Ilker Unal

The effect of HER2 expression on cisplatin-based chemotherapy in advanced non-small cell lung cancer patients

IntroductionThe prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial. The relationship between HER2 expression, and platinum resistance and patient survival, was investigated.MethodsSeventy-three consecutive patients (median age, 61 years) with stage IIIB and IV non-small cell lung cancer, admitted between February 2004 and December 2006, were included in this study. Sixty-one patients received gemcitabine, given as two 1250 mg/m2 doses on days 1 and 8 and, cisplatin, given as a 75 mg/m2 dose on day 8. Twelve patients received vinorelbine, given as two 25 mg/m2 doses on day 1 and 8, and cisplatin, given as a 75 mg/m2 dose on day 1. Both treatment paradigms were repeated on a 21-day cycle. Tumor response was evaluated by comparing tumor size on computerized tomography scans before and after three cycles of chemotherapy. HER2 status was examined by immunohistochemical analysis of paraffin-embedded specimens.ResultsHER2 was positive in 21 of 73 patients (28.8%). Of the 21 patients with HER2 positivity, 13 (61.9%) responded to chemotherapy with either a complete response, partial remission, or evidence of stable disease. Of 52 HER2-negative patients, 48 (92.3%) exhibited a response to chemotherapy. The difference in response to therapy between HER2-positive and -negative patients was statistically significant (p = 0.003). The median overall survival duration for all patients was 13 months. Median overall survival time was 14 months for HER2-negative patients and 10 months for HER2-positive patients (log-rank p = 0.007).ConclusionNon-small cell lung cancer patients with high expression of HER2 exhibited resistance to cisplatin-based chemotherapies that are the standard treatment for this disease. Our results indicate that HER2 status may be a predictive and prognostic factor for cisplatin- based therapy response and disease survival.

Evaluation of Choroidal Vascular Changes in Patients with Multiple Sclerosis Using Enhanced Depth Imaging Optical Coherence Tomography

Objective: To evaluate the choroidal thickness in patients with multiple sclerosis (MS) using enhanced depth imaging optical coherence tomography (EDI-OCT). Methods: In this observational comparative study, 68 eyes of 34 MS patients and 60 eyes of 30 healthy subjects were evaluated. All participants underwent complete ophthalmologic examination and OCT scanning. Choroidal thickness measurements were performed at seven points. Results: The mean subfoveal choroidal thickness was reduced significantly in MS patients (310.71 ± 61.85 μm) versus healthy controls (364.85 ± 41.81 μm) (p < 0.001). The difference was also significant at all six measurement points (p < 0.001 for all). Choroidal thickness measurements revealed no significant difference between MS eyes with a prior optic neuritis (ON) history (MS ON) and those without ON history (MS non-ON). Subfoveal choroidal thickness did not correlate with retinal nerve fiber layer and Expanded Disability Status Scale score, but reduced choroidal thickness was associated with longer disease duration (r = -0.28, p = 0.019) in MS patients. Conclusion: In MS patients, choroidal structural changes occur both in MS ON and MS non-ON eyes. The decreased choroidal thickness might provide evidence to support a potential role of vascular dysregulation in the pathophysiology of MS.

The prognostic value of arterial stiffness in systolic heart failure

BACKGROUND Increased arterial stiffness is an indicator of mortality. This study consists of an 18-month follow-up of the mortality in advanced heart failure patients with increased arterial stiffness. METHODS The study followed up 98 patients with a diagnosis of heart failure in NYHA class III and IV (76 males, 22 females and mean age of 60 ± 12 years) with a left ventricular ejection fraction ≤ 35% as determined by the Simpson method. Augmentation index (Aix) and pulse wave propagation velocity (PWV) parameters were used as indicators of arterial stiffness. Aix and PWV values were measured by arteriography. RESULTS 36 patients died. Both Aix and PWV were powerful determinants of mortality, independent of other prognostic variables (p = 0.013, OR: 0.805; p = 0.025, OR: 0.853). A cutoff value for Aix of -14.33 gave 91.2%, 80.3% sensitivity and specificity. A cutoff value for PWV of 11.06 gave 82.4%, 65.4% sensitivity and specificity mortality was predicted. Left ventricular ejection fraction (p = 0.008, OR: 0.859) and B-type natriuretic peptide (p = 0.01, OR: 0.833) was the other independent determinant of mortality. A significant difference was found in both Aix and PWV between the compensated measurements and decompensated heart failure measurements made in 70 patients (p = 0.035, p = 0.048). CONCLUSIONS Measurement of arterial stiffness is a convenient, inexpensive and reliable method for predicting mortality in patients with advanced heart failure.

