Cox Test Research Articles

Pre-Operative Combination of Normal BMI with Elevated YKL-40 and Leptin but Lower Adiponectin Level Is Linked to a Higher Risk of Breast Cancer Relapse: A Report of Four-Year Follow-Up Study.

Adipokines are powerful agents involved in the development of obesity-dependent cancers. This prospective study aimed to investigate the association between pre-treatment body mass index (BMI) and serum YKL-40, leptin, and adiponectin concentrations as well as the plasma activity of tissue factor (TF) and the future prognosis of early, non-metastatic breast cancer (BrC) subjects. The serum levels of YKL-40, leptin, and adiponectin as well as plasma TF activity, anthropometric parameters, and clinicopathological parameters were analysed in 81 treatment-naïve females with invasive BrC. The predictive value of YKL-40, BMI, leptin, adiponectin, and TF was determined with a 95% confidence interval (CI). Kaplan–Meier plots and log-rank and F Cox tests were used to determine the clinical outcomes of progression-free survival (PFS). The median follow-up duration was 44 months with complete follow-up for the first event. Follow-up revealed a significantly higher incidence of disease relapse in BrC patients with a high baseline concentration of YKL-40 (22.22%) and TF activity (21.43%). Body mass index was an independent predictor of survival, with women who were overweight/obese being less prone to relapse (hazard ratio (HR): 0.75; 95% CI: 0.59 to 0.95). The recurrence rates for normal-weight BrC cases was 21.05% versus 7.14% for their overweight counterparts. The receiver operating characteristic analysis showed the strong ability of the analysed biomarkers to predict disease progression, with an area under the receiver operating characteristics (ROC) curve of 0.84 (95% CI, 0.823 to 0.931). In a prospective cohort of invasive BrC patients, overweight/obesity was associated with improved future outcomes. The combination of a normal BMI with high leptin and low adiponectin levels and high TF activity was associated with an increased risk of recurrence and decreased survival.

Effect of resin cement space on the fatigue behavior of bonded CAD/CAM leucite ceramic crowns

This study evaluated the influence of occlusal resin cement space on the fatigue performance of bonded-leucite crowns to a dentin-analogue material. Leucite anatomical crowns were adhesively cemented to dentin-like preparations having distinct occlusal cement space (50, 100 and 300 μm) (n = 18), and subjected to step-stress fatigue testing (150 N – 350 N; step-size: 25 N; 20,000 cycles/step; 20 Hz). Fatigue data (load and number of cycles for failure) were analyzed using Kaplan–Meier and Mantel–Cox (log-rank) tests (p <0.05). Fractographic analysis and occlusal internal space measurements were also performed. There was no significant difference for the distinct occlusal cement layer (50 μm: 289 N, 136,111 cycles; 100 μm: 285 N, 132,778 cycles; 300 μm: 246 N, 101,667 cycles). Occlusal internal space analysis showed a mean thickness of 120.4 (50 μm), 174.9 (100 μm) and 337.2 (300 μm). All failures were radial cracks originating at the ceramic-cement interface. Distinct occlusal cement spaces had no effect on the fatigue behavior of anatomical leucite crowns.

ADAR expression and copy number variation in patients with advanced gastric cancer

BackgroundGastric cancer (GC) is a world health problem and it is the third leading cause of cancer deaths worldwide. The current practice for prognosis assessment in GC is based on radiological and pathological criteria and they may not result in an accurate prognosis. The aim of this study is to evaluate expression and copy number variation of the ADAR gene in advanced GC and clarify its correlation with survival and histopathological characteristics.MethodsForty two patients with stage III and IV GC were included in this study. ADAR gene expression and copy number variation were measured by real-time PCR and Quantitative multiplex fluorescent-PCR, respectively. Survival analysis performed based on the Kaplan–Meier method and Mantel–Cox test.ResultsADAR mRNA was significantly overexpressed in the tumor tissues when compared to the adjacent normal tissues (p < 0.01). Also, ADAR expression level in stage IV was higher than stage III. 40% of patients showed amplification in ADAR gene and there was a positive correlation between ADAR copy number and expression. Increased ADAR expression was clearly correlated with poorer survival outcomes and Mantel–Cox test showed statistically significant differences between low and high expression groups (p < 0.0001). ADAR overexpression and amplification were significantly associated with metastasis, size and stage of tumor.ConclusionsTogether, our data indicate that amplification leads to over expression of ADAR and it could be used as a prognostic biomarker for disease progression, especially for the metastatic process in GC.

