Significant Independent Impact Research Articles

PURE vs. mixed clear cell ovarian carcinomas: Is there any impact on survival?

ObjectiveOur primary aim in this study is to define the clinical characteristics of patients with clear-cell ovarian carcinoma and evaluate the prognostic factors affecting survival. Study designRecords of 85 patients, operated between 2000 and 2018, for an adnexal mass and whose final pathology reported clear cell ovarian carcinoma were reviewed. The study considered demographic data, clinical characteristics of the patients, as well as pure and mixed-type clear cell histology. The patients' follow-up time, disease-free and overall survival recorded. The primary outcomes were disease-free survival (DFS) and overall survival (OS). ResultsThe median age of the patients at diagnosis was 52. In 64.7 % of the cases, clear cell histology was pure, while the others (35.3 %) were mixed. Patients with ovarian endometriosis constituted 27.1 % of the whole population. The median OS for the entire population was 92 months (95 %CI:72–124). On univariate and multivariate analyses, advanced age was found to have a significant independent impact on OS and DFS (p < 0.05) and, was associated with a worse prognosis. Also, the multivariate analyses showed that the presence of endometriosis has a significant independent impact on OS (p < 0.05). When examining the relationship between the histological origin (mixed vs. pure) and 5-year survival, the mixed type showed longer OS and DFS rates (76.8 % vs. 69.8 %, 61.5 % vs. 53.8 %), the difference was not statistically significant (p > 0.05). ConclusionThis retrospective study showed that although mixed type histological origin was associated with higher OS and DFS rates compared to pure type in patients with CCOC, the difference was not statistically significant. Advanced age and the presence of endometriosis was found to have a significant independent effect on OS and DFS and was associated with a worse prognosis. Overall, this study provides useful insights into the clinical characteristics of patients with CCOC and identifies important prognostic factors affecting survival.

Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer.

Radium-223 improves overall survival (OS) and reduces skeletal events in patients with bone metastatic castration-resistant prostate cancer (CRPC), but relevant biomarkers are lacking. We evaluated automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses as potential biomarkers of prognosis and activity. Patients with bone metastatic CRPC were enrolled on a prospective single-arm study of standard radium-223. 99mTc-MDP bone scan images at baseline, 2 months, and 6 months were quantitated using aBSI. CTCs at baseline, 1 month, and 2 months were enumerated and assessed for RNA expression of prostate cancer-specific genes using microfluidic enrichment followed by droplet digital polymerase chain reaction. The median OS was 21.3 months in 22 patients. Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months were each associated with better OS (P = .00341 and P = .0139, respectively). The higher baseline CTC count of ≥5 CTC/7.5 mL was associated with worse OS (median, 10.1 v 32.9 months; P = .00568). CTCs declined at 2 months in four of 15 patients with detectable baseline CTCs. Among individual genes in CTCs, baseline expression of the splice variant AR-V7 was significantly associated with worse OS (hazard ratio, 5.20 [95% CI, 1.657 to 16.31]; P = .00195). Baseline detectable AR-V7, higher aBSI, and CTC count ≥5 CTC/7.5 mL continued to have a significant independent negative impact on OS after controlling for prostate-specific antigen or alkaline phosphatase. Quantitative bone scan assessment with aBSI and CTC analyses are prognostic markers in patients treated with radium-223. AR-V7 expression in CTCs is a particularly promising prognostic biomarker and warrants validation in larger cohorts.

African Caribbean Ethnicity Is an Independent Predictor of Significant Decline in Kidney Function in People With Type 1 Diabetes.

The aim of the study was to identify the demographic and clinical features in an urban cohort of people with type 1 diabetes who developed a ≥50% decline in estimated glomerular filtration rate (eGFR). We evaluated 5,261 people with type 1 diabetes (51% female, 13.4% African Caribbean) with baseline eGFR >45 mL/min/1.73 m2 between 2004 and 2018. The primary end point was an eGFR decline of ≥50% from baseline with a final eGFR <30 mL/min/1.73 m2. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the cohort, 263 (5%) reached the primary end point. These individuals were more likely to be of African Caribbean ethnicity, be older, have a longer duration of diabetes, have higher systolic blood pressure and HbA1c, have more prevalent retinopathy, and have higher albuminuria (all P < 0.05). In multivariable Cox regression models, African Caribbean ethnicity emerged as a significant risk factor for the primary end point (hazard ratio 1.57, 95% CI 1.19, 2.08) compared with other ethnicities and independent of established risk factors (P < 0.01). The incidence rate for the primary end point in African Caribbean people was double that in non-African Caribbean people (16 vs. 7.7 per 1000 patient-years, P < 0.001). A similar significant independent impact of African Caribbean ethnicity for secondary end points (≥40% and ≥30% fall in eGFR) was observed. We report a novel observation that African Caribbean ethnicity increased the risk of kidney function loss in people with type 1 diabetes, an effect that was independent of traditional risk factors. Further studies are needed to examine the associated pathophysiology that may explain this observation.

