Targeting disialoganglioside (GD2) on neuroblastoma (NB) with T cells expressing a first-generation chimeric antigen receptor (CAR) was safe, but the cells had poor expansion and long-term persistence. We developed a third-generation GD2-CAR (GD2-CAR3) and hypothesized that GD2-CAR3 T cells (CARTs) would be safe and effective. This phase 1 study enrolled relapsed or refractory NB patients in three cohorts. Cohort 1 received CART alone, cohort 2 received CARTs plus cyclophosphamide and fludarabine (Cy/Flu), and cohort 3 was treated with CARTs, Cy/Flu, and a programmed death-1 (PD-1) inhibitor. Eleven patients were treated with CARTs. The infusions were safe, and no dose-limiting toxicities occurred. CARTs were detectable in cohort 1, but the lymphodepletion induced by Cy/Flu increased circulating levels of the homeostatic cytokine interleukin (IL)-15 (p = 0.003) and increased CART expansion by up to 3 logs (p = 0.03). PD-1 inhibition did not further enhance expansion or persistence. Antitumor responses at 6 weeks were modest. We observed a striking expansion of CD45/CD33/CD11b/CD163 myeloid cells (change from baseline, p = 0.0126) in all patients, which may have contributed to the modest early antitumor responses; the effect of these cells merits further study. Thus, CARTs are safe, and Cy/Flu can further increase their expansion.

Background: Ego defense mechanisms are unconscious psychological processes that help an individual to prevent anxiety when exposed to a stressful situation. These mechanisms are important in psychiatric practice to assess an individual’s personality dynamics, psychopathologies, and modes of coping with stressful situations, and hence, to design appropriate individualized treatment. Our study delineates the relationship of ego defense mechanisms with anxiety, depression, and academic performance of Pakistani medical students.Methods: This cross-sectional study was done at CMH Lahore Medical College and Fatima Memorial Hospital Medical and Dental College, both in Lahore, Pakistan, from December 1, 2014 to January 15, 2015. Convenience sampling was used and only students who agreed to take part in this study were included. The questionnaire consisted of three sections: 1) Demographics, documenting demographic data and academic scores on participants’ most recent exams; 2) Hospital Anxiety and Depression Scale (HADS); and 3) Defense Style Questionnaire-40 (DSQ-40). The data were analyzed with SPSS v. 20. Mean scores and frequencies were calculated for demographic variables and ego defense mechanisms. Bivariate correlations, one-way ANOVA, and multiple linear regression were used to identify associations between academic scores, demographics, ego defense mechanisms, anxiety, and depression.Results: A total of 409 medical students participated, of whom 286 (70%) were females and 123 (30%) were males. Mean percentage score on the most recent exams was 75.6% in medical students. Bivariate correlation revealed a direct association between mature and neurotic ego defense mechanisms and academic performance, and an indirect association between immature mechanisms and academic performance. One-way ANOVA showed that moderate levels of anxiety (P < .05) and low levels of depression (P < .05) were associated with higher academic performance.Conclusion: There was a significant association between academic performance and ego defense mechanisms, anxiety, and depression levels in our sample of Pakistani medical students.

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The diagnostic accuracy of FDG-PET images acquired on a PET/MR scanner and generated using MR-based attenuation correction was not inferior to that of PET images processed by traditional CT-based correction.

Loss of mural stratification, peri-appendiceal fat inflammation and an appendicolith are significant predictors of appendicitis in children with otherwise equivocal US exams. While maximum appendiceal diameter is not statistically associated with appendicitis in our study, mean appendiceal diameter of 6.7 mm in those without appendicitis suggests that the customary upper normal limit of 6 mm is too sensitive.

Oxygen is a World Health Organisation listed essential drug yet provision of oxygen in developing countries often fails to meet demand. The aim of this study was to evaluate the need for supplementary oxygen against oxygen delivery capacity at a large teaching hospital in Malawi. A cross-sectional study of all adult medical inpatients and assessment of oxygen provision over a 24-hour period was conducted. 144 patients were included in the study, 14 of whom met local and international criteria for oxygen therapy (oxygen saturations of <90%). Four were receiving oxygen. Of the 8 oxygen concentrators available, only 4 were functional. In conclusion, we identified a need for oxygen that was greater than the supply.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder that is usually benign and self-limiting. We present a case of atypical, aggressive JXG harboring a novel mitogen-activated protein kinase (MAPK) pathway mutation in the MAPK1 gene, which encodes mitogen-activated protein kinase 1 or extracellular signal-regulated 2 (ERK2). Our analysis revealed that the mutation results in constitutive ERK activation that is resistant to BRAF or MEK inhibitors but susceptible to an ERK inhibitor. These data highlight the importance of identifying specific MAPK pathway alterations as part of the diagnostic workup for patients with histiocytic disorders rather than initiating empiric treatment with MEK inhibitors.

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