Effect of inhibiting the activity of double-stranded RNA-dependent protein kinase in sepsis mice

Objective: To observe the effects of 2-aminopurine (2-AP), a double-stranded RNA-dependent protein kinase (PKR) inhibitor, on organ function, plasma inflammatory factor expression and 7 days mortality in sepsis mice induced by cecal ligation puncture (CLP). Methods: Forty specific specific pathogen free C57BL/6 mice were randomly divided into sham group (n=10), CLP group (n=10), CLP+2-AP group (n=10) and 2-AP group (n=10). CLP was used to establish sepsis mice models.Peripheral blood serum was collected 24 hours after operation, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Cr), blood urea nitrogen (BUN) and inflammatory factors (IL-1β, IL-10 and TNF-α) were detected; peripheral blood and peritoneal lavage fluid were taken for bacterial clearance detection. Another 60 C57BL/6 mice were selected to observe the 7-day survival rate according to the above groups (n=15). Independent sample t test was used to compare the measurement data between groups. Results: The levels of ALT, AST, Cr and BUN in CLP Group and CLP+2-AP group were significantly higher than those in sham group (all P<0.001). The levels of ALT and AST in CLP+2-AP group were significantly lower than those in CLP Group (t=27.88, 11.33, both P<0.001); the levels of Cr and BUN in CLP+2-AP group were significantly lower than those in CLP Group (t=11.02, 7.15, bothP<0.001). Compared with sham group, the levels of pro-inflammatory (IL-1β and TNF-α) and anti-inflammatory (IL-10) cytokines in CLP group were significantly higher (all P<0.001); the levels of IL-1β and IL-10 in CLP+2-AP group were significantly lower (all P<0.001), but the levels of TNF-α in CLP+2-AP group were not significantly lower (P=0.33). The 7-day survival rate was 100% in sham group, 13.3% in CLP+2-AP group, 86.7% in 2-AP group and 20.0% in CLP+2-AP group. Inhibition of PKR activation slightly improved the trend of 7-days survival rate of CLP model mice (analysis by mantel Cox test, χ(2)=0.0012, P=0.97). Conclusion: In sepsis mice model, inhibition of PKR activity can reduce the expression of inflammatory factors in plasma, decrease bacterial load in blood and abdominal cavity, and protect organ function, which could suggest that inhibition of PKR activity has potential application in sepsis treatment.

Zika virus envelope nanoparticle antibodies protect mice without risk of disease enhancement.

BackgroundZika virus (ZIKV), an arbovirus capable of causing neurological abnormalities, is a recognised human pathogen, for which a vaccine is required. As ZIKV antibodies can mediate antibody-dependent enhancement (ADE) of dengue virus (DENV) infection, a ZIKV vaccine must not only protect against ZIKV but must also not sensitise vaccinees to severe dengue.MethodsThe N-terminal 80% of ZIKV envelope protein (80E) was expressed in Pichia pastoris and its capacity to self-assemble into particulate structures evaluated using dynamic light scattering and electron microscopy. Antigenic integrity of the 80E protein was evaluated using ZIKV-specific monoclonal antibodies. Its immunogenicity and protective efficacy were assessed in BALB/c and C57BL/6 Stat2−/− mice, respectively. Its capacity to enhance DENV and ZIKV infection was assessed in AG129 and C57BL/6 Stat2−/− mice, respectively.FindingsZIKV-80E protein self-assembled into discrete nanoparticles (NPs), which preserved the antigenic integrity of neutralising epitopes on E domain III (EDIII) and elicited potent ZIKV-neutralising antibodies predominantly against this domain in BALB/c mice. These antibodies conferred statistically significant protection in vivo (p = 0.01, Mantel–Cox test), and did not exacerbate sub-lethal DENV-2 or ZIKV challenges in vivo.InterpretationYeast-expressed ZIKV-80E, which forms highly immunogenic EDIII-displaying NPs, elicits ZIKV EDIII-specific antibodies capable of offering significant protection in vivo, without the potential risk of ADE upon subsequent DENV-2 or ZIKV infection. This offers a promising vaccine candidate for further development.FundingThis study was supported partly by ICGEB, India, and by NIAID, USA.

