Papillary thyroid carcinoma with a high tumor mutation burden has a poor prognosis

BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8⁺ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected.     

IMP3与CD44v6在甲状腺乳头状癌中的表达及临床意义

目的 探讨IMP3及CD44v6在甲状腺乳头状癌（PTC）中的表达及其临床意义.方法 应用免疫组织化学方法检测30例甲状腺乳头状癌（甲状腺滤泡型乳头状癌10例,非滤泡型乳头状癌20例）,20例甲状腺乳头状癌并颈部淋巴结转移,20例甲状腺良性组织（10例正常组织,10例结节性甲状腺肿）中IMP3和CD44v6表达水平,检测结果用Biosens Digital Imaging System vl.6专业图像分析软件进行定量分析,选择积分光密度（IOD）作为评价参数.结果 IMP3与CD44V6在PTC中的表达高于良性组织中的表达,差异有统计学意义（P ＜0.05）;IMP3与CD44v6在PTC有淋巴结转移中的表达高于无淋巴结转移组织中的表达,差异有统计学意义（P ＜0.05）;IMP3与CD44v6在PTC中的表达呈正相关（r=0.903,P＜0.05）.结论 IMP3与CD44v6在甲状腺乳头状癌中呈高表达,有作为分子标志物协助PTC的诊断及判断PTC的侵袭力及转移力的价值.     

Cervical spine computed tomography utilization in pediatric trauma patients

Background

Guidelines for evaluating the cervical spine in pediatric trauma patients recommend cervical spine CT (CSCT) when plain radiographs suggest an injury. Our objective was to compare usage of CSCT between a pediatric trauma center (PTC) and referral general emergency departments (GEDs).

Methods

Patient data from a pediatric trauma registry from 2002 to 2011 were analyzed. Rates of CSI and CSCT of patients presenting to the PTC and GED were compared. Factors associated with use of CSCT were assessed using multivariate logistic regression.

Results

5148 patients were evaluated, 2142 (41.6%) at the PTC and 3006 (58.4%) at the GED. Groups were similar with regard to age, gender, GCS, and triage category. GED patients had a higher median ISS (14 vs. 9, p < 0.05) and more frequent ICU admissions (44.3% vs. 26.1% p < 0.05). CSI rate was 2.1% (107/5148) and remained stable. CSCT use increased from 3.5% to 16.1% over time at the PTC (mean 9.6% 95% CI = 8.3, 10.9) and increased from 6.8% to 42.0% (mean 26.9%, CI = 25.4, 28.4) at the GED. Initial care at a GED remained strongly associated with CSCT.

Conclusions

Despite a stable rate of CSI, rate of CSCT increased significantly over time, especially among patients initially evaluated at a GED.     

An examination of associations between the inability to taste phenylthiocarbamide (PTC) and clinical characteristics and trait markers in first-episode,nonaffective psychotic disorders

Research findings are mixed as to whether or not the inability to taste phenylthiocarbamide (PTC) might represent an endophenotypic trait marker for schizophrenia. We hypothesized associations between PTC-tasting status and select clinical characteristics and trait markers in patients with psychotic disorders that, if present, would provide support for the inability to taste PTC as a trait marker. In a first-episode psychosis sample (n=93), we measured PTC tasting, family history of psychosis, age at onset of prodrome and psychosis, severity of positive and negative symptoms, global impairment in functioning, neurological soft signs, and four neurocognitive domains (verbal learning/memory, visual learning/memory, verbal working memory, and spatial working memory). Associations between PTC-non-tasting and clinical/neurocognitive variables were examined with χ² tests and independent samples t tests. Among participants, 67.7% tasted PTC in comparison to a strip of control paper, and 25.8% were non-tasters. Tasters and non-tasters did not show statistically significant differences with respect to family history, age at onset, severity of symptoms, neurological soft signs, or the four neurocognitive domains. In conjunction with other findings, it is unlikely that PTC-non-tasting is a trait marker of schizophrenia, though a conclusive study is warranted.     

The role of aquaporin-1 in idiopathic and drug-induced intracranial hypertension

Idiopathic intracranial hypertension is a common disorder affecting mainly healthy, young, overweight women. The pathogenesis of this condition is unknown, but it has been shown to follow treatment with several compounds including corticosteroids and vitamin A derivatives. This paper will offer a novel hypothesis and insight on the pathogenesis of drug induced intracranial hypertension following a review and analysis of the literature. Both corticosteroids and vitamin A derivatives have been shown to upregulate the expression of aquaporin 1, a water channel protein. Aquaporin 1 is widely distributed in the human brain and is associated with water secretion into the subarachnoid space. Aquaporin 1 was also shown to participate in the regulation of weight. Agents used for treating idiopathic intracranial hypertension reduce aquaporin 1 expression. Based on these observations, we propose that aquaporin 1 has a pathogenetic role in drug induced idiopathic intracranial hypertension. Over expression of this gene causes increased intracranial pressure, and downregulation reduces pressure and alleviates the symptomatology and complications of idiopathic intracranial hypertension.     

The relationship between taste sensitivity to phenylthiocarbamide and anhedonia

It has been proposed that taste sensitivity to bitter compounds such as, phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), represents a genetic marker for an increased vulnerability to depressive illness. Previous explorations of this idea have proven equivocal. This study refines and further explores this idea by focusing specifically on anhedonia (diminished hedonic capacity), a key symptom in some depressive illness, linked also with sensory pleasure. It is hypothesized that diminished PTC taste sensitivity will be associated with more general decrements in hedonic capacity (anhedonia). An opportunity sample of 198 university students were assessed using paper strips impregnated with PTC, the same participants also completed a widely used assessment of hedonic capacity, the Snaith-Hamilton Pleasure Scale (SHAPS). Hedonic capacity scores positively correlated with PTC taste sensitivity; specifically, heightened hedonic capacity was associated with heightened sensitivity to the bitter taste of PTC. Furthermore, modest differences were observed between those least (non-tasters) and most (supertasters) sensitive to PTC, with non-tasters reporting significantly lower hedonic capacity scores than supertasters. PTC taste sensitivity may represent a peripheral risk factor for anhedonia.