SDF-1/CXCR4 as prognostic markers for postoperative radiochemotherapy in head and neck cancer

Outcomes of patients affected by locally advanced head and neck squamous cell carcinomas (HNSCC) and treated with surgery and adjuvant radio-chemotherapy are still unsatisfactory, being the overall survival (OS) still settled around 50% at five years, with poor outcomes especially among HPV negative patients. Therefore, patients’ stratification based on biomarker profiles is required for personalised therapies. SDF-1/CXCR4 is known as the most important chemokine pathway involved in tumour development, progression and metastasis. Nevertheless, no clear data exist regarding the role of SDF-1/CXCR4 among HNSCC patients. The present study aims to investigate the prognostic value of SDF-1 and CXCR4 in a large and homogeneous cohort of HNSCC patients treated with post-operative RT-CT, as part of a multicentre biomarker study within the German Cancer Consortium Radiation Oncology Group. The results of the study have been published [1]. 221 patients affected by stage III and IVA HNSCC of the oral cavity, oropharynx and hypopharynx were treated with surgery and adjuvant RT-CT. Tumour microarrays with the post-surgical tumour material were generated and stained for SDF-1 and CXCR4 using immunofluorescence. 201 patients were analysed for SDF-1 and 190 for CXCR4. The univariate and multivariate analyses showed that higher SDF-1 intracellular expression significantly correlated with poor locoregional control (LRC) in the whole patients’ cohort as well as in the HPV16 negative patients. Higher CXCR4 intracellular expression correlated with poor LRC in the univariate analysis, but this trend was not confirmed in the multivariate analysis. Not high SDF-1 nor high CXCR4 expression correlated with distant metastasis free survival or OS. In summary, we could show for the first time in a large and homogeneous cohort of HNSCC patients treated with adjuvant RT-CT that SDF-1 correlates with worse LRC. These results are exploratory and need to be validated prospectively, but support further investigation of SDF-1/CXCR4 as potential biomarker for treatment individualization and as a target to overcome resistance to RT

Should the early surgery threshold be moved to 72 h in over-85 patients with hip fracture? A single-center retrospective evaluation on 941 patients

Aim: Aim of the study was to assess whether early surgery and other clinical and orthogeriatric parameters could affect mortality rate in hip fracture patients aged > 85. Materials and methods: Data regarding a 42-month period were retrospectively obtained from the institutional medical records and registry data. Gender, age, fracture pattern, surgical technique, type of anesthesia, timing of surgical intervention (within 24, 48 or 72 h from admission), days of hospitalization, mortality rate divided in intra-hospital, at 30 days and at 1 year were collected for the whole population. Some additional data were collected for an orthogeriatric subgroup. Results: 941 patients were considered, with a mean age of 89 years. Surgery was performed within 24, 48 and 72 h in 24.4%, 54.5% and 66.1% of cases, respectively. Intra-hospital mortality rate resulted to be 3.4%, while mortality at 30 days and 1 year resulted to be 4.5% and 31%, respectively. Early surgery within 48 and 72 h were significantly associated with a lower intra-hospital and 30-day mortality rate. In the orthogeriatric subgroup (394 patients), a significant association with a higher mortality rate was found for general anesthesia, number of comorbidities, ADL (Activities of Daily Living) < 3, transfer to other departments. Conclusions: In over-85 hip fracture patients, the threshold for early surgery might be moved to 72 h to allow patients pre-operative stabilization and medical optimization as intra-hospital and 30-day mortality rates remain significantly lower. Advanced age, male sex, number of comorbidities, pre-operative dependency in ADL, general anesthesia, length of hospitalization and transfer to other departments were significantly related to mortality rate

Poor nutritional status but not cognitive or functional impairment per se independently predict 1 year mortality in elderly patients with hip-fracture

Hip fractures are strongly associated with mortality in the elderly. Studies investigating predisposing factors have suggested a negative impact of poor nutritional, cognitive and functional status on patient survival, however their independent prognostic impact as well as their interactions remain undefined. This study aimed to determine whether poor nutritional status independently predicts 1 year post-fracture mortality after adjusting for cognitive and functional status and for other clinically relevant covariates. METHODS: 1211 surgically treated hip fracture elderly (age 65 65) patients consecutively admitted to the Orthopaedic Surgery Unit of the "Azienda Sanitaria Universitaria Integrata Trieste" (ASUITs), Cattinara Hospital, Trieste, Italy and managed by a dedicated orthogeriatric team. Pre-admission nutritional status was evaluated by Mini Nutritional Assessment (MNA) questionnaire, cognitive status by Short Portable Mental Status Questionnaire (SPMSQ) and functional status by Activity of Daily Living (ADL) questionnaire. All other clinical data, including comorbidities, type of surgery, post-operative complications (delirium, deep vein thrombosis, cardiovascular complications, infections, need for blood transfusions) were obtained by hospital clinical records and by mortality registry. RESULTS: Poor nutritional status (defined as MNA 6423.5), increased cognitive and functional impairment were all associated with 3-, 6- and 12 month mortality (p < 0.001). Both cognitive and functional impairment were associated with poor nutritional status (p < 0.001). Logistic regression analysis demonstrated that the association between nutritional status and 3-, 6- and 12- month mortality was independent of age, gender, comorbidities, type of surgery and post-operative complications as well as of cognitive and functional impairment (p < 0.001). In contrast, the associations between mortality and cognitive and functional impairment were independent (p < 0.001) of demographic (age, gender) and clinical covariates but not of malnutrition. Kaplan-Meier analysis showed a lower mean survival time (p < 0.001) in patients with poor nutritional status compared with those well-nourished. CONCLUSIONS: In hip fracture elderly patients, poor nutritional status strongly predicts 1 year mortality, independently of demographic, functional, cognitive and clinical risk factors. The negative prognostic impact of functional and cognitive impairment on mortality is mediated by their association with poor nutritional statu