SUN-308 URINARY EPIDERMAL GROWTH FACTOR/CREATININE RATIO AND GRAFT FAILURE IN KIDNEY TRANSPLANT RECIPIENTS: A PROSPECTIVE COHORT STUDY

Graft failure remains a major clinical challenge to improving long-term outcomes in kidney transplant recipients (KTR). Early identification of KTR at higher risk of graft failure is key to potentially improve this outcome. Epidermal growth factor (EGF) is involved in kidney tissue proliferation and integrity, with a reduction of its urinary excretion being associated with early fibrotic processes and a wide range of kidney diseases. We aimed to investigate whether, in KTR, urinary EGF (uEGF) is prospectively associated with graft failure. In this prospective cohort study, KTR with a functioning allograft ≥1-year were recruited and followed-up for three years. uEGF was measured at baseline by ELISA in 24-hours urine samples and normalized by urinary creatinine (Cr). Its association with risk of graft failure was assessed by multivariable Cox-regression analyses and its predictive ability by C-statistic. In 706 patients, uEGF/Cr ratio at enrollment was 6.43 (IQR, 4.07–10.77) ng/mg. During follow-up, 41 (6%) KTR developed graft failure. uEGF/Cr ratio was inversely associated with the risk of GF (HR 0.68, 95% CI 0.59‒0.78; P<0.001), which remained independent of adjustment for several potential confounders including immunosuppressive therapy, human leukocyte antigen mismatch, estimated glomerular filtration rate and proteinuria. C-statistic of uEGF/Cr ratio for graft failure was 0.81 (P<0.001) and when added to urinary protein excretion significantly improved its predictive ability (C-statistic from 0.76 to 0.81; P<0.00 1). Kaplan Meier curves by tertiles of uEGF/Cr on graft failure. Tertile 1:<4.78 ng/mg; Tertile 2:4.78-8.80 ng/mg; Tertile 3:>8.80 ng/mg. P value was obtained from the log-rank (Mantel cox) test. uEGF/Cr, urinary epidermal growth factor/creatinine ratio. In KTR, uEGF/Cr ratio is independently and inversely associated with the risk of graft failure and depicts strong prediction ability for this outcome. Further studies seem warranted to elucidate whether uEGF might be a promising biomarker for clinical uptake post-kidney transplantation.

Pancreatic metastases from renal cancer: comparing surgery and pharmacotherapy efficacy

Background. Today, targeted therapy is a standard treatment in advanced renal cell carcinoma, while the surgical method plays the role of a possible approach in a select category of patients with solitary and single metastases.The study objective to compare the effectiveness of two alternative treatment approaches: the surgical method and modern pharmacotherapy in achieving long-term overall survival of patients with pancreatic metastases of renal cell carcinoma.Materials and methods. A retrospective two-center study was conducted. The cohort of surgical treatment included patients (n = 56) who underwent surgery for pancreatic metastases from renal cell carcinoma at the N.N. Blokhin National Medical Research Center of Oncology and A.V. Vishnevsky National Medical Research Center of Surgery in the period from 1990 to 2019. Operations were performed for all types of pancreatic lesions: synchronous/metachronous, solitary/single and multiple, isolated/combined with lesions of other organs. Postoperative mortality rate was 5 % (3 patients). The pharmacotherapy cohort (n = 28) included patients with potentially resectable pancreatic metastases from clear cell renal cell carcinoma who underwent targeted therapy. Survival was assessed using the Kaplan–Mayer method. The Mantel–Cox test was used to test null hypothesis.Results. The 5-year overall survival rate was 68 % in the surgery group compared to 35 % for the pharmacotherapy group. Median overall survival for surgical and non-surgical patients was 82 months and 43 months, respectively (p = 0.01). The advantage of the surgical method was also found in a subgroup survival analysis of patients with extrapancreatic disease (p = 0.037). In this case, the 5-year overall survival rate was 66 % in the surgery subgroup (n = 25) compared to 35 % for the pharmacotherapy subgroup (n = 24). Conclusion. Radical surgical treatment in comparison with modern pharmacotherapy allows to achieve significantly higher rates of overall survival in patients with pancreatic metastases of renal cell carcinoma and can be considered as a priority.