Identifying biomarkers associated with tumor growth rate: a longitudinal preoperative magnetic resonance imaging follow-up of low-grade gliomas.

BackgroundAlthough the influence of molecular biomarkers on the biological behavior of tumor cells has been investigated, their quantitative influence on the velocity of tumor growth remains unclear. This study aimed to identify the molecular biomarkers associated with tumor growth rates in World Health Organization (WHO) grade II gliomas, or low-grade gliomas (LGGs).MethodsPreoperative magnetic resonance imaging (MRI) data of patients with LGGs were retrospectively reviewed. Patients with at least 2 preoperative MRIs taken more than 90 days apart were enrolled. Patients with isocitrate dehydrogenase (IDH) wild-type tumors or with no recorded IDH status were excluded. A linear mixed-effects model was used to assess the velocity of tumor diameter expansion. The effect of biomarker expression on tumor growth rate was assessed using a multivariate linear mixed-effects regression model.ResultsData from 56 patients were used in our study. The overall velocity of diameter expansion (VDE) for LGGs was 2.1 mm/year. Higher expression level of mutant p53 were significantly associated with a higher tumor growth rate (+1.9 mm/year, P<0.01), while higher expression level of alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX) were significantly associated with a lower tumor growth rate (−1.3 mm/year, P<0.01). Tumors with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation were found to grow significantly more slowly than those with no methylation (−3.1 mm/year, P<0.01). The telomerase reverse transcriptase (TERT) promoter type and expressions levels of Ki-67 and epidermal growth factor receptor (EGFR) showed no significant independent impact on tumor growth rates.ConclusionsThe status of biomarkers is significantly associated with the tumor growth rate in LGGs.

Structural variants shape the genomic landscape and clinical outcome of multiple myeloma

Deciphering genomic architecture is key to identifying novel disease drivers and understanding the mechanisms underlying myeloma initiation and progression. In this work, using the CoMMpass dataset, we show that structural variants (SV) occur in a nonrandom fashion throughout the genome with an increased frequency in the t(4;14), RB1, or TP53 mutated cases and reduced frequency in t(11;14) cases. By mapping sites of chromosomal rearrangements to topologically associated domains and identifying significantly upregulated genes by RNAseq we identify both predicted and novel putative driver genes. These data highlight the heterogeneity of transcriptional dysregulation occurring as a consequence of both the canonical and novel structural variants. Further, it shows that the complex rearrangements chromoplexy, chromothripsis and templated insertions are common in MM with each variant having its own distinct frequency and impact on clinical outcome. Chromothripsis is associated with a significant independent negative impact on clinical outcome in newly diagnosed cases consistent with its use alongside other clinical and genetic risk factors to identify prognosis.

Sex-Based Clinical Outcome in Advanced NSCLC Patients Undergoing PD-1/PD-L1 Inhibitor Therapy-A Retrospective Bi-Centric Cohort Study.

Simple SummaryRetrospective analyses suggest that men treated with immune-checkpoint inhibitor (ICI) monotherapy for non-small cell lung cancer (NSCLC) have better outcomes than women. However, female patients have more favorable responses when chemotherapy (CHT) is given together with ICI. We aimed to explore the clinical impact of such sex differences in two cohorts, receiving ICI monotherapy or ICI-CHT combination, respectively. We found no significant difference in outcomes between men and women treated with either therapeutic regimen. However, known predictive factors for ICI response such as the expression of programmed-death ligand 1 (PD-L1) on tumor cells or patient performance status had significant implications for men rather than for women. Our results warrant increased research efforts to clarify sex-specific differences in anti-tumor immune response mechanisms and in the efficacy of ICI therapies, especially in women. Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n = 228) or ICI-CHT combination treatment (n = 80) for advanced NSCLC. Kaplan–Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10–3.29, p = 0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00–1.11, p = 0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32–3.15, p = 0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03–1.14, p = 0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41–11.2, p = 0.009) significant for PFS; and ECOG ≥ 2 (HR 5.58, 95%CI: 1.88–16.5, p = 0.002) and CRP (HR 1.19, 95%CI: 1.06–1.32, p = 0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, while ECOG ≥ 2 had a significant interaction with OS (HR 1.90, 95%CI 1.04–3.46, p = 0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02–1.16, p = 0.007) and OS (HR 1.11, 95%CI: 1.03–1.19, p = 0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.

