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Abstract Background Posterior fossa irradiation with or without whole brain irradiation results in high doses of radiation to the thalamus, hippocampus, and putamen, structures critical to cognitive functioning. As a result, children with brain tumors treated with cranial irradiation (CRT) may experience significant cognitive late effects. We sought to determine the effect of radiation to those structures on neuropsychological outcome. Methods Forty‐seven children with a history of posterior fossa tumor (17 treated with surgery; 11 with surgery and chemotherapy; and 19 with surgery, chemotherapy, and CRT) underwent neuroimaging and neuropsychological assessment at a mean of 4.8 years after treatment, along with 17 healthy sibling controls. The putamen, thalamus, and hippocampus were segmented on each participant's magnetic resonance imaging for diffusion indices and volumes, and in the radiation treatment group, radiation dose to each structure was calculated. Results Performance on visuoconstruction and spatial learning and memory was lower in patient groups than controls. Volume of the thalamus, when controlling for age, was smaller in the patient group treated with CRT than other groups. Higher radiation doses to the putamen correlated with higher fractional anisotropy in that structure. Higher radiation dose to the hippocampus correlated with lower spatial learning, and higher dose to thalami and putamina to lower verbal and nonverbal reasoning. Conclusions All children with posterior fossa tumors, regardless of treatment modality, had cognitive deficits compared to their sibling controls. Posterior fossa irradiation may affect thalamic volume and aspects of verbal and nonverbal cognitive functioning.

Background: Previous studies suggest that housing relocation may be stressful for captive non-human primates. Our study investigated the stress levels of Japanese macaques during a housing relocation by measuring their daily fecal cortisol metabolites, which are often used as an indicator of stress., Methods: Ten adult Japanese macaques, single-housed for research purposes, were relocated to a new facility. Fecal samples were collected daily for 7 days. Cortisol metabolite concentrations were determined via enzyme immunoassay., Results: No significant differences in cortisol metabolite levels were found in 7 days, but concentration levels showed that the highest median was associated to the relocation day., Conclusions: The minimal cortisol metabolite increase suggests that there was a slight activity increase in the hypothalamic-pituitary-adrenal axis. Techniques encouraging cooperation of the monkeys, the short time duration of the relocation, and consistency in the environment may have contributed to the minimal stress levels observed., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chimeric antigen receptor (CAR) T cells targeting the CD19 (cluster of differentiation 19) cell surface glycoprotein have emerged as a highly effective immunologic therapy in patients with relapsed or refractory B-cell malignancies. The engagement of CAR T cells with CD19 on the surface of neoplastic B cells causes a systemic cytokine release, which can compromise the blood-brain barrier and cause an immune effector cell-associated neurotoxicity syndrome (ICANS). In a small proportion of ICANS patients who demonstrate neuroimaging abnormalities, certain distinct patterns have been recognized, including signal changes in the thalami, external capsule, and brainstem, the subcortical and/or periventricular white matter, the splenium of the corpus callosum, and the cerebellum. On careful review of the underlying pathophysiology of ICANS, we noticed that these changes closely mirror the underlying blood-brain barrier disruption and neuroinflammatory and excitotoxic effects of the offending cytokines released during ICANS. Furthermore, other uncommon complications of CD19 CAR T-cell therapy such as posterior reversible encephalopathy syndrome, ocular complications, and opportunistic fungal infections can be catastrophic if not diagnosed in a timely manner, with neuroimaging playing a significant role in management. In this narrative review, we will summarize the current literature on the spectrum of neuroimaging findings in ICANS, list appropriate differential diagnoses, and explore the imaging features of other uncommon central nervous system complications of CD19 CAR T-cell therapy using illustrative cases from two tertiary care institutions., (© 2023 American Society of Neuroimaging.)

