (2009-2018). Demographic, clinical, and molecular characteristics were evaluated. NGS interrogating 205-genes was performed. Primary outcome was survival from GK-SRS assessed by Kaplan-Meier method and multivariable Cox proportional-hazards. RESULTS: Sixty-three lesions (43-patients) were treated at 1st recurrence. Median age was 61-years. All patients were treated with resection and chemoradiotherapy. Median time from diagnosis to 1st recurrence was 8.7-months. Median cumulative volume was 2.895 cm3 and SRS median marginal dose was 18 Gy (median isodose-54%). Bevacizumab was administered in 81.4% patients. PFS from SRS was 12.9-months. Survival from SRS was 18.2-months. PTEN-mutant patients had a longer PFS (p = 0.049) and survival from SRS (p = 0.013) in multivariable analysis. Although no statistically significant PTEN-mutants patients had higher frequency of radiation necrosis (21.4% vs. 3.4%) and lower in-field recurrence (28.6% vs. 37.9%) compared to PTEN-WT patients. CONCLUSIONS: SRS is a safe and effective treatment option for selected rGBM-IDH-WT patients following first recurrence. rGBM-IDH-WT harboring PTEN-mutation have improved survival with salvage SRS compared to PTEN-WT patients. PTEN may be used as a molecular biomarker to identify a subset of rGBM patients who may benefit the most from SRS.

Role of Ethnicity and Geographic Location on Glioblastoma IDH1/IDH2 Mutations.

BACKGROUND: Previous studies have demonstrated possible differences in glioblastoma (GBM) survival attributable to ethnicity. The goal of this study was to quantify oncogenic differences and evaluate the overall survival (OS) and progression-free survival (PFS) differences in GBM patients across race/ethnicity using both population-based surveillance and institutional data sets from the United States (US) and Mexico. METHODS: Retrospective cohort study comprising the Texas Cancer Registry (TCR, n = 4134) and referral institutions located in US (n = 254) and Mexico (n = 47) were evaluated. Primary outcomes include OS and PFS. Oncogenic differences attributable to ethnicity were assessed. IDH1/IDH2 status was evaluated by sequencing in US and Mexico samples. Kaplan-Meier and Cox proportional hazards regression for survival analysis. RESULTS: A total of 4134 GBM patients were identified from the TCR data set, ethnicity comparison demonstrated that Hispanic patients were diagnosed at a significantly younger age compared to non-Hispanic white patients (NHW) (median: 58 vs. 62, P < 0.001) and had improved OS (hazard ratio: 0.82, P < 0.001). In the oncogenic analysis, we observed a significant enrichment of IDH1/IDH2 mutations in Mexican Hispanic patients compared to US Hispanic patients (29.8% vs. 7.9%, P = 0.012); IDH2 mutations drove this difference. Post-progression survival was significantly shorter in patients from Mexico than US (3.0 vs. 11.4 months; P < 0.001), while OS remained similar. CONCLUSIONS: IDH2 mutations are more prevalent in Mexican Hispanic individuals compared to US individuals and may be a crucial contributor to the previously reported survival benefit of Hispanic individuals in large population databases. These findings are critical for both screening of IDH2 mutations and targeted interventions in GBM.

Probiotic Bacterium and Microalga Interaction on Rearing Kumamoto Oyster Crassostrea sikamea Spat.

This study assessed in vitro interaction between Bacillus bacteria and microalgae and their posterior in vivo effect on rearing Kumamoto oyster Crassostrea sikamea. The probiotic strains Bacillus licheniformis (MAt32), B. subtilis (MAt43) and B. subtilis (GAtB1) were individually inoculated in triplicate into 250 mL flasks containing 1 × 104 colony forming units (CFU) mL-1 of bacteria and 4.5 × 104 cell mL-1 of microalgae (Isochrysis galbana or Chaetoceros calcitrans) to evaluate their growth during a 7-day culture. Single cultures of microalgae or bacilli served as control. Additionally, C. sikamea spat was treated for 28 days with four single/combined bacillus treatments in triplicate at a concentration of 1 × 106 CFU mL-1 as follows: (a) control, without treatments; (b) combination of two antibiotics (10 mg L-1); (c) B. licheniformis; (d) B. subtilis; (e) B. subtilis subtilis and (f) mixed bacilli. The results showed a significantly (P < 0.05) increased growth of Bacillus strains co-cultured with microalgae, while the growth of I. galbana co-cultured with bacteria was not reduced significantly (P > 0.05) compared with the control group. C. sikamea spat treated with Bacillus showed significantly (P < 0.05) higher growth and survival than the control group. In this study, C. calcitrans microalgae were susceptible to the presence of probiotic bacteria. Nonetheless, this reduction in microalgal growth observed in vitro increased growth and survival of C. sikamea spat exposed to probiotic bacteria when compared to spat without probiotics.

Landscape of Genomic Alterations in IDH Wild-Type Glioblastoma Identifies PI3K as a Favorable Prognostic Factor.