Factors Affecting Time to Emergence From General Anesthesia Following Clipping of Ruptured Aneurysms: A Prospective Observational Study.

Early emergence from anesthesia is valuable, especially among neurosurgical patients for postoperative neurological evaluation and appropriate interventions. However, the factors affecting the emergence in patients undergoing clipping of ruptured aneurysms have not been studied. This was a prospective observational study on patients of aneurysmal subarachnoid hemorrhage with World Federation of Neurological Surgeons (WFNS) Grades I to III, undergoing surgical clipping. All relevant preoperative and intraoperative details were collected and analyzed to assess the factors affecting emergence time. A total of 67 patients with a median age of 46 years were included in the study. The number of patients with Fisher Grades I, II, III, and IV was 6, 20, 25, and 16, respectively. The median time to emergence was 17 minutes (interquartile range 10-240 minutes). On univariate analysis, the factors that were found to have a significant relationship with time to emergence were preoperative Glasgow Coma Score (GCS; P = 0.02), WFNS grade (P = 0.005, temporary clipping time (P = 0.03), and the temperature at the end of surgery (P < 0.001) In the multivariate analysis using generalized linear model, preinduction GCS (P < 0.001), patient's temperature at the end of surgery (P < 0.001), and temporary clipping time (P = 0.01) had a significant impact on the emergence time, independent of age, American Society of Anesthesiologists grade, Fisher grade, duration of anesthesia and of each other, with GCS and temperature having the maximum impact. ROC curve for temperature had a cutoff value at 35.3°C with an 83% probability of awakening beyond 15 minutes if the temperature decreased below 35.3°C. The preinduction GCS, the temperature of patients at the end of surgery, and the duration of temporary clipping have a significant independent impact on the time to emergence from neurosurgical anesthesia, in the order of the strength of the association.

Differential independent impact of the intraoperative use of navigation and angled endoscopes on the surgical outcome of endonasal endoscopy for pituitary tumors: a prospective study.

Despite widespread popularity of navigation and angled endoscopes in endonasal endoscopy, there are hardly few studies on their efficacy with the extent of resection or retreatment. This is probably the firststudy to assess the independent impact of these adjuncts among pituitary tumors. Patients with pituitary tumors undergoing endonasal endoscopy were prospectively studied for their demographics, clinico-radiological features, intraoperative use of navigation, and angled endoscopes, in relation to gross total resection (GTR), near total resection (NTR), endocrine remission, and retreatment. Pertinent statistical analyses were performed. Among a total of 139 patients, navigation and angled endoscopes could be used in 54 and 48 patients, respectively, depending upon their availability rather than chosen as per the case. There was no significant difference in baseline characteristics in relation to their use. The surgeon's perception of immediate benefit was noted among 51.9% while using navigation. The use of angled endoscopes towards the end of resection could help with additional tumor removal in 62.5% of patients. Overall, the use of navigation resulted in a significantly higher GTR (80.8% vs. 59.7%, OR 2.83, p= 0.01), a higher GTR/NTR (86.5% vs. 70.8%, OR 2.65, p= 0.04), and a lower retreatment rate (7.7% vs. 20.8%, OR 3.15, p= 0.05) than the others. In functioning tumors with cavernous sinus invasion, navigation had significantly increased remission rates (69.2% vs. 0%, p= 0.03). The use of angled endoscopes yielded a significantly higher GTR/NTR (91.7% vs. 70.6%, p= 0.04) and a lower retreatment rate (0% vs. 15.7%, p= 0.05) among only non-functioning adenomas. In multivariate analyses, the use of neuronavigation had a significant association with both GTR and retreatment rates (p values 0.005 and 0.02 respectively), independent of other confounding factors. The elective intraoperative use of navigation has a significant independent impact on the extent of resection and retreatment overall. While navigation results in better remission rates among functioning tumors with cavernous sinus invasion, angled endoscopy has a significant association with surgical outcomes in non-functioning tumors.

Cardiovascular and cerebrovascular responses to cardio-respiratory events in preterm infants during the transitional period.