Objective: To identify the prevalence and risk factors for musculoskeletal pain in keyboard musicians., Design: Systematic review METHODS: A systematic review was conducted according to the MOOSE recommendations and it was registered with the PROSPERO database under registration number CRD42016042913. We included observational studies through the electronic databases PubMed, Scopus, ScienceDirect, Web of Science, Répertoire International de Littérature Musicale (RILM), Retrospective Index to Music Periodicals (RIPM), Scielo, and Google Scholar, with combinations of the keywords pianists, keyboard players, musculoskeletal pain, muscular disease, tendinitis, tendinopathy, observational, case-control, prevalence, and risk factors. Data from population, information about pain, and risk factors were extracted from studies that fulfilled the eligibility criteria. The methodological quality of the studies was classified through the Newcastle-Ottawa Scale. The risk of bias and quality of evidence was assessed using the GRADE system., Results: Twelve articles (case-controls) were included for the qualitative synthesis. The quality of the studies was classified as fair (n = 6) and good (n = 6). Prevalence was observed between 25.8% and 77.0% of musculoskeletal pain among keyboard musicians, with a higher prevalence in wrists and hands (13.8%-65.8%), neck (9.8%-64.2%), and shoulders (9.8%-59.8%). The only consistent risk factor found in the 4 studies was being female, with OR ranging from 1.05-1.90. Age greater than 18 years; weekly training more than 20 hours; training for more than 60 minutes without a rest break; not having a habit of practicing sports; and playing despite the pain were also described as risks factors for musculoskeletal pain. It was not possible to perform the meta-analysis due to the heterogeneity of the studies., Conclusion: Keyboard musicians presented a high prevalence of musculoskeletal pain, especially in the upper extremity regions of the body. Female, ageing, playing behaviors, and sedentary lifestyle showed an increased likelihood to report musculoskeletal pain., Level of Evidence: II., (Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether the chemical shift of residual N-acetylaspartate (NAA) signal in pilocytic astrocytomas (PA) is consistent with the position of the NAA peak in controls., Methods: MR spectra from 27 pediatric World Health Organization (WHO) grade I pilocytic astrocytoma patients, fifteen patients with WHO grade II and high-grade (III-IV) astrocytomas, and 36 controls were analyzed. All spectra were acquired with a short echo time (35 ms), single voxel point-resolved spectroscopy sequence on clinical 3 tesla scanners. Fully automated LCModel software was used for processing, which included the fitting of peak positions for NAA and creatine (Cr)., Results: The chemical shift difference between the NAA and Cr peaks was significantly smaller (by 0.016 ± 0.005 parts per million, P < 1e-10) in PAs than in controls and was also smaller than what was observed in infiltrative astrocytomas., Conclusion: The chemical shift position of the residual NAA peak in PAs is not consistent with NAA. The signal likely originates from an N-acetyl group of one or more other chemicals such as N-acetylated sugars. Magn Reson Med 78:452-456, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Background: Transrectal prostate biopsy (TRPB) is a well established procedure used to obtain tissue for the histological diagnosis of carcinoma of the prostate. Despite the fact that TRPB is generally considered a safe procedure, it may be accompanied by traumatic and infective complications, including asymptomatic bacteriuria (bacteria in the urine), urinary tract infection (UTI), transitory bacteremia (bacteria in the blood), fever episodes, and sepsis (pathogenic microorganisms or their toxins in the blood). Although infective complications after TRPB are well known, there is uncertainty about the necessity and effectiveness of routine prophylactic antibiotics and their adverse effects, as well as a clear lack of standardization., Objectives: To evaluate the effectiveness and adverse effects of prophylactic antibiotic treatment in TRPB., Search Strategy: The search covered the principal electronic databases: MEDLINE, EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL). Experts were consulted and references from the relevant articles were scanned., Selection Criteria: All randomized, controlled trials (RCTs) of men who underwent TRPB and received prophylactic antibiotics or placebo/no treatment, were selected, and all RCTs looking at one type of antibiotic versus another, including comparable dosages, routes of administration, frequency of administration, and duration of antibiotic treatment., Data Collection and Analysis: Two reviewers (ELZ, OACC) independently selected included trials and extracted study data. Any disagreements were resolved by a third party (NRNJ)., Main Results: Overall, more than 3500 references were considered and 19 original reports with a total of 3599 patients were included.There were 9 trials analysing antibiotics versus placebo/no treatment, with all outcomes significantly favouring antibiotic use (P < 0.05) (I(2) = 0%), including bacteriuria (risk ratio (RR) 0.25 (95% confidence interval (CI) 0.15 to 0.42), bacteremia (RR 0.67, 95% CI 0.49 to 0.92), fever (RR 0.39, 95% CI 0.23 to 0.64), urinary tract infection (RR 0.37, 95% CI 0.22 to 0.62), and hospitalization (RR 0.13, 95% CI 0.03 to 0.55). Several classes of antibiotics were effective prophylactically for TRPB, while the quinolones, with the highest number of studies (5) and patients (1188), were the best analysed. For 'antibiotics versus enema', we analysed four studies with a limited number of patients. The differences between groups for all outcomes were not significant. For 'antibiotic versus antibiotic + enema', only the risk of bacteremia (RR 0.25, 95% CI 0.08 to 0.75) was diminished in the 'antibiotic + enema group'. Seven trials reported the effects of short-course (1 day) versus long-course (3 days) antibiotics. Long course was significantly better than short-course treatment only for bacteriuria (RR 2.09, 95% CI 1.17 to 3.73). For 'single versus multiple dose', there was significantly greater risk of bacteriuria for single-dose treatment (RR 1.98, 95% CI 1.18 to 3.33). Comparing oral versus systemic administration - intramuscular injection (IM), or intravenous (IV) - of antibiotics, there were no significant differences in the groups for bacteriuria, fever, UTI and hospitalization., Authors' Conclusions: Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose.