PURPOSE: IDH wild-type (WT) glioblastoma (GBM) is an aggressive tumor with poor survival despite current therapies. The aim of this study was to characterize its genomic profile and determine whether a particular molecular signature is associated with improved survival outcomes. PATIENTS AND METHODS: Tumor samples from 232 patients with IDH-WT GBM were sequenced, and the landscape of genomic alterations was fully delineated. Genomics data from The Cancer Genome Atlas (TCGA) cohort were analyzed for confirmation. Association of alterations with survival was evaluated in both univariable and multivariable approaches. RESULTS: The genomic landscape of IDH-WT GBM revealed a high frequency of CDKN2A/B loss, TERT promoter mutations, PTEN loss, EGFR alteration, and TP53 mutations. Novel variants or gene mutations, such as ARID1B and MLL2, were identified. To better understand synergistic effects and facilitate decision making for precision medicine, we identified 11 pairs of gene alterations that tended to co-occur or were mutually exclusive, which were confirmed in the TCGA cohort. Survival analysis showed that genomic alterations in TP53 were associated with worse overall survival (OS). However, alterations in PI3K class I genes were associated with significantly better OS (univariable analysis: P = .002; multivariable analysis: hazard ratio [HR], 0.5785; P = .00162) and longer progression-free survival (univariable analysis: P = .0043; multivariable analysis: HR, 0.6228; P = .00913). CONCLUSION: Genomic alterations in PI3K class I are a favorable prognostic factor in IDH-WT GBM. This new prognostic biomarker may facilitate risk stratification of patients, assist in clinical trial enrollment, and provide potential therapeutic targets.

Impact of facility type and volume in low-grade glioma outcomes.

OBJECTIVE: The object of this study was to investigate the impact of facility type (academic center [AC] vs non-AC) and facility volume (high-volume facility [HVF] vs low-volume facility [LVF]) on low-grade glioma (LGG) outcomes. METHODS: This retrospective cohort study included 5539 LGG patients (2004-2014) from the National Cancer Database. Patients were categorized by facility type and volume (non-AC vs AC, HVF vs LVF). An HVF was defined as the top 1% of facilities according to the number of annual cases. Outcomes included overall survival, treatment receipt, and postoperative outcomes. Kaplan-Meier and Cox proportional-hazards models were applied. The Heller explained relative risk was computed to assess the relative importance of each survival predictor. RESULTS: Significant survival advantages were observed at HVFs (HR 0.67, 95% CI 0.55-0.82, p < 0.001) and ACs (HR 0.84, 95% CI 0.73-0.97, p = 0.015), both prior to and after adjusting for all covariates. Tumor resection was 41% and 26% more likely to be performed at HVFs vs LVFs and ACs vs non-ACs, respectively. Chemotherapy was 40% and 88% more frequently to be utilized at HVFs vs LVFs and ACs vs non-ACs, respectively. Prolonged length of stay (LOS) was decreased by 42% and 24% at HVFs and ACs, respectively. After tumor histology, tumor pattern, and codeletion of 1p19q, facility type and surgical procedure were the most important contributors to survival variance. The main findings remained consistent using propensity score matching and multiple imputation. CONCLUSIONS: This study provides evidence of survival benefits among LGG patients treated at HVFs and ACs. An increased likelihood of undergoing resections, receiving adjuvant therapies, having shorter LOSs, and the multidisciplinary environment typically found at ACs and HVFs are important contributors to the authors' finding.

Genetically-engineered plants yield an orally immunogenic PirA-like toxin from Vibrio parahaemolyticus.

Vibrio parahaemolyticus is the main etiological agent of human gastroenteritis by seafood consumption and some strains from this species causing the Acute Hepatopancreatic Necrosis Disease in shrimp have been recently reported. The PirA-like toxin from V. parahaemolyticus (ToxA) has been recently reported as an attractive antigen implicated in subunit vaccine development. Since plants are attractive hosts for the production and delivery of vaccines in the present study plants expressing ToxA were developed to account with a low cost platform for the production and oral delivery of ToxA. Tobacco plants were genetically engineered by Agrobacterium-mediated transformation to stably integrate the ToxA-coding gene into the nuclear genome. Transgenic lines were rescued in kanamycin-containing medium and analyzed by ELISA to determine ToxA yields observing levels up to 9 µg g-1 FW leaf tissues. Western blot analysis confirmed the presence of the ToxA protein in plant extracts. Immunogenicity assessment of the plant-made ToxA was performed in mice, comprising a 4-dose oral immunization scheme; revealing the induction of anti-ToxA humoral responses (IgG in serum and IgA in feces). This study opens the path for the development of low cost plant-based vaccines against Vibrio parahaemolyticus.

Maternal care activates the ventral tegmental area but not dopaminergic cells in the rat.