Non-invasive simultaneous multiparametric monitoring allows the in vivo evaluation of cerebral and cardiovascular haemodynamic responses to different types of recurrent episodes of intermittent hypoxia and/or bradycardia, also defined as cardio-respiratory events (CRE), in preterm neonates during postnatal transition. By decreasing left cardiac output, bradycardia further contributes to cerebral hypoxia during CRE. The presence of a haemodynamically significant patent ductus arteriosus results in a deeper impairment of cerebral oxygen status in response to CRE, whereas the brain-sparing remodelling of the fetal circulation resulting from placental insufficiency is associated with more favourable haemodynamic responses to intermittent hypoxia. During transition, the haemodynamic impact of CRE is influenced not only by the event type, but also by specific clinical features; this highlights the importance of developing individualized approaches to reduce the hypoxic burden in this delicate phase. The present observational prospective study aimed to investigate cerebral and cardiovascular haemodynamic responses to different types of cardio-respiratory events (CRE) in preterm infants during postnatal transition, as well as evaluate the impact of relevant clinical characteristics. Infants with gestational age (GA) <32 weeks and/or birth weight <1500 g were enrolled after birth. Cerebral oxygenation index (cTOI), fractional oxygen extraction (cFTOE), cardiac output (CO), cardiac contractility (iCON) and systemic vascular resistances (sVR) were simultaneously monitored over the first 72 h by near-infrared spectroscopy and electrical velocimetry. CRE were clustered into isolated bradycardia (IB), isolated desaturation (ID) and combined desaturation/bradycardia (DB). For each parameter, percentage changes from baseline (%Δ) were calculated. The impact of different CRE types and clinical variables on %Δ was evaluated with generalized estimating equations. In total, 1426 events were analysed. %ΔcTOI significantly differed among ID, IB and DB (P < 0.001), with the latter showing the greatest drop. %ΔcFTOE decreased significantly during DB (P < 0.001) and ID (P < 0.001) compared to IB. DB and IB were associated with more negative %ΔCO (P < 0.001) and more positive %ΔsVR (P < 0.001) compared to ID. A slight iCON reduction was observed during DB compared to ID (P = 0.043). Antenatal umbilical Doppler impairment, GA and the presence of a haemodynamically significant patent ductus arteriosus had a significant independent impact on %ΔcTOI, %ΔcFTOE and %ΔCO. During the transitional period, the haemodynamic responses to CRE are influenced by the event type and by specific neonatal characteristics, suggesting the importance of targeted individualized approaches for minimizing the risk of cerebral injury in the preterm population.

Impact of hypertension, overweight, hypertriglyceridemia and their combination for mortality rate according to the results of a 27-year cohort prospective study

To study influence of hypertension, overweight, hypertriglyceridemia and their combinations for all-cause and cardiovascular mortality risk formation.Methods.The prevalence of hypertension, overweight and hypertriglyceridemia was studied (1988-1991) by 27-year prospective cohort study of unorganized population of Tomsk (1546 persons - 916 female and 630 male). The predictive value of these risk factors for all-cause and cardiovascular mortality risk formation were researched in 2015. Hypertension was diagnosed in persons with blood pressure greater or equal to 140/90 mm Hg, overweight was diagnosed in people with body mass index 25 kg/m2, hypertriglyceridemia was diagnosed in individuals having high blood level of triglycerides (greater or equal to 1.7).Results. Influence of hypertension for all-cause (relative risk (RR) 2.2) and cardiovascular mortality (RR 3.38) risk formation was detected. A hypertension related elevation of mortality risk was observed both among women and men and in all age groups with the exception of men 40-59 years (the results for cardiovascular mortality in these persons was statistically insignificant). We established that hypertension had the independent significant contribution for mortality risk formation. It is shown that RR of all-cause mortality 1.25 times (cardiovascular mortality 1.8 times) more in overweight persons. Increase of relative mortality risk was detected in overweight women, especially in women 20-39 years old. Hypertriglyceridemia increases relative risk of all-cause mortality 1.46 times, relative risk of cardiovascular mortality 2.15 times, especially in individuals 40-59 years old. It was revealed that hypertriglyceridemia is significant risk factor for all-cause mortality formation only in women. Combination of hypertension and overweight increases the risk of all-cause mortality 2.23 times and the risk of cardiovascular mortality 4.0 times, combination of hypertension and hypertriglyceridemia - 2.83 and 5.06 times, combination of overweight and hypertriglyceridemia - 1.73 and 2.99 times, respectively. We detected the additional risk of hypertriglyceridemia in individuals with overweight for all-cause (RR 1.53) and cardiovascular (RR 2.18) mortality risk formation compared with overweight persons with normal level of triglycerides and also the additional risk of hypertriglyceridemia (RR 1.51 and 2.04, respectively) in individuals with hypertension compared with normotensive persons (p&lt;0,05). The additional risk of overweight in individuals with hypertension for all-cause mortality was found only in women (RR 3.23).Conclusion.The independent significant impact of hypertension for all-cause and cardiovascular mortality risk formation was revealed by the results of 27-year prospective study. Combination of hypertension and hypertriglyceridemia increases the risk of all-cause mortality 2.8 times and the risk of cardiovascular mortality 5.1 times, combination of hypertension and overweight - 2.2 and 4 times, combination of overweight and hypertriglyceridemia - 1.7 and 3 times, respectively. We detected the additional risk of hypertriglyceridemia for all-cause mortality in overweight people (RR 1.5) and in individuals with hypertension (RR 1.5). Also, the additional risk of hypertriglyceridemia for cardiovascular mortality risk formation in overweight people (RR 2.2) and in persons with hypertension (RR 2.0) was found.