In vivo antimalarial potential of tinospora crispa miers in mice and identification of the bioactive compound

Background: Malaria is a serious disease that is causing huge toll on human health. The parasites causing this disease have developed resistance toward the current mainstream drugs. Tinospora crispa Miers is a well-known ethnopharmacological plant of Malaysia and has been traditionally used to treat malaria, fever, and other parasite-related illnesses. Objective: The present study investigated the potential of the crude methanol extract and antiparasitic fractions of T. crispa stem to exert antimalarial activity against Plasmodium berghei. Materials and Methods: The potent antiparasitic fractions of T. crispa, F4, and F5 were isolated in the previous study against Toxoplasma gondii. The same antiparasitic fractions along with crude methanol extract of different doses (10, 50, 100 mg/kg b. w.) were employed in the present study to determine the antimalarial activity against P. berghei ANKA strain. The survival curves of the treated mice were plotted by employing the log-rank (Mantel–Cox) test. The chemical composition of the most potent fraction F5 was determined spectrometrically using electrospray ionization-mass spectrometry (MS). Results: In a murine P. berghei model, fraction F5 displayed the highest parasitemia suppression effects compared to the crude methanol extract and other fraction. Subsequent chemical analysis by MS on fraction F5 has led to the tentative identification of 13-hydroperoxyoctadeca-9, 11-dienoic acid (13[S]-HPODE) compound. Conclusion: The crude methanol extract of T. crispa and its fraction F5 possess potent antimalarial activities, and the tentative discovery of the 13(S)-HPODE bioactive compound may serve as a precursor for developing a semisynthetic antiparasitic drug with enhanced efficacy and low toxicity.

Changes in Body Composition During Adjuvant FOLFOX Chemotherapy and Overall Survival in Non-Metastatic Colon Cancer

The impact of longitudinal anthropometric changes during adjuvant chemotherapy on long-term survival in non-metastatic colon cancer is unclear. Herein, we analyzed the prognostic significance of computed tomography (CT)-measured body composition changes in colon cancer patients who underwent surgery followed by adjuvant FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) chemotherapy. Data of 167 patients with stage III or high-risk stage II colon cancer were analyzed. Skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral fat index (VFI), subcutaneous fat index (SFI), and total fat index (TFI) changes during chemotherapy were calculated using preoperative and postchemotherapy CT image data. The Cox proportional hazard model was used to determine the correlation between changes in anthropometric values and overall survival (OS). The median changes (%) in SMI, SMR, VFI, SFI, and TFI over 210 days during chemotherapy were 8.7% (p < 0.001), 3.4% (p = 0.001), −19% (p < 0.001), −3.4% (p = 0.936), and −11.9% (p < 0.001), respectively. Cut-off values of changes in SMI (skeletal muscle index change, SMIC) and SMR (skeletal muscle radiodensity change, SMRC) were defined at −2% and −2 Hounsfield units (HU) respectively, whereas those of changes in VFI (visceral fat index change, VFIC), SFI (subcutaneous fat index change, SFIC), and TFI (total fat index change, TFIC) were based on values that provided the largest χ2 on the Mantel–Cox test. Multivariable analysis revealed that low SMR measured on a postchemotherapy CT scan (hazard ratio, HR: 0.32, 95% confidence interval, CI: 0.15–0.70, p = 0.004) and visceral fat loss of at least 46.57% (HR: 0.31, 95% CI: 0.14–0.69, p = 0.004) were independent poor prognostic factors for OS. Severe visceral fat loss during FOLFOX chemotherapy and low skeletal muscle radiodensity measured on postchemotherapy CT scans are associated with poor OS in stage III and high-risk stage II colon cancer patients.

A Novel Test for Absolute Fit of Evolutionary Models Provides a Means to Correctly Identify the Substitution Model and the Model Tree.

A novel test is described that visualizes the absolute model-data fit of the substitution and tree components of an evolutionary model. The test utilizes statistics based on counts of character state matches and mismatches in alignments of observed and simulated sequences. This comparison is used to assess model-data fit. In simulations conducted to evaluate the performance of the test, the test estimator was able to identify both the correct tree topology and substitution model under conditions where the Goldman–Cox test—which tests the fit of a substitution model to sequence data and is also based on comparing simulated replicates with observed data—showed high error rates. The novel test was found to identify the correct tree topology within a wide range of DNA substitution model misspecifications, indicating the high discriminatory power of the test. Use of this test provides a practical approach for assessing absolute model-data fit when testing phylogenetic hypotheses.

Complement alternative pathway activation associated with pulmonary hypertension in lupus nephritis patients.