Usefulness of N-Terminal Pro-B-Type Natriuretic Peptide Increase With Exercise for Predicting Cardiovascular Mortality in Patients With Heart Failure

N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) level at rest is related to left ventricular (LV) function and cardiovascular mortality in patients with heart failure (HF). There are limited and controversial data regarding changes in NT-pro-BNP level during exercise in patients with HF. The aim of this study was to investigate the effects of exercise on NT-pro-BNP levels and the relation between increases in NT-pro-BNP and the LV ejection fraction and cardiovascular mortality in patients with HF. Seventy-five patients with HF (New York Heart Association classes I to III) and 20 healthy subjects were enrolled in the study. Echocardiographic examination was performed. The modified Bruce protocol was used for symptom-limited exercise testing. Levels of NT-pro-BNP were measured at rest and after peak exercise. The patients were followed up for 690 to 840 days for cardiovascular mortality. Exercise induced significant increases in NT-pro-BNP in patients and controls. Except for a relative increase in NT-pro-BNP during exercise (relative DeltaNT-pro-BNP), NT-pro-BNP concentrations at rest and during peak exercise and absolute increases in NT-pro-BNP during exercise (absolute DeltaNT-pro-BNP) were significantly higher in patients with HF (p <0.001). Absolute DeltaNT-pro-BNP was positively correlated with NT-pro-BNP at rest (p <0.001). The level of absolute DeltaNT-pro-BNP was the most important parameter in predicting a LV ejection fraction <30% (p <0.001). Absolute DeltaNT-pro-BNP and LV end-systolic volume were found to be independent predictors of mortality (p = 0.012 and p = 0.015, respectively). In conclusion, exercise induced increases in NT-pro-BNP in patients and healthy subjects. Absolute increase in NT-pro-BNP is a reliable parameter in predicting a low LV ejection fraction and may help in the identification of patients at high risk for mortality.

Evaluation of the Innermost Retinal Layers and Visual Evoked Potentials in Patients with Multiple Sclerosis

ABSTRACT Purpose: The present study was conducted to investigate alterations in the innermost layers of the retina using optical coherence tomography (OCT) and to assess potential associations of structural measures with functional markers in patients with Multiple Sclerosis (MS). Materials and Methods: Ninety-four eyes of 47 MS patients and 60 eyes of 30 healthy individuals were included in the study. All patients underwent complete ophthalmological examination and OCT imaging to analyze peripapillary retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness. Visual evoked potentials (VEPs) and expanded disability status scale (EDSS) score were assessed for MS patients. Results: The average RNFL and GCIPL thicknesses were thinner in MS patients (86.2 ± 11.9 µm and 73.6 ± 9.7 µm, respectively) when compared with those of healthy controls (96.7 ± 8.2 µm and 85.9 ± 4.6 µm, respectively, p < 0.001 for both). Within MS patients, the average RNFL and GCIPL thicknesses were lower in eyes with a prior history of optic neuritis (MS ON) than in eyes with no optic neuritis history (MS non-ON) (p = 0.012 and p < 0.001, respectively). RNFL and GCIPL thicknesses were inversely correlated with VEP latency (r = −0.40, p < 0.001 and r = −0.36, p < 0.001, respectively) in MS patient eyes. There was a correlation between GCIPL thickness and VEP amplitude in eyes with previous ON history (r = 0.34, p = 0.035). No significant correlations were found between OCT measurements and EDSS score. Conclusions: Innermost layers of the retina are highly affected by the pathophysiologic process in MS disease, manifesting as a reduction in RNFL and GCIPL thickness. The structural retinal changes show correlation with alterations in potentials showing the optic pathway function.

Factors Affecting Epilepsy Development and Epilepsy Prognosis in Cerebral Palsy

A study was conducted between November 2006 and October 2009 to determine the factors predicting the presence and prognosis of epilepsy in patients with cerebral palsy. We enrolled 2 groups of patients: 42 with cerebral palsy in group 1 and 56 patients with cerebral palsy and epilepsy in group 2. The subjects in group 2 were considered to have good epilepsy prognosis if they were free of seizures for the previous year; otherwise they were considered to have poor epilepsy prognosis. In group 2, neonatal epilepsy, family history of epilepsy, and moderate to severe mental retardation were significantly higher than in group 1 (P < 0.05). In univariate analysis, neonatal seizures, epileptic activity as measured by electroencephalography, and polytherapy were found to be predictors of poor epilepsy prognosis. Additionally, the need for long-term medication to control seizures unfavorably affects prognosis. In logistic regression analysis, neonatal seizure and interictal epileptic activity in electroencephalography were found to be independent predictors of poor epilepsy outcome. In addition, logistic regression analysis revealed that increasing age reduces the success of epilepsy treatment. Neonatal seizures, family history of epilepsy, and mental retardation were found to be important and independent predictors of development of epilepsy in patients with cerebral palsy.

Diagnostic values of detrusor wall thickness, postvoid residual urine, and prostate volume to evaluate lower urinary tract symptoms in men.

