Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

The influence of different error estimates in the detection of post-operative cognitive dysfunction using reliable change indices with correction for practice effects.

The reliable change index (RCI) expresses change relative to its associated error, and is useful in the identification of post-operative cognitive dysfunction (POCD). This paper examines four common RCIs that each account for error in different ways. Three rules incorporate a constant correction for practice effects and are contrasted with the standard RCI that had no correction for practice. These rules are applied to 160 patients undergoing coronary artery bypass graft (CABG) surgery who completed neuropsychological assessments preoperatively and 1 week post-operatively using error and reliability data from a comparable healthy non-surgical control group. The rules all identify POCD in a similar proportion of patients, but the use of the within subject standard deviation, expressing the effects of random error, as an error estimate is a theoretically appropriate denominator when a constant error correction, removing the effects of systematic error, is deducted from the numerator in a RCI.     

Improved graft survival for flow cytometry and antihuman globulin crossmatch-negative retransplant recipients

We compared our standard NIH (extended incubation) crossmatch (XM) with antihuman globulin (AHG) and flow cytometry XMs and correlated the results with rejection episodes and graft survivals. For 89 CsA-Pred, primary renal allograft recipients, AHG and/or FCXM results did not improve on the NIH-XM-negative (NEG) graft survival results, whether testing pretransplant or historical (Hx) sera. Similarly, there was no association of a positive (POS) AHG or FCXM with increased rejection episodes in these primary recipients. However, for retransplant (Re-Tx) recipients a neg AHG or FCXM did discriminate fewer rejections and an improved graft survival compared with the NIH-XM-neg. results. The overall one-year graft survival for the 47 Re-Tx recipients studied herein was 66% (based on a neg pre-Tx NIH-XM). Pre-Tx AHG-NEG, Re-Tx recipients displayed an improved graft survival compared with NIH-XM NEG recipients (77% vs. 66%, P less than 0.05) and with AHG-POS recipients (77% vs. 47%, P less than 0.05). Similarly, pre-Tx, FCXM-NEG, Re-Tx recipients displayed improved graft survivals compared with NIH-XM-NEG recipients (83% vs. 66%, P less than 0.05) and FCXM-POS recipients (83% vs. 48%, P less than 0.05). Re-Tx recipients displaying a POS AHG and/or FCXM experienced a significantly greater number of rejections than NEG-XM recipients (P less than 0.05, respectively). The AHG and FCXM results correlated with rejections and graft survivals whether testing pre-Tx or Hx high-PRA sera. Re-Tx recipients who were AHG-XM-NEG but FCXM-POS, experienced more rejection episodes than recipients who displayed a negative XM reactivity for both AHG and FCXM (P less than 0.02), but with no resulting differences in graft survival. HLA matching, pre-Tx blood transfusions and PRA did not impact on these crossmatch and graft survival results. Use of AHG and/or FCXMs for Re-Tx, but not primary, recipients should help to improve graft survival for these high-risk recipients.     

Improvement in men inpatients in an alcoholism rehabilitation unit: a week-by-week comparison

The Brief Symptom Inventory (BSI), a 53-item psychiatric symptom checklist, was administered to 57 alcoholic inpatients on days 2, 10, 18 and 26 of their 28-day stay in an alcoholism rehabilitation unit at a Veterans Administration hospital. The results of the test show a steady decline in the patients' psychiatric symptomatology from week 1 to week 4 with the most dramatic improvement evidenced between weeks 1 and 2.