Pulmonary hypertension occurs in systemic lupus erythematosus (SLE) for several reasons, such as vasculopathy. Previous studies have indicated that the excessive activation of the complement alternative pathway might be involved in the pathogenesis of lupus nephritis, especially in the absence of factor H or its functional impairment. However, the clinical and pathological significance of the alternative complement activation in lupus nephritis patients with pulmonary hypertension remains elusive. The data on patients with pulmonary hypertension and non-pulmonary hypertension lupus nephritis were retrospectively analyzed in our centre. Major plasma levels of complement components were evaluated. The depositions of Bb, C3d and C5b-9 in the lung specimens of pulmonary hypertension combined with SLE patients were detected by immunofluorescence staining. Among 352 lupus nephritis cases, 24 were diagnosed with pulmonary hypertension and 328 with non-pulmonary hypertension. Higher levels of Bb and lower levels of factor H were detected in the pulmonary hypertension group in comparison with the negative group (P = 0.049, P = 0.024, respectively). Pulmonary hypertension was a risk factor for renal outcome as deduced by the log-rank and Cox test for survival analysis. C3d, C5b-9 and Bb were found to be positive in lung specimens of lupus nephritis patients with pulmonary hypertension. We concluded that activation of the complement alternative pathway may be involved in the pathogenesis of pulmonary hypertension in lupus nephritis.

Analysis of prognostic factors and nomogram for predicting survival for patients with locally resectable esophageal cancer after preoperative chemoradiation therapy

Objective The SEER database was utilized to analyze the prognosis and related factors for patients with locally resectable esophageal cancer undergoing preoperative chemoradiotherapy. A nomogram for predicting survival was established to provide reference for screening patients receiving preoperative chemoradiotherapy. Methods Patients diagnosed with stage T1b-4aN0-3M0(7th version AJCC in 2010) resectable esophageal cancer receiving preoperative chemoradiotherapy between 2010 and 2015 were selected from the SEER database. The survival rate was determined by Kaplan-Meier method. The univariate analysis was performed by log-rank test. The multivariate analysis was conducted by Cox test. The nomogram for survival prediction was established by using R software. The predicting accuracy of the nomogram was evaluated by C-index and calibration curve. Results A total of 1 697 eligible patients were included. Univariate analysis showed that sex, T stage, N stage and tumor differentiation were significantly associated with overall survival (OS) and cancer-specific survival rate (CSS)(all P<0.001), and age (P=0.027) was significantly correlated with OS.Multivariate analysis demonstrated that age, sex, tumor differentiation and N stage were significantly associated with OS.Sex, tumor differentiation, T stage and N stage were significantly correlated with CSS (all P<0.05). After the prognostic factors were included into the nomogram, the C-index for 5-year OS and CSS was 0.60 and 0.61.The model for predicting survival of patients with esophageal squamous cell cancer was established by using the same method. The C-index for the OS and CSS was 0.62 and 0.64. Conclusions Sex, clinical stage and tumor differentiation are prognostic factors of CSS in patients with locally resectable esophageal cancer undergoing preoperative chemoradiotherapy followed by surgery. The nomogram established according to the data above can provide certain reference for the selection of preoperative chemoradiotherapy combined with surgery. Key words: Esophageal neoplasms/preoperative chemoradiotherapy; Prognosis; Nomogram model

DETERMINATION OF THE PREVALENCE AND THE RISK OF DEVELOPING PATHOLOGIES OF THE ORAL MUCOSA IN THE MAULE REGION, CHILE

Introduction There are few studies that report the prevalence of Pathologies of the oral mucosa (POM) in Latin America. The development of these can be associated with environmental, genetic, cultural and social factors. Establishing the prevalence of POM and its association with these factors is very important to create public policies in oral health. Objectives Establish the prevalence and risk factors associated with the development of POM in the Maule Region, Chile. Materials and Methods 2417 people, from all the communities of the Maule Region, were clinically examined by 5 students, previously calibrated with the teachers of the Oral Pathology Unit of the University of Talca. The examination technique, the registers and forms were standarized with the recommendations and the WHO criteria. Age, sex, rural-urban condition, the presence of systemic and oral pathologies, smoking and the clinical diagnostics of POM were taken as parameters. A risk analysis was performed with the Cox and Snell test. Results 17.2% of the subjects presented POM, with a higher prevalence of reactive lesions in the groups of 6, 12 and 15 years and fungal infections in the groups of 35-45 and 65-79 years. The greatest risk of presence of POM was associated with sex and age (groups of 35-45 years and 65-79 years), but not with the urban-rural condition, smoking or the presence of diabetes or hypertension. Discussion The prevalence of POM is very similar to other reports around the world. Most of the POMs detected can be diagnosed and treated by the general dentist. It is important to prioritize the teaching of these POMs in the undergraduate programs and focus the publics heath programs in its treatement. Conclusion The most prevalent POMs are those of reactive etiology and fungal infections in very well-established age groups. Age and gender increase the risk of POMs.