Increased Bone Marrow Interleukin-7 (IL-7)/IL-7R Levels but Reduced IL-7 Responsiveness in HIV-Positive Patients Lacking CD4+ Gain on Antiviral Therapy

Background: The bone marrow (BM) cytokine milieu might substantially affect T-lymphocyte homeostasis in HIV-positive individuals. Interleukin-7 (IL-7) is a bone marrow-derived cytokine regulating T-cell homeostasis through a CD4+-driven feedback loop. CD4+ T-lymphopenia is associated with increased free IL-7 levels and reduced IL-7R expression/function, which are only partially reverted by highly active antiretroviral therapy (HAART). We investigated the BM production, peripheral expression and signaling (pStat5+ and Bcl-2+ CD4+/CD8+ T cells) of IL-7/IL-7Ra in 30 HAART-treated HIV-positive patients who did not experience CD4+ recovery (CD4+ #200/ml) and who had different levels of HIV viremia; these patients included 18 immunological nonresponders (INRs; HIV-RNA#50), 12 complete failures (CFs; HIV-RNA.1000), and 23 HIVseronegative subjects. Methods: We studied plasma IL-7 levels, IL-7Ra+CD4+/CD8+ T-cell proportions, IL-7Ra mRNA expression in PBMCs, spontaneous IL-7 production by BM mononuclear cells (BMMCs), and IL-7 mRNA/IL-7Ra mRNA in BMMC-derived stromal cells (SCs). We also studied T-cell responsiveness to IL-7 by measuring the proportions of pStat5+ and Bcl-2+ CD4+/CD8+ T cells. Results: Compared to HIV-seronegative controls, CFs and INRs presented elevated plasma IL-7 levels and lower IL-7Ra CD4+/CD8+ cell-surface expression and peripheral blood production, confirming the most relevant IL-7/IL-7R disruption. Interestingly, BM investigation revealed a trend of higher spontaneous IL-7 production in INRs (p = .09 vs. CFs) with a nonsignificant trend toward higher IL-7-Ra mRNA levels in BMMC-derived stromal cells. However, upon IL-7 stimulation, the proportion of pStat5+CD4+ T cells did not increase in INRs despite higher constitutive levels (p = .06); INRs also displayed lower Bcl-2+CD8+ T-cell proportions than controls (p = .04). Conclusions: Despite severe CD4+ T-lymphopenia and a disrupted IL-7/IL-7R profile in the periphery, INRs display elevated BM IL-7/IL-7Ra expression but impaired T-cell responsiveness to IL-7, suggesting the activity of a central compensatory pathway targeted to replenish the CD4+ compartment, which is nevertheless inappropriate to compensate the dysfunctional signaling through IL-7 receptor

Voice disorders assessed by (cross-) Sample Entropy of electroglottogram and microphone signals

The quantitative analysis of vocal disorders by nonlinear signal processing methods has been extensively used in the last two decades. In this work, two algorithms for nonlinear time-series analysis, Sample Entropy and cross-Sample Entropy, are used on electroglottogram (EGG) and microphone (MIC) signals recorded from 51 normal and 80 dysphonic subjects, to obtain summary measures of voice disorders through SampEn and cross-SampEn indices. Such parameters quantify, respectively, the degree of irregularity (in the sense of self-dissimilarity) within a time-series and of asynchrony (in the sense of cross-dissimilarity) between two distinct time-series. The aims of this work are: to determine if statistically significant differences in terms of signal irregularity quantified by SampEn occur between normal and pathological subjects, investigating whether or not such differences can be equally seen in EGG and MIC; to assess if cross-SampEn reveals different degrees of asynchrony between EGG and MIC signals in the two groups. Results show that SampEn in pathological subjects is higher than in normal subjects for both EGG and MIC time-series, with a statistically significant difference detectable from both signals (Pe < 10-4 for EGG and Pe < 10-7 for MIC). Cross-SampEn exhibits a statistically significant difference too, showing a higher degree of cross-dissimilarity between EGG and MIC time-series for pathological subjects (Pe < 10-4). In conclusion, SampEn and cross-SampEn well quantify the increase of complexity of both EGG and MIC signals and the decrease of their cross-similarity in presence of vocal disorders. Thanks to the complementarity of nonlinear indicators to the traditionally considered linear ones, SampEn and cross-SampEn appear as suitable candidates to enter the pool of approaches to investigate speech pathologies and to obtain potentially new insights on their nature