Knowledge of German-speaking urologists regarding the association between penile cancer and human papilloma virus: results of a survey of the European PROspective Penile Cancer Study (E-PROPS)

A recent meta-analysis showed that penile cancer (PeC) is associated with the human papilloma virus (HPV) in 50 % of patients in Europe. It is unknown whether urologists are aware of the impact of viral carcinogenesis. A (German-language) survey comprising 14 items was created and sent to urologists of 45 clinical centres in Germany (n = 34), Austria (n = 8), Switzerland (n = 2) and Italy/South Tyrol (n = 1) once in Q3/2018. According to a predefined quality standard, a total of 557 surveys were eligible for final data analysis (response rate: 85.7 %). Among other questions, urologists were asked to state the frequency of HPV-associated PeC in Europe. 4 potential answers were provided: (A)-"< 25 %", (B)-"25 - 50 %", (C)-"> 50 - 75 %", (D)-"level of association unknown". For the final calculation, a tolerance of ± 50 % was considered acceptable, so B and C were deemed correct answers. Based on a bootstrap-adjusted multivariate logistic regression model, criteria independently predicting a correct answer were identified. Categories A-D were selected in 19.2 % (n = 107), 48.8 % (n = 272), 12.9 % (n = 72) and 19 % (n = 106), respectively, representing a rate of 61.8 % of urologists (n = 344) reaching the endpoint (B + C). Autonomous performance of chemotherapy for PeC by urologists within the given centre (OR 1.55, p[Bootstrap] = 0.036) and the centre's number of urological beds (OR 1.02, p[Bootstrap] = 0.025) were the only parameters showing a significant independent impact on the endpoint. In contrast, the status of a university centre (p = 0.143), a leading position of the responding urologist (p = 0.375) and the number of PeC patients treated per year and centre (p = 0.571) did not significantly predict a correct answer. Our results demonstrate insufficient knowledge on the association of PeC and HPV among German-speaking urologists.

Fetuin-A Thr256Ser gene polymorphism as a mortality predictor in patients with chronic kidney disease on maintenance haemodialysis in Medan, Indonesia.

Aim To investigate an impact of Fetuin-A Thr256Ser gene polymorphism on the mortality rate of chronic kidney disease on maintenance haemodialysis patients in Indonesia. Methods This is an analytic-longitudinal observational study using survival analysis with nine-month follow up on 106 maintenance haemodialysis patients. The PCR-RFLP is used to determine Fetuin-A Thr256Ser gene polymorphism and Fetuin-A serum level measured by using ELISA methods. We use time-independent cox regression analysis to investigate factors that contribute to patient survival. Results The mean survival time of this study is 8.49±1.53 months, with a median survival of 9 months (range 1-9 months). Among 12 (11.3%) deceased patients, most of them carried GG genotype with 8.87 times risk of mortality compared to those with CC+CG genotype (p=0.005). The group of patients with IL-6 level ≥86.9 pg/mL had higher mortality with 3.64 times greater risk compared to those with IL-6 level, <86.9 pg/mL (p=0.03). Conclusion This study revealed a significant dominance independent impact of the Fetuin-A Thr256Ser gene polymorphism on the survival rate of maintenance haemodialysis patients. These results suggest that genotype variation of Fetuin-A gene could be a potential marker to identify high mortality risk in Indonesia's maintenance haemodialysis patients, especially in Medan.

