Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF72‐associated amyotrophic lateral sclerosis

As potential treatments for C9ORF72‐associated amyotrophic lateral sclerosis (c9ALS) approach clinical trials, the identification of prognostic biomarkers for c9ALS becomes a priority. We show that levels of phosphorylated neurofilament heavy chain (pNFH) in cerebrospinal fluid (CSF) predict disease status and survival in c9ALS patients, and are largely stable over time. Moreover, c9ALS patients exhibit higher pNFH levels, more rapid disease progression, and shorter survival after disease onset than ALS patients without C9ORF72 expansions. These data support the use of CSF pNFH as a prognostic biomarker for clinical trials, which will increase the likelihood of successfully developing a treatment for c9ALS. Ann Neurol 2017;82:139–146     

Analysis of the therapeutic evolution in the management of airway infantile hemangioma

AIM: To analyze the evolution in the management of airway infantile hemangioma (AIH) and to report the results from 3 pediatric tertiary care institutions.METHODS: A retrospective study of patients with diagnosis of AIH and treated in 3 pediatric tertiary care institutions from 1996 to 2014 was performed.RESULTS: Twenty-three patients with diagnosis of AIH were identified. Mean age at diagnosis was 6 mo (range, 1-27). Single therapy was indicated in 16 patients and 7 patients received combined therapy. Two therapeutic groups were identified: Group A included 14 patients who were treated with steroids, interferon, laser therapy and/or surgery; group B included 9 patients treated with oral propranolol. In group A, oral corticosteroids were used in 9 patients with a good response in 3 cases (no requiring other therapeutic option), the other patients required additional treatment options. Cushing syndrome was observed in 3 patients. One patient died of a fulminant sepsis. Open surgical excision and endoscopic therapy were performed in 11 patients (in 5 of them as a single treatment) with a response rate of 54.5%. Stridor persisted in 2 cases, and one patient died during the clinical course of bronchial aspiration. In group B, oral propranolol was used in 9 patients (in 8 of them as a single treatment) with a response rate of 100%, with an mean treatment duration of 7 mo (range, 5-10); complications were not observed.CONCLUSION: Our experience and the medical literature support the use of propranolol as a first line of treatment in AIH.     

Advanced gastric cancer:Current treatment landscape and future perspectives

Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease(locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2(HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer.     

Quantitative assessment of SSTR2 expression in patients with non-small cell lung cancer using68Ga-DOTATOC PET and comparison with18F-FDG PET

Purpose Dynamic PET studies with⁶⁸Ga-DOTATOC were performed in patients with non-small cell lung cancer (NSCLC) to assess the somatostatin receptor 2 (SSTR2) expression. Furthermore, dynamic¹⁸F-fluorodeoxyglucose (FDG) studies were performed in the same patients to compare the SSTR2 expression with the tumour viability. Methods The study population comprised nine patients, examined with both tracers on two different days within 1 week. Standardised uptake values (SUVs) were calculated and a two-tissue compartment model was applied to the data. Furthermore, a non-compartment model based on the fractal dimension (FD) was applied to the data. Results The DOTATOC uptake was generally lower than the FDG uptake. Moderately enhanced DOTATOC uptake was noted in seven of the nine tumours. All kinetic parameters exceptk ₄ were lower for DOTATOC than for FDG. The mean SUV was 2.018 for DOTATOC, in comparison to 5.683 for FDG. In particular,k ₃ was highly variable for DOTATOC and showed an overlap with the normal lung tissue. The fractional blood volumeV _B was relatively low for both tracers, not exceeding 0.3. The highest significant logarithmic correlation was found for the FD of the two tracers (r=0.764,p=0.017). The logarithmic correlation for SUVs was also significant (r=0.646,p=0.060), as was that forV _B (r=0.629,p=0.069). In contrast, none of the eight metastases which were positive on FDG PET showed any DOTATOC uptake. Conclusion The results demonstrated moderate⁶⁸Ga-DOTATOC uptake in primary NSCLC but did not provide any evidence for SSTR2 expression in metastases. This may be caused by loss of the gene expression in metastases as compared with the primary tumours.     

Influence of Angiotensin-converting enzyme polymorphism on neuropsychological subacute performance in moderate and severe traumatic brain injury

Traumatic brain injury (TBI) frequently results in cerebrovascular lesions that may increase secondary damage and cause neuropsychological impairment. Previous studies suggest an association among the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE), cardiovascular disease, and cognitive performance. Clinical and experimental studies have demonstrated the beneficial effects of ACE inhibitor treatment on vascular injury, hypertension, brain ischemia, and cognitive functioning. In a sample of 73 moderate and severe TBI patients, the authors assessed whether cognitive sequelae differed in relation to the ACE I/D polymorphism. D allele carrier patients performed worse than those with I/I polymorphism on tests involving attention and processing speed. Findings suggest that the physiopathological changes associated with TBI may have greater consequences in ACE D allele carriers.     

Adult attachment style as mediator between childhood neglect/abuse and adult depression and anxiety

BACKGROUND: There has been little prospective investigation of the relationship between adult attachment style and clinical levels of anxiety and major depression. This paper seeks to address this, as well as examining the potentially mediating role of adult insecure attachment styles in the relationship between childhood adverse experience and adult disorder. METHODS: 154 high-risk community women studied in 1990-1995, were followed-up in 1995-1999 to test the role of insecure attachment style in predicting new episodes of anxiety and/or major depressive disorder. The Childhood Experience of Care and Abuse (CECA) and the Attachment Style Interview (ASI) were administered at first interview and the Structured Clinical Interview for DSM-IV (SCID) administered at first and follow-up interview. Major depression and clinical level anxiety disorders (GAD, Social Phobia or Panic and/or Agoraphobia) were assessed at first contact and for the intervening follow-up period. RESULTS: 55% (85/154) of the women had at least one case level disorder in the follow-up period. Only markedly or moderately (but not mildly) insecure attachment styles predicted both major depression and case anxiety in follow-up. Some specificity was determined with Fearful style significantly associated both with depression and Social Phobia, and Angry-Dismissive style only with GAD. Attachment style was unrelated to Panic Disorder and/or Agoraphobia. In addition, Fearful and Angry-Dismissive styles were shown to partially mediate the relationship between childhood adversity and depression or anxiety. CONCLUSION: In order to correctly interpret lifespan models of adult psychiatric disorder, it is necessary to test for mediating factors. Attachment theory provides a framework for explaining how dysfunctional interpersonal style arising from early childhood perpetuates vulnerability to affective disorders. This has implications for intervention and treatment to break cycles of risk.