Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA

IntroductionEGFR mutated (EGFRm) NSCLC tumors occasionally express programmed cell death ligand 1 (PD-L1), although frequency and clinical relevance are not fully characterized. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following treatment with osimertinib or comparator EGFR tyrosine kinase inhibitors in the FLAURA trial (phase III, NCT02296125).MethodsOf 231 tissue blocks available from the screened population (including EGFRm-positive and -negative samples), 197 had sufficient tissue for PD-L1 testing using the SP263 (Ventana, Tucson, Arizona) immunohistochemical assay. Tumor cell (TC) staining thresholds of PD-L1 TC greater than or equal to 1%, TC greater than or equal to 25%, and TC greater than or equal to 50% were applied. Progression-free survival (PFS) was investigator-assessed, per Response Evaluation Criteria in Solid Tumor, version 1.1, according to PD-L1 expressors (TC ≥ 1%) or negatives (TC < 1%) in randomized patients.ResultsPD-L1 staining was successful in 193 of 197 patient formalin-fixed paraffin-embedded blocks; of these, 128 of 193 were EGFRm-positive and 106 of 128 patients were randomized to treatment (osimertinib: 54; comparator: 52). At the PD-L1 TC greater than or equal to 25% threshold, 8% (10 of 128) of EGFRm-positive tumors expressed PD-L1 versus 35% (23 of 65) of EGFRm-negative tumors. With the TC greater than or equal to 1% threshold, 51% (65 of 128) versus 68% (44 of 65) were mutation-positive and –negative, respectively, and with the TC greater than or equal to 50% threshold, 5% (7 of 128) versus 28% (18 of 65), were mutation-positive and -negative, respectively. For PD-L1 expressors (TC ≥ 1%), median PFS was 18.4 months with osimertinib and 6.9 months with comparator (hazard ratio = 0.30; 95% confidence interval: 0.15–0.60). For PD-L1–negative patients (TC < 1%), median PFS was 18.9 months with osimertinib and 10.9 months with comparator (hazard ratio = 0.37; 95% confidence interval: 0.17–0.74).ConclusionsClinical benefit with osimertinib was unaffected by PD-L1 expression status.     

How far do patients with sensory ataxia benefit from so-called “proprioceptive rehabilitation”?

A rehabilitation program including foot sensory stimulation, balance and gait training with limited vision was performed in 24 patients with clinically defined sensory ataxia. There were 15 patients with bilateral somatosensory loss related to chronic neuropathy and nine patients with unilateral loss-related to multiple sclerosis. After training, balance control assessed using the Berg Balance Test improved similarly in both groups, and Romberg's sign disappeared in some patients, suggesting an improvement in dynamic balance and in the proprioceptive contribution. Conversely, balance assessed on a static force platform remained similar in the open-eyes condition and improved in the closed-eyes condition only in patients with unilateral sensory loss. These results show that ataxic patients can improve their balance with better results in dynamic conditions and that the relative contribution of proprioceptive and visual inputs may depend on the extent of somatosensory loss.     

An unusual cause of adult onset cerebellar ataxia with hypogonadism

We report an unusual case of sporadic adult onset cerebellar ataxia with hypogonadism. A 40-year-old unmarried man presented with progressive ataxia and dysarthria along with complaints of non-development of secondary sexual characteristics and erectile dysfunction. There were complaints of intermittent diarrhea. Clinical examination revealed a pan-cerebellar syndrome with features of hypoandrogenism. No eye movement abnormalities were evident. There were signs of malabsorption. Investigations confirmed the presence of auto-antibodies found in celiac disease, and a duodenal biopsy confirmed the same. Hypoandrogenism was postulated to be due to hypergonadotropic hypogonadism which has been mentioned in a few patients of celiac disease. However, the pattern seen in our patient was of a hypogonadotropic hypogonadism. This is probably secondary to an autoimmune hypophysitis seen in some patients in the absence of other clinical manifestations. Autoantibody testing should be a diagnostic necessity in any adult with a sporadic cerebellar ataxia.     

Cerebellar ataxia in the eastern and southern parts of Norway

Introduction –  The relative frequencies of different ataxias vary among different ethnic and geographic groups. The aim of this study was to examine patients with cerebellar ataxia and find the occurrence of autosomal dominant and recessive cerebellar ataxias in the population of the southern and eastern parts of Norway and estimate its prevalence.
Materials and methods –  Probands were systematically tested for spinocerebellar ataxia 1, 2, 3, 6 and Friedreich's ataxia. A total of 94 patients with ataxia were assessed.
Results –  We registered 60 patients from 39 unrelated families with hereditary ataxias. One family with SCA2 (two patients), one family with Friedreich's ataxia (two patients), two patients heterozygote for Friedreich's ataxia and one metabolic ataxia were identified.
Conclusions –  We have few Friedreich's ataxia and SCA 1,2,3 and 6 in our population. Prevalence in Oslo County was estimated at 2.2/100,000 for autosomal recessive and 3.0/100,000 for autosomal dominant ataxia, respectively.     

The modular architecture of the neglect syndrome: Implications for action control in visual neglect

In our recent review of action control deficits in hemispatial neglect we concluded that many patients with the disorder have deficits in visuomotor control [Coulthard, E., Parton, A., & Husain, M. (2006). Action control in visual neglect. Neuropsychologia, 44(13), 2717-2733]. This conclusion has been questioned and it has been argued instead that there are no action deficits in neglect [Himmelbach, M., Karnath, H.-O., & Perenin, M.-T. (2007). Action control is not affected by spatial neglect: A comment on Coulthard et al. Neuropsychologia, 45(8), 1979-1981]. We proposed that rather than being specific to the neglect syndrome, action control deficits are more likely to relate to lesion location. Although many of these impairments may contribute to the manifestation of neglect, they may also occur in brain-damaged patients without the condition. In this article, we explore this framework further, discussing how neglect behaviour may emerge from damage to a set of visuomotor or cognitive modules, or their connections. Central to our view is the idea that the critical combination of deficits leading to neglect varies considerably between cases, and that visuomotor or cognitive modules disrupted in the syndrome may not, in fact, be specific to neglect.     

Q开关Nd:YAG激光不同波长治疗面部毛细血管扩张疗效比较

目的：观察Q开关Nd：YAG激光不同波长治疗面部毛细血管扩张的疗效及副反应。方法：128例病人按治疗波长随机分为532nm组75例，585nm组53例，治疗光斑2．0mm，能量密度2．2-6．8J／cm。，脉宽10ns；术后3个月根据术前照片判定疗效，标准分为Ⅳ级。结果：治疗次数1-4次，间隔时间3-5个月，两组共治愈71例(55，47％)，疗效与治疗次数成正相关。其中532nm组治愈36例(48．00％)，平均治愈次数2．64次；585nm组治愈35例(66．04％，)，平均治愈次数2．40次，两组痊愈率及副反应差异无显性。结论：Q开关Nd:YAG激光倍频532／nm和585nm两种波长对密度较低、直径较细的面部毛细血管扩张均有可靠疗效，术后除色素沉着发生较高外，其他不良反应较少。