Involvement of catalase in the endometrium of patients with endometriosis and adenomyosis

OBJECTIVE: To determine the distribution of catalase in eutopic and ectopic endometria in patients with endometriosis or adenomyosis. DESIGN: Retrospective randomized study. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): Thirty-three patients with endometriosis, 36 with adenomyosis, and 47 fertile controls (total, 116 women). MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining of endometrial cells obtained by biopsy sampling, followed by calculation of an evaluation nomogram score. RESULT(S): The score of catalase in the glandular epithelium of controls group fluctuated during the menstrual cycle; it was lowest in the early proliferative phase and peaked in the late secretory phase. In patients with endometriosis, catalase scores did not fluctuate during the cycle, and scores were high compared with controls throughout the menstrual cycle. Catalase scores did not vary in patients with adenomyosis, and scores in this group were consistently higher than those in patients with endometriosis throughout the cycle. CONCLUSION(S): Abnormal expression of catalase in the eutopic and ectopic endometrium strongly suggests pathologic involvement of free radicals in endometriosis and adenomyosis.     

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy

The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4^＋ and CD8^＋ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs.     

Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study

New treatments, particularly second‐line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody–drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single‐arm, open‐label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non‐Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1–2 prior lines of therapy. In part 1, no dose‐limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment‐emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non‐Japanese patients.     

A comparative study of degree of colorectal distention with manual air insufflation or automated CO2 insufflation at CT colonography as a preoperative examination

Objectives

The purpose of this study was to compare the degree of colorectal distention between manual insufflation using room air and automatic insufflation using carbon dioxide for computed tomography colonography performed as a preoperative examination for patients with colon cancer.

Materials and methods

Participants comprised 200 patients who underwent computed tomography colonography immediately after colonoscopy from October 2011–2012. The first 100 patients were examined using manual insufflation, and the remaining 100 patients were examined using automated insufflation. Two radiologists independently assessed colorectal distention using a 4-point scale in six segments: cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Mean scores of the two radiologists were used to analyze whether any differences existed between techniques in terms of the degree of distention per segment.

Results

Mean distention values for the colonic lumen were better using the automated technique than with the manual technique in both positions (p < 0.05). In segments, distention was significantly better using the automated technique than using the manual technique in the sigmoid and descending colon for prone patients, and in all segments for supine patients.

Conclusions

Automated carbon dioxide insufflation offered significantly improved colorectal distention scores compared to manual room air insufflation.     

Repetitive transcranial magnetic stimulation for protection against delayed neuronal death induced by transient ischemia

OBJECT: Data in the present study demonstrate that repetitive transcranial magnetic stimulation (rTMS) induces ischemic tolerance against delayed neuronal death (DND) of hippocampal neurons following an otherwise lethal ischemic insult. METHODS: Various regimens of rTMS were delivered to adult gerbils at various times prior to an episode of ischemia induced by transient (5-minute) bilateral common carotid artery (CCA) occlusion. The extent of DND in the CA1 region of the hippocampus was assessed quantitatively 7 days after the transient ischemic episode. When rTMS was delivered 2 to 5 days prior to bilateral CCA occlusion, DND was substantially attenuated; delivery of rTMS 12 to 24 hours prior to occlusion induced partial tolerance. In the group of animals that had received stimulation 2 days prior to occlusion, neuron density in the CA1 sector was significantly higher (three gerbils, 210.33, 86.01% of normal) than in the group that experienced ischemia only (three gerbils, 10.66, 4.36% of normal). A similar degree of neuron sparing occurred when stimulation was delivered 3, 4, or 5 days prior to occlusion. Note that rTMS was effective when it was delivered at frequencies of 25 and 50 Hz. Stimulation at 25 Hz for 128 seconds (3200 pulses) was more effective than stimulation at 50 Hz for 64 seconds (3200 pulses) or 128 seconds (6400 pulses), however. CONCLUSIONS: Noninvasive rTMS represents an important tool for exploring the mechanisms of ischemic tolerance and preventing ischemic neuronal damage.     

Application of a Machine Learning Algorithm for Structural Brain Images in Chronic Schizophrenia to Earlier Clinical Stages of Psychosis and Autism Spectrum Disorder: A Multiprotocol Imaging Dataset Study

Background and HypothesisMachine learning approaches using structural magnetic resonance imaging (MRI) can be informative for disease classification; however, their applicability to earlier clinical stages of psychosis and other disease spectra is unknown. We evaluated whether a model differentiating patients with chronic schizophrenia (ChSZ) from healthy controls (HCs) could be applied to earlier clinical stages such as first-episode psychosis (FEP), ultra-high risk for psychosis (UHR), and autism spectrum disorders (ASDs).Study DesignTotal 359 T1-weighted MRI scans, including 154 individuals with schizophrenia spectrum (UHR, n = 37; FEP, n = 24; and ChSZ, n = 93), 64 with ASD, and 141 HCs, were obtained using three acquisition protocols. Of these, data regarding ChSZ (n = 75) and HC (n = 101) from two protocols were used to build a classifier (training dataset). The remainder was used to evaluate the classifier (test, independent confirmatory, and independent group datasets). Scanner and protocol effects were diminished using ComBat.Study ResultsThe accuracy of the classifier for the test and independent confirmatory datasets were 75% and 76%, respectively. The bilateral pallidum and inferior frontal gyrus pars triangularis strongly contributed to classifying ChSZ. Schizophrenia spectrum individuals were more likely to be classified as ChSZ compared to ASD (classification rate to ChSZ: UHR, 41%; FEP, 54%; ChSZ, 70%; ASD, 19%; HC, 21%).ConclusionWe built a classifier from multiple protocol structural brain images applicable to independent samples from different clinical stages and spectra. The predictive information of the classifier could be useful for applying neuroimaging techniques to clinical differential diagnosis and predicting disease onset earlier.     

Validation of a reference control for an SYBR-Green fluorescence assay-based real-time PCR for detection of bovine herpesvirus 5 in experimentally exposed bovine embryos

The objective of this study was to optimize an internal control to improve SYBR-Green-based qPCR to amplify/detect the BoHV-5 US9 gene in bovine embryos produced in vitro and experimentally exposed to the virus. We designed an SYBR-Green-based binding assay that is quick to perform, reliable, easily optimized and compares well with the published assay. Herein we demonstrated its general applicability to detect BoHV-5 US9 gene in bovine embryos produced in vitro experimentally exposed to BoHV-5. In order to validate the assay, three different reference genes were tested; and the histone 2a gene was shown to be the most adequate for normalizing the qPCR reaction, by considering melting and standard curves (p < 0.05). On the other hand, no differences were found in the development of bovine embryos in vitro whether they were exposed to BoHV-5 reference and field strains comparing to unexposed embryos. The developed qPCR assay may have important field applications as it provides an accurate BoHV-5 US9 gene detection using a proven reference gene and is considerably less expensive than the TaqMan qPCR currently employed in sanitary programs.