Intravoxel incoherent motion imaging kinetics during chemoradiotherapy for human papillomavirus‐associated squamous cell carcinoma of the oropharynx: preliminary results from a prospective pilot study

This study aims to identify the temporal kinetics of intravoxel incoherent motion (IVIM) MRI in patients with human papillomavirus‐associated (HPV+) oropharyngeal squamous cell carcinoma. Patients were enrolled under an Institutional Review Board (IRB)‐approved protocol as part of an ongoing prospective clinical trial. All patients underwent two MRI studies: a baseline scan before chemoradiotherapy and a mid‐treatment scan 3–4 weeks after treatment initiation. Parametric maps representing pure diffusion coefficient (D), pseudo‐diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) were generated. The Mann–Whitney U‐test was used to assess the temporal variation of IVIM metrics. Bayesian quadratic discriminant analysis (QDA) was used to evaluate the extent to which mid‐treatment changes in IVIM metrics could be combined to predict sites that would achieve complete response (CR) in multivariate analysis. Thirty‐one patients were included in the final analysis with 59 lesions. Pretreatment ADC and D values of the CR lesions (n = 19) were significantly lower than those of non‐CR lesions (n = 33). Mid‐treatment ADC, D and f values were significantly higher (p < 0.0001) than pretreatment values for all lesions. Each increase in normalized ΔADC of size 0.1 yielded a 1.45‐fold increase in the odds of CR (p < 0.0003), each increase in normalized ΔD of size 0.1 yielded a 1.53‐fold increase in the odds of CR (p < 0.0002), and each unit increase in Δf yielded a 2.29‐fold increase in the odds of CR (p < 0.02). Combined ΔD and ΔADC were integrated into a multivariate prediction model and attained an AUC of 0.87 (95% confidence interval: 0.79, 0.96), as well as a sensitivity of 0.63, specificity of 0.85 and accuracy of 0.78, under leave‐one‐out cross‐validation. In conclusion, IVIM is feasible and potentially useful in the prediction and assessment of the early response of HPV+ oropharyngeal squamous cell carcinoma to chemoradiotherapy. Copyright © 2015 John Wiley & Sons, Ltd.     

Phase II study of oxaliplatin in children with recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors: a pediatric brain tumor consortium study

BACKGROUND: An open-label Phase II study of oxaliplatin was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB), supratentorial primitive neuroectodermal tumors (SPNET), and atypical teratoid rhabdoid tumor (ATRT). METHODS: Patients were stratified as follows: stratum IA, first recurrence MB with measurable disease; IB, recurrent MB with only cerebral spinal fluid (CSF) positivity or linear leptomeningeal disease (LLD); IC, MB > or =second recurrence; stratum II, recurrent SPNET; stratum III, recurrent ATRT. Patients received oxaliplatin, 130 mg/m(2) intravenously over 2 hours every 3 weeks. The primary objective was to estimate the sustained response rate in stratum 1A. Plasma ultrafiltrate platinum pharmacokinetics were evaluated. RESULTS: A total of 43 patients with a median age of 8.5 years (range, 0.6-18.9 years) were enrolled. In stratum 1A, 2 of 15 had partial responses (PRs, 1 sustained PR). No responses were observed in other strata. The most frequent Grade 3 and 4 toxicities included thrombocytopenia (25.6%), neutropenia (16.3%), leukopenia (12%), increase in serum alanine transaminase (ALT) (7%), vomiting (4.7%), and sensory neuropathy (4.7%). No severe ototoxicity or nephrotoxicity was reported. Plasma ultrafiltrate platinum pharmacokinetic parameters were similar to adults, with a median clearance of 12.2 L/hr (range, 4.4-30 L/hr) and median area under the curve (AUC(0-infinity)) of 9.4 microg/mL/hr (range, 6.2-13.9 microg/mL/hr). CONCLUSIONS: Oxaliplatin was well tolerated in children but has limited activity in children with recurrent CNS embryonal tumors previously treated with platinum compounds.     