Combined test versus logrank/Cox test in 50 randomised trials

BackgroundThe logrank test and the Cox proportional hazards model are routinely applied in the design and analysis of randomised controlled trials (RCTs) with time-to-event outcomes. Usually, sample size and power calculations assume proportional hazards (PH) of the treatment effect, i.e. the hazard ratio is constant over the entire follow-up period. If the PH assumption fails, the power of the logrank/Cox test may be reduced, sometimes severely. It is, therefore, important to understand how serious this can become in real trials, and for a proven, alternative test to be available to increase the robustness of the primary test.MethodsWe performed a systematic search to identify relevant articles in four leading medical journals that publish results of phase 3 clinical trials. Altogether, 50 articles satisfied our inclusion criteria. We digitised published Kaplan–Meier curves and created approximations to the original times to event or censoring at the individual patient level. Using the reconstructed data, we tested for non-PH in all 50 trials. We compared the results from the logrank/Cox test with those from the combined test recently proposed by Royston and Parmar.ResultsThe PH assumption was checked and reported only in 28% of the studies. Evidence of non-PH at the 0.10 level was detected in 31% of comparisons. The Cox test of the treatment effect was significant at the 0.05 level in 49% of comparisons, and the combined test in 55%. In four of five trials with discordant results, the interpretation would have changed had the combined test been used. The degree of non-PH and the dominance of the p value for the combined test were strongly associated. Graphical investigation suggested that non-PH was mostly due to a treatment effect manifesting in an early follow-up and disappearing later.ConclusionsThe evidence for non-PH is checked (and, hence, identified) in only a small minority of RCTs, but non-PH may be present in a substantial fraction of such trials. In our reanalysis of the reconstructed data from 50 trials, the combined test outperformed the Cox test overall. The combined test is a promising approach to making trial design and analysis more robust.

Stastistical impact of the influence of a restrictive type of infusion therapy on the gastrointestinal motility recovery after pancreaticoduodenectomy

Introduction. Recently, a paradigm shift appears in concepts of perioperative infusion management towards limited infusion volume. The basis for this was research that showed that an excess in volumes of crystalloid solutions intercauses fluid deposition in the intestitinum, disrupting tissue perfusion and oxygenation, which subsequently induces postoperative complications, primarily delayed gastric emptying (DGE).Materials and methods. To evaluate the efficacy of the perioperative treatment regimens, a prospective retrospective study was conducted. The results of pancreaticoduodenectomy (PD) in 78 patients with benign and malignant lesions of the biliopancreatoduodenal zone from 2003 to 2017 were analyzed. From 2015, an enhanced recovery program (ERAS) was started in our clinic for patients undergoing PD. For the purpose of comparative analysis, the patients were divided into two groups: in I group 39 patients were included treated in accordance with the ERAS. In II group, 39 patients were retrospectively selected the treatment of which was carried out according to the traditional method. The volume of intraoperative infusion therapy, cardiac index, lactate, blood pressure, albumin level, time to recovery of gastrointestinal motility (GIM) and the frequency of DGE were studied. Results. Intraoperative infusion therapy by volume of applied solutions was significantly lower in I group (2100 ml 95% CI: [2100; 2300] vs 3300 ml 95% CI: [3100; 3500]; p &lt;0.001). In patients of I group after the use of intraoperative infusion therapy of restrictive type, the medians index of cardiac index according to the Fik‘s formula was 3.6 l / min / m2, lactate – 1.2 mmol / l, systolic blood pressure – 126 mmHg, diastolic blood pressure / 75 mmHg and albumin level in the first postoperative day – 33 g / l. Patients in I group returned to normal diet faster than patients in the group II (1 day 95% CI: [1; 1] vs 6 days 95% CI: [6; 7] p &lt; 0.001). The restriction of intraoperative infusion, removal of nasogastric tube (NGT) with the onset of oral nutrition from the first day significantly affected the significant decrease in the frequency of DGE in I group compared to II (14 (35.9%) versus 6 (15.4%) (by Cox test -Fishera p = 0.0098). In the statistical analysis, according to the ROC curve, the relationship between the volume of intraoperative infusion and the term for removal of the NGT and the recovery of oral nutrition in the postoperative period was revealed.Conclusions. The use of the restrictive type of infusion therapy in the concept of ERAS significantly reduces the реriod of recovery of the gastrointestinal motility, reducing the rate of DGE in patients after PD. The statistically significant factor influencing the possibility of early oral nutrition was the volume of intraoperative infusion in patients after PD.