The ventral tegmental area (VTA), together with the preoptic area, is part of a neural circuit necessary for the expression of maternal behaviour (MB); destruction of either area disrupts MB in postpartum rats. Central to the proposal of VTA activation are dopaminergic cells, for which the cell bodies lie in the VTA and project to forebrain structures. This mesolimbic system is a motivational circuit involved in rewarding behaviours such as sex and MB. Despite their recognised importance, surprisingly, unlike the preoptic area, there are no anatomical descriptions of the pattern of VTA activation or of the dopaminergic cell activation, specifically in relation to MB in the rat. In the present study, we explore the possible activation (as indicated by Fos protein via immunohistochemistry) of the anterior and medial portions of the VTA and in the dopaminergic cells in these regions, as well as in the medial preoptic area, in lactating rats, at postpartum day 7 (after a 12-hour mother/pups separation), and in dioestrous females. After 12 hours, mothers were perfused at that moment or after a 90 minutes of interaction, or not, with their pups. We found a strong significant Fos induction in both the preoptic area and in the anterior portion of VTA in dams that interacted with their pups. The number of dopaminergic cells that coexpressed Fos did not differ across groups. Additionally, we determined Fos and GABA colocalisation in the anterior part of the VTA and found dense GABAergic processes, possibly varicosities, in the area of increased Fos expression. The results of the present study support a proposed GABAergic pathway from medial preoptic area to VTA cells, critical for the expression of MB. Future experiments are warranted to explore the neurochemical identity of the Fos and no-Fos expressing cells that are recipients of GABAergic processes in the VTA, aiming to better understand the neural circuitry of the VTA in relation to MB.

Epstein-Barr Virus-Positive Large Cell Neuroendocrine Carcinoma of the Nasopharynx: Report of One Case and Review of the Literature.

Epstein-Barr Virus (EBV)-positive neuroendocrine carcinoma (NEC) of the nasopharynx is exceedingly rare, only two cases have been reported in the literature. While EBV infection is strongly associated with nasopharyngeal carcinoma, which is carcinoma with squamous differentiation, the link between EBV and NEC is not well known, and can be diagnostically challenging. In this study, we report the third case of EBV-positive large cell NEC of nasopharynx with neck lymph node metastasis. The patient was treated with combined radiation and chemotherapy and showed complete clinical and radiological response. Similar treatment response has been reported in another patient with high stage EBV-positive large cell NEC, suggesting that EBV status is an important prognostic factor. Recognition of this rare tumor is important for disease management and patient prognosis. We also review the literature about the clinical and pathologic presentation of neuroendocrine tumors of nasopharynx.

Planned Gamma Knife Boost After Chemoradiotherapy for Selected Sinonasal and Nasopharyngeal Cancers.

OBJECTIVE: To determine the feasibility of a Gamma Knife boost after intensity-modulated radiation therapy in combination with multimodal therapy in patients with nasopharyngeal carcinoma and sinonasal malignancies with skull base or cavernous sinus involvement. METHODS: Nine patients were treated with intensity-modulated radiation therapy followed by a Gamma Knife boost. In one case Gamma Knife was given as salvage treatment after resection. Five patients had sinonasal malignancies and 4 had nasopharyngeal carcinoma. The mean radiation therapy dose was 64.3 Gy (range, 54-70 Gy) at 2 Gy per fraction. The median interval from completion of radiation therapy to Gamma Knife boost was 2.2 months (range, 1-4 months). The most common indication for Gamma Knife boost was involvement of the cavernous sinus, which was identified in 7 patients. The median margin Gamma Knife dose delivered was 13 Gy (range, 12-20 Gy), with median prescription isodose of 50%. RESULTS: All patients tolerated the procedure well, with minimal toxicity. Local control rates were achieved in all patients and no acute grade 3-5 toxicity was observed. One patient experienced late grade 4 toxicity, which was potentially attributable to treatment. Distant failure occurred in 3 patients (1 patient with nasopharyngeal carcinoma and 2 patients with sinonasal malignancies). CONCLUSIONS: Planned Gamma Knife boost followed intensity-modulated radiation therapy is feasible, safe, and provides excellent local control in patients with sinonasal malignancies and nasopharyngeal carcinoma, particularly in cases with cavernous sinus involvement. Further follow-up will be necessary to determine the long-term effectiveness and complication profile.

Adipositas Cordis: A Rare and Poorly Understood Cardiomyopathy.

Adipositas cordis is a rare cardiomyopathy characterized by diffuse fatty infiltration of the ventricular myocardium or interventricular septum. This occurs without myocardial cell destruction, unlike arrhythmogenic right ventricular cardiomyopathy. A 40-year-old obese woman was found to have a II/VI systolic murmur that worsened with standing. A transthoracic echocardiogram showed interventricular septal hypertrophy with a preserved left ventricular ejection fraction. Cardiac magnetic resonance imaging revealed a fatty mass in the interventricular septum. An endomyocardial biopsy revealed structurally normal myocytes with diffuse adipose cell infiltration and no evidence of malignant cells. Left and right cardiac catheterizations and stress echocardiography showed no abnormalities. This case shows the importance of considering a broad differential when approaching rare diseases. It also demonstrates the utility of noninvasive imaging and its impact on clinical decision making.

Disruption of behavior and brain metabolism in artificially reared rats.

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017.