Favourable outcome without psychotherapy in patients with functional neurologic disorder

ObjectiveTo investigate whether patients with functional neurologic disorder (FND) may improve without psychotherapy as was suggested by a retrospective study. MethodsWe prospectively studied patients with newly diagnosed FND. At baseline and at 12 months participants filled out a set of self-reported health questionnaires. During the one-year follow up we recorded the use of psychotherapy. ResultsThe study group consisted of 193 included participants. After 12 months 60 participants (60/193 = 31.1%) perceived a favourable outcome. Sixty participants (60/191 = 31.4%) were referred for psychotherapy. Multivariable logistic regression showed that participants with a high level of somatisation were less likely to have a favourable outcome (adjusted OR = 0.55; 95% CI: 0.29 to 1.04; p = 0.07). We could not demonstrate an independent significant impact of the use of psychotherapy on favourable outcome (adjusted OR = 0.65; 95% CI: 0.33 to 1.30; p = 0.22). ConclusionOur study confirms the results of the retrospective study. The association between a high level of somatisation and a less favourable outcome suggests that neurologists should pay more attention to symptoms other than the neurological, but this does not necessarily mean referral for a psychological intervention.

C-reactive protein is a significant predictor of improved survival in patients with advanced non-small cell lung cancer.

This study tries to evaluate the associations between circulating C-reactive protein (CRP) and the overall survival of patients with non-small cell lung cancer (NSCLC).One hundred ninety-two patients with advanced NSCLC who treated with chemotherapy were enrolled in this study. The cut-off value of CRP concentration was 5.0 mg/L. The patients were divided into low, intermediate and high 3 groups respectively according to the baseline level of CRP before the treatment. Kaplan–Meier analysis and Cox proportional-hazard models were used to evaluate the relationship between the CRP and overall survival time of patients.After adjusting for age, gender, smoking history, pathologic type, CRP was a significant independent impact which predicts the survival prognosis of patients with NSCLC. For all patients, the hazard ratio with high CRP levels for NSCLC-specific survival was 1.83 [95%confidenceinterval (CI) = 0.96, 3.48] compared with low CRP levels. The level of CRP was significantly correlated with survival time (hazard ratio = 1.77; 95% CI = 0.73, 4.26) for the patient with first-line chemotherapy. Patients with high level of circulating CRP also responded poorly to chemotherapy.A high level of circulating CRP was associated with a poor response and worse survival in patients with NSCLC.

The relationship between occupational stress, health status, and temporary and permanent work disability among security guards in Serbia

Purpose. This study aimed to examine the influence of occupational stress on health status and work disability among security guards in Serbia. Methods. Three hundred and ninty nine male security guards (aged 25–65 years) were examined during regular medical preventive check-ups at the Institute of Occupational Health. Data on their health status and permanent and temporary work disability were obtained, and correlations with the levels of occupational stress (measured by occupational stress index [OSI] questionnaire) were analysed. Results. A high prevalence of health impairments, including diabetes (38.8%), dyslipidaemia (82.7%), hypertension (69.9%) and metabolic syndrome (77.7%), was found. Highly significant correlations were shown between reported levels of total stress at work (total OSI score) and measured values of glucose, lipids, blood pressure, heart rate, Framingham cardiovascular risk scale, occurrence of diabetes and impaired fasting glucose, dyslipidaemia, hypertension, metabolic syndrome, coronary heart disease, cerebrovascular insults, degenerative eye-fundus changes, and temporary and permanent work disability. All of these correlations remained significant even after adjustments for age, body mass index and smoking status. Regression analysis confirmed the independent effect of occupational stress on the analysed parameters. Conclusions. There is a significant independent impact of occupational stress on development of health impairments and work disability among security guards.