PURPOSE This prospective, controlled clinical study aimed to assess the diagnostic values of detrusor wall thickness (DWT), postvoid residual urine volume (PVR), and prostate volume in men with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS During an 18-month period, a total of 243 males were included in the study. Three groups were assessed due to their International Prostate Symptom Score (IPSS): men with normal lower urinary tracts (n = 51; control group), men with mild LUTS (n = 60; Group 1), and men with moderate to severe LUTS (n = 132; Group 2). DWT, bladder, and prostate volumes and PVR were measured by suprapubic ultrasonography. DWT was measured when the bladder was full (DWT-1) and when it was empty (DWT-2). RESULTS The mean age for the study population was 60.0 ± 0.6 years, while the mean IPSS for the whole group was 8.0 ± 0.4. Both the bladder and prostate volumes in Group 2 were statistically significantly higher than the control group and Group 1. The mean DWT-1 values were significantly lower in the control group when compared to Groups 1 and 2. However, when study groups were compared with each other, no statistical significance was noticed (1.12 vs. 1.17 mm). In contrast, the mean PVR and DWT-2 values were significantly different in each group. There was a significant correlation between IPSS questionnaire results and all individual parameters. CONCLUSION Suprapubic transabdominal ultrasonographic assessment of the lower urinary tract in a noninvasive manner allows the clinician to assess LUTS severity in men without morbidity. Additional studies are necessary to provide further conclusions regarding this clinical procedure.

Evaluating Choroidal Characteristics in Systemic Sclerosis Using Enhanced Depth Imaging Optical Coherence Tomography

ABSTRACT Purpose: To evaluate choroidal thickness (CT) and investigate the involvement of choroidal circulation in patients with systemic sclerosis (SSc). Methods: A total of 120 eyes of 60 SSc patients and 60 eyes of 30 healthy controls were evaluated. CT measurements were performed at the subfoveal region, 1000 µm nasal and 1000 µm temporal to the fovea, using enhanced depth imaging optical coherence tomography. CT measurements were compared between the patients and controls. Results: The average subfoveal, parafoveal nasal and parafoveal temporal CT were significantly thinner in SSc patients when compared with healthy controls (297.77 ± 60.8 µm vs 339.8 ± 50.4 µm; 267.32 ± 51.1 µm vs 308.65 ± 49.9 µm; 270.63 ± 46.3 µm vs 309.22 ± 42.4 µm, respectively; p<0.001 for all). Conclusions: Reduced CT in SSc patients supports the hypothesis of widespread vascular injury, including the ocular microcirculation.

The prevalance of and factors associated with intra-abdominal hypertension on admission Day in critically Ill pediatric patients: A multicenter study

PURPOSE To investigate admission prevalence of intraabdominal hypertension (IAH) and to determine clinical and laboratory characteristics on admission day associated with IAH in critically ill pediatric patients. MATERIALS AND METHODS One hundred thirty newly admitted critically ill pediatric patients were included. Intra-abdominal pressure (IAP) was measured 4 times (every 6 hours) with the bladder pressure method. Data included the demographics, diagnostic category, pediatric logistic organ dysfunction score and pediatric risk of mortality score II, clinical concomitant factors, and conditions potentially associated with increased intra-abdominal pressure. RESULTS Seventy patients (56.1%) had a normal IAP (≤10 mmHg, mean IAP [mmHg] 7.18 ± 1.85), while 60 patients (43.9%) had IAP >10 mmHg (mean IAP [mmHg] 15.46 ± 5.21). Hypothermia frequency, lactate levels, number of patients with oligo-anuria, and mechanical ventilation requirement were higher among patients with IAH compared to patients without IAH (both, P< .05). Hypothermia (OR, 3.899; 95% CI, 1.305-11.655; P< .03) and lactate levels (OR, 1.283 for each mmol/L increase; 95% CI, 1.138-1.447; P< .001) were only significantly associated with IAH. CONCLUSIONS Intra-abdominal hypertension seems to affect nearly half of newly admitted critically ill pediatric patients. Lactate level and the presence of hypothermia seem to be the independent predictors of the presence of IAH.

Comparing the methods of measuring multi-rater agreement on an ordinal rating scale: a simulation study with an application to real data

Agreement among raters is an important issue in medicine, as well as in education and psychology. The agreement among two raters on a nominal or ordinal rating scale has been investigated in many articles. The multi-rater case with normally distributed ratings has also been explored at length. However, there is a lack of research on multiple raters using an ordinal rating scale. In this simulation study, several methods were compared with analyze rater agreement. The special case that was focused on was the multi-rater case using a bounded ordinal rating scale. The proposed methods for agreement were compared within different settings. Three main ordinal data simulation settings were used (normal, skewed and shifted data). In addition, the proposed methods were applied to a real data set from dermatology. The simulation results showed that the Kendalls W and mean gamma highly overestimated the agreement in data sets with shifts in data. ICC4 for bounded data should be avoided in agreement studies with rating scales<5, where this method highly overestimated the simulated agreement. The difference in bias for all methods under study, except the mean gamma and Kendalls W, decreased as the rating scale increased. The bias of ICC3 was consistent and small for nearly all simulation settings except the low agreement setting in the shifted data set. Researchers should be careful in selecting agreement methods, especially if shifts in ratings between raters exist and may apply more than one method before any conclusions are made.