Early postoperative MRI after resection of brain metastases-complete tumour resection associated with prolonged survival.

This study aimed to investigate the incidence of residual tumour after resection of brain metastases using early postoperative magnetic resonance imaging (MRI) and the influence of residual tumour on overall patient survival. Data from 72 consecutive adult patients undergoing surgery for cerebral metastases over an 18-month study period were retrospectively collected. Early postoperative MRI was used to determine the presence of postoperative residual tumour. Patients were divided into three groups according to the presence of tumour remnant on early postoperative MRI: "no residual tumour", "non-measurable residual tumour" and "measurable residual tumour". Survival analysis (mean estimate survival time) was performed using the Kaplan-Meier and log-rank (mantel cox) tests and compared between groups. Surgical reports were evaluated with regard to the surgeon statement about intraoperative extent of resection (EOR) and compared with the presence of tumour remnant found on the early postoperative MRI. Sixty-eight procedures were followed by early postoperative MRI. MRI verified the presence of "measurable residual tumour" following 15 procedures (22%). MRI confirmed complete resection in 57%. Gross total resection was described by the operating surgeon in 85% of the procedures. There was a significant difference in survival time after surgery between the group having no residual tumour on MRI and the group with measurable residual tumour (p= 0.025). This difference could not be explained by the differences in postoperative radiation therapy. The longest survival was found in patients with non-measurable and no residual tumour on early postoperative MRI, who also received postoperative radiotherapy. Residual tumour was seen on MRI after 22% of the procedures. The intraoperative assessment of EOR performed by the surgeon diverged from the early postoperative MRI in 40% of procedures. Correct assessment of residual tumour thus requires early postoperative MRI. Measurable residual tumour on early postoperative MRI was associated with shorter overall survival independent on postoperative radiotherapy.

Fatigue performance of adhesively cemented glass-, hybrid- and resin-ceramic materials for CAD/CAM monolithic restorations

ObjectiveTo evaluate the fatigue failure load, number of cycles until failure, and survival probability of adhesively cemented materials with different microstructures (glass-, hybrid- and resin-ceramic) used to manufacture CAD/CAM monolithic restorations. MethodsDisc-shaped specimens (n=15; Ø=10mm; thickness=1.0mm) were produced from CAD/CAM blocks as follows: feldspathic (FEL); leucite (LEU); lithium disilicate (LD); zirconia-reinforced lithium silicate (ZRLS); polymer-infiltrated ceramic network (PICN); and resin nanoceramic (RNC). Adhesive cementation was performed onto epoxy discs (dentin analogue- Ø=10mm; thickness=2.5mm). The cemented assemblies were subjected to fatigue testing using a step–stress approach (400N–2200N; step-size of 200N; 10,000 cycles per step; 1.4Hz). Fatigue data were analyzed using Kaplan–Meier and Mantel–Cox (log-rank) tests (p<0.05) and Weibull statistical analysis. Fractographic analysis was also performed. ResultsAll RNC specimens survived the fatigue test (100% probability of survival at 2200N; 100,000 cycles) and presented occlusal deformation in response to loading, while all other tested materials failed in distinct loading steps with radial cracks starting from the bonding surface. LD (1146.7N; 47,333) and ZRLS (1013.3N; 40,666) materials obtained the highest fatigue failure loads and cycles until failure, meanwhile all PICN specimens failed during the first step (0% probability of survival at 400N; 10,000). FEL had similar Weibull modulus to LD and ZRLS and higher than LEU for both load and number of cycles outcomes. SignificanceThe microstructure of adhesively cemented glass-, hybrid- and resin-ceramic CAD/CAM restorative materials influence their response during fatigue testing, which aids in suggesting the best clinical indications.