Using fMRI, we compared the patterns of fusiform activity produced by viewing English and Chinese for readers who were either English speakers learning Chinese or Chinese-English bilinguals. The pattern of fusiform activity depended on both the writing system and the reader's native language. Native Chinese speakers fluent in English recruited bilateral fusiform areas when viewing both Chinese and English. English speakers learning Chinese, however, used heavily left-lateralized fusiform regions when viewing English, but recruited an additional right fusiform region for viewing Chinese. Thus, English learners of Chinese show an accommodation pattern, in which the reading network accommodates the new writing system by adding neural resources that support its specific graphic requirements. Chinese speakers show an assimilation pattern, in which the reading network established for L1 includes procedures sufficient for the graphic demands of L2 without major change.

Iron-induced cardiac dysfunction is a leading cause of death in transfusion-dependent anemia. MRI relaxation rates R2(1/T2) and R2*(1/T2*) accurately predict liver iron concentration, but their ability to predict cardiac iron has been challenged by some investigators. Studies in animal models support similar R2 and R2* behavior with heart and liver iron, but human studies are lacking. To determine the relationship between MRI relaxivities and cardiac iron, regional variations in R2 and R2* were compared with iron distribution in one freshly deceased, unfixed, iron-loaded heart. R2 and R2* were proportionally related to regional iron concentrations and highly concordant with one another within the interventricular septum. A comparison of postmortem and in vitro measurements supports the notion that cardiac R2* should be assessed in the septum rather than the whole heart. These data, along with measurements from controls, provide bounds on MRI-iron calibration curves in human heart and further support the clinical use of cardiac MRI in iron-overload syndromes., (Copyright (c) 2006 Wiley-Liss, Inc.)

Proton-decoupled (31)P and (1)H MRS was used to quantify markers of membrane synthesis and breakdown in eight pediatric patients with untreated brain tumors and in six controls. Quantitation of these compounds in vivo in humans may provide important indicators for tumor growth and malignancy, tumor classification, and provide prognostic information. The ratios of phosphoethanolamine to glycerophosphoethanolamine (PE/GPE) and phosphocholine to glycerophosphocholine (PC/GPC) were significantly higher in primitive neuroectodermal tumors (PNET) (16.30 +/- 5.73 and 2.97 +/- 0.93) when compared with controls (3.42 +/- 1.62, P < 0.0001 and 0.45 +/- 0.13, P < 0.0001) and with other tumors (3.93 +/- 3.42, P < 0.001 and 0.65 +/- 0.30, P < 0.0001). Mean PC/PE was elevated in tumors relative to controls (0.48 +/- 0.11 versus 0.24 +/- 0.05, P < 0.001), but there was no difference between PNET and other tumors. Total choline concentration determined with quantitative (1)H MRS was significantly elevated (4.78 +/- 3.33 versus 1.73 +/- 0.56 mmol/kg, P < 0.05), whereas creatine was reduced in tumors (4.89 +/- 1.83 versus 8.28 +/- 1.50 mmol/kg, P < 0.05). A quantitative comparison of total phosphorylated cholines (PC+GPC)/ATP measured with (31)P MRS and total choline measured with (1)H MRS showed that in tumors a large fraction of the choline signal (>54 +/- 36%) was not accounted for by PC and GPC. The fraction of unaccounted choline was particularly large in PNET (>78 +/- 7%). The pH of tumor tissue was higher than the pH of normal brain tissue (7.06 +/- 0.03 versus. 6.98 +/- 0.03, P < 0.001)., (Copyright 2004 Wiley-Liss, Inc.)