Unsuccessful Cytogenetics and Outcomes in Acute Leukemia

Introduction:Cytogenetic features at diagnosis have significant independent prognostic impact in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Failed or unsuccessful cytogenetics (UC) is estimated to occur in 10% of AML cases and 25-30% of ALL cases (Grimwade, 2010; Pullarkat, 2008). Previous studies suggest worse outcomes in AML patients (pts) with UC, similar to pts with unfavorable karyotype with lower response rates to induction chemotherapy and poor 5-year (yr) survival rates (Medeiros, 2014; Lazarevic, 2015). Hydroxyurea (HU) and steroids are often given urgently for cytoreduction prior to obtaining cytogenetics. The effects of such pretreatment on rates of UC have not been studied previously. In this study, we compared clinical outcomes of acute leukemia pts with UC versus successful cytogenetics (SC) and determined whether the use of HU or steroids affects cytogenetics success rates.Methods:All pts <70 yrs with de novo acute leukemia (AML or ALL) with available diagnostic bone marrow and cytogenetics testing seen at the Leukemia/Bone Marrow Transplant (BMT) Program of British Columbia between January 2010 and December 2016 were included. Pertinent information was reviewed from the program database. Cytogenetic failure was defined by the presence of <10 metaphases with a normal karyotype in the absence of a clinically actionable FISH abnormality. Pts with SC were risk stratified based on NCCN guideline criteria (NCCN, 2018). Baseline features of pts with SC and UC were compared using Chi-squared and two-tailed t-testing. Overall survival (OS) was calculated from the date of initial diagnosis to the date of death from any cause. Disease free survival (DFS) was calculated from the date of attaining first complete remission (CR1) to the date of relapse or death from any cause. Survival outcomes were estimated using the Kaplan-Meier method, with p values determined using the log rank test. A p < 0.05 was considered significant.Results:We identified 654 cases of acute leukemia (AML N=515; ALL N=139). Of these, 39 (6%) had UC (AML N=16, 3%; ALL N=23, 17%). There was no difference in age at diagnosis between groups (UC vs SC, 46 vs 51 yrs, p=0.08). AML pts with UC had higher initial white blood count (WBC) at diagnosis (71 vs 34, p<0.001). No effect of WBC was seen in ALL pts with UC versus SC. HU and/or steroid use prior to cytogenetics was similar between UC and SC groups in both AML and ALL pts (UC vs SC, HU: 8% vs 12%, p=0.61; steroids: 5% vs 1%, p=0.07. Therapy with intensive induction was also similar between groups (UC vs SC, 92% vs 90%; p=1.00). 137 (27%) of AML pts with SC had favorable risk disease, 182 (37%) intermediate, and 180 (36%) high risk. In ALL pts with SC, 32 (28%) had standard risk, and 84 (72%) had high risk disease. Follow up time in UC and SC groups was similar (32 vs 27m, p=0.18).CR rates in AML pts with UC was 81%, which was similar to pts with intermediate risk disease (84%, p=0.72) and better than CR rates of 39% observed in high risk pts (p=0.03). Compared to pts with SC, AML pts with UC had similar 5-yr OS and DFS as pts with intermediate risk disease (5-yr OS 25% vs 37%, p=0.45; 5-yr DFS 28% vs 28%, p=0.84), superior survival to high risk pts (5-yr OS 25% vs 17%, p=0.01; 5-yr DFS 28% vs 13%, p=0.036), and inferior survival to favorable risk pts (5-yr OS 25% vs 68%, p=0.07, 5-yr DFS 28% vs 52%, p=0.008), Figure 1.CR rates in ALL pts with UC was 83% and not significantly different than standard (94%, p=0.22) or high risk pts (86%, p=0.74). Compared to pts with SC, ALL pts with UC had similar 5-yr OS and DFS to pts with standard and high risk disease (UC vs standard vs high; 5-yr OS 58% vs 51% (p=0.93) vs 55% (p=0.85); 5-yr DFS 50% vs 37% (p=0.86) vs 36% (p=0.27)). Subgroup analysis of UC pts demonstrated no difference in survival in UC pts receiving BMT (N=12) vs no BMT (N=27). UC pts with high WBC >20 (N=14) had inferior survival compared to those with WBC ≤ 20 (N=25) (5-yr OS 60% vs 29%, p=0.025; 5-yr DFS 52% vs 12%, p=0.013).Conclusions:Unsuccessful cytogenetics was more frequently observed in ALL as compared to AML pts, though at lower rates than reported in previous studies. HU and steroid use had no effect on the rates of cytogenetic success. In comparison to previous reports, UC in AML was not associated with inferior outcomes, and survival was similar to intermediate risk pts. High initial WBC count was prognostic in pts with UC, and further studies are warranted to evaluate factors that affect outcomes in pts with UC. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Minimal/Measurable Residual Disease Monitoring in NPM1-Mutated Acute Myeloid Leukemia: A Clinical Viewpoint and Perspectives.