Primary surgical treatment versus salvage surgery: Results of free flap reconstruction performed in 100 patients with oropharyngeal cancer

This research sought to analyze the functional results of free flap reconstruction in two groups of patients with head and neck cancer: first group started with radiochemotherapy followed by reconstructive surgery, second group underwent initiative surgery. Materials and methodsIn a group of 100 patients, surgery was used as the primary form of treatment in 55 (55%) patients, and the remaining 45 patients (45%) had chemoradiotherapy introduced first. Statistical analysis was performed with Statistica v. 12. The chi-square test and test of proportion were used for categorical data. Student's t-test was used for continuous data. Probability of survival was calculated using the Kaplan–Meier method where the censoring variable was time to death. To compare survival between cohorts, we used the Cox's test. The level of significance was set at p < 0.05. Results and conclusionsInitial radiochemotherapy prior to surgical treatment indicated an increased risk of local tumor recurrence, flap degeneration, and other local complications.

Acute promyelocytic leukemia: Epidemiology, clinical presentation, and outcome over a 10-year period of follow-up at Nanakali Hospital of Erbil city “Single-center study”

BACKGROUND: Among the subtypes of acute myeloid leukemia, acute promyelocytic leukemia (APL) is a distinctive one. There are no published data regarding APL in Kurdistan, Iraq, so the data on this disease is limited. OBJECTIVES: The aims of this study was to recognize the epidemiology, clinical presentation, and to find out the outcome among APL patients at Nanakali hospital in Erbil city. PATIENTS AND METHODS: This was a retrospective study performed at Nanakali Hospital for blood diseases and cancer, Erbil, Iraq. Patients older than 18 years diagnosed with APL from January 2007 to December 2016 were involved in the study. Chi-square test, Kaplan–Meier survival curves, and the Log-Rank (Mantel–Cox) test were used for data analysis. RESULTS: During the period of the study, APL was diagnosed in 90 patients. The mean age (± standard deviations) was 37.5 ± 15.5 years, and the median was 35.5 years, the male: female ratio was 1.3:1. Around 70% were living in urban areas. Regarding clinical presentations: 71.4% of the patients presented with generalized weakness, 64.44% with bleeding, 48.9% with fever, and 2.2% presented with thrombosis. The mean hemoglobin was 8.31 ± 2.69 g/dL, mean white blood cell count of 22.3 ± 29.4 × 109/L, and mean platelet count was 33.37 ± 27.5 × 109/L. The complete remission rate was 68.2%. Early death rate was 46.4% and the 5-year survival rate was 37.8%. CONCLUSION: The clinical and epidemiological features were compared with previously published studies. High-risk patients predominate in our study population. There was a significant association between the overall survival and risk score.

Expression of CD117, MITF and NAT10 and their prognostic values in sinonasal mucosal melanoma

Objective: To investigate the correlation between the expression of CD117, MITF, NAT10 and clinical parameters in sinonasal mucosal melanoma (SNMM). Methods: Formalin-fixed paraffin-embedded tumor specimens of 80 cases of SNMM at the Eye, Ear, Nose and Throat Hospital, Fudan University, from December 1999 to November 2013 were analyzed for CD117, MITF and NAT10 expression by immunohistochemistry. Results: There were 40 men and 40 women. The median age was 61 years, age 26 to 85 years. There was no correlation of the expression of CD117, MITF and NAT10 with the patients' age, gender, tumor site, stage, therapy method and brain metastases (P>0.05). The expression of MITF and NAT10 was associated with lymph node metastasis and the tumors were more likely to metastasize when MITF and NAT10 were positive. However, expression of CD117 had no correlation with lymph node metastasis. Log-rank test revealed that the expression of CD117 was correlated with both three-year and five survival rate (P=0.012, P=0.023; respectively) and patients with tumor having low expression of CD117 had the worse outcome. COX test revealed that low CD117 expression, advanced age and lymph node metastasis were independent risk factors (P<0.05). No significant association was found between the expression of CD117, MITF and NAT10 with disease free survival (P>0.05). Conclusions: Patients with SNMM expressing low level of CD117 have decreased survival rate. Tumors with high level of MITF and NAT10 expression are more likely to metastasize. The expression level of CD117 can be used as an important indicator for the patient survival, and the expression of MITF and NAT10 can be used as a predictor of tumor metastasis.