Diagnosis by newborn screening and the implementation of a phenylalanine-restricted diet have resulted in normal neurological development in approximately 10,000 persons with phenylketonuria (PKU) in the United States. While it is accepted that a phenylalanine-restricted diet is necessary in childhood, the recommended concentration of phenylalanine in the blood varies. Clinicians now must make recommendations for adults with PKU who probably tolerate higher levels of phenylalanine than children. This factor, quality of life issues, the expense of the diet, and varying genetic and socioeconomic backgrounds, make the choice of dietary recommendations difficult. Molecular analysis of the mutations in PKU has provided insight but has not resulted in clear recommendations for phenylalanine concentration in the blood. Magnetic resonance imaging has provided the recognition that white-matter changes are present in PKU. However, owing to poor correlation of white-matter changes with clinical factors, analysis of white-matter changes has not proved useful. We hypothesize that measurement of brain phenylalanine directly will aid in clinical decision making. Twenty-one subjects with PKU had blood and brain phenylalanine measured simultaneously. Fifteen were randomly selected, 2 were examined for clinical reasons and 4 exceptional patients were chosen because they had maintained high IQs, despite having high historic blood concentrations and having been off the diet for at least 10 years. The correlation of blood and brain phenylalanine is in general poor. However, the four exceptional patients all had relatively low concentrations of phenylalanine in their brains compared to their blood. We suggest that their good clinical status, despite high historic blood levels, is due to their comparatively low brain levels of phenylalanine. We further suggest that measurement of brain phenylalanine concentration is useful in the management of PKU patients.

Adults and children with brain stem gliomas have a mean survival time of 15 months after radiation therapy (XRT). Infants with this tumor present additional complexities for treatment because of possible neurotoxicity of the radiation to the developing brain. We report a 15-month-old child with biopsy-proven brain stem glioma with clinical and radiographic evidence of disease progression. She was treated with 24 monthly courses of carboplatin without radiation therapy and has had a 39+ month response. The clinical response started after 3 months and the radiographic evidence was documented at 10 months by magnetic resonance imaging. The toxicity was minimal. Longitudinal neuropsychological assessment demonstrated continued improvement at 36 months post diagnosis but with some motor functioning below expected age levels. Cervico-medullary astrocytoma in a young patient may be the appropriate clinical setting for future trials of chemotherapy without XRT.

One hundred and sixty-two cases of Stage IA microinvasive carcinoma of the cervix are presented. These patients represent the combined experience at the University of Miami School of Medicine, Miami, Florida, and Downstate Medical Center, Brooklyn, New York. The criteria used in both institutions are 1) penetration of invasive carcinoma beneath the basement membrane of less than 1 mm and 2) absence of invasion of blood vessel or lymphatic spaces. All tissue specimens have been measured accurately by use of calibrated optics. The literature has been reviewed for criteria of diagnosis of microinvasive cancer, as well as methods of management. Our method of accurately determining depth of penetration is described and the evolution of microinvasive cancer is presented in a series of photomicrographs in which measurements are accurate to 0.1 mm. In the literature, when depth of penetration of up to 5 mm is used as criterion for microinvasive carcinoma, the incidence of nodal metastasis may be as high as 3.5%. Since, in our combined institutions, the mortality rate with radical hysterectomy is less than 1% and the incidence of ureterovaginal fistulas is 1.2%, we conclude that simple hysterectomy is not adequate therapy for lesions with stromal invasion to a depth of 5 mm.

The current rules of staging are reviewed briefly in this paper, and the various diagnostic procedures of value outlined. The use of the pretreatment laparotomy is discussed as it applies to cervical, endometrial, and ovarian malignancies. It has been shown to be of significant benefit in endometrial carcinoma under selected situations, whereas in cervical carcinoma there is new information indicating benefit to patients as well. It has enhanced our knowledge of the natural history of the diseases. The important details of its use are discussed along with current data showing the importance of the diaphragm, paraaortic nodes, and peritoneal cytology in defining the extent of disease.