Acute myeloid leukemia (AML) with NPM1 gene mutations is currently recognized as a distinct entity, due to its unique biological and clinical features. We summarize here the results of published studies investigating the clinical application of minimal/measurable residual disease (MRD) in patients with NPM1-mutated AML, receiving either intensive chemotherapy or hematopoietic stem cell transplantation. Several clinical trials have so far demonstrated a significant independent prognostic impact of molecular MRD monitoring in NPM1-mutated AML and, accordingly, the Consensus Document from the European Leukemia Net MRD Working Party has recently recommended that NPM1-mutated AML patients have MRD assessment at informative clinical timepoints during treatment and follow-up. However, several controversies remain, mainly with regard to the most clinically significant timepoints and the MRD thresholds to be considered, but also with respect to the optimal source to be analyzed, namely bone marrow or peripheral blood samples, and the correlation of MRD with other known prognostic indicators. Moreover, we discuss potential advantages, as well as drawbacks, of newer molecular technologies such as digital droplet PCR and next-generation sequencing in comparison to conventional RQ-PCR to quantify NPM1-mutated MRD. In conclusion, further prospective clinical trials are warranted to standardize MRD monitoring strategies and to optimize MRD-guided therapeutic interventions in NPM1-mutated AML patients.

The role of technical progress in promoting economic growth in the MENA region

The objective of this applied study is to identify the impact of adopting corporate citizenship practices of Egyptian mobile service companies on the customer loyalty through a questionnaire to analyze opinions of a random sample for customers of these companies in Dakahlia Governorate. Much literature has agreed that corporate citizenship has four aspects of application: Economic citizenship, legal citizenship, ethical citizenship, and philanthropic citizenship, which were adopted in designing the conceptual framework of this study. The findings of the study indicate many points of importance, the most important of which is nullifying the main hypothesis of the study, which is “no significant impact of corporate citizenship dimensions on the customer loyalty.” The findings have indicated that there is a significant independent impact of each of the four corporate citizenship dimensions on the loyalty of the mobile company customers.

Dimensions of Corporate Citizenship and its Impact on Customer Loyalty An Applied Study to the Customers of the Mobile Companies in Dakahlia Governorate

The objective of this applied study is to identify the impact of adopting corporate citizenship practices of Egyptian mobile service companies on the customer loyalty through a questionnaire to analyze opinions of a random sample for customers of these companies in Dakahlia Governorate. Much literature has agreed that corporate citizenship has four aspects of application: Economic citizenship, legal citizenship, ethical citizenship, and philanthropic citizenship, which were adopted in designing the conceptual framework of this study. The findings of the study indicate many points of importance, the most important of which is nullifying the main hypothesis of the study, which is “no significant impact of corporate citizenship dimensions on the customer loyalty.” The findings have indicated that there is a significant independent impact of each of the four corporate citizenship dimensions on the loyalty of the mobile company customers.

Cognitive Impairments After Clipping of Ruptured Anterior Circulation Aneurysms

The cognitive impairments after treatment of ruptured aneurysms have often been underestimated. This study sought to assess their prevalence and analyze various associated factors. Patients who were operated on for ruptured anterior circulation aneurysms and discharged with a Glasgow Outcome Scale score of 4-5 were studied at 3 months for various cognitive impairments. Continuous scales of memory (recent, remote, verbal, visual, and overall memory), verbal fluency (phonemic and category fluency), and others were studied in relation to various factors. Univariate and multivariate analyses were performed using SPSS version21. A total of 87 patients were included in our study. Phonemic fluency was the most affected, noted in 66% of patients. Although 56% had some memory-related impairments, 13 (15%) and 6 (7%) had moderate and severe deficits in recent memory and 19 (22%) and 12 (14%) had moderate and severe deficits in remote memory, respectively. Patients operated on for anterior cerebral artery (ACA) aneurysms had significantly greater impairments in recent (34% vs. 8%) and remote memory (43% vs. 28%) compared with the rest, both in univariate (P= 0.01 and 0.002, respectively) and multivariate analyses (P= 0.01 and 0.03, respectively). ACA-related aneurysms also had significantly greater independent impairments in phonemic fluency (P= 0.04), compared with others. The clinical grade had a significant independent impact only on remote memory (P= 0.01). Cognitive impairments are frequent after treatment of ruptured anterior circulation aneurysms. Impairments in recent memory, remote memory, and phonemic fluency are significantly greater after treatment of ACA-related aneurysms, compared with others, independent of other factors.