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.     

Measuring hope amongst Tanzanian women who participate in microfinance: An evaluation of the Snyder hope scale

ABSTRACT

Measuring hope reliably and accurately remains an important research objective, not least in less prosperous settings where ‘holding on to hope’ may be critically important in the struggle against adverse life conditions. The State Hope Scale was designed for use in the US. Despite reported application in diverse cultures and using translations the scale has not been extensively validated outside US populations. This study contributes to a larger project exploring the measurement of hope and provides a critique of Snyder’s scale as used in a Tanzanian female population of 1021 urban microfinance participants. We evaluate the scale’s validity through assessment of the empirical distribution of scores, item response profiles, internal consistency and discriminatory ability. Participants mostly scored very high and many reached very near the maximum attainable score. Hardly any endorsed the negative half of the response scale. Several problems are discussed including poor discrimination and strong evidence of acquiescence response bias. We also found little association of the scale scores with hypothesised correlates of hope. Future improvements on the measurement of hope are recommended, especially in studies outside the narrow Western context in which the scale was devised.     

Altered functional status of the hypothalamic dopaminergic tone in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a pilot study.

We compared the functional status of the hypothalamic dopaminergic tone in patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (GVHD) with that observed in patients with allo-HSCT without chronic GVHD and in healthy controls. The effect of acute dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL) concentrations was evaluated. Twenty volunteers, 20 to 52 years of age, seronegative for both hepatitis C virus and the human immunodeficiency virus, were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT, 5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and 2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations were measured both fasting and after intravenous administration of metoclopramide (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2 were older than those in groups 1 and 3 (P<.018), but their body mass index was similar. Fasting serum PRL concentrations were similar among the 3 groups; however, group 2 had higher PRL concentrations throughout the test (P<.001) and a greater area under the PRL curve than groups 1 and 3 (P<.001), without differences between the last 2 groups. The differences remained significant after adjustment for age (P<.01). Our results in a small group of patients with chronic GVHD after allo-HSCT suggest the existence of an increased functional level of their hypothalamic dopamine tone, which would favor a tendency toward a diminished endogenous production, release of pituitary PRL, or both. This could represent an adaptive mechanism aiming to maintain circulating PRL concentrations within a physiological range.     

颈动脉内膜切除术的恰当应用

在颈动脉内膜切除术(CEA)首创的头30年里,一直没有明确的标准来确定哪些颈内动脉疾病患者适合这一手术.最近,从7项临床随机试验中得出了哪些有症状与无症状患者适合行CEA的结论.对于颈内动脉狭窄70%以上的患者,卒中的危险性最大,手术的益处也最大.在这些研究中,CEA对以下患者最有益半球短暂性脑缺血发作、颅内外联合病灶和无侧支循环且除此之外身体状况良好的老年患者.下列患者虽然能从手术中获益,但围手术期卒中和死亡的危险性较高广泛白质疏松、对侧颈内动脉闭塞和腔内有血栓者.狭窄50%～69%的患者较少获益,包括女性和仅有一过性单眼盲在内的一些患者行CEA甚至可能有害.腔隙性卒中和一侧颈内动脉接近闭塞的患者有手术指征,但益处不大;狭窄＜50%的患者不能从手术中获益.在最大的一项无症状患者随机试验中,围手术期卒中和死亡的危险性非常小(1.5%),但要在2年内防止1例卒中发生需要相当多的病例(83例)接受CEA治疗.以后的文献报道围手术期危险性较高(2.8%～5.6%).近一半无症状患者的卒中是心源性栓塞和小血管疾病所致.这些局限性抵消了任何潜在的益处.其他试验正在进行,并可能确认哪些无症状患者亚组可从手术中获益.同时,大多数无症状患者内科治疗效果也较好.     

Million Behavioral Health Inventory: its utility in predicting physical function in patients with low back pain

The present study evaluated the use of psychologic measures, in particular, the relatively new Million Behavioral Health Inventory (MBHI), in predicting change in physical function of chronic low back pain patients undergoing a functional restoration program. The first 134 consecutive patients completing this program were assessed. Results demonstrated that various clinical scales of the MBHI were predictive of improvement in physical function. In addition, various scales enabled discrimination between patients who completed the program and those who prematurely dropped out. Although this inventory shows promise in helping to predict response to treatment, no single psychologic test can reliably be used as the sole predictor in clinical cases.