There were no significant differences between the mean blood plasma (leukocyte-free) RNAase activity among 128 healthy women volunteers age 13-70 and 49 women with benign gynecological tumors. Exceptions to this finding were three apparently healthy women volunteers who had plasma enzyme activity which was higher than two standard deviations from the mean of the control subjects. Increased plasma RNAase activity was also demonstrated for 21 of 22 patients with ovarian carcinomas of differential histological types. This group included two patients with Stage IA, two patients with Stage IC ovarian carcinoma, and 17 patients with advanced ovarian carcinoma. The one exception was a patient with a well encapsulated, mucinous cystadenocarcinoma, Stage IA. The plasma RNAase activity returned to normal values in all of the cancer patients who had no clinical evidence of residual malignant tissue after surgical treatment. However, the enzyme activity also returned to a normal value in one of the 17 women in whom all of the malignant tissue was not removed. These data indicate that plasma RNAase activity can be utilized as a tumor marker for the presence of ovarian malignancies of various histological types, and to differentiate between malignant and benign neoplasms.

A pilot study using low-dose preoperative radiation therapy, i.e., 10 Gy in 3 to 4 days as an adjuvant preoperative procedure for grade 2 or 3 (FIGO classification) endometrial carcinoma, was done. The concept of low-dose preoperative radiation therapy is to administer treatment, either surgical or radiotherapeutic, postoperatively according to the surgical and pathologic findings, allowing identification of those patients with previously undiagnosed extensive metastatic disease outside the pelvis found at laparotomy in whom routine pelvic radiation therapy is futile, as well as those patients with relatively low risk of recurrence who may not require further radiotherapy. Forty-four patients with clinical Stage I, grade 2 or 3 with adenocarcinoma of the endometrium were entered into the pilot study. Following surgery, 68% remained Stage I by pathologic examination, and in the remaining patients the stages were changed to II in seven, III in three, and IV in four. Postoperative treatment was administered according to extent of the disease found at surgery. The 4-year actuarial probability of survival rate for the entire group of patients with clinical Stage I disease was 80%; corresponding disease-free rate was 77%. For the Stage I disease confirmed by pathologic examination, the corresponding rate was 96%. The rates for Stages II through IV, as shown by pathologic findings at laparotomy, were 53% and 42%, respectively. In this pilot stud, a treatment policy for clinical Stage I, grade 2 or 3 adenocarcinoma of the endometrium using low-dose preoperative radiation therapy is recommended.

Renewed emphasis on pretreatment staging of gynecologic malignancies has resulted from a number of reports on surgical staging of malignant cervical, endometrial, and ovarian lesions. These reports have shown that by pretreatment staging, in significant numbers of patients, more advanced disease was detectable than by the usual clinical methods. From 32% to 46% of patients with stage III cervical carcicarcicarcinoma have been found to have metastatic disease in the para-aortic nodes. Diaphragmatic and para-aortic node metastases have been reported in patients with ovarian carcinoma recently in significantly higher incidences than as previously detected. The pelvic lymph nodes have been shown to be involved in 11% to 13.5% of patients with stage I endometrial carcinoma. Twelve and one-half percent had metastases to the para-aortic nodes. These data suggest the need for more accurate definition of extent of disease prior to treatment. Improvement in survival rates will not necessarily follow, but modifications in treatment must be tried.

The sensitivity of a bacterial bioluminescent acute toxicity test was compared to the sensitivity of the USP mouse safety, rabbit intramuscular implantation, rabbit intracutaneous, mouse systemic injection, and the MEM elution tissue culture tests. A variety of industrial plastics were used to evaluate the comparative sensitivities. Additional tests were conducted on low-density polyethylene containing a range of dibutyltin dichloride or trans-cinnamic acid concentrations. The bacterial bioluminescent test was more sensitive than any of the in vivo acute toxicity tests. The luminescent bacterial test was generally more sensitive than the tissue culture acute toxicity assay. The bacterial bioluminescent test offers a sensitive, rapid, uncomplicated, and inexpensive means for preliminary compatibility evaluation of biomaterials.