Influence of diet complexity on intestinal adaptation following massive small bowel resection in a preclinical model

AIMS: To investigate the effect of dietary complexity on intestinal adaptation using a preclinical model. METHODS: Four-week-old piglets underwent a 75% proximal small bowel resection or transection operation (control). Post-operatively, animals received either pig chow (n = 15), polymeric formula (n = 9), polymeric formula plus fiber (n = 6), or elemental formula (n = 7). RESULTS: The weight gain of all groups was reduced compared with controls that were fed the same diet. Animals that had a resection, which were fed elemental formula, had significantly reduced weight gain compared with the other groups (4.7 4.2 vs 30.7 7.1 kg chow and 11.5 1.3 kg polymeric formula). Villus height was increased in the jejunum, ileum and terminal ileum of resected animals compared with controls in animals fed with pig chow, polymeric formula and elemental formula. The animals that had a resection had a significant reduction in the transepithelial conductance (10.4 5.5 vs 25.4 6.5 mS/cm2) and 51Chromium-EDTA flux (2.8 1.9 vs 4.8 4.9 microL/h per cm2) compared with the controls. CONCLUSIONS: A complex diet was found to be superior to an elemental diet in terms of the morphological and functional features of adaptation following massive small bowel resection.     

Prospective audit of cytomegalovirus-negative blood product utilization in haematology/oncology patients

The transfusion management of immunocompromised patients often requires special blood product use such as cytomegalovirus (CMV)-negative cellular products, which are more costly than standard blood products and occasionally in short supply. We audited the use of CMV-negative products in haematology/oncology patients to determine the appropriateness of their use. A concurrent-prospective audit was conducted of all orders for CMV-negative packed red blood cell (PRBC) and platelet products in 201 haematology/ oncology patients. Once CMV serostatus was determined, orders for inappropriate CMV-negative units were cancelled, and filled as CMV untested units. During the 21-month period of this audit, the rates of inappropriate transfusions decreased for PRBC from 73.2% to 14.3% (chi2 = 68.4, P<0.001) and for platelets from 68.1% to 10.6% (chi2 = 65.6, P<0.001). The median time to cancellation of inappropriate CMV-negative orders was 11 days. This audit resulted in estimated cost savings of $16500 over the 21-month duration. Inappropriate requests for scarce and expensive blood products are substantially reduced by concurrent-prospective auditing of transfusion practice, in a manner that is both simple and cost effective.     

The Schizophrenia–Rheumatoid Arthritis Connection: Infectious, Immune, or Both?

Schizophrenia and rheumatoid arthritis share an impressive number of similarities. Both are chronic, relapsing diseases of unknown etiology. Both became prominent in the early 19th century and have prevalences of approximately 1% in North America and Europe. Both run in families, have pairwise concordance rates of approximately 30% among monozygotic twins, and are more common among individuals born in urban areas. For both diseases, studies have reported greater exposure to cats in childhood than in controls. Both diseases have been associated with similar class II HLA antigens. Both have also been suspected of having infectious etiology, with similar agents—retroviruses, herpesviruses including EBV, and Toxoplasma gondii—having been associated in some cases. Since there is also a well-documented inverse correlation between these two diseases, it is possible that they share a common infectious and/or immune etiology and that once a person gets one of the diseases then they are relatively immune to the other.     

Psychiatric Genocide: Nazi Attempts to Eradicate Schizophrenia

Although the Nazi genocide of Jews during World War II is well known, the concurrent Nazi genocide of psychiatric patients is much less widely known. An attempt was made to estimate the number of individuals with schizophrenia who were sterilized and murdered by the Nazis and to assess the effect on the subsequent prevalence and incidence of this disease. It is estimated that between 220 000 and 269 500 individuals with schizophrenia were sterilized or killed. This total represents between 73% and 100% of all individuals with schizophrenia living in Germany between 1939 and 1945. Postwar studies of the prevalence of schizophrenia in Germany reported low rates, as expected. However, postwar rates of the incidence of schizophrenia in Germany were unexpectedly high. The Nazi genocide of psychiatric patients was the greatest criminal act in the history of psychiatry. It was also based on what are now known to be erroneous genetic theories and had no apparent long-term effect on the subsequent incidence